https://www.textbookofcardiology.org/api.php?action=feedcontributions&user=NiloferT&feedformat=atomTextbook of Cardiology - User contributions [en]2024-03-28T19:01:28ZUser contributionsMediaWiki 1.39.5https://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2490Infective Endocarditis2013-12-05T22:13:27Z<p>NiloferT: /* References */</p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>vi</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>ix</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>x</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xi</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiii</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xiv</cite><cite>xv</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|[http://www.echopedia.org/images/2/24/E00404.swf PLAX: vegetations on PMVL]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/6/6a/E00405.swf A4CH]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|[http://www.echopedia.org/images/1/10/E00114.swf PLAX: showing an aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/5/5b/E00117.swf PLAX: aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvi</cite><br />
<br />
[http://circ.ahajournals.org/content/111/23/3167.full The American Heart Association recommendation for specific antimicrobial therapy shows this.]<br />
<br />
[http://eurheartj.oxfordjournals.org/content/30/19/2369.long The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology shows this.]<br />
<br />
===Prophylaxis===<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xvii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xvii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xviii</cite><cite>xix</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xx</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxi</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxii</cite><cite>xxiii</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxiv</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxv</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxvi</cite> hemodialysis, congestive heart failure,<cite>xxvii</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxviii</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxix</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxx</cite><br />
<br />
==References==<br />
<biblio><br />
#i [http://www.nejm.org/doi/full/10.1056/NEJMcp1206782 "Infective Endocarditis - N Engl J Med 2013." 12 Sep. 2013]<br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. "Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years." Circulation.2002;106(19):547. <br />
#iii pmid=12092473<br />
#iv pmid=22870738<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#ix pmid=16767483<br />
#x pmid=19665088<br />
#xi pmid=9046942<br />
#xii pmid=15956145<br />
#xiii pmid=10770721<br />
#xiv pmid=15145856<br />
#xv pmid=2768712<br />
#xvi pmid=19713420 <br />
#xvii pmid=17446442<br />
#xviii [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xix pmid=3259778<br />
#xx pmid=22110106<br />
#xxi pmid=11479467<br />
#xxii pmid=12957420<br />
#xxiii pmid=23906859<br />
#xxiv pmid=15983252<br />
#xxv pmid=18491965<br />
#xxvi pmid=16857604<br />
#xxvii pmid=23906529<br />
#xxviii pmid=23994421<br />
#xxix pmid=16291003<br />
#xxx pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2489Infective Endocarditis2013-12-05T22:09:38Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>vi</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>ix</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>x</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xi</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiii</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xiv</cite><cite>xv</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|[http://www.echopedia.org/images/2/24/E00404.swf PLAX: vegetations on PMVL]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/6/6a/E00405.swf A4CH]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|[http://www.echopedia.org/images/1/10/E00114.swf PLAX: showing an aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/5/5b/E00117.swf PLAX: aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvi</cite><br />
<br />
[http://circ.ahajournals.org/content/111/23/3167.full The American Heart Association recommendation for specific antimicrobial therapy shows this.]<br />
<br />
[http://eurheartj.oxfordjournals.org/content/30/19/2369.long The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology shows this.]<br />
<br />
===Prophylaxis===<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xvii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xvii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xviii</cite><cite>xix</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xx</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxi</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxii</cite><cite>xxiii</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxiv</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxv</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxvi</cite> hemodialysis, congestive heart failure,<cite>xxvii</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxviii</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxix</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxx</cite><br />
<br />
==References==<br />
<biblio><br />
#i [http://www.nejm.org/doi/full/10.1056/NEJMcp1206782 "Infective Endocarditis - N Engl J Med 2013." 12 Sep. 2013]<br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. "Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years." Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Ri´o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#ix pmid=16767483<br />
#x pmid=19665088<br />
#xi pmid=9046942<br />
#xii pmid=15956145<br />
#xiii pmid=10770721<br />
#xiv pmid=15145856<br />
#xv pmid=2768712<br />
#xvi pmid=19713420 <br />
#xvii pmid=17446442<br />
#xviii [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xix pmid=3259778<br />
#xx pmid=22110106<br />
#xxi pmid=11479467<br />
#xxii pmid=12957420<br />
#xxiii pmid=23906859<br />
#xxiv pmid=15983252<br />
#xxv pmid=18491965<br />
#xxvi pmid=16857604<br />
#xxvii pmid=23906529<br />
#xxviii pmid=23994421<br />
#xxix pmid=16291003<br />
#xxx pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2488Infective Endocarditis2013-12-04T19:42:00Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>vi</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>ix</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>x</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xi</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiii</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xiv</cite><cite>xv</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|[http://www.echopedia.org/images/2/24/E00404.swf PLAX: vegetations on PMVL]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/6/6a/E00405.swf A4CH]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|[http://www.echopedia.org/images/1/10/E00114.swf PLAX: showing an aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/5/5b/E00117.swf PLAX: aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvi</cite><br />
<br />
[http://circ.ahajournals.org/content/111/23/3167.full The American Heart Association recommendation for specific antimicrobial therapy shows this.]<br />
<br />
[http://eurheartj.oxfordjournals.org/content/30/19/2369.long The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology shows this.]<br />
<br />
===Prophylaxis===<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xvii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xvii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xviii</cite><cite>xix</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xx</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxi</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxii</cite><cite>xxiii</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxiv</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxv</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxvi</cite> hemodialysis, congestive heart failure,<cite>xxvii</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxviii</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxix</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxx</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Ri´o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#ix pmid=16767483<br />
#x pmid=19665088<br />
#xi pmid=9046942<br />
#xii pmid=15956145<br />
#xiii pmid=10770721<br />
#xiv pmid=15145856<br />
#xv pmid=2768712<br />
#xvi pmid=19713420 <br />
#xvii pmid=17446442<br />
#xviii [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xix pmid=3259778<br />
#xx pmid=22110106<br />
#xxi pmid=11479467<br />
#xxii pmid=12957420<br />
#xxiii pmid=23906859<br />
#xxiv pmid=15983252<br />
#xxv pmid=18491965<br />
#xxvi pmid=16857604<br />
#xxvii pmid=23906529<br />
#xxviii pmid=23994421<br />
#xxix pmid=16291003<br />
#xxx pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2487Infective Endocarditis2013-12-04T19:40:16Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>vi</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>ix</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>x</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xi</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiii</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xiv</cite><cite>xv</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|[http://www.echopedia.org/images/2/24/E00404.swf PLAX: vegetations on PMVL]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/6/6a/E00405.swf A4CH]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|[http://www.echopedia.org/images/1/10/E00114.swf PLAX: showing an aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/5/5b/E00117.swf PLAX: aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvi</cite><br />
<br />
[http://circ.ahajournals.org/content/111/23/3167.full The American Heart Association recommendation for specific antimicrobial therapy shows this.]<br />
<br />
[http://eurheartj.oxfordjournals.org/content/30/19/2369.long The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology shows this.]<br />
<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xvii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xvii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xviii</cite><cite>xix</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xx</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxi</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxii</cite><cite>xxiii</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxiv</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxv</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxvi</cite> hemodialysis, congestive heart failure,<cite>xxvii</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxviii</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxix</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxx</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Ri´o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#ix pmid=16767483<br />
#x pmid=19665088<br />
#xi pmid=9046942<br />
#xii pmid=15956145<br />
#xiii pmid=10770721<br />
#xiv pmid=15145856<br />
#xv pmid=2768712<br />
#xvi pmid=19713420 <br />
#xvii pmid=17446442<br />
#xviii [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xix pmid=3259778<br />
#xx pmid=22110106<br />
#xxi pmid=11479467<br />
#xxii pmid=12957420<br />
#xxiii pmid=23906859<br />
#xxiv pmid=15983252<br />
#xxv pmid=18491965<br />
#xxvi pmid=16857604<br />
#xxvii pmid=23906529<br />
#xxviii pmid=23994421<br />
#xxix pmid=16291003<br />
#xxx pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2486Infective Endocarditis2013-12-04T19:21:30Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|[http://www.echopedia.org/images/2/24/E00404.swf PLAX: vegetations on PMVL]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/6/6a/E00405.swf A4CH]<br>Video courtesy: AMC Echolab, AMC, The Netherlands<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|[http://www.echopedia.org/images/1/10/E00114.swf PLAX: showing an aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|[http://www.echopedia.org/images/5/5b/E00117.swf PLAX: aortic valve vegetation]<br>Video courtesy: J. Vleugels, AMC, The Netherlands<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xviii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i [http://www.nejm.org/doi/full/10.1056/NEJMcp1206782 Bruno Hoen, M.D., Ph.D., and Xavier Duval, M.D., Ph.D. "Infective Endocarditis - N Engl J Med" 2013; 368:1425-1433April 11, 2013DOI: 10.1056/NEJMcp1206782.]<br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. "Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years." Circulation.2002;106(19):547. <br />
#iii pmid=12092473<br />
#iv pmid=22870738<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#ix pmid=16767483<br />
#x pmid=19665088<br />
#xi pmid=9046942<br />
#xii pmid=15956145<br />
#xiii pmid=10770721<br />
#xiv pmid=15145856<br />
#xv pmid=2768712<br />
#xvi pmid=19713420 <br />
#xvii pmid=17446442<br />
#xviii [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xix pmid=3259778<br />
#xx pmid=22110106<br />
#xxi pmid=11479467<br />
#xxii pmid=12957420<br />
#xxiii pmid=23906859<br />
#xxiv pmid=15983252<br />
#xxv pmid=18491965<br />
#xxvi pmid=16857604<br />
#xxvii pmid=23906529<br />
#xxviii pmid=23994421<br />
#xxix pmid=16291003<br />
#xxx pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2485Infective Endocarditis2013-12-03T20:06:56Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xviii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i [http://www.nejm.org/doi/full/10.1056/NEJMcp1206782 Bruno Hoen, M.D., Ph.D., and Xavier Duval, M.D., Ph.D. "Infective Endocarditis - N Engl J Med" 2013; 368:1425-1433April 11, 2013DOI: 10.1056/NEJMcp1206782.]<br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. "Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years." Circulation.2002;106(19):547. <br />
#iii pmid=12092473<br />
#iv pmid=22870738<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#ix pmid=16767483<br />
#x pmid=19665088<br />
#xi pmid=9046942<br />
#xii pmid=15956145<br />
#xiii pmid=10770721<br />
#xiv pmid=15145856<br />
#xv pmid=2768712<br />
#xvi pmid=19713420 <br />
#xvii pmid=17446442<br />
#xviii [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xix pmid=3259778<br />
#xx pmid=22110106<br />
#xxi pmid=11479467<br />
#xxii pmid=12957420<br />
#xxiii pmid=23906859<br />
#xxiv pmid=15983252<br />
#xxv pmid=18491965<br />
#xxvi pmid=16857604<br />
#xxvii pmid=23906529<br />
#xxviii pmid=23994421<br />
#xxix pmid=16291003<br />
#xxx pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2484Infective Endocarditis2013-12-03T20:04:41Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xviii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i [http://www.nejm.org/doi/full/10.1056/NEJMcp1206782 Bruno Hoen, M.D., Ph.D., and Xavier Duval, M.D., Ph.D. "Infective Endocarditis - N Engl J Med" 2013; 368:1425-1433April 11, 2013DOI: 10.1056/NEJMcp1206782.]<br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. "Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years." Circulation.2002;106(19):547. <br />
#iii pmid=12092473<br />
#iv pmid=22870738<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#x pmid=16767483<br />
#xi pmid=19665088<br />
#xii pmid=9046942<br />
#xiii pmid=15956145<br />
#xiv pmid=10770721<br />
#xv pmid=15145856<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii pmid=17446442<br />
#xix [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xx pmid=3259778<br />
#xxi pmid=22110106<br />
#xxii pmid=11479467<br />
#xxiii pmid=12957420<br />
#xxiv pmid=23906859<br />
#xxv pmid=15983252<br />
#xxvi pmid=18491965<br />
#xxvii pmid=16857604<br />
#xxviii pmid=23906529<br />
#xxix pmid=23994421<br />
#xxx pmid=16291003<br />
#xxxi pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2483Infective Endocarditis2013-12-03T18:17:15Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xviii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v pmid=23720451<br />
#vi pmid=21685200<br />
#vii pmid=22624837<br />
#viii pmid=16028160<br />
#x pmid=16767483<br />
#xi pmid=19665088<br />
#xii pmid=9046942<br />
#xiii pmid=15956145<br />
#xiv pmid=10770721<br />
#xv pmid=15145856<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii pmid=17446442<br />
#xix <br />
#xx [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xxi pmid=3259778<br />
#xxii <br />
#xxiii pmid=22110106<br />
#xxiv pmid=11479467<br />
#xxv pmid=12957420<br />
#xxvi pmid=23906859<br />
#xxvii pmid=15983252<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2482Infective Endocarditis2013-11-29T14:11:15Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xviii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x pmid=16767483<br />
#xi pmid=19665088<br />
#xii pmid=9046942<br />
#xiii pmid=15956145<br />
#xiv pmid=10770721<br />
#xv pmid=15145856<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii pmid=17446442<br />
#xix <br />
#xx [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xxi pmid=3259778<br />
#xxii <br />
#xxiii pmid=22110106<br />
#xxiv pmid=11479467<br />
#xxv pmid=12957420<br />
#xxvi pmid=23906859<br />
#xxvii pmid=15983252<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2481Infective Endocarditis2013-11-29T13:59:19Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xviii</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii pmid=9046942<br />
#xiii pmid=15956145<br />
#xiv pmid=10770721<br />
#xv pmid=15145856<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii pmid=17446442<br />
#xix <br />
#xx [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xxi pmid=3259778<br />
#xxii <br />
#xxiii pmid=22110106<br />
#xxiv pmid=11479467<br />
#xxv pmid=12957420<br />
#xxvi pmid=23906859<br />
#xxvii pmid=15983252<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2480Infective Endocarditis2013-11-29T11:45:01Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv pmid=10770721<br />
#xv pmid=15145856<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii pmid=17446442<br />
#xix <br />
#xx [http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362 The National Center for Biotechnology Information. "UniSTS." 2006. 20 Nov. 2013]<br />
#xxi pmid=3259778<br />
#xxii pmid=15956145<br />
#xxiii pmid=22110106<br />
#xxiv pmid=11479467<br />
#xxv pmid=12957420<br />
#xxvi pmid=23906859<br />
#xxvii pmid=15983252<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2479Infective Endocarditis2013-11-29T00:57:12Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii pmid=22110106<br />
#xxiv pmid=11479467<br />
#xxv pmid=12957420<br />
#xxvi pmid=23906859<br />
#xxvii pmid=15983252<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2478Infective Endocarditis2013-11-28T23:28:55Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii pmid=15983252<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2477Infective Endocarditis2013-11-28T23:24:43Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii Thuny, Franck et al. "Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography A Prospective Multicenter Study." Circulation 112.1 (2005): 69-75.<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx pmid=23906529<br />
#xxxi pmid=23994421<br />
#xxxii pmid=16291003<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2476Infective Endocarditis2013-11-28T23:16:54Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii Thuny, Franck et al. "Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography A Prospective Multicenter Study." Circulation 112.1 (2005): 69-75.<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx Nakagawa, Tom et al. "Clinical features of infective endocarditis: Comparison between the 1990s and 2000s." Journal of cardiology (2013).<br />
#xxxi Bikdeli, Behnood et al. "Trends in Hospitalization Rates and Outcomes of Endocarditis among Medicare Beneficiaries." Journal of the American College of Cardiology (2013).<br />
#xxxii Wang, Andrew et al. "The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort." American heart journal 150.5 (2005): 1086-1091.<br />
#xxxiii pmid=20159831<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2475Infective Endocarditis2013-11-28T23:13:09Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi pmid=2768712<br />
#xvii pmid=19713420 <br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii Thuny, Franck et al. "Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography A Prospective Multicenter Study." Circulation 112.1 (2005): 69-75.<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx Nakagawa, Tom et al. "Clinical features of infective endocarditis: Comparison between the 1990s and 2000s." Journal of cardiology (2013).<br />
#xxxi Bikdeli, Behnood et al. "Trends in Hospitalization Rates and Outcomes of Endocarditis among Medicare Beneficiaries." Journal of the American College of Cardiology (2013).<br />
#xxxii Wang, Andrew et al. "The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort." American heart journal 150.5 (2005): 1086-1091.<br />
#xxxiii Lalani, Tahaniyat et al. "Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis use of propensity score and instrumental variable methods to adjust for treatment-selection bias." Circulation 121.8 (2010): 1005-1013.<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2474Infective Endocarditis2013-11-28T22:51:26Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii pmid=16028160<br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi pmid=2768712<br />
#xvii "Guidelines on the prevention, diagnosis, and treatment of infective ..." 2012. 20 Nov. 2013 <http://eurheartj.oxfordjournals.org/content/30/19/2369/T17.expansion.html><br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii Thuny, Franck et al. "Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography A Prospective Multicenter Study." Circulation 112.1 (2005): 69-75.<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx Nakagawa, Tom et al. "Clinical features of infective endocarditis: Comparison between the 1990s and 2000s." Journal of cardiology (2013).<br />
#xxxi Bikdeli, Behnood et al. "Trends in Hospitalization Rates and Outcomes of Endocarditis among Medicare Beneficiaries." Journal of the American College of Cardiology (2013).<br />
#xxxii Wang, Andrew et al. "The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort." American heart journal 150.5 (2005): 1086-1091.<br />
#xxxiii Lalani, Tahaniyat et al. "Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis use of propensity score and instrumental variable methods to adjust for treatment-selection bias." Circulation 121.8 (2010): 1005-1013.<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2473Infective Endocarditis2013-11-28T22:40:16Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi pmid=21685200<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii Miro, JM. "Staphylococcus aureus native valve infective endocarditis: report of ..." 2005. <http://www.ncbi.nlm.nih.gov/pubmed/16028160><br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi Mügge, A. "PubMed." 1989. <http://www.ncbi.nlm.nih.gov/pubmed/2768712><br />
#xvii "Guidelines on the prevention, diagnosis, and treatment of infective ..." 2012. 20 Nov. 2013 <http://eurheartj.oxfordjournals.org/content/30/19/2369/T17.expansion.html><br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii Thuny, Franck et al. "Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography A Prospective Multicenter Study." Circulation 112.1 (2005): 69-75.<br />
#xxviii pmid=18491965<br />
#xxix pmid=16857604<br />
#xxx Nakagawa, Tom et al. "Clinical features of infective endocarditis: Comparison between the 1990s and 2000s." Journal of cardiology (2013).<br />
#xxxi Bikdeli, Behnood et al. "Trends in Hospitalization Rates and Outcomes of Endocarditis among Medicare Beneficiaries." Journal of the American College of Cardiology (2013).<br />
#xxxii Wang, Andrew et al. "The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort." American heart journal 150.5 (2005): 1086-1091.<br />
#xxxiii Lalani, Tahaniyat et al. "Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis use of propensity score and instrumental variable methods to adjust for treatment-selection bias." Circulation 121.8 (2010): 1005-1013.<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2472Infective Endocarditis2013-11-28T22:24:49Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
*Dental procedures require prophylaxis:<br />
**Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
*Respiratory tract procedures require prophylaxis:<br />
**Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
#i "Infective Endocarditis — NEJM." 2013. 12 Sep. 2013 <http://www.nejm.org/doi/full/10.1056/NEJMcp1206782><br />
#ii Cabell CH, Fowler VG, Jr, Engemann JJ, et al. Endocarditis in the elderly: Incidence, surgery, and survival in 16,921 patients over 12 years. Circulation.2002;106(19):547. <br />
#iii Miró, José M, Ana del Rı́o, and Carlos A Mestres. "Infective endocarditis in intravenous drug abusers and HIV-1 infected patients." Infectious disease clinics of North America 16.2 (2002): 273-295.<br />
#iv Ipek, Esra Gucuk et al. "Infections of implantable cardiac rhythm devices: predisposing factors and outcome." Acta cardiologica 67.3 (2012): 303.<br />
#v Pappelbaum, Karin I et al. "Ultra-Large von Willebrand Factor Fibers Mediate Luminal Staphylococcus Aureus Adhesion to an Intact Endothelial Cell Layer under Shear Stress." Circulation (2013).<br />
#vi Rasmussen, RV. "Prevalence of infective endocarditis in patients with Staphylococcus ..." 2011. <http://www.ncbi.nlm.nih.gov/pubmed/21685200><br />
<br />
#vii Duval, Xavier et al. "Temporal Trends in Infective Endocarditis in the Context of Prophylaxis Guideline ModificationsThree Successive Population-Based Surveys." Journal of the American College of Cardiology 59.22 (2012): 1968-1976.<br />
#viii Miro, JM. "Staphylococcus aureus native valve infective endocarditis: report of ..." 2005. <http://www.ncbi.nlm.nih.gov/pubmed/16028160><br />
#ix Rasmussen, Rasmus V et al. "Prevalence of infective endocarditis in patients with Staphylococcus aureus bacteraemia: the value of screening with echocardiography." European Journal of Echocardiography 12.6 (2011): 414-420.<br />
#x Lalani, T et al. "Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database." European Journal of Clinical Microbiology and Infectious Diseases 25.6 (2006): 365-368.<br />
#xi McDonald, Jay R. "Acute infective endocarditis." Infectious disease clinics of North America 23.3 (2009): 643-664.<br />
#xii Das, MD, M et al. "Infective endocarditis caused by HACEK microorganisms." Annual review of medicine 48.1 (1997): 25-33.<br />
#xiii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xiv Li, Jennifer S et al. "Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis." Clinical infectious diseases 30.4 (2000): 633-638.<br />
#xv Evangelista, A, and MT Gonzalez-Alujas. "Echocardiography in infective endocarditis." Heart 90.6 (2004): 614-617.<br />
#xvi Mügge, A. "PubMed." 1989. <http://www.ncbi.nlm.nih.gov/pubmed/2768712><br />
#xvii "Guidelines on the prevention, diagnosis, and treatment of infective ..." 2012. 20 Nov. 2013 <http://eurheartj.oxfordjournals.org/content/30/19/2369/T17.expansion.html><br />
#xviii Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xix Wilson, Walter et al. "Prevention of Infective Endocarditis Guidelines From the American Heart Association: A Guideline From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee, Council on Cardiovascular Disease in the Young, and the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and the Quality of Care and Outcomes Research Interdisciplinary Working Group." Circulation 116.15 (2007): 1736-1754.<br />
#xx "UniSTS." 2006. 20 Nov. 2013 <http://www.ncbi.nlm.nih.gov/genome/sts/sts.cgi?uid=85362><br />
#xxi Hollanders, G et al. "A six years review on 53 cases of infective endocarditis: clinical, microbiological and therapeutical features." Acta cardiologica 43.2 (1987): 121-132.<br />
#xxii Baddour, Larry M et al. "Infective Endocarditis Diagnosis, Antimicrobial Therapy, and Management of Complications: A Statement for Healthcare Professionals From the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: Endorsed by the Infectious Diseases Society of America." Circulation 111.23 (2005): e394-e434.<br />
#xxiii Kiefer, T, and T Kiefer. "Article - JAMA Network." 2011. <https://jama.jamanetwork.com/article.aspx?articleid=1104665&link=xref><br />
#xxiv Meine, Trip J et al. "Cardiac conduction abnormalities in endocarditis defined by the Duke criteria." American heart journal 142.2 (2001): 280-285.<br />
#xxv Homma, Shunichi, and Cairistine Grahame-Clarke. "Toward reducing embolic complications from endocarditis." Journal of the American College of Cardiology 42.5 (2003): 781-783.<br />
#xxvi Hubert, Sandrine et al. "Prediction of Symptomatic Embolism in Infective EndocarditisConstruction and Validation of a Risk Calculator in a Multicenter Cohort." Journal of the American College of Cardiology 62.15 (2013): 1384-1392.<br />
#xxvii Thuny, Franck et al. "Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography A Prospective Multicenter Study." Circulation 112.1 (2005): 69-75.<br />
#xxviii Snygg-Martin, U. "Cerebrovascular complications in patients with left-sided infective ..." 2008. <http://www.ncbi.nlm.nih.gov/pubmed/18491965><br />
#xxix Kourany, WM. "Influence of diabetes mellitus on the clinical manifestations and ..." 2006. <http://www.ncbi.nlm.nih.gov/pubmed/16857604><br />
#xxx Nakagawa, Tom et al. "Clinical features of infective endocarditis: Comparison between the 1990s and 2000s." Journal of cardiology (2013).<br />
#xxxi Bikdeli, Behnood et al. "Trends in Hospitalization Rates and Outcomes of Endocarditis among Medicare Beneficiaries." Journal of the American College of Cardiology (2013).<br />
#xxxii Wang, Andrew et al. "The use and effect of surgical therapy for prosthetic valve infective endocarditis: a propensity analysis of a multicenter, international cohort." American heart journal 150.5 (2005): 1086-1091.<br />
#xxxiii Lalani, Tahaniyat et al. "Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis use of propensity score and instrumental variable methods to adjust for treatment-selection bias." Circulation 121.8 (2010): 1005-1013.<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2471Infective Endocarditis2013-11-28T21:47:07Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
!Roth Spots<br />
|-<br />
|[[Image:Heart4.JPG|500px]]<br />
|}<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
<br />
Dental procedures require prophylaxis:<br />
<br />
*Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
<br />
Respiratory tract procedures require prophylaxis:<br />
<br />
*Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=File:Heart4.JPG&diff=2470File:Heart4.JPG2013-11-28T21:38:29Z<p>NiloferT: </p>
<hr />
<div></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2469Infective Endocarditis2013-11-28T04:54:18Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0"<br />
|-<br />
|[[Image:Heart1.JPG|500px]]<br />
|-<br />
!Large lesions on non coronary and left coronary cusps normal valves otherwise<br />
|- <br />
|[[Image:Heart2.JPG|500px]]<br />
|-<br />
!Vegetations on tricuspid valve<br />
|-<br />
|[[Image:Heart3.JPG|500px]]<br />
|-<br />
!Septic emboli to the conjunctiva<br />
|}<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
===Roth Spots===<br />
[[Image: |Roth Spots]]<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
<br />
Dental procedures require prophylaxis:<br />
<br />
*Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
<br />
Respiratory tract procedures require prophylaxis:<br />
<br />
*Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=File:Heart3.JPG&diff=2468File:Heart3.JPG2013-11-28T04:46:34Z<p>NiloferT: </p>
<hr />
<div></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=File:Heart2.JPG&diff=2467File:Heart2.JPG2013-11-28T04:45:13Z<p>NiloferT: </p>
<hr />
<div></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=File:Heart1.JPG&diff=2466File:Heart1.JPG2013-11-28T04:43:14Z<p>NiloferT: </p>
<hr />
<div></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2465Infective Endocarditis2013-11-28T04:16:10Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
[[Image: |Large lesions on noncoronary and left coronary cusps normal valves otherwise.]]<br />
<br />
[[Image: |Vegetations on tricuspid valve.]]<br />
<br />
[[Image: |Septic emboli to the conjunctiva.]]<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%.<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
===Roth Spots===<br />
[[Image: |Roth Spots]]<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis:<cite>xviii</cite><br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
*Previous infective endocarditis<br />
*Congenital heart disease (CHD)<br />
**Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
**Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
**Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
*Cardiac transplantation recipients who develop cardiac valvulopathy<br />
<br />
Dental procedures require prophylaxis:<br />
<br />
*Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
<br />
Respiratory tract procedures require prophylaxis:<br />
<br />
*Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients.<cite>xix</cite><br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients.<cite>xxiv</cite> <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk.<cite>xxvxxvi</cite> Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality.<cite>xxvii</cite> Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic.<cite>xxviii</cite> <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes,<cite>xxix</cite> hemodialysis, congestive heart failure,<cite>xxx</cite> complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%.<cite>xxxi</cite> Prosthetic valve endocarditis has a significant in hospital mortality of ~24%,<cite>xxxii</cite> while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically.<cite>xxxiii</cite><br />
<br />
==References==<br />
<biblio><br />
<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2464Infective Endocarditis2013-11-28T02:13:34Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
[[Image: |Large lesions on noncoronary and left coronary cusps normal valves otherwise.]]<br />
<br />
[[Image: |Vegetations on tricuspid valve.]]<br />
<br />
[[Image: |Septic emboli to the conjunctiva.]]<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Endocarditis of prosthetic mitral valve<br />
|-<br />
|http://www.echopedia.org/images/2/24/E00404.swf<br />
|http://www.echopedia.org/images/6/6a/E00405.swf<br />
|-<br />
!colspan="2"|Endocarditis of the aortic valve<br />
|-<br />
|http://www.echopedia.org/images/1/10/E00114.swf<br />
|http://www.echopedia.org/images/5/5b/E00117.swf<br />
|}<br />
<br />
===Roth Spots==<br />
[[Image: |Roth Spots]]<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis :<br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
- Previous infective endocarditis<br />
- Congenital heart disease (CHD)<br />
- Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
- Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
- Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
- Cardiac transplantation recipients who develop cardiac valvulopathy<br />
<br />
Dental procedures require prophylaxis:<br />
<br />
- Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
<br />
Respiratory tract procedures require prophylaxis:<br />
<br />
- Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients .<br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients . <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk . Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality . Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic. <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes , hemodialysis, congestive heart failure , complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%. Prosthetic valve endocarditis has a significant in hospital mortality of ~24%, while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically .<br />
<br />
==References==<br />
<biblio><br />
<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2463Infective Endocarditis2013-11-28T01:42:48Z<p>NiloferT: </p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
[[Image: |Large lesions on noncoronary and left coronary cusps normal valves otherwise.]]<br />
<br />
[[Image: |Vegetations on tricuspid valve.]]<br />
<br />
[[Image: |Septic emboli to the conjunctiva.]]<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class="wikitable" cellpadding="0" cellspacing="0" border="0" width="700px"<br />
|-<br />
!colspan="2"|Major Criteria (microbiology)<br />
|-<br />
|Typical organisms x 2 blood cultures <br />
|e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
|-<br />
|Persistent bacteremia <br />
|With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
|-<br />
|Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800<br />
|<br />
|- <br />
!colspan="2"|Major Criteria (valve)<br />
|-<br />
|Echocardiogram with evidence of vegetation <br />
|TTE or TEE<br />
|-<br />
|New valvular regurgitation<br />
|<br />
|-<br />
!colspan="2"|Minor Criteria <br />
|-<br />
|Predisposing cardiac condition or IV drug use<br />
|<br />
|-<br />
|Fever <br />
|>38 degrees celsius or <br />
<br />
>100.4 fahrenheit)<br />
|-<br />
|Vascular phenomena <br />
|major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
|-<br />
|Immune phenomena <br />
|glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
|-<br />
|Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE<br />
|<br />
|}<br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively.<cite>xvxvi</cite><br />
<br />
===Endocarditis of prosthetic mitral valve===<br />
<br />
http://www.echopedia.org/images/2/24/E00404.swf<br />
http://www.echopedia.org/images/6/6a/E00405.swf<br />
<br />
===Endocarditis of the aortic valve===<br />
<br />
http://www.echopedia.org/images/1/10/E00114.swf<br />
http://www.echopedia.org/images/5/5b/E00117.swf<br />
<br />
===Roth Spots==<br />
[[Image: |Roth Spots]]<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves.<cite>xvii</cite><br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
===Prophylaxis===<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis :<br />
<br />
*Any prosthetic heart valve, or prosthetic material used for valve repair<br />
- Previous infective endocarditis<br />
- Congenital heart disease (CHD)<br />
- Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
- Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
- Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
- Cardiac transplantation recipients who develop cardiac valvulopathy<br />
<br />
Dental procedures require prophylaxis:<br />
<br />
- Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
<br />
Respiratory tract procedures require prophylaxis:<br />
<br />
- Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients .<br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis.<cite>xxxxi</cite> It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%).<cite>xxii</cite> The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30%.<cite>xxiii</cite> <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients . <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk . Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality . Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic. <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes , hemodialysis, congestive heart failure , complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%. Prosthetic valve endocarditis has a significant in hospital mortality of ~24%, while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically .<br />
<br />
==References==<br />
<biblio><br />
<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Infective_Endocarditis&diff=2462Infective Endocarditis2013-11-28T00:50:08Z<p>NiloferT: Created page with "==Introduction== Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by ..."</p>
<hr />
<div>==Introduction==<br />
Infective endocarditis (IE) is an infectious and inflammatory process of endothelial lining of the heart structures and valves. It is most commonly caused by bacterial and fungal infections, although non-infective causes of endocarditis occur, this chapter will concentrate on infective causes.<br />
<br />
==Epidemiology==<br />
The global incidence of endocarditis varies in literature with a wide range of 3 to 9 cases per 100,000 person years<cite>i</cite>. Although it appears that in the elderly population the incidence rate is remarkably higher reaching 20.4 cases per 100,000 person years<cite>ii</cite>. This is likely related to increased hospitalization, valve replacement surgeries and intra-cardiac instrumentation in the elderly population. In addition to aging, the prevalence of chronic diseases predisposing to bacteremias such as human immunodeficiency syndrome, end-stage renal disease, organ transplantations and diabetes have also increased. IE is a dreaded complication of intravenous drug use, most commonly affecting the tricuspid valve, with a yearly incidence of 1-5% among chronic users<cite>iii</cite>. IE related to implantable rhythm devices remains relatively low but is on the rise due to increased patient population requiring rhythm devices<cite>iv</cite>.<br />
<br />
==Pathogenesis and Causes==<br />
Generally, endothelial damage to heart valves predisposes to bacterial infections as it is generally resistant to bacterial infections. This may be caused by turbulent blood flow in damaged valves, septal defects or instrumentation. Although, recent evidence suggests that A-type von Willebrand factor may contribute to S. aureus binding in endothelial intact valves<cite>v</cite>. Specifically, in patients with S. aureus bacteremia, native valve endocarditis was reported to be in 19% of patients, and 38% in those with prosthetic valves<cite>vi</cite>. <br />
<br />
While many microorganisms have been implicated in endocarditis syndromes, few infectious bacteria account for the majority of cases. <br />
<br />
Staphylococcal endocarditis is most commonly caused by S.aureus. It is the most lethal organism implicated in endocarditis with mortality rates approaching 37%<cite>vii</cite>. S.aureus is a highly virulent organism and may cause significant valve destruction, abscess formation, conduction abnormalities and embolization. It often enters the bloodstream from the nares or skin. Patients with left sided involvement often require surgery. In intravenous drug users is the most common cause of IE<cite>viii</cite>. Patients who are found to have Staphylococcal bacteremia should undergo echocardiography to rule out endocarditis. The prevalence of endocarditis in patients with S.aureus bacteremia was reported in 19% and 38% in those with native and prosthetic valves respectively<cite>ix</cite>.<br />
<br />
S. epidermidis is an important cause of prosthetic valve endocarditis and is associated with a particularly high incidence of heart failure and valvular abscess formation and a mortality rate of 36%<cite>x</cite>.<br />
<br />
Viridans group streptococcus often account for 30% of community acquired native valve endocarditis<cite>xi</cite>. They are part of the oral cavity flora and may gain entry into the bloodstream via dental caries or trauma. The virulence is generally low and eradication rates are high.<br />
<br />
Streptococcus bovis is part of the lower gastrointestinal and urinary tract and is commonly implicated in underlying colorectal disease if found to be the cause of endocarditis. Patients who are found to have S.bovis endocarditis should undergo a colonoscopy to exclude colorectal malignancy or polyps.<br />
<br />
Enterococcal endocarditis is part of the gastrointestinal and genitourinary flora and is often implicated in patients in patients undergoing genitourinary or gastrointestinal procedures. Enterococcal endocarditis is generally difficult to treat due to high rates of antibiotic resistance and often require multi-drug regimen.<br />
<br />
Gram negative bacilli IE is rather uncommon, the HACEK organisms (Haemophillus spp, Actinobacillus, Cardiobacterium hominis, Eikenella corrodens, Kingella spp) are responsible for approximately 3% of endocarditis cases and are the most common cause for gram negative endocarditis in non-intravenous drug users<cite>xii</cite>. Non-HACEK organisms are a rare cause for endocarditis and only account for <1-2% of causes. <br />
<br />
Fungal endocarditis occurs in patients who receive prolonged parenteral nutrition or antibiotics through intravenous catheters. It has also been described in intravenous drug users. Patients are often immunocompromised. The most common organisms implicated are Candida species, Histoplasma capsulatum, and Aspergillus. Mortality rates associated with fungal endocarditis exceed 80%<cite>xiii</cite>. <br />
<br />
[[Image: |Large lesions on noncoronary and left coronary cusps normal valves otherwise.]]<br />
<br />
[[Image: |Vegetations on tricuspid valve.]]<br />
<br />
[[Image: |Septic emboli to the conjunctiva.]]<br />
<br />
==Diagnosis==<br />
Several diagnostic criteria have been proposed for the diagnosis of IE. In clinical practice, it is the global clinical picture that leads to decision making in the diagnosis and treatment of endocarditis. The modified DUKE criteria for diagnosis is often widely used, with a sensitivity and specificity approaching ~80%<cite>xiv</cite> The DUKE criteria divides into Definite IE, Possible IE, or Rejected IE. It uses Major criteria (microbiology, valvular abnormalities) and Minor criteria (systemic symptoms described below). Using the diagnostic criteria for IE should not override clinical judgment.<br />
<br />
===Definite IE:===<br />
<br />
*Pathologic Criteria:<br />
**Microorganisms demonstrated by culture or histologic examination of vegetation, a vegetation that has embolized, or an intracardiac abscess specimen OR pathologic lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis<br />
*Clinical Criteria<br />
**2 major criteria '''OR''' 1 major and 3 minor criteria '''OR''' 5 minor criteria<br />
<br />
===Possible IE:===<br />
<br />
*1 Major criterion + 1 Minor criterion '''OR''' 3 minor criteria<br />
<br />
===Rejected IE:===<br />
<br />
*Firm alternate diagnosis explaining evidence of IE '''OR'''<br />
*Resolution of IE syndrome with =<4 days of antibiotics therapy '''OR'''<br />
*No pathologic evidence of IE at surgery or autopsy with antibiotic therapy for =<4 days '''OR'''<br />
*Does not meet criteria for IE, as above<br />
<br />
{| class<br />
|-<br />
!Major Criteria (microbiology)<br />
!<br />
|-<br />
|Typical organisms x 2 blood cultures |e.g S. viridans, S. bovis, HACEK (Haemophilus spp, Aggregatibacter, Cardiobacterium hominis, Eikenella spp, Kingella kingae), S. aureus, Enterecoccus with no primary source<br />
Persistent bacteremia With blood cultures drawn >12 hours apart OR 3 out of 3, or 3 out of 4 positive blood cultures<br />
Single positive blood culture for Coxiella burnetti or antiphase I IgG antibody titer >1:800 <br />
Major Criteria (valve) <br />
Echocardiogram with evidence of vegetation TTE or TEE<br />
New valvular regurgitation <br />
Minor Criteria <br />
Predisposing cardiac condition or IV drug use <br />
Fever >38 degrees celsius or >100.4 fahrenheit)<br />
Vascular phenomena major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, janeway lesions<br />
Immune phenomena glomerulonephritis, Osler nodes, Roth spots, positive RF<br />
Positive blood culture not meeting above major criteria or serological evidence of active infection with organism consistent with IE <br />
<br />
The sensitivity of detecting on echocardiogram varies. Transthoracic and transesophageal echocardiogram sensitivities for detecting vegetations are 50% and 90% respectively .<br />
<br />
Endocarditis of prosthetic mitral valve <br />
<br />
http://www.echopedia.org/images/2/24/E00404.swf<br />
http://www.echopedia.org/images/6/6a/E00405.swf<br />
<br />
Endocarditis of the aortic valve<br />
<br />
http://www.echopedia.org/images/1/10/E00114.swf<br />
http://www.echopedia.org/images/5/5b/E00117.swf<br />
<br />
Roth Spots<br />
<br />
<br />
Roth Spots<br />
<br />
<br />
==Therapy==<br />
Empiric therapy for infective endocarditis should only be used when there is a high index of suspicion in the absence of positive blood cultures. Three blood cultures should be drawn 30 minutes apart prior to initiating treatment. When there a high clinical probability of infective endocarditis in acute settings, empiric therapy is geared towards MRSA and coagulase negative staphylococcus. In healthcare settings and in injection drug users coverage should also include gram negative bacilli. Options for such therapy include Vancomycin + Gentamicin or, Nafcillin/Oxacillin + Tobramycin/Gentamicin.<br />
<br />
When considering coverage for subacute endocarditis, coveraged is geared more towards streprococci spp. Options commonly include Ampicillin/Sulbactam + Gentamicin/Tobramycin, or Ceftriaxone + Vancomycin. <br />
<br />
As soon as blood cultures become available antibiotics should be adjusted to target the identified microorganisms. <br />
<br />
In cases of prosthetic valve endocarditis (PVE), microbiological activity depends on early (<2 months post op) or late (>2 months post op). In early PVE S.aureus accounts for 40% of the cases, followed by coagulase negative staphylococcus (17%). In late PVE coagulase negative staphylococcus accounts for 20% of cases, followed by S. aureus (18%). Coverage for enterococci, streptococci, and gram negative should be considered in empiric therapy in both groups. Rifampin + Vancomycin + Gentamicin should be initiated for PVE <12 post op. Suspected PVE >12 months post op may be treated with the same regimen as for native valves .<br />
<br />
The American Heart Association recommendation for specific antimicrobial therapy is shown below:<br />
http://circ.ahajournals.org/content/111/23/3167.full<br />
<br />
The guidelines on treatment of endocarditis from the task force for treatment of Infective endocarditis of the European Society of Cardiology is shown below:<br />
http://eurheartj.oxfordjournals.org/content/30/19/2369.long<br />
<br />
Prophylaxis<br />
<br />
According the American Heart Association guidelines published in 2007 the following groups of patients are considered to be high-risk and require prophylaxis :<br />
<br />
- Any prosthetic heart valve, or prosthetic material used for valve repair<br />
- Previous infective endocarditis<br />
- Congenital heart disease (CHD)<br />
- Unrepaired cyanotic CHD, including all palliative shunts and conduits<br />
- Completely repaired congenital heart defect with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure<br />
- Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)<br />
- Cardiac transplantation recipients who develop cardiac valvulopathy<br />
<br />
Dental procedures require prophylaxis:<br />
<br />
- Manipulation of gingival tissue, or the periapical region of teeth or perforation of oral mucosa<br />
<br />
Respiratory tract procedures require prophylaxis:<br />
<br />
- Incision or biopsy of the respiratory mucosa, or procedures involving treatment of abscess of empyema<br />
<br />
Antibiotic prophylaxis is also recommended for any procedures on infected skin/skin structures or musculoskeletal tissue in high risk patients .<br />
<br />
==Complications of Endocarditis==<br />
Common complications arising from IE can be divided into local and systemic. Local complications often arise from direct extension of the infection into cardiac structures. Systemic complications arise from embolization and bacteremias. <br />
<br />
Heart failure occurs in 26-30% of patients with endocarditis . It may occur acutely or over time, it is often times due to anatomical disruption from valve vegetations or destruction of nearby tissue. Development of heart failure in the setting of IE is correlated with worse outcomes. Heart failure occurs most commonly with aortic (29%) and mitral valve (20%) infections and less with tricuspid valve (8%). The overall in hospital mortality rate for patients diagnosed with heart failure approaches 30% . <br />
<br />
Conduction abnormalities, commonly characterized by heart blocks in endocarditis are associated with infection extension, increased risk of embolization and increased mortality. They are reported to be present in 26%-28% of patients . <br />
<br />
Embolization is a dreaded complication of IE and most commonly affects the spleen, brain, kidneys in cases of left sided endocarditis, and the lung in right sided endocarditis. Studies report a rate of 8.5-25% and are associated with significant mortality risk . Vegetation length, especially >10mm, infection with S. aureus, S. bovis are predictive factors for a higher rate of embolization and increased in mortality . Embolization to the brain can result in mycotic aneurysms which can present with a variety of neurologic manifestations depending on the anatomic location and spread of infection in the surrounding area. Up to 30% of patients with evidence of embolization to the brain are reported to be asymptomatic. <br />
<br />
==Prognosis==<br />
Prognosis of IE is largely dependent on the patient’s comorbid conditions such as diabetes , hemodialysis, congestive heart failure , complications of endocarditis, prosthetic valve and the microorganism identified. Generally the outcome largely depends on the organism involved. According to recent data it, the over 30 day mortality is ~15% and the 1-year mortality is ~34%. Prosthetic valve endocarditis has a significant in hospital mortality of ~24%, while native valve endocarditis carries a lower in hospital mortality of 12% if treated early and surgically .</div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Cardiac_Pharmacology&diff=2452Cardiac Pharmacology2013-09-18T02:02:56Z<p>NiloferT: </p>
<hr />
<div>{{DevelopmentPhase}}<br />
''Heather Melrose, Jonas de Jong''<br />
<br />
__TOC__<br />
<br />
Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease.<br />
<br />
==Renin-Angiotensin-Aldosterone System==<br />
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. <br />
<br />
'''Angiotensin II causes increases in blood pressure by actions at various sites:'''<br />
<br />
*'''Adrenal Glands:''' Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance.<br />
<br />
*'''Kidneys:''' Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow.<br />
<br />
*'''Cardiovascular System:''' Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy.<br />
<br />
*'''Central Nervous System:''' In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased ''thirst'', encouraging water intake.<br />
<br />
Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease.<br />
<br />
==Neural Control of the Cardiovascular System==<br />
===Sympathetic (Adrenergic) Nervous System===<br />
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. <br />
<br />
====Vasculature====<br />
The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately results in myocyte contraction, vasoconstriction and consequent increases in systemic blood pressure.<br />
<br />
====Heart====<br />
Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the ß-receptor subfamily and include ß1 and ß3 receptors. Catecholamine binding to ß1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However ß3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart.<br />
<br />
Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias.<br />
<br />
===Parasympathetic Nervous System===<br />
The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body. <br />
<br />
====Vasculature====<br />
Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation.<br />
<br />
====Heart====<br />
Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions.<br />
<br />
==Platelet/Clotting System==<br />
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. <br />
<br />
There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and ischaemia or stroke; less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process.<br />
<br />
===Anti-coagulants===<br />
Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia.<br />
<br />
As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin’s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A<sub>2</sub> reduces platelet aggregation and thus prevents clot formation.<br />
<br />
P2Y<sub>12</sub> inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y<sub>12</sub> subtype of the platelet ADP receptor. By blocking P2Y<sub>12</sub>, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. <br />
<br />
Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation.<br />
<br />
==Pharmacokinetics==<br />
When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" <br />
|-<br />
!Property <br />
!Description <br />
!Standard units (Abbreviation) <br />
!Formula<br />
|-<br />
!Dose <br />
|Amount of active drug given to patient <br />
|align="center"|mg (D) <br />
|Drug Specific (From clinical studies)<br />
|-<br />
!Concentration <br />
|Amount of drug in a given plasma volume <br />
|align="center"|µg/ml (C) <br />
|align="center"|= D / Vd<br />
|-<br />
!EC<sub>50</sub> <br />
|The concentration of drug needed to elicit a response halfway between zero and maximal responses. <br />
|align="center"|µg/ml (EC<sub>50</sub>) <br />
|align="center"|y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient)<br />
|-<br />
!Volume of Distribution<br />
|The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. <br />
|align="center"|L (Vd) <br />
|align="center"|D / C<br />
|-<br />
!Elimination Constant (Rate) <br />
|The rate at which the drug is removed from the body. <br />
|align="center"|h-1 (Ke) <br />
|align="center"|ln(2) / t1/2 or CL / Vd<br />
|-<br />
!Bioavailability <br />
|How much of the administered dose is available for actual use by the body. <br />
|no units as expressing a fraction (f) <br />
|align="center"|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po))<br />
<br />
AUC = Area under curve po = oral administration iv = intravenous administration<br />
|-<br />
!Cmax or Cmin <br />
|The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration <br />
|align="center"|µg/ml (Cmax or Cmin) <br />
|Identified via direct measurement of plasma C<br />
|-<br />
!tmax <br />
|The time it takes for a drug to reach Cmax following administration <br />
|align="center"|h (tmax) <br />
|Identified via direct measurement of plasma C over time<br />
|-<br />
!Half-life <br />
|The time it takes for a drug to reach half its original concentration <br />
|align="center"|h (t1/2) <br />
|align="center"|ln(2) / Ke<br />
|-<br />
!Drug Clearance <br />
|The volume of plasma cleared of the drug over a set time <br />
|align="center"|l/h (CL) <br />
|align="center"|Vd x Ke or D / Area under curve<br />
|}<br />
<br />
==Common Drug-Drug Interactions==<br />
It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug—drug interactions related to cardiovascular drugs are listed below:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Drug <br />
!Drugs that <big>↑</big> drug action <br />
!Drugs that <big>↓</big> drug action<br />
|-<br />
!Digoxin <br />
|valign="top"|<br />
*Diuretics<br />
*Antiarrhythmics<br />
*Macrolide antibiotics<br />
*Cholestyramine<br />
*Neomycin<br />
*Keto- and intraconazole<br />
*Calcium antagonists<br />
*Cyclosporine, indomethacin<br />
*HMG CoA reductase inhibitors<br />
*Benzodiazepines<br />
*Amiodarone<br />
*Verapamil <br />
|valign="top"|<br />
*Rifampicin<br />
*Antacids (liquid)<br />
|-<br />
!Warfarin <br />
|valign="top"|<br />
*Furosemide<br />
*Amiodarone<br />
*Sulfa<br />
*Macrolide and quinolone antibiotics<br />
*NSAIDs<br />
|valign="top"|<br />
*Azathioprine<br />
*Phenobarbitone<br />
*Carbamazepine<br />
*Dexamethasone<br />
*Prednisolone<br />
*Rifampicin<br />
*Vitamin K<br />
*Raloxifene<br />
|-<br />
!Clopidogrel <br />
|valign="top"|<br />
*Rifampicin<br />
*Caffeine<br />
*Methylxanthines<br />
*Phosphodiesterase inhibitors <br />
|valign="top"|<br />
*Statins<br />
*Calcium channel blockers<br />
*Warfarin<br />
*Proton pump inhibitors<br />
|-<br />
!Furosemide <br />
|<br />
|valign="top"|<br />
*NSAIDs<br />
*Phenytoin<br />
*Colesevelam<br />
|-<br />
!ACE Inhibitors <br />
|valign="top"|<br />
*NSAIDs<br />
*Probenecid<br />
*Calcium channel blockers <br />
|valign="top"|<br />
*Indomethacin<br />
*Antacids<br />
|-<br />
!ß-blockers <br />
|valign="top"|<br />
*Amiodarone<br />
*Calcium channel blockers<br />
*Diltiazem<br />
*Phenoxybenzamine <br />
|valign="top"|<br />
*Phenobarbital<br />
*Rifampicin<br />
*Cimetidine<br />
*Antacids (liquid)<br />
*NSAIDs<br />
|-<br />
!Statins <br />
|valign="top"|<br />
*Amiodarone<br />
*Verapamil<br />
*Fibrates<br />
*Amprenavir<br />
*Diltiazem <br />
|valign="top"|<br />
*Nevirapine<br />
*Rifampicin<br />
|}<br />
<br />
There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g. toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by-product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below: <br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Enzyme <br />
!Substrates (e.g.) <br />
!Inhibitors (e.g.) <br />
!Inducers (e.g.)<br />
|-<br />
!CYP2C19 <br />
|valign="top"|<br />
*Clopidogrel<br />
*Propranolol<br />
*Warfarin <br />
|valign="top"|<br />
*Moclobemide<br />
*Chloramphenicol<br />
*Many anti-convulsants (Valproate)<br />
*Proton pump inhibitors (Omeprazole)<br />
|valign="top"|<br />
*Rifampicin<br />
*Carbamazepine<br />
*Prednisone<br />
|-<br />
!CYP3A4 <br />
|valign="top"|<br />
*Donepezil<br />
*Statins (Atorvastatin)<br />
*Ca-channel blockers (Nifedipine)<br />
*Amiodarone<br />
*Dronedarone<br />
*Quinidine<br />
*PDE5 Inhibitors (Sildenafil)<br />
*Kinins<br />
*Caffeine<br />
*Eplerenone<br />
*Propranolol<br />
*Salmeterol<br />
*Warfarin<br />
*Clopidogrel <br />
|valign="top"|<br />
*Protease inhibitors (Ritonavir)<br />
*Macrolides (Clarithromycin)<br />
*Chloramphenicol<br />
*Nefazodone<br />
*Some Ca-channel blockers (Verapamil)<br />
*Cimetidine<br />
*Some azole anti-fungals (Ketaconazole)<br />
*Grapefruit juice <br />
|valign="top"|<br />
*Some anti-convulsants (Carbamazepine)<br />
*Baribiturates (Phenobarbital)<br />
*St. John’s Wort<br />
*Some reverse transcriptase inhibitors (Efavirenz)<br />
*Some Hypoglycaemics (Pioglitazone)<br />
*Glucocorticoids<br />
*Modafinil<br />
|-<br />
!CYP2C9 <br />
|valign="top"|<br />
*Fluvastatin<br />
*Angiotensin receptor II agonists (losartan)<br />
*Warfarin<br />
*Torasemide <br />
|valign="top"|<br />
*Some azole anti-fungals (Fluconazole)<br />
*Amiodarone<br />
*Antihistamines (Cyclizine)<br />
*Chloramphenicol<br />
*Fluvastatin<br />
*Fluvoxamine<br />
*Probenecid<br />
*Sertraline <br />
|valign="top"|<br />
*Rifampicin<br />
*Secobarbital<br />
|-<br />
!CYP2D6 <br />
|valign="top"|<br />
*ß-blockers (Propranolol)<br />
*Class I anti-arrythmics (Flecainide)<br />
*Donepezil<br />
|valign="top"|<br />
*SSRIs (Fluoxetine)<br />
*Quinidine<br />
*Sertraline<br />
*Terbinafine<br />
*Amiodarone<br />
*Cinacalcet<br />
*Ritonavir<br />
*Antipsychotics (Haloperidol)<br />
*Antihistamines (Promethazine)<br />
*Metoclopramide<br />
*Ranitidine<br />
*Mibefradil <br />
|valign="top"|<br />
*Rifampicin<br />
*Dexamethasone<br />
*Glutethimide<br />
|}<br />
<br />
In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: [http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/GeneralUseofMedicine/UCM229033.pdf General Use of Medicine]<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
|+Cardiovascular Drugs<br />
|- <br />
!Drug Type <br />
!Examples (generic name)<br />
!Indications <br />
!Typical Dosage<br />
!Guidelines / Class of Indication <br />
!Side Effects (Prevalence %)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|:'''Anti-hypertensives''' <br />
|-<br />
|rowspan="2"|Diuretics <br />
|rowspan="2"|Furosemide<br />
|Oedema<br />
|Furosemide: 20-40mg once daily<br />
|<br />
|rowspan="2" valign="top"|Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus).<br />
|-<br />
|Resistant Hypertension<br />
|Furosemide: 40-80mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC <cite>Esc1</cite><br />
|-<br />
|rowspan="4"|ACE Inhibitors <br />
|rowspan="4"|Captopril, Monopril <br />
|Hypertension <br />
|Captopril: 12.5mg twice daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc3</cite> <br />
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.<br />
|-<br />
|Heart Failure <br />
|Captopril: 12.5mg 3 times daily<br />
|Post STEMI: Class IA <cite>Esc4</cite><br />
<br />
Diabetic patients: Class IC <cite>Esc2</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc1</cite><br />
|-<br />
|Prophylaxis Following MI <br />
|Captopril: 6.25mg once daily<br />
| <br />
|-<br />
|Diabetic nephropathy <br />
|Captopril: 75-100mg once daily<br />
|<br />
|-<br />
|rowspan="3"|Angiotensin Receptor Blockers <br />
|rowspan="3"|Losartan, Candesartan<br />
|Hypertension <br />
|Losartan: 50mg once daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;<br />
|-<br />
|Left ventricular hypertrophy <br />
|Losartan: 12.5-150mg daily<br />
|LVH: Class IB <cite>Esc4</cite><br />
|- <br />
|Diabetic nephropathy <br />
|Losartan: 50mg daily<br />
|<br />
|-<br />
|rowspan="3"|Alpha Blockers <br />
|rowspan="3"|Prazosin, Doxazosin <br />
|Hypertension <br />
|Prazosin: 1-10mg 2-3 times daily <br />
|<br />
|rowspan="3" valign="top"|Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8-18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema.<br />
|-<br />
|Congestive Heart Failure <br />
|Prazosin: 4-20mg daily<br />
|<br />
|-<br />
|Raynaud’s Syndrome <br />
|Prazosin: 1-2mg daily<br />
|<br />
|- <br />
|rowspan="4"|Beta Blockers <br />
|rowspan="4"|Atenolol, Propranolol <br />
|Hypertension <br />
|Atenolol: 25-50mg daily<br />
|<br />
|rowspan="4" valign="top"|Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes.<br />
|-<br />
|Angina <br />
|Atenolol: 100mg once/twice daily<br />
|ACS: Class IIaB <cite>Esc2</cite><br />
<br />
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite><br />
|-<br />
|Arrhythmias <br />
|Atenolol: 50-100mg daily <br />
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc4</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc1</cite><br />
<br />
SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc5</cite><br />
|-<br />
|Migraine <br />
|Atenolol: 50-200mg daily <br />
| <br />
|-<br />
|rowspan="3"|Calcium Channel Blockers <br />
|rowspan="3"|Nifedipine, Verapamil, Diltiazem<br />
|Hypertension <br />
|Nifedipine: 20-30mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;<br />
|-<br />
|Raynaud’s Syndrome <br />
|Nifedipine: 5-20mg 3 times daily<br />
|<br />
|-<br />
|Angina (prophylaxis) <br />
|Nifedipine: 5-20mg 3 times daily<br />
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc1</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''<br />
|- <br />
|Class I (sodium channel blockers)<br />
|Flecainide, Lidocaine, Procainamide<br />
|Ventricular Arrhythmias <br />
|Flecainide: 50-100mg twice daily<br />
|Sustained VT and VF: Class IIbC <cite>Esc4</cite><br />
<br />
Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc5</cite><br />
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.<br />
|-<br />
|Class II (Beta blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|Class III (Potassium channel blockers) <br />
|Amiodarone, Sotalol <br />
|Ventricular, Arrhythmias <br />
|Amiodarone: 200mg 2-3 times daily <br />
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc4</cite><br />
<br />
Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc1</cite><br />
<br />
SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc5</cite> <br />
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes<br />
|-<br />
|Class IV (Calcium channel blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|rowspan="2"|<br />
|rowspan="2"|Digoxin <br />
|Supra-ventricular Arrhythmias <br />
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily <br />
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc5</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.<br />
|-<br />
|Heart Failure <br />
|62.5-125 µg daily <br />
|Symptomatic (NYHA class II-IV) HF: Class IIbB<br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc1</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''<br />
|- <br />
|rowspan="7"|<br />
|rowspan="2"|Aspirin <br />
|Prevention of thrombotic cerebro- or cardio-vascular disease <br />
|75mg once/day<br />
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc2</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc3</cite><br />
<br />
Post-MI: Class Ia <cite>Esc3</cite><br />
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).<br />
|-<br />
|Pain / pyrexia <br />
|300-600mg every 4-6 hours as necessary <br />
|<br />
|-<br />
|rowspan="3"|Clopidogrel <br />
|Prevention of thrombotic events (esp. when warfarin not tolerated) <br />
|75mg once/day<br />
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc2</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.<br />
|-<br />
|Acute myocardial infarction <br />
|300mg daily initially then 75mg once/day<br />
|Post STEMI: Class IA <cite>Esc4</cite><br />
|-<br />
|Acute coronary syndrome <br />
|300mg daily initially then 75mg once/day<br />
|ACS: Class IIaC <cite>Esc2</cite><br />
|-<br />
|Prasugrel <br />
|Prevention of thrombotic events. <br />
|60mg bolus then 5-10mg once daily<br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite><br />
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.<br />
|-<br />
|Ticragelor <br />
|Prevention of thrombotic events. <br />
|180mg bolus then 90mg twice daily <br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite><br />
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Vitamin K Antagonists'''<br />
|-<br />
|<br />
|Warfarin <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|5-10mg initially then tailored to individual (usually 3-9mg once daily at the same time)<br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|<br />
|Acenocoumarol <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|4mg initially, followed by 1-8mg daily <br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Lipid-Lowering Drugs'''<br />
|- <br />
|rowspan="3"|Statins <br />
|rowspan="3"|Simvastatin, Atorvastatin <br />
|Primary hyper-cholesterolaemia, combined hyperlipidaemia <br />
|Simvastatin: 10-20mg once daily<br />
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc2</cite><br />
<br />
Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)<br />
|-<br />
|Familial hyper-cholesterolaemia <br />
|Simvastatin: 40mg once daily<br />
|HeFH: Class IC <cite>Esc2</cite><br />
|-<br />
|Prevention of cardiovascular events <br />
|20-40mg once daily<br />
|Class IA <cite>Esc2</cite><br />
|-<br />
|rowspan="2"|Fibrates <br />
|Gemfibrozil <br />
|Hyperlipidaemias of types IIa, IIb, III, IV and V <br />
|Gemfibrozil: 0.9-1.2mg daily<br />
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc6</cite><br />
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity<br />
|-<br />
|Ezetimibe <br />
|Primary and familial hyper-cholesterolaemia <br />
|10mg once daily <br />
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc6</cite><br />
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis<br />
|}<br />
<br />
==References==<br />
<biblio><br />
#Esc1 pmid=22611136<br />
#Esc2 pmid=17220161<br />
#Esc3 pmid=22555213<br />
#Esc4 pmid=22922416<br />
#Acc5 pmid=14557344<br />
#Esc6 pmid=21712404<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Cardiac_Pharmacology&diff=2451Cardiac Pharmacology2013-09-18T01:52:49Z<p>NiloferT: </p>
<hr />
<div>{{DevelopmentPhase}}<br />
''Heather Melrose, Jonas de Jong''<br />
<br />
__TOC__<br />
<br />
Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease.<br />
<br />
==Renin-Angiotensin-Aldosterone System==<br />
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. <br />
<br />
'''Angiotensin II causes increases in blood pressure by actions at various sites:'''<br />
<br />
*'''Adrenal Glands:''' Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance.<br />
<br />
*'''Kidneys:''' Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow.<br />
<br />
*'''Cardiovascular System:''' Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy.<br />
<br />
*'''Central Nervous System:''' In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased ''thirst'', encouraging water intake.<br />
<br />
Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease.<br />
<br />
==Neural Control of the Cardiovascular System==<br />
===Sympathetic (Adrenergic) Nervous System===<br />
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. <br />
<br />
====Vasculature====<br />
The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately results in myocyte contraction, vasoconstriction and consequent increases in systemic blood pressure.<br />
<br />
====Heart====<br />
Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the ß-receptor subfamily and include ß1 and ß3 receptors. Catecholamine binding to ß1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However ß3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart.<br />
<br />
Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias.<br />
<br />
===Parasympathetic Nervous System===<br />
The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body. <br />
<br />
====Vasculature====<br />
Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation.<br />
<br />
====Heart====<br />
Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions.<br />
<br />
==Platelet/Clotting System==<br />
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. <br />
<br />
There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and ischaemia or stroke; less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process.<br />
<br />
===Anti-coagulants===<br />
Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia.<br />
<br />
As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin’s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A<sub>2</sub> reduces platelet aggregation and thus prevents clot formation.<br />
<br />
P2Y<sub>12</sub> inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y<sub>12</sub> subtype of the platelet ADP receptor. By blocking P2Y<sub>12</sub>, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. <br />
<br />
Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation.<br />
<br />
==Pharmacokinetics==<br />
When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" <br />
|-<br />
!Property <br />
!Description <br />
!Standard units (Abbreviation) <br />
!Formula<br />
|-<br />
!Dose <br />
|Amount of active drug given to patient <br />
|align="center"|mg (D) <br />
|Drug Specific (From clinical studies)<br />
|-<br />
!Concentration <br />
|Amount of drug in a given plasma volume <br />
|align="center"|µg/ml (C) <br />
|align="center"|= D / Vd<br />
|-<br />
!EC<sub>50</sub> <br />
|The concentration of drug needed to elicit a response halfway between zero and maximal responses. <br />
|align="center"|µg/ml (EC<sub>50</sub>) <br />
|align="center"|y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient)<br />
|-<br />
!Volume of Distribution<br />
|The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. <br />
|align="center"|L (Vd) <br />
|align="center"|D / C<br />
|-<br />
!Elimination Constant (Rate) <br />
|The rate at which the drug is removed from the body. <br />
|align="center"|h-1 (Ke) <br />
|align="center"|ln(2) / t1/2 or CL / Vd<br />
|-<br />
!Bioavailability <br />
|How much of the administered dose is available for actual use by the body. <br />
|no units as expressing a fraction (f) <br />
|align="center"|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po))<br />
<br />
AUC = Area under curve po = oral administration iv = intravenous administration<br />
|-<br />
!Cmax or Cmin <br />
|The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration <br />
|align="center"|µg/ml (Cmax or Cmin) <br />
|Identified via direct measurement of plasma C<br />
|-<br />
!tmax <br />
|The time it takes for a drug to reach Cmax following administration <br />
|align="center"|h (tmax) <br />
|Identified via direct measurement of plasma C over time<br />
|-<br />
!Half-life <br />
|The time it takes for a drug to reach half its original concentration <br />
|align="center"|h (t1/2) <br />
|align="center"|ln(2) / Ke<br />
|-<br />
!Drug Clearance <br />
|The volume of plasma cleared of the drug over a set time <br />
|align="center"|l/h (CL) <br />
|align="center"|Vd x Ke or D / Area under curve<br />
|}<br />
<br />
==Common Drug-Drug Interactions==<br />
It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug—drug interactions related to cardiovascular drugs are listed below:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Drug <br />
!Drugs that <big>↑</big> drug action <br />
!Drugs that <big>↓</big> drug action<br />
|-<br />
!Digoxin <br />
|valign="top"|<br />
*Diuretics<br />
*Antiarrhythmics<br />
*Macrolide antibiotics<br />
*Cholestyramine<br />
*Neomycin<br />
*Keto- and intraconazole<br />
*Calcium antagonists<br />
*Cyclosporine, indomethacin<br />
*HMG CoA reductase inhibitors<br />
*Benzodiazepines<br />
*Amiodarone<br />
*Verapamil <br />
|valign="top"|<br />
*Rifampicin<br />
*Antacids (liquid)<br />
|-<br />
!Warfarin <br />
|valign="top"|<br />
*Furosemide<br />
*Amiodarone<br />
*Sulfa<br />
*Macrolide and quinolone antibiotics<br />
*NSAIDs<br />
|valign="top"|<br />
*Azathioprine<br />
*Phenobarbitone<br />
*Carbamazepine<br />
*Dexamethasone<br />
*Prednisolone<br />
*Rifampicin<br />
*Vitamin K<br />
*Raloxifene<br />
|-<br />
!Clopidogrel <br />
|valign="top"|<br />
*Rifampicin<br />
*Caffeine<br />
*Methylxanthines<br />
*Phosphodiesterase inhibitors <br />
|valign="top"|<br />
*Statins<br />
*Calcium channel blockers<br />
*Warfarin<br />
*Proton pump inhibitors<br />
|-<br />
!Furosemide <br />
|<br />
|valign="top"|<br />
*NSAIDs<br />
*Phenytoin<br />
*Colesevelam<br />
|-<br />
!ACE Inhibitors <br />
|valign="top"|<br />
*NSAIDs<br />
*Probenecid<br />
*Calcium channel blockers <br />
|valign="top"|<br />
*Indomethacin<br />
*Antacids<br />
|-<br />
!ß-blockers <br />
|valign="top"|<br />
*Amiodarone<br />
*Calcium channel blockers<br />
*Diltiazem<br />
*Phenoxybenzamine <br />
|valign="top"|<br />
*Phenobarbital<br />
*Rifampicin<br />
*Cimetidine<br />
*Antacids (liquid)<br />
*NSAIDs<br />
|-<br />
!Statins <br />
|valign="top"|<br />
*Amiodarone<br />
*Verapamil<br />
*Fibrates<br />
*Amprenavir<br />
*Diltiazem <br />
|valign="top"|<br />
*Nevirapine<br />
*Rifampicin<br />
|}<br />
<br />
There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g. toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by-product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below: <br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Enzyme <br />
!Substrates (e.g.) <br />
!Inhibitors (e.g.) <br />
!Inducers (e.g.)<br />
|-<br />
!CYP2C19 <br />
|valign="top"|<br />
*Clopidogrel<br />
*Propranolol<br />
*Warfarin <br />
|valign="top"|<br />
*Moclobemide<br />
*Chloramphenicol<br />
*Many anti-convulsants (Valproate)<br />
*Proton pump inhibitors (Omeprazole)<br />
|valign="top"|<br />
*Rifampicin<br />
*Carbamazepine<br />
*Prednisone<br />
|-<br />
!CYP3A4 <br />
|valign="top"|<br />
*Donepezil<br />
*Statins (Atorvastatin)<br />
*Ca-channel blockers (Nifedipine)<br />
*Amiodarone<br />
*Dronedarone<br />
*Quinidine<br />
*PDE5 Inhibitors (Sildenafil)<br />
*Kinins<br />
*Caffeine<br />
*Eplerenone<br />
*Propranolol<br />
*Salmeterol<br />
*Warfarin<br />
*Clopidogrel <br />
|valign="top"|<br />
*Protease inhibitors (Ritonavir)<br />
*Macrolides (Clarithromycin)<br />
*Chloramphenicol<br />
*Nefazodone<br />
*Some Ca-channel blockers (Verapamil)<br />
*Cimetidine<br />
*Some azole anti-fungals (Ketaconazole)<br />
*Grapefruit juice <br />
|valign="top"|<br />
*Some anti-convulsants (Carbamazepine)<br />
*Baribiturates (Phenobarbital)<br />
*St. John’s Wort<br />
*Some reverse transcriptase inhibitors (Efavirenz)<br />
*Some Hypoglycaemics (Pioglitazone)<br />
*Glucocorticoids<br />
*Modafinil<br />
|-<br />
!CYP2C9 <br />
|valign="top"|<br />
*Fluvastatin<br />
*Angiotensin receptor II agonists (losartan)<br />
*Warfarin<br />
*Torasemide <br />
|valign="top"|<br />
*Some azole anti-fungals (Fluconazole)<br />
*Amiodarone<br />
*Antihistamines (Cyclizine)<br />
*Chloramphenicol<br />
*Fluvastatin<br />
*Fluvoxamine<br />
*Probenecid<br />
*Sertraline <br />
|valign="top"|<br />
*Rifampicin<br />
*Secobarbital<br />
|-<br />
!CYP2D6 <br />
|valign="top"|<br />
*ß-blockers (Propranolol)<br />
*Class I anti-arrythmics (Flecainide)<br />
*Donepezil<br />
|valign="top"|<br />
*SSRIs (Fluoxetine)<br />
*Quinidine<br />
*Sertraline<br />
*Terbinafine<br />
*Amiodarone<br />
*Cinacalcet<br />
*Ritonavir<br />
*Antipsychotics (Haloperidol)<br />
*Antihistamines (Promethazine)<br />
*Metoclopramide<br />
*Ranitidine<br />
*Mibefradil <br />
|valign="top"|<br />
*Rifampicin<br />
*Dexamethasone<br />
*Glutethimide<br />
|}<br />
<br />
In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: [http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/GeneralUseofMedicine/UCM229033.pdf General Use of Medicine]<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
|+Cardiovascular Drugs<br />
|- <br />
!Drug Type <br />
!Examples (generic name)<br />
!Indications <br />
!Typical Dosage<br />
!Guidelines / Class of Indication <br />
!Side Effects (Prevalence %)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|:'''Anti-hypertensives''' <br />
|-<br />
|rowspan="2"|Diuretics <br />
|rowspan="2"|Furosemide<br />
|Oedema<br />
|Furosemide: 20-40mg once daily<br />
|<br />
|rowspan="2" valign="top"|Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus).<br />
|-<br />
|Resistant Hypertension<br />
|Furosemide: 40-80mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC <cite>Esc1</cite><br />
|-<br />
|rowspan="4"|ACE Inhibitors <br />
|rowspan="4"|Captopril, Monopril <br />
|Hypertension <br />
|Captopril: 12.5mg twice daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc3</cite> <br />
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.<br />
|-<br />
|Heart Failure <br />
|Captopril: 12.5mg 3 times daily<br />
|Post STEMI: Class IA <cite>Esc4</cite><br />
<br />
Diabetic patients: Class IC <cite>Esc2</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc1</cite><br />
|-<br />
|Prophylaxis Following MI <br />
|Captopril: 6.25mg once daily<br />
| <br />
|-<br />
|Diabetic nephropathy <br />
|Captopril: 75-100mg once daily<br />
|<br />
|-<br />
|rowspan="3"|Angiotensin Receptor Blockers <br />
|rowspan="3"|Losartan, Candesartan<br />
|Hypertension <br />
|Losartan: 50mg once daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;<br />
|-<br />
|Left ventricular hypertrophy <br />
|Losartan: 12.5-150mg daily<br />
|LVH: Class IB <cite>Esc4</cite><br />
|- <br />
|Diabetic nephropathy <br />
|Losartan: 50mg daily<br />
|<br />
|-<br />
|rowspan="3"|Alpha Blockers <br />
|rowspan="3"|Prazosin, Doxazosin <br />
|Hypertension <br />
|Prazosin: 1-10mg 2-3 times daily <br />
|<br />
|rowspan="3" valign="top"|Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8-18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema.<br />
|-<br />
|Congestive Heart Failure <br />
|Prazosin: 4-20mg daily<br />
|<br />
|-<br />
|Raynaud’s Syndrome <br />
|Prazosin: 1-2mg daily<br />
|<br />
|- <br />
|rowspan="4"|Beta Blockers <br />
|rowspan="4"|Atenolol, Propranolol <br />
|Hypertension <br />
|Atenolol: 25-50mg daily<br />
|<br />
|rowspan="4" valign="top"|Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes.<br />
|-<br />
|Angina <br />
|Atenolol: 100mg once/twice daily<br />
|ACS: Class IIaB <cite>Esc2</cite><br />
<br />
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite><br />
|-<br />
|Arrhythmias <br />
|Atenolol: 50-100mg daily <br />
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc4</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc1</cite><br />
<br />
SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc5</cite><br />
|-<br />
|Migraine <br />
|Atenolol: 50-200mg daily <br />
| <br />
|-<br />
|rowspan="3"|Calcium Channel Blockers <br />
|rowspan="3"|Nifedipine, Verapamil, Diltiazem<br />
|Hypertension <br />
|Nifedipine: 20-30mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;<br />
|-<br />
|Raynaud’s Syndrome <br />
|Nifedipine: 5-20mg 3 times daily<br />
|<br />
|-<br />
|Angina (prophylaxis) <br />
|Nifedipine: 5-20mg 3 times daily<br />
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc1</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''<br />
|- <br />
|Class I (sodium channel blockers)<br />
|Flecainide, Lidocaine, Procainamide<br />
|Ventricular Arrhythmias <br />
|Flecainide: 50-100mg twice daily<br />
|Sustained VT and VF: Class IIbC <cite>Esc4</cite><br />
<br />
Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc5</cite><br />
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.<br />
|-<br />
|Class II (Beta blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|Class III (Potassium channel blockers) <br />
|Amiodarone, Sotalol <br />
|Ventricular, Arrhythmias <br />
|Amiodarone: 200mg 2-3 times daily <br />
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc4</cite><br />
<br />
Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc1</cite><br />
<br />
SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc5</cite> <br />
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes<br />
|-<br />
|Class IV (Calcium channel blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|rowspan="2"|<br />
|rowspan="2"|Digoxin <br />
|Supra-ventricular Arrhythmias <br />
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily <br />
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc5</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.<br />
|-<br />
|Heart Failure <br />
|62.5-125 µg daily <br />
|Symptomatic (NYHA class II-IV) HF: Class IIbB<br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc1</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''<br />
|- <br />
|rowspan="7"|<br />
|rowspan="2"|Aspirin <br />
|Prevention of thrombotic cerebro- or cardio-vascular disease <br />
|75mg once/day<br />
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc2</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc3</cite><br />
<br />
Post-MI: Class Ia <cite>Esc3</cite><br />
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).<br />
|-<br />
|Pain / pyrexia <br />
|300-600mg every 4-6 hours as necessary <br />
|<br />
|-<br />
|rowspan="3"|Clopidogrel <br />
|Prevention of thrombotic events (esp. when warfarin not tolerated) <br />
|75mg once/day<br />
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc2</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.<br />
|-<br />
|Acute myocardial infarction <br />
|300mg daily initially then 75mg once/day<br />
|Post STEMI: Class IA <cite>Esc4</cite><br />
|-<br />
|Acute coronary syndrome <br />
|300mg daily initially then 75mg once/day<br />
|ACS: Class IIaC <cite>Esc2</cite><br />
|-<br />
|Prasugrel <br />
|Prevention of thrombotic events. <br />
|60mg bolus then 5-10mg once daily<br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite><br />
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.<br />
|-<br />
|Ticragelor <br />
|Prevention of thrombotic events. <br />
|180mg bolus then 90mg twice daily <br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite><br />
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Vitamin K Antagonists'''<br />
|-<br />
|<br />
|Warfarin <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|5-10mg initially then tailored to individual (usually 3-9mg once daily at the same time)<br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|<br />
|Acenocoumarol <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|4mg initially, followed by 1-8mg daily <br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Lipid-Lowering Drugs'''<br />
|- <br />
|rowspan="3"|Statins <br />
|rowspan="3"|Simvastatin, Atorvastatin <br />
|Primary hyper-cholesterolaemia, combined hyperlipidaemia <br />
|Simvastatin: 10-20mg once daily<br />
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc2</cite><br />
<br />
Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)<br />
|-<br />
|Familial hyper-cholesterolaemia <br />
|Simvastatin: 40mg once daily<br />
|HeFH: Class IC <cite>Esc2</cite><br />
|-<br />
|Prevention of cardiovascular events <br />
|20-40mg once daily<br />
|Class IA <cite>Esc2</cite><br />
|-<br />
|rowspan="2"|Fibrates <br />
|Gemfibrozil <br />
|Hyperlipidaemias of types IIa, IIb, III, IV and V <br />
|Gemfibrozil: 0.9-1.2mg daily<br />
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc6</cite><br />
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity<br />
|-<br />
|Ezetimibe <br />
|Primary and familial hyper-cholesterolaemia <br />
|10mg once daily <br />
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc6</cite><br />
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis<br />
|}<br />
<br />
==References==<br />
<biblio><br />
#Esc1 pmid=22611136<br />
#Esc2 pmid=23996285<br />
#Esc3 pmid=22555213<br />
#Esc4 pmid=22922416<br />
#Acc5 pmid=14557344<br />
#Esc6 pmid=21712404<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Cardiac_Pharmacology&diff=2450Cardiac Pharmacology2013-09-17T17:18:05Z<p>NiloferT: </p>
<hr />
<div>{{DevelopmentPhase}}<br />
''Heather Melrose, Jonas de Jong''<br />
<br />
__TOC__<br />
<br />
Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease.<br />
<br />
==Renin-Angiotensin-Aldosterone System==<br />
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. <br />
<br />
'''Angiotensin II causes increases in blood pressure by actions at various sites:'''<br />
<br />
*'''Adrenal Glands:''' Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance.<br />
<br />
*'''Kidneys:''' Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow.<br />
<br />
*'''Cardiovascular System:''' Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy.<br />
<br />
*'''Central Nervous System:''' In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased ''thirst'', encouraging water intake.<br />
<br />
Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease.<br />
<br />
==Neural Control of the Cardiovascular System==<br />
===Sympathetic (Adrenergic) Nervous System===<br />
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. <br />
<br />
====Vasculature====<br />
The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately results in myocyte contraction, vasoconstriction and consequent increases in systemic blood pressure.<br />
<br />
====Heart====<br />
Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the ß-receptor subfamily and include ß1 and ß3 receptors. Catecholamine binding to ß1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However ß3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart.<br />
<br />
Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias.<br />
<br />
===Parasympathetic Nervous System===<br />
The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body. <br />
<br />
====Vasculature====<br />
Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation.<br />
<br />
====Heart====<br />
Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions.<br />
<br />
==Platelet/Clotting System==<br />
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. <br />
<br />
There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and ischaemia or stroke; less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process.<br />
<br />
===Anti-coagulants===<br />
Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia.<br />
<br />
As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin’s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A<sub>2</sub> reduces platelet aggregation and thus prevents clot formation.<br />
<br />
P2Y<sub>12</sub> inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y<sub>12</sub> subtype of the platelet ADP receptor. By blocking P2Y<sub>12</sub>, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. <br />
<br />
Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation.<br />
<br />
==Pharmacokinetics==<br />
When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" <br />
|-<br />
!Property <br />
!Description <br />
!Standard units (Abbreviation) <br />
!Formula<br />
|-<br />
!Dose <br />
|Amount of active drug given to patient <br />
|align="center"|mg (D) <br />
|Drug Specific (From clinical studies)<br />
|-<br />
!Concentration <br />
|Amount of drug in a given plasma volume <br />
|align="center"|µg/ml (C) <br />
|align="center"|= D / Vd<br />
|-<br />
!EC<sub>50</sub> <br />
|The concentration of drug needed to elicit a response halfway between zero and maximal responses. <br />
|align="center"|µg/ml (EC<sub>50</sub>) <br />
|align="center"|y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient)<br />
|-<br />
!Volume of Distribution<br />
|The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. <br />
|align="center"|L (Vd) <br />
|align="center"|D / C<br />
|-<br />
!Elimination Constant (Rate) <br />
|The rate at which the drug is removed from the body. <br />
|align="center"|h-1 (Ke) <br />
|align="center"|ln(2) / t1/2 or CL / Vd<br />
|-<br />
!Bioavailability <br />
|How much of the administered dose is available for actual use by the body. <br />
|no units as expressing a fraction (f) <br />
|align="center"|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po))<br />
<br />
AUC = Area under curve po = oral administration iv = intravenous administration<br />
|-<br />
!Cmax or Cmin <br />
|The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration <br />
|align="center"|µg/ml (Cmax or Cmin) <br />
|Identified via direct measurement of plasma C<br />
|-<br />
!tmax <br />
|The time it takes for a drug to reach Cmax following administration <br />
|align="center"|h (tmax) <br />
|Identified via direct measurement of plasma C over time<br />
|-<br />
!Half-life <br />
|The time it takes for a drug to reach half its original concentration <br />
|align="center"|h (t1/2) <br />
|align="center"|ln(2) / Ke<br />
|-<br />
!Drug Clearance <br />
|The volume of plasma cleared of the drug over a set time <br />
|align="center"|l/h (CL) <br />
|align="center"|Vd x Ke or D / Area under curve<br />
|}<br />
<br />
==Common Drug-Drug Interactions==<br />
It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug—drug interactions related to cardiovascular drugs are listed below:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Drug <br />
!Drugs that <big>↑</big> drug action <br />
!Drugs that <big>↓</big> drug action<br />
|-<br />
!Digoxin <br />
|valign="top"|<br />
*Diuretics<br />
*Antiarrhythmics<br />
*Macrolide antibiotics<br />
*Cholestyramine<br />
*Neomycin<br />
*Keto- and intraconazole<br />
*Calcium antagonists<br />
*Cyclosporine, indomethacin<br />
*HMG CoA reductase inhibitors<br />
*Benzodiazepines<br />
*Amiodarone<br />
*Verapamil <br />
|valign="top"|<br />
*Rifampicin<br />
*Antacids (liquid)<br />
|-<br />
!Warfarin <br />
|valign="top"|<br />
*Furosemide<br />
*Amiodarone<br />
*Sulfa<br />
*Macrolide and quinolone antibiotics<br />
*NSAIDs<br />
|valign="top"|<br />
*Azathioprine<br />
*Phenobarbitone<br />
*Carbamazepine<br />
*Dexamethasone<br />
*Prednisolone<br />
*Rifampicin<br />
*Vitamin K<br />
*Raloxifene<br />
|-<br />
!Clopidogrel <br />
|valign="top"|<br />
*Rifampicin<br />
*Caffeine<br />
*Methylxanthines<br />
*Phosphodiesterase inhibitors <br />
|valign="top"|<br />
*Statins<br />
*Calcium channel blockers<br />
*Warfarin<br />
*Proton pump inhibitors<br />
|-<br />
!Furosemide <br />
|<br />
|valign="top"|<br />
*NSAIDs<br />
*Phenytoin<br />
*Colesevelam<br />
|-<br />
!ACE Inhibitors <br />
|valign="top"|<br />
*NSAIDs<br />
*Probenecid<br />
*Calcium channel blockers <br />
|valign="top"|<br />
*Indomethacin<br />
*Antacids<br />
|-<br />
!ß-blockers <br />
|valign="top"|<br />
*Amiodarone<br />
*Calcium channel blockers<br />
*Diltiazem<br />
*Phenoxybenzamine <br />
|valign="top"|<br />
*Phenobarbital<br />
*Rifampicin<br />
*Cimetidine<br />
*Antacids (liquid)<br />
*NSAIDs<br />
|-<br />
!Statins <br />
|valign="top"|<br />
*Amiodarone<br />
*Verapamil<br />
*Fibrates<br />
*Amprenavir<br />
*Diltiazem <br />
|valign="top"|<br />
*Nevirapine<br />
*Rifampicin<br />
|}<br />
<br />
There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g. toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by-product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below: <br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Enzyme <br />
!Substrates (e.g.) <br />
!Inhibitors (e.g.) <br />
!Inducers (e.g.)<br />
|-<br />
!CYP2C19 <br />
|valign="top"|<br />
*Clopidogrel<br />
*Propranolol<br />
*Warfarin <br />
|valign="top"|<br />
*Moclobemide<br />
*Chloramphenicol<br />
*Many anti-convulsants (Valproate)<br />
*Proton pump inhibitors (Omeprazole)<br />
|valign="top"|<br />
*Rifampicin<br />
*Carbamazepine<br />
*Prednisone<br />
|-<br />
!CYP3A4 <br />
|valign="top"|<br />
*Donepezil<br />
*Statins (Atorvastatin)<br />
*Ca-channel blockers (Nifedipine)<br />
*Amiodarone<br />
*Dronedarone<br />
*Quinidine<br />
*PDE5 Inhibitors (Sildenafil)<br />
*Kinins<br />
*Caffeine<br />
*Eplerenone<br />
*Propranolol<br />
*Salmeterol<br />
*Warfarin<br />
*Clopidogrel <br />
|valign="top"|<br />
*Protease inhibitors (Ritonavir)<br />
*Macrolides (Clarithromycin)<br />
*Chloramphenicol<br />
*Nefazodone<br />
*Some Ca-channel blockers (Verapamil)<br />
*Cimetidine<br />
*Some azole anti-fungals (Ketaconazole)<br />
*Grapefruit juice <br />
|valign="top"|<br />
*Some anti-convulsants (Carbamazepine)<br />
*Baribiturates (Phenobarbital)<br />
*St. John’s Wort<br />
*Some reverse transcriptase inhibitors (Efavirenz)<br />
*Some Hypoglycaemics (Pioglitazone)<br />
*Glucocorticoids<br />
*Modafinil<br />
|-<br />
!CYP2C9 <br />
|valign="top"|<br />
*Fluvastatin<br />
*Angiotensin receptor II agonists (losartan)<br />
*Warfarin<br />
*Torasemide <br />
|valign="top"|<br />
*Some azole anti-fungals (Fluconazole)<br />
*Amiodarone<br />
*Antihistamines (Cyclizine)<br />
*Chloramphenicol<br />
*Fluvastatin<br />
*Fluvoxamine<br />
*Probenecid<br />
*Sertraline <br />
|valign="top"|<br />
*Rifampicin<br />
*Secobarbital<br />
|-<br />
!CYP2D6 <br />
|valign="top"|<br />
*ß-blockers (Propranolol)<br />
*Class I anti-arrythmics (Flecainide)<br />
*Donepezil<br />
|valign="top"|<br />
*SSRIs (Fluoxetine)<br />
*Quinidine<br />
*Sertraline<br />
*Terbinafine<br />
*Amiodarone<br />
*Cinacalcet<br />
*Ritonavir<br />
*Antipsychotics (Haloperidol)<br />
*Antihistamines (Promethazine)<br />
*Metoclopramide<br />
*Ranitidine<br />
*Mibefradil <br />
|valign="top"|<br />
*Rifampicin<br />
*Dexamethasone<br />
*Glutethimide<br />
|}<br />
<br />
In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: [http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/GeneralUseofMedicine/UCM229033.pdf General Use of Medicine]<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
|+Cardiovascular Drugs<br />
|- <br />
!Drug Type <br />
!Examples (generic name)<br />
!Indications <br />
!Typical Dosage<br />
!Guidelines / Class of Indication <br />
!Side Effects (Prevalence %)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|:'''Anti-hypertensives''' <br />
|-<br />
|rowspan="2"|Diuretics <br />
|rowspan="2"|Furosemide<br />
|Oedema<br />
|Furosemide: 20-40mg once daily<br />
|<br />
|rowspan="2" valign="top"|Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus).<br />
|-<br />
|Resistant Hypertension<br />
|Furosemide: 40-80mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC <cite>Esc1</cite><br />
|-<br />
|rowspan="4"|ACE Inhibitors <br />
|rowspan="4"|Captopril, Monopril <br />
|Hypertension <br />
|Captopril: 12.5mg twice daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc3</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc4</cite> <br />
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.<br />
|-<br />
|Heart Failure <br />
|Captopril: 12.5mg 3 times daily<br />
|Post STEMI: Class IA <cite>Esc5</cite><br />
<br />
Diabetic patients: Class IC <cite>Esc6</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc7</cite><br />
|-<br />
|Prophylaxis Following MI <br />
|Captopril: 6.25mg once daily<br />
| <br />
|-<br />
|Diabetic nephropathy <br />
|Captopril: 75-100mg once daily<br />
|<br />
|-<br />
|rowspan="3"|Angiotensin Receptor Blockers <br />
|rowspan="3"|Losartan, Candesartan<br />
|Hypertension <br />
|Losartan: 50mg once daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc4</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;<br />
|-<br />
|Left ventricular hypertrophy <br />
|Losartan: 12.5-150mg daily<br />
|LVH: Class IB <cite>Esc8</cite><br />
|- <br />
|Diabetic nephropathy <br />
|Losartan: 50mg daily<br />
|<br />
|-<br />
|rowspan="3"|Alpha Blockers <br />
|rowspan="3"|Prazosin, Doxazosin <br />
|Hypertension <br />
|Prazosin: 1-10mg 2-3 times daily <br />
|<br />
|rowspan="3" valign="top"|Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8-18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema.<br />
|-<br />
|Congestive Heart Failure <br />
|Prazosin: 4-20mg daily<br />
|<br />
|-<br />
|Raynaud’s Syndrome <br />
|Prazosin: 1-2mg daily<br />
|<br />
|- <br />
|rowspan="4"|Beta Blockers <br />
|rowspan="4"|Atenolol, Propranolol <br />
|Hypertension <br />
|Atenolol: 25-50mg daily<br />
|<br />
|rowspan="4" valign="top"|Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes.<br />
|-<br />
|Angina <br />
|Atenolol: 100mg once/twice daily<br />
|ACS: Class IIaB <cite>Esc9</cite><br />
<br />
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc10</cite><br />
|-<br />
|Arrhythmias <br />
|Atenolol: 50-100mg daily <br />
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc11</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc12</cite><br />
<br />
SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc13</cite><br />
|-<br />
|Migraine <br />
|Atenolol: 50-200mg daily <br />
| <br />
|-<br />
|rowspan="3"|Calcium Channel Blockers <br />
|rowspan="3"|Nifedipine, Verapamil, Diltiazem<br />
|Hypertension <br />
|Nifedipine: 20-30mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;<br />
|-<br />
|Raynaud’s Syndrome <br />
|Nifedipine: 5-20mg 3 times daily<br />
|<br />
|-<br />
|Angina (prophylaxis) <br />
|Nifedipine: 5-20mg 3 times daily<br />
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc14</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''<br />
|- <br />
|Class I (sodium channel blockers)<br />
|Flecainide, Lidocaine, Procainamide<br />
|Ventricular Arrhythmias <br />
|Flecainide: 50-100mg twice daily<br />
|Sustained VT and VF: Class IIbC <cite>Esc15</cite><br />
<br />
Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc16</cite><br />
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.<br />
|-<br />
|Class II (Beta blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|Class III (Potassium channel blockers) <br />
|Amiodarone, Sotalol <br />
|Ventricular, Arrhythmias <br />
|Amiodarone: 200mg 2-3 times daily <br />
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc17</cite><br />
<br />
Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc18</cite><br />
<br />
SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc19</cite> <br />
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes<br />
|-<br />
|Class IV (Calcium channel blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|rowspan="2"|<br />
|rowspan="2"|Digoxin <br />
|Supra-ventricular Arrhythmias <br />
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily <br />
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc20</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.<br />
|-<br />
|Heart Failure <br />
|62.5-125 µg daily <br />
|Symptomatic (NYHA class II-IV) HF: Class IIbB <cite>Esc21</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc22</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''<br />
|- <br />
|rowspan="7"|<br />
|rowspan="2"|Aspirin <br />
|Prevention of thrombotic cerebro- or cardio-vascular disease <br />
|75mg once/day<br />
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc23</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc25</cite><br />
<br />
Post-MI: Class Ia <cite>Esc26</cite><br />
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).<br />
|-<br />
|Pain / pyrexia <br />
|300-600mg every 4-6 hours as necessary <br />
|<br />
|-<br />
|rowspan="3"|Clopidogrel <br />
|Prevention of thrombotic events (esp. when warfarin not tolerated) <br />
|75mg once/day<br />
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc27</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc28</cite><br />
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.<br />
|-<br />
|Acute myocardial infarction <br />
|300mg daily initially then 75mg once/day<br />
|Post STEMI: Class IA <cite>Esc5</cite><br />
|-<br />
|Acute coronary syndrome <br />
|300mg daily initially then 75mg once/day<br />
|ACS: Class IIaC <cite>Esc29</cite><br />
|-<br />
|Prasugrel <br />
|Prevention of thrombotic events. <br />
|60mg bolus then 5-10mg once daily<br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc30</cite><br />
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.<br />
|-<br />
|Ticragelor <br />
|Prevention of thrombotic events. <br />
|180mg bolus then 90mg twice daily <br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc30</cite><br />
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Vitamin K Antagonists'''<br />
|-<br />
|<br />
|Warfarin <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|5-10mg initially then tailored to individual (usually 3-9mg once daily at the same time)<br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|<br />
|Acenocoumarol <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|4mg initially, followed by 1-8mg daily <br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Lipid-Lowering Drugs'''<br />
|- <br />
|rowspan="3"|Statins <br />
|rowspan="3"|Simvastatin, Atorvastatin <br />
|Primary hyper-cholesterolaemia, combined hyperlipidaemia <br />
|Simvastatin: 10-20mg once daily<br />
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc31</cite><br />
<br />
Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc32</cite><br />
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)<br />
|-<br />
|Familial hyper-cholesterolaemia <br />
|Simvastatin: 40mg once daily<br />
|HeFH: Class IC <cite>Esc33</cite><br />
|-<br />
|Prevention of cardiovascular events <br />
|20-40mg once daily<br />
|Class IA <cite>Esc34</cite><br />
|-<br />
|rowspan="2"|Fibrates <br />
|Gemfibrozil <br />
|Hyperlipidaemias of types IIa, IIb, III, IV and V <br />
|Gemfibrozil: 0.9-1.2mg daily<br />
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc36</cite><br />
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity<br />
|-<br />
|Ezetimibe <br />
|Primary and familial hyper-cholesterolaemia <br />
|10mg once daily <br />
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc35</cite><br />
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis<br />
|}<br />
<br />
==References==<br />
<biblio><br />
#Esc1 pmid=22611136<br />
#Esc2 pmid=23996285<br />
#Esc3 pmid=22555213<br />
#Esc4 pmid=22922416<br />
#Acc5 pmid=14557344<br />
#Esc6 pmid=21712404<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2449Chest Pain / Angina Pectoris2013-09-16T12:50:56Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities <sup>a</sup> in patients with stable chest pain symptoms. <Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF" | <b><sup>a</sup></b> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in <i>white boxes</i> have a PTP <15% and hence can be managed without further testing.<br />
*Groups in <i>blue boxes</i> have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in <i>light pink boxes</i> have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in <i>dark pink boxes</i> the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
! width="100"| ''Class''<br />
| ''Level of Symptoms''<br />
|-<br />
! valign="top"| Class I<br />
| 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
! valign="top"| Class II<br />
| 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
! valign="top"| Class III<br />
| 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
! valign="top"| Class IV<br />
| 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease. <Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG <sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography <sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT <sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography <sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI <sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography <sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT <sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI <sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA <sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET <sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3" bgcolor="#FFFFFF"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<b><sup>a</sup></b> Results without/with minimal referral bias.<br />
<br />
<b><sup>b</sup></b> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<b><sup>c</sup></b> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1.<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2448Chest Pain / Angina Pectoris2013-09-16T12:41:38Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities <sup>a</sup> in patients with stable chest pain symptoms. <Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF" | <b><sup>a</sup></b> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in <i>white boxes</i> have a PTP <15% and hence can be managed without further testing.<br />
*Groups in <i>blue boxes</i> have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in <i>light pink boxes</i> have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in <i>dark pink boxes</i> the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
! width="100"| ''Class''<br />
| ''Level of Symptoms''<br />
|-<br />
! valign="top"| Class I<br />
| 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
! valign="top"| Class II<br />
| 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
! valign="top"| Class III<br />
| 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
! valign="top"| Class IV<br />
| 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease. <Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG <sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography <sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT <sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography <sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI <sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography <sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT <sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI <sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA <sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET <sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3" bgcolor="#FFFFFF"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<b><sup>a</sup></b> Results without/with minimal referral bias.<br />
<br />
<b><sup>b</sup></b> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<b><sup>c</sup></b> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina <b>see Figure 1</b>.<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2447Chest Pain / Angina Pectoris2013-09-16T12:34:45Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities <sup>a</sup> in patients with stable chest pain symptoms. <Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF" | <b><sup>a</sup></b> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in <i>white boxes</i> have a PTP <15% and hence can be managed without further testing.<br />
*Groups in <i>blue boxes</i> have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in <i>light pink boxes</i> have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in <i>dark pink boxes</i> the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease. <Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG <sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography <sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT <sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography <sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI <sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography <sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT <sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI <sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA <sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET <sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3" bgcolor="#FFFFFF"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<b><sup>a</sup></b> Results without/with minimal referral bias.<br />
<br />
<b><sup>b</sup></b> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<b><sup>c</sup></b> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina <b>see Figure 1</b>.<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2446Chest Pain / Angina Pectoris2013-09-16T12:33:01Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms. <Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF" | <b><sup>a</sup></b> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in <i>white boxes</i> have a PTP <15% and hence can be managed without further testing.<br />
*Groups in <i>blue boxes</i> have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in <i>light pink boxes</i> have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in <i>dark pink boxes</i> the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease. <Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG <sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography <sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT <sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography <sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI <sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography <sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT <sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI <sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA <sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET <sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3" bgcolor="#FFFFFF"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<b><sup>a</sup></b> Results without/with minimal referral bias.<br />
<br />
<b><sup>b</sup></b> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<b><sup>c</sup></b> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina <b>see Figure 1</b>.<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2445Chest Pain / Angina Pectoris2013-09-16T12:21:26Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms. <Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" | <sup>a</sup> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in <i>white boxes</i> have a PTP <15% and hence can be managed without further testing.<br />
*Groups in <i>blue boxes</i> have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in <i>light pink boxes</i> have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in <i>dark pink boxes</i> the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease. <Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG <sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography <sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT <sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography <sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI <sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography <sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT <sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI <sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA <sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET <sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<sup>a</sup> Results without/with minimal referral bias.<br />
<br />
<sup>b</sup> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<sup>c</sup> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2444Chest Pain / Angina Pectoris2013-09-16T12:17:43Z<p>NiloferT: /* Stress Testing in Combination with Imaging */</p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" | <sup>a</sup> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in white boxes have a PTP <15% and hence can be managed without further testing.<br />
*Groups in blue boxes have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in light pink boxes have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in dark pink boxes the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease<Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG <sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography <sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT <sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography <sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI <sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography <sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT <sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI <sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA <sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET <sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<sup>a</sup> Results without/with minimal referral bias.<br />
<br />
<sup>b</sup> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<sup>c</sup> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2443Chest Pain / Angina Pectoris2013-09-16T12:13:54Z<p>NiloferT: /* Stress Testing in Combination with Imaging */</p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" | <sup>a</sup> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in white boxes have a PTP <15% and hence can be managed without further testing.<br />
*Groups in blue boxes have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in light pink boxes have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in dark pink boxes the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease<Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| <b>Exercise ECG<sup>a, 91, 94, 95</sup></b><br />
!45–50 <br />
!85–90<br />
|-<br />
| <b>Exercise stress echocardiography<sup>96</sup></b><br />
!80–85 <br />
!80–88<br />
|-<br />
| <b>Exercise stress SPECT<sup>96-99</sup></b><br />
!73–92 <br />
!63–87<br />
|-<br />
| <b>Dobutamine stress echocardiography<sup>96</sup></b><br />
!79–83 <br />
!82–86<br />
|-<br />
| <b>Dobutamine stress MRI<sup>b,100</sup></b><br />
!79–88 <br />
!81–91<br />
|-<br />
| <b>Vasodilator stress echocardiography<sup>96</sup></b><br />
!72–79 <br />
!92–95<br />
|-<br />
| <b>Vasodilator stress SPECT<sup>96, 99</sup></b><br />
!90–91 <br />
!75–84<br />
|-<br />
| <b>Vasodilator stress MRI<sup>b,98, 100-102</sup></b><br />
!67–94 <br />
!61–85<br />
|-<br />
| <b>Coronary CTA<sup>c,103-105</sup></b><br />
!95–99 <br />
!64–83<br />
|-<br />
| <b>Vasodilator stress PET<sup>97, 99, 106</sup></b><br />
!81–97 <br />
!74–91<br />
|-<br />
| colspan="3"| <b>CAD</b> = coronary artery disease; <b>CTA</b> = computed tomography angiography; <b>ECG</b> = electrocardiogram; <b>MRI</b> = magnetic resonance imaging; <b>PET</b> = positron emission tomography; <b>SPECT</b> = single photon emission computed tomography.<br />
|-<br />
| colspan="3"|<sup>a</sup> Results without/with minimal referral bias.<br />
<br />
<sup>b</sup> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<sup>c</sup> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2442Chest Pain / Angina Pectoris2013-09-16T11:33:50Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" | <sup>a</sup> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in white boxes have a PTP <15% and hence can be managed without further testing.<br />
*Groups in blue boxes have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in light pink boxes have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in dark pink boxes the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
|colspan = "7" | <b>Table 4. Characteristics of tests commonly used to diagnose the presence of coronary artery disease<Cite>REFNAME20</Cite></b><br />
|- <br />
| bgcolor="#FFFFFF" rowspan="2"|<br />
|align="center" colspan="2" bgcolor="#FFFFFF" | <b>Diagnosis of CAD</b><br />
|-<br />
| align="center" bgcolor="#FFFFFF" | <b>Sensitivity (%)</b><br />
| align="center" bgcolor="#FFFFFF" | <b>Specificity (%)</b><br />
|-<br />
| Exercise ECG<sup>a, 91, 94, 95</sup><br />
|45–50 <br />
|85–90<br />
|-<br />
| Exercise stress echocardiography<sup>96</sup><br />
|80–85 <br />
|80–88<br />
|-<br />
| Exercise stress SPECT<sup>96-99</sup><br />
|73–92 <br />
|63–87<br />
|-<br />
| Dobutamine stress echocardiography<sup>96</sup><br />
|79–83 <br />
|82–86<br />
|-<br />
| Dobutamine stress MRI<sup>b,100</sup><br />
|79–88 <br />
|81–91<br />
|-<br />
| Vasodilator stress echocardiography<sup>96</sup><br />
|72–79 <br />
|92–95<br />
|-<br />
| Vasodilator stress SPECT<sup>96, 99</sup><br />
|90–91 <br />
|75–84<br />
|-<br />
| Vasodilator stress MRI<sup>b,98, 100-102</sup><br />
|67–94 <br />
|61–85<br />
|-<br />
| Coronary CTA<sup>c,103-105</sup><br />
|95–99 <br />
|64–83<br />
|-<br />
| Vasodilator stress PET<sup>97, 99, 106</sup><br />
|81–97 <br />
|74–91<br />
|-<br />
|colspan="3"|CAD = coronary artery disease; CTA = computed tomography angiography; ECG = electrocardiogram; MRI = magnetic resonance imaging; PET = positron emission tomography; SPECT = single photon emission computed tomography.<br />
|-<br />
|colspan="3"|<sup>a</sup> Results without/with minimal referral bias.<br />
<br />
<sup>b</sup> Results obtained in populations with medium-to-high prevalence of disease without compensation for referral bias.<br />
<br />
<sup>c</sup> Results obtained in populations with low-to-medium prevalence of disease.<br />
|}<br />
<br />
If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2441Chest Pain / Angina Pectoris2013-09-16T10:59:13Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! Age<br />
! Men<br />
! Women<br />
! Men <br />
! Women<br />
! Men<br />
! Women<br />
|-<br />
! 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" | <sup>a</sup> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in white boxes have a PTP <15% and hence can be managed without further testing.<br />
*Groups in blue boxes have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in light pink boxes have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in dark pink boxes the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2440Chest Pain / Angina Pectoris2013-09-16T08:04:02Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities<sup>a</sup> in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! align="center" | Age<br />
! align="center" | Men<br />
! align="center" | Women<br />
! align="center" | Men <br />
! align="center" | Women<br />
! align="center" | Men<br />
! align="center" | Women<br />
|-<br />
! align="center" | 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! align="center" | 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! align="center" | 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! align="center" | 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! align="center" | 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! align="center" | >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|-<br />
| colspan = "7" bgcolor="#FFFFFF"|<br />
|-<br />
! colspan = "7" | ECG = electrocardiogram; PTP = pre-test probability; SCAD = stable coronary artery disease.<br />
|-<br />
| colspan = "7" | <sup>a</sup> Probabilities of obstructive coronary disease shown reflect the estimates for patients aged 35, 45, 55, 65, 75 and 85 years.<br />
*Groups in white boxes have a PTP <15% and hence can be managed without further testing.<br />
*Groups in blue boxes have a PTP of 15–65%. They could have an exercise ECG if feasible as the initial test. However, if local expertise and availability permit a non-invasive imaging based test for ischaemia this would be preferable given the superior diagnostic capabilities of such tests. In young patients radiation issues should be considered.<br />
*Groups in light pink boxes have PTPs between 66–85% and hence should have a non-invasive imaging functional test for making a diagnosis of SCAD.<br />
*In groups in dark pink boxes the PTP is >85% and one can assume that SCAD is present. They need risk stratification only.<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2439Chest Pain / Angina Pectoris2013-09-13T13:01:46Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! align="center" | Age<br />
! align="center" | Men<br />
! align="center" | Women<br />
! align="center" | Men <br />
! align="center" | Women<br />
! align="center" | Men<br />
! align="center" | Women<br />
|-<br />
! align="center" | 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! align="center" | 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! align="center" | 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! align="center" | 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! align="center" | 70-79<br />
| align="center" bgcolor="#FF69B4" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! align="center" | >80<br />
| align="center" bgcolor="#FF69B4" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2438Chest Pain / Angina Pectoris2013-09-13T13:00:14Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! align="center" | Age<br />
! align="center" | Men<br />
! align="center" | Women<br />
! align="center" | Men <br />
! align="center" | Women<br />
! align="center" | Men<br />
! align="center" | Women<br />
|-<br />
! align="center" | 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! align="center" | 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! align="center" | 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! align="center" | 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#F0F8FF" | 58<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 44<br />
| align="center" bgcolor="#F0F8FF" | 17<br />
|-<br />
! align="center" | 70-79<br />
| align="center" bgcolor="#FF0099" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! align="center" | >80<br />
| align="center" bgcolor="#FF0099" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2437Chest Pain / Angina Pectoris2013-09-13T12:58:48Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! align="center" | Age<br />
! align="center" | Men<br />
! align="center" | Women<br />
! align="center" | Men <br />
! align="center" | Women<br />
! align="center" | Men<br />
! align="center" | Women<br />
|-<br />
! align="center" | 30-39<br />
| align="center" bgcolor="#F0F8FF" | 59<br />
| align="center" bgcolor="#F0F8FF" | 28<br />
| align="center" bgcolor="#F0F8FF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#F0F8FF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! align="center" | 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#F0F8FF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! align="center" | 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 49<br />
| align="center" bgcolor="#F0F8FF" | 20<br />
| align="center" bgcolor="#F0F8FF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! align="center" | 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#99CCFF" | 58<br />
| align="center" bgcolor="#99CCFF" | 59<br />
| align="center" bgcolor="#99CCFF" | 28<br />
| align="center" bgcolor="#99CCFF" | 44<br />
| align="center" bgcolor="#99CCFF" | 17<br />
|-<br />
! align="center" | 70-79<br />
| align="center" bgcolor="#FF0099" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#F0F8FF" | 37<br />
| align="center" bgcolor="#F0F8FF" | 54<br />
| align="center" bgcolor="#F0F8FF" | 24<br />
|-<br />
! align="center" | >80<br />
| align="center" bgcolor="#FF0099" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#F0F8FF" | 47<br />
| align="center" bgcolor="#F0F8FF" | 65<br />
| align="center" bgcolor="#F0F8FF" | 32<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2436Chest Pain / Angina Pectoris2013-09-13T12:56:37Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center"|<br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Typical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Atypical angina</b><br />
| align="center" colspan="2" bgcolor="#FFFFFF" | <b>Non-anginal pain</b><br />
|-<br />
! align="center" | Age<br />
! align="center" | Men<br />
! align="center" | Women<br />
! align="center" | Men <br />
! align="center" | Women<br />
! align="center" | Men<br />
! align="center" | Women<br />
|-<br />
! align="center" | 30-39<br />
| align="center" bgcolor="#99CCFF" | 59<br />
| align="center" bgcolor="#99CCFF" | 28<br />
| align="center" bgcolor="#99CCFF" | 29<br />
| align="center" bgcolor="#FFFFFF" | 10<br />
| align="center" bgcolor="#99CCFF" | 18<br />
| align="center" bgcolor="#FFFFFF" | 5<br />
|-<br />
! align="center" | 40-49<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#99CCFF" | 37<br />
| align="center" bgcolor="#99CCFF" | 38<br />
| align="center" bgcolor="#FFFFFF" | 14<br />
| align="center" bgcolor="#99CCFF" | 25<br />
| align="center" bgcolor="#FFFFFF" | 8<br />
|-<br />
! align="center" | 50-59<br />
| align="center" bgcolor="#FFCCCC" | 77<br />
| align="center" bgcolor="#99CCFF" | 47<br />
| align="center" bgcolor="#99CCFF" | 49<br />
| align="center" bgcolor="#99CCFF" | 20<br />
| align="center" bgcolor="#99CCFF" | 34<br />
| align="center" bgcolor="#FFFFFF" | 12<br />
|-<br />
! align="center" | 60-69<br />
| align="center" bgcolor="#FFCCCC" | 84<br />
| align="center" bgcolor="#99CCFF" | 58<br />
| align="center" bgcolor="#99CCFF" | 59<br />
| align="center" bgcolor="#99CCFF" | 28<br />
| align="center" bgcolor="#99CCFF" | 44<br />
| align="center" bgcolor="#99CCFF" | 17<br />
|-<br />
! align="center" | 70-79<br />
| align="center" bgcolor="#FF0099" | 89<br />
| align="center" bgcolor="#FFCCCC" | 68<br />
| align="center" bgcolor="#FFCCCC" | 69<br />
| align="center" bgcolor="#99CCFF" | 37<br />
| align="center" bgcolor="#99CCFF" | 54<br />
| align="center" bgcolor="#99CCFF" | 24<br />
|-<br />
! align="center" | >80<br />
| align="center" bgcolor="#FF0099" | 93<br />
| align="center" bgcolor="#FFCCCC" | 76<br />
| align="center" bgcolor="#FFCCCC" | 78<br />
| align="center" bgcolor="#99CCFF" | 47<br />
| align="center" bgcolor="#99CCFF" | 65<br />
| align="center" bgcolor="#99CCFF" | 32<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2435Chest Pain / Angina Pectoris2013-09-13T12:44:49Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center" |<br />
| align="center" colspan="2" | Typical angina<br />
| align="center" colspan="2" | Atypical angina<br />
| align="center" colspan="2" | Non-anginal pain<br />
|-<br />
! align="center" | Age<br />
! align="center" | Men<br />
! align="center" | Women<br />
! align="center" | Men <br />
! align="center" | Women<br />
! align="center" | Men<br />
! align="center" | Women<br />
|-<br />
! align="center" | 30-39<br />
| align="center" | 59<br />
| align="center" |28<br />
| align="center" | 29<br />
| align="center" | 10<br />
| align="center" | 18<br />
| align="center" | 5<br />
|-<br />
! align="center" | 40-49<br />
| align="center" | 69<br />
| align="center" | 37<br />
| align="center" | 38<br />
| align="center" | 14<br />
| align="center" | 25<br />
| align="center" | 8<br />
|-<br />
! align="center" | 50-59<br />
| align="center" | 77<br />
| align="center" | 47<br />
| align="center" | 49<br />
| align="center" | 20<br />
| align="center" | 34<br />
| align="center" | 12<br />
|-<br />
! align="center" | 60-69<br />
| align="center" | 84<br />
| align="center" | 58<br />
| align="center" | 59<br />
| align="center" | 28<br />
| align="center" | 44<br />
| align="center" | 17<br />
|-<br />
! align="center" | 70-79<br />
| align="center" | 89<br />
| align="center" | 68<br />
| align="center" | 69<br />
| align="center" | 37<br />
| align="center" | 54<br />
| align="center" | 24<br />
|-<br />
! align="center" | >80<br />
| align="center" | 93<br />
| align="center" | 76<br />
| align="center" | 78<br />
| align="center" | 47<br />
| align="center" | 65<br />
| align="center" | 32<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Chest_Pain_/_Angina_Pectoris&diff=2434Chest Pain / Angina Pectoris2013-09-13T12:09:20Z<p>NiloferT: </p>
<hr />
<div>[[File:Heart_coronary_artery.jpg|thumb|400px|An epicardial coronary artery with a atherosclerotic narrowing]]<br />
Stable angina (pectoris) is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back, or arms, typically elicited by exertion or emotional stress and relieved<br />
by rest or nitroglycerin. It can be attributed to myocardial ischemia which is most commonly caused by atherosclerotic coronary artery disease or aortic valve stenosis. <br />
<br />
Three major coronary arteries supply the heart with oxygenated blood, the right coronary artery (RCA), the left anterior descending coronary artery (LAD) and the left circumflex artery (LCx). When the coronary arteries are affected by atherosclerosis and the lumen of the coronary arteries progressively narrow, a dysbalance between myocardial oxygen supply and myocardial oxygen consumption may occur, causing myocardial ischemia. <br />
In stable angina this imbalance mainly occurs when oxygen demand increases due to exercise, increased heart rate, contractility or wall stress.<br />
<br />
A complete history and physical examination are essential to support the diagnosis (stable) angina pectoris and to exclude other (acute) causes of chest pain such as an acute coronary syndrome, aortic dissection, arrhythmias, pulmonary embolism, (tension) pneumothorax or pneumonia, gastroesophageal reflux or spams, hyperventilation or musculoskeletal pain. <Cite>REFNAME2</Cite> In addition, laboratory tests and specific cardiac investigations are often necessary.<br />
<br />
==History==<br />
[[File:Chest_pain_areas.svg|thumb|Typical chest pain is retrosternal. Pain may radiate to the arms, jaw, and / or back.]]<br />
Patients often describe angina pectoris as pressure, tightness, or heaviness located centrally in the chest, and sometimes as strangling, constricting, or burning. The pain often radiates elsewhere in the upper body, mainly arms, jaw and/or back. <Cite>REFNAME3</Cite> Some patients only complain about abdominal pain so the presentation can be aspecific. <Cite>REFNAME4</Cite>, <Cite>REFNAME5</Cite><br />
<br />
Angina pectoris however has some characteristics that can help to differentiate between other causes of (chest) pain. Angina pectoris is usually is brief and gradual in onset and offset, with the intensity increasing and decreasing over several minutes. The pain does not change with respiration or position. If patients had angina pectoris previously they are often able to recognize the pain immediately. <Cite>REFNAME6</Cite><br />
Angina pectoris is a manifestation of arterial insufficiency and usually occurs with increasing oxygen demand such as during exercise. As soon as the demand is decreased (by stopping the exercise for example) complaints usually disappears within a few minutes. <br />
Another way to relieve pain is by administration of nitro-glycerine. Nitro-glycerine spray is a vasodilator which reduces venous return to the heart and therefore decreases the workload and therefore oxygen demand. It also dilates the coronary arteries and increases coronary blood flow. <Cite>REFNAME7</Cite> The response to nitro-glycerine is however not specific for angina pectoris, a similar response may be seen with oesophageal spasm or other gastrointestinal problems because nitro-glycerine relaxes smooth muscle tissue. <Cite>REFNAME8</Cite><br />
<br />
Depending on the characteristics, chest pain can be identified as typical angina, atypical angina or non-cardiac chest pain, see Table 1. <br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! align="center" colspan="2" | Table 1. Clinical classification of chest pain <Cite>REFNAME17</Cite><br />
|-<br />
|valign="top" align="left"|Typical angina (definite)<br />
|Meets three of the following characteristics:<br />
*Substernal chest discomfort of characteristic quality and duration<br />
*Provoked by exertion or emotional stress<br />
*Relieved by rest and/or nitroglycerine<br />
|-<br />
| valign="top"|Atypical angina (probable)<br />
|Meets two of these characteristics<br />
|-<br />
| valign="top"|Non-cardiac chest pain<br />
|Meets one or none of the characteristics<br />
|}<br />
<br />
The classification of chest pain in combination with age and sex is helpful in estimating the pretest likelihood of angiographically significant coronary artery disease, see Table 2. <br />
<br />
{| class="wikitable" border="1" width="600px"<br />
|-<br />
! align="left" colspan = "7" | Table 2. Clinical pre-test probabilities in patients with stable chest pain symptoms<Cite>REFNAME20</Cite><br />
|- <br />
| align="center" |<br />
| align="center" colspan="2" | Typical angina<br />
| align="center" colspan="2" | Atypical angina<br />
| align="center" colspan="2" | Non-anginal pain<br />
|-<br />
| align="center" | Age<br />
| align="center" | Men<br />
| align="center" | Women<br />
| align="center" | Men <br />
| align="center" | Women<br />
| align="center" | Men<br />
| align="center" | Women<br />
|-<br />
| align="center" | 30-39<br />
| align="center" | 59<br />
| align="center" |28<br />
| align="center" | 29<br />
| align="center" | 10<br />
| align="center" | 18<br />
| align="center" | 5<br />
|-<br />
| align="center" | 40-49<br />
| align="center" | 69<br />
| align="center" | 37<br />
| align="center" | 38<br />
| align="center" | 14<br />
| align="center" | 25<br />
| align="center" | 8<br />
|-<br />
| align="center" | 50-59<br />
| align="center" | 77<br />
| align="center" | 47<br />
| align="center" | 49<br />
| align="center" | 20<br />
| align="center" | 34<br />
| align="center" | 12<br />
|-<br />
| align="center" | 60-69<br />
| align="center" | 84<br />
| align="center" | 58<br />
| align="center" | 59<br />
| align="center" | 28<br />
| align="center" | 44<br />
| align="center" | 17<br />
|-<br />
| align="center" | 70-79<br />
| align="center" | 89<br />
| align="center" | 68<br />
| align="center" | 69<br />
| align="center" | 37<br />
| align="center" | 54<br />
| align="center" | 24<br />
|-<br />
| align="center" | >80<br />
| align="center" | 93<br />
| align="center" | 76<br />
| align="center" | 78<br />
| align="center" | 47<br />
| align="center" | 65<br />
| align="center" | 32<br />
|}<br />
<br />
The severity of complaints can be classified according to the Canadian Cardiovascular Society as shown in Table 3<br />
<br />
{| class="wikitable" border="1" width="400px"<br />
|-<br />
! colspan="2" | Table 3. Classification of angina severity according to the Canadian Cardiovascular Society<br />
|-<br />
| width="100" align="left" | ''Class''<br />
| align="left" | ''Level of Symptoms''<br />
|-<br />
| valign="top" align="left" | Class I<br />
| align="left" | 'Ordinary activity does not cause angina'<br />
Angina with strenuous or rapid or prolonged exertion only<br />
|-<br />
| valign="top" align="left" | Class II<br />
| align="left" | 'Slight limitation of ordinary activity'<br />
Angina on walking or climbing stairs rapidly, walking uphill or exertion after meals, in cold weather, when under emotional stress, or only during the first few hours after awakening<br />
|-<br />
| valign="top" align="left" | Class III<br />
| align="left" | 'Marked limitation of ordinary physical activity'<br />
Angina on walking one or two blocks on the level or one flight of stairs at a normal pace under normal conditions<br />
|-<br />
| valign="top" align="left" | Class IV<br />
| align="left" | 'Inability to carry out physical activity without discomfort' or 'angina at rest'<br />
|}<br />
<br />
During angina pectoris ‘vegetative’ symptoms can occur, including sweating, nausea, paleface, anxiety and agitation. This is probably caused by the autonomic nerve system in reaction to stress. <Cite>REFNAME9</Cite><br />
<br />
Finally, it is important to differentiate unstable angina (indicating an acute coronary syndrome or even myocardial infarction requiring urgent treatment) from stable angina. Unstable angina typically is severe, occurs without typical provocation and does not disappear with rest, and has a longer duration than stable angina. It is important to initiate prompt treatment in these patients, as described in the acute coronary syndromes chapter.<br />
<br />
==Physical Examination==<br />
<br />
There are no specific signs in angina pectoris. Physical examination of a patient with (suspected) angina pectoris is important to assess the presence of hypertension,<br />
valvular heart disease (in particular aortic valve stenosis) or hypertrophic obstructive cardiomyopathy. It should include the body-mass index, evidence of non-coronary vascular disease which may be asymptomatic and other signs of co-morbid conditions. E.g.: absence of palpable pulsations in the dorsal foot artery is associated with an 8 fold increase in the likelihood of coronary artery disease.<br />
<br />
==Electrocardiogram (ECG)==<br />
The electrocardiogram (ECG) is an important tool to differentiate between unstable angina (acute coronary syndrome) and stable angina in addition to the patient’s history. Patients with unstable angina pectoris are likely to show abnormalities on the ECG at rest, in particular ST-segment deviations. <br />
Although a resting ECG may show signs of coronary artery disease such as pathological Q-waves indicating a previous MI or other abnormalities, many patients with stable angina pectoris have a normal ECG at rest. Therefore exercise ECG testing may be necessary to show signs of myocardial ischemia. <Cite>REFNAME10</Cite><br />
<br />
'''Exercise ECG testing''' is performed with gradually increasing intensity on a treadmill or a bicycle ergo-meter. Exercise increases the oxygen demand of the heart, potentially revealing myocardial ischemia by the occurrence of ST-segment depression on the ECG. <Cite>REFNAME11</Cite><br />
<br />
==Laboratory Testing==<br />
Laboratory testing in the setting of angina pectoris can be useful to differentiate between different causes of the pain, including an acute coronary syndrome in which there will be elevation of the marker of myocardial necrosis. Anaemia should be ruled out as a cause of ischemia. Renal function is important for pharmacological therapy. Moreover, it might assist in establishing a cardiovascular risk profile.<br />
<br />
==Stress Testing in Combination with Imaging==<br />
Some patients are unable to perform physical exercise. Furthermore, in patients with resting ECG abnormalities the exercise ECG is associated with low sensitivity and specificity. If the ECG made during exercise testing does not show any abnormalities myocardial ischemia becomes unlikely as cause of the complaints. If the diagnosis is still in doubt, the following additional tests may be performed. <br />
#Exercise echocardiography means that an echocardiography is made before and during different stages up to peak exercise in order to identify wall motion abnormalities. <Cite>REFNAME12</Cite> An alternative is pharmacological stress testing using dobutamine.<br />
#Myocardium Perfusion Scintigraphy (MPS) is able to show the perfusion of the heart during exercise and at rest based on radiopharmaceutical tracer uptake . <Cite>REFNAME13</Cite><br />
#Magnetic Resonance Imaging can be done with vasodilatory adenosine or stimulating dobutamine to detect wall motion abnormalities induced by ischemia during pharmacological stress. <Cite>REFNAME14</Cite> <br />
<br />
The findings on stress testing can be used to determine the choice between medical therapy only or medical therapy and invasive assessment of the coronary anatomy in patients with stable angina. Coronary angiography is recommended based upon the severity of symptoms, likelihood of ischemic disease, and risk of the patient for subsequent complications including mortality based on risk scores. <Cite>REFNAME15</Cite> For the algorithm for the initial evaluation of patients with clinical symptoms of angina see Figure 1<br />
<br />
[[File:Algorithm_for_the_initial_evaluation_of_patients_with_clinical_symptoms_of_angina.svg|thumb|right|500px|Figure 1. Algorithm for the initial evaluation of patients with clinical symptoms of angina]]<br />
<br />
==Coronoary Angiography==<br />
Coronary angiography (CAG) can assist in the diagnosis and the selection of treatment options for stable angina pectoris. During CAG, the coronary anatomy is visualized including the presence of coronary luminal stenoses. A catheter is inserted into the femoral artery or into the radial artery. The tip of the catheter is positioned at the beginning of the coronary arteries and contrast fluid is injected. The contrast is made visible by X ray and the images that are obtained are called angiograms. <br />
If stenoses are visible, the operator will judge whether this stenosis is significant and eligible for percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). <br />
<br />
==Treatment==<br />
Stable angina pectoris is always treated with medical therapy aimed at reducing risk and at alleviating symptoms. Current guidelines recommend revascularization in patients with persistent symptoms despite optimal medical therapy. <Cite>REFNAME16</Cite> Furthermore, revascularization is indicated in case of large areas of myocardial ischemia (such as a left main stem stenosis, a proximal LAD stenosis or significant three vessel disease) and in the presence of high-risk features such as ventricular arrhythmia, heart failure, widening of QRS during ischemia, axis deviation during ischemia or hypotension during ischemia. The choice between PCI and CABG depends on the coronary anatomy and clinical characteristics and the choice should be made in a team including (interventional) cardiologists and thoracic surgeons. <br />
<br />
==Medical Therapy==<br />
Initial treatment of stable angina pectoris focuses on medication reducing the oxygen demand of the heart. ß blockers lower heart rate and blood pressure. <Cite>REFNAME17</Cite> Nitrates dilatate the coronary arteries and reduce venous return if used to abort an episode of pain. <Cite>REFNAME18</Cite> Antiplatelet therapy (aspirin) reduces the risk of development of a thrombus and thus acute (coronary) ischemic events. <Cite>REFNAME19</Cite><br />
Risk factors like smoking, overweight, hypertension, dyslipidemia and diabetes need to be treated in order to prevent disease progression and future events. See chronic coronary diseases. <br />
<br />
==PCI==<br />
The procedure of PCI is similar to a CAG, except this time a catheter with an inflatable balloon will be brought to the site of the stenosis. Inflation of the balloon within the coronary artery will crush the atherosclerosis and eliminate the stenosis. To prevent collapse of the arteric wall and restenosis, a stent is often positioned at the site of the stenosis. <br />
<br />
==CABG==<br />
With CABG, a bypass is placed around the stenosis using the internal thoracic arteries or the saphenous veins from the legs. The bypass originates proximal from the stenosis and terminates distally from the stenosis. The operation usually requires the use of cardiopulmonary bypass and cardiac arrest, however in certain cases the grafts can be placed on the beating heart (“off-pump” surgery) <br />
<br />
== References ==<br />
<biblio><br />
#REFNAME1 pmid=11756201<br />
#REFNAME2 pmid=4997794<br />
#REFNAME3 pmid=10099685<br />
#REFNAME4 pmid=10866870<br />
#REFNAME5 pmid=10751787<br />
#REFNAME6 pmid=6831781<br />
#REFNAME7 pmid=3925741<br />
#REFNAME8 pmid=14678917<br />
#REFNAME9 pmid=15289388<br />
#REFNAME10 pmid=8375424<br />
#REFNAME11 pmid=17162834<br />
#REFNAME12 pmid=1352191<br />
#REFNAME13 pmid=2007701<br />
#REFNAME14 pmid=12566362<br />
#REFNAME15 pmid=18061078<br />
#REFNAME16 pmid=20802248<br />
#REFNAME17 pmid=16735367<br />
#REFNAME18 pmid=3925741<br />
#REFNAME19 pmid=9355934<br />
#REFNAME20 pmid=23996286<br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Cardiac_Pharmacology&diff=2433Cardiac Pharmacology2013-09-13T09:23:28Z<p>NiloferT: </p>
<hr />
<div>{{DevelopmentPhase}}<br />
''Heather Melrose, Jonas de Jong''<br />
<br />
__TOC__<br />
<br />
Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease.<br />
<br />
==Renin-Angiotensin-Aldosterone System==<br />
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. <br />
<br />
'''Angiotensin II causes increases in blood pressure by actions at various sites:'''<br />
<br />
*'''Adrenal Glands:''' Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance.<br />
<br />
*'''Kidneys:''' Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow.<br />
<br />
*'''Cardiovascular System:''' Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy.<br />
<br />
*'''Central Nervous System:''' In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased ''thirst'', encouraging water intake.<br />
<br />
Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease.<br />
<br />
==Neural Control of the Cardiovascular System==<br />
===Sympathetic (Adrenergic) Nervous System===<br />
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. <br />
<br />
====Vasculature====<br />
The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately results in myocyte contraction, vasoconstriction and consequent increases in systemic blood pressure.<br />
<br />
====Heart====<br />
Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the ß-receptor subfamily and include ß1 and ß3 receptors. Catecholamine binding to ß1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However ß3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart.<br />
<br />
Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias.<br />
<br />
===Parasympathetic Nervous System===<br />
The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body. <br />
<br />
====Vasculature====<br />
Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation.<br />
<br />
====Heart====<br />
Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions.<br />
<br />
==Platelet/Clotting System==<br />
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. <br />
<br />
There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and ischaemia or stroke; less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process.<br />
<br />
===Anti-coagulants===<br />
Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia.<br />
<br />
As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin’s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A<sub>2</sub> reduces platelet aggregation and thus prevents clot formation.<br />
<br />
P2Y<sub>12</sub> inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y<sub>12</sub> subtype of the platelet ADP receptor. By blocking P2Y<sub>12</sub>, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. <br />
<br />
Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation.<br />
<br />
==Pharmacokinetics==<br />
When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" <br />
|-<br />
!Property <br />
!Description <br />
!Standard units (Abbreviation) <br />
!Formula<br />
|-<br />
!Dose <br />
|Amount of active drug given to patient <br />
|align="center"|mg (D) <br />
|Drug Specific (From clinical studies)<br />
|-<br />
!Concentration <br />
|Amount of drug in a given plasma volume <br />
|align="center"|µg/ml (C) <br />
|align="center"|= D / Vd<br />
|-<br />
!EC<sub>50</sub> <br />
|The concentration of drug needed to elicit a response halfway between zero and maximal responses. <br />
|align="center"|µg/ml (EC<sub>50</sub>) <br />
|align="center"|y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient)<br />
|-<br />
!Volume of Distribution<br />
|The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. <br />
|align="center"|L (Vd) <br />
|align="center"|D / C<br />
|-<br />
!Elimination Constant (Rate) <br />
|The rate at which the drug is removed from the body. <br />
|align="center"|h-1 (Ke) <br />
|align="center"|ln(2) / t1/2 or CL / Vd<br />
|-<br />
!Bioavailability <br />
|How much of the administered dose is available for actual use by the body. <br />
|no units as expressing a fraction (f) <br />
|align="center"|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po))<br />
<br />
AUC = Area under curve po = oral administration iv = intravenous administration<br />
|-<br />
!Cmax or Cmin <br />
|The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration <br />
|align="center"|µg/ml (Cmax or Cmin) <br />
|Identified via direct measurement of plasma C<br />
|-<br />
!tmax <br />
|The time it takes for a drug to reach Cmax following administration <br />
|align="center"|h (tmax) <br />
|Identified via direct measurement of plasma C over time<br />
|-<br />
!Half-life <br />
|The time it takes for a drug to reach half its original concentration <br />
|align="center"|h (t1/2) <br />
|align="center"|ln(2) / Ke<br />
|-<br />
!Drug Clearance <br />
|The volume of plasma cleared of the drug over a set time <br />
|align="center"|l/h (CL) <br />
|align="center"|Vd x Ke or D / Area under curve<br />
|}<br />
<br />
==Common Drug-Drug Interactions==<br />
It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug—drug interactions related to cardiovascular drugs are listed below:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Drug <br />
!Drugs that <big>↑</big> drug action <br />
!Drugs that <big>↓</big> drug action<br />
|-<br />
!Digoxin <br />
|valign="top"|<br />
*Diuretics<br />
*Antiarrhythmics<br />
*Macrolide antibiotics<br />
*Cholestyramine<br />
*Neomycin<br />
*Keto- and intraconazole<br />
*Calcium antagonists<br />
*Cyclosporine, indomethacin<br />
*HMG CoA reductase inhibitors<br />
*Benzodiazepines<br />
*Amiodarone<br />
*Verapamil <br />
|valign="top"|<br />
*Rifampicin<br />
*Antacids (liquid)<br />
|-<br />
!Warfarin <br />
|valign="top"|<br />
*Furosemide<br />
*Amiodarone<br />
*Sulfa<br />
*Macrolide and quinolone antibiotics<br />
*NSAIDs<br />
|valign="top"|<br />
*Azathioprine<br />
*Phenobarbitone<br />
*Carbamazepine<br />
*Dexamethasone<br />
*Prednisolone<br />
*Rifampicin<br />
*Vitamin K<br />
*Raloxifene<br />
|-<br />
!Clopidogrel <br />
|valign="top"|<br />
*Rifampicin<br />
*Caffeine<br />
*Methylxanthines<br />
*Phosphodiesterase inhibitors <br />
|valign="top"|<br />
*Statins<br />
*Calcium channel blockers<br />
*Warfarin<br />
*Proton pump inhibitors<br />
|-<br />
!Furosemide <br />
|<br />
|valign="top"|<br />
*NSAIDs<br />
*Phenytoin<br />
*Colesevelam<br />
|-<br />
!ACE Inhibitors <br />
|valign="top"|<br />
*NSAIDs<br />
*Probenecid<br />
*Calcium channel blockers <br />
|valign="top"|<br />
*Indomethacin<br />
*Antacids<br />
|-<br />
!ß-blockers <br />
|valign="top"|<br />
*Amiodarone<br />
*Calcium channel blockers<br />
*Diltiazem<br />
*Phenoxybenzamine <br />
|valign="top"|<br />
*Phenobarbital<br />
*Rifampicin<br />
*Cimetidine<br />
*Antacids (liquid)<br />
*NSAIDs<br />
|-<br />
!Statins <br />
|valign="top"|<br />
*Amiodarone<br />
*Verapamil<br />
*Fibrates<br />
*Amprenavir<br />
*Diltiazem <br />
|valign="top"|<br />
*Nevirapine<br />
*Rifampicin<br />
|}<br />
<br />
There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g. toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by-product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below: <br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Enzyme <br />
!Substrates (e.g.) <br />
!Inhibitors (e.g.) <br />
!Inducers (e.g.)<br />
|-<br />
!CYP2C19 <br />
|valign="top"|<br />
*Clopidogrel<br />
*Propranolol<br />
*Warfarin <br />
|valign="top"|<br />
*Moclobemide<br />
*Chloramphenicol<br />
*Many anti-convulsants (Valproate)<br />
*Proton pump inhibitors (Omeprazole)<br />
|valign="top"|<br />
*Rifampicin<br />
*Carbamazepine<br />
*Prednisone<br />
|-<br />
!CYP3A4 <br />
|valign="top"|<br />
*Donepezil<br />
*Statins (Atorvastatin)<br />
*Ca-channel blockers (Nifedipine)<br />
*Amiodarone<br />
*Dronedarone<br />
*Quinidine<br />
*PDE5 Inhibitors (Sildenafil)<br />
*Kinins<br />
*Caffeine<br />
*Eplerenone<br />
*Propranolol<br />
*Salmeterol<br />
*Warfarin<br />
*Clopidogrel <br />
|valign="top"|<br />
*Protease inhibitors (Ritonavir)<br />
*Macrolides (Clarithromycin)<br />
*Chloramphenicol<br />
*Nefazodone<br />
*Some Ca-channel blockers (Verapamil)<br />
*Cimetidine<br />
*Some azole anti-fungals (Ketaconazole)<br />
*Grapefruit juice <br />
|valign="top"|<br />
*Some anti-convulsants (Carbamazepine)<br />
*Baribiturates (Phenobarbital)<br />
*St. John’s Wort<br />
*Some reverse transcriptase inhibitors (Efavirenz)<br />
*Some Hypoglycaemics (Pioglitazone)<br />
*Glucocorticoids<br />
*Modafinil<br />
|-<br />
!CYP2C9 <br />
|valign="top"|<br />
*Fluvastatin<br />
*Angiotensin receptor II agonists (losartan)<br />
*Warfarin<br />
*Torasemide <br />
|valign="top"|<br />
*Some azole anti-fungals (Fluconazole)<br />
*Amiodarone<br />
*Antihistamines (Cyclizine)<br />
*Chloramphenicol<br />
*Fluvastatin<br />
*Fluvoxamine<br />
*Probenecid<br />
*Sertraline <br />
|valign="top"|<br />
*Rifampicin<br />
*Secobarbital<br />
|-<br />
!CYP2D6 <br />
|valign="top"|<br />
*ß-blockers (Propranolol)<br />
*Class I anti-arrythmics (Flecainide)<br />
*Donepezil<br />
|valign="top"|<br />
*SSRIs (Fluoxetine)<br />
*Quinidine<br />
*Sertraline<br />
*Terbinafine<br />
*Amiodarone<br />
*Cinacalcet<br />
*Ritonavir<br />
*Antipsychotics (Haloperidol)<br />
*Antihistamines (Promethazine)<br />
*Metoclopramide<br />
*Ranitidine<br />
*Mibefradil <br />
|valign="top"|<br />
*Rifampicin<br />
*Dexamethasone<br />
*Glutethimide<br />
|}<br />
<br />
In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: [http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/GeneralUseofMedicine/UCM229033.pdf General Use of Medicine]<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
|+Cardiovascular Drugs<br />
|- <br />
!Drug Type <br />
!Examples (generic name)<br />
!Indications <br />
!Typical Dosage<br />
!Guidelines / Class of Indication <br />
!Side Effects (Prevalence %)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|:'''Anti-hypertensives''' <br />
|-<br />
|rowspan="2"|Diuretics <br />
|rowspan="2"|Furosemide<br />
|Oedema<br />
|Furosemide: 20-40mg once daily<br />
|<br />
|rowspan="2" valign="top"|Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus).<br />
|-<br />
|Resistant Hypertension<br />
|Furosemide: 40-80mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC <cite>Esc1</cite><br />
|-<br />
|rowspan="4"|ACE Inhibitors <br />
|rowspan="4"|Captopril, Monopril <br />
|Hypertension <br />
|Captopril: 12.5mg twice daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc3</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc4</cite> <br />
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.<br />
|-<br />
|Heart Failure <br />
|Captopril: 12.5mg 3 times daily<br />
|Post STEMI: Class IA <cite>Esc5</cite><br />
<br />
Diabetic patients: Class IC <cite>Esc6</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc7</cite><br />
|-<br />
|Prophylaxis Following MI <br />
|Captopril: 6.25mg once daily<br />
| <br />
|-<br />
|Diabetic nephropathy <br />
|Captopril: 75-100mg once daily<br />
|<br />
|-<br />
|rowspan="3"|Angiotensin Receptor Blockers <br />
|rowspan="3"|Losartan, Candesartan<br />
|Hypertension <br />
|Losartan: 50mg once daily<br />
|Hypertension: Class IA <cite>Esc2</cite><br />
<br />
Hypertension in diabetics: Class IA <cite>Esc4</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;<br />
|-<br />
|Left ventricular hypertrophy <br />
|Losartan: 12.5-150mg daily<br />
|LVH: Class IB <cite>Esc8</cite><br />
|- <br />
|Diabetic nephropathy <br />
|Losartan: 50mg daily<br />
|<br />
|-<br />
|rowspan="3"|Alpha Blockers <br />
|rowspan="3"|Prazosin, Doxazosin <br />
|Hypertension <br />
|Prazosin: 1-10mg 2-3 times daily <br />
|<br />
|rowspan="3" valign="top"|Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8-18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema.<br />
|-<br />
|Congestive Heart Failure <br />
|Prazosin: 4-20mg daily<br />
|<br />
|-<br />
|Raynaud’s Syndrome <br />
|Prazosin: 1-2mg daily<br />
|<br />
|- <br />
|rowspan="4"|Beta Blockers <br />
|rowspan="4"|Atenolol, Propranolol <br />
|Hypertension <br />
|Atenolol: 25-50mg daily<br />
|<br />
|rowspan="4" valign="top"|Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes.<br />
|-<br />
|Angina <br />
|Atenolol: 100mg once/twice daily<br />
|ACS: Class IIaB <cite>Esc9</cite><br />
<br />
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc10</cite><br />
|-<br />
|Arrhythmias <br />
|Atenolol: 50-100mg daily <br />
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc11</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc12</cite><br />
<br />
SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc13</cite><br />
|-<br />
|Migraine <br />
|Atenolol: 50-200mg daily <br />
| <br />
|-<br />
|rowspan="3"|Calcium Channel Blockers <br />
|rowspan="3"|Nifedipine, Verapamil, Diltiazem<br />
|Hypertension <br />
|Nifedipine: 20-30mg once daily<br />
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc3</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;<br />
|-<br />
|Raynaud’s Syndrome <br />
|Nifedipine: 5-20mg 3 times daily<br />
|<br />
|-<br />
|Angina (prophylaxis) <br />
|Nifedipine: 5-20mg 3 times daily<br />
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc14</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''<br />
|- <br />
|Class I (sodium channel blockers)<br />
|Flecainide, Lidocaine, Procainamide<br />
|Ventricular Arrhythmias <br />
|Flecainide: 50-100mg twice daily<br />
|Sustained VT and VF: Class IIbC <cite>Esc15</cite><br />
<br />
Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc16</cite><br />
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.<br />
|-<br />
|Class II (Beta blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|Class III (Potassium channel blockers) <br />
|Amiodarone, Sotalol <br />
|Ventricular, Arrhythmias <br />
|Amiodarone: 200mg 2-3 times daily <br />
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc17</cite><br />
<br />
Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc18</cite><br />
<br />
SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc19</cite> <br />
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes<br />
|-<br />
|Class IV (Calcium channel blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
| <br />
|(See above)<br />
|-<br />
|rowspan="2"|<br />
|rowspan="2"|Digoxin <br />
|Supra-ventricular Arrhythmias <br />
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily <br />
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc20</cite><br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.<br />
|-<br />
|Heart Failure <br />
|62.5-125 µg daily <br />
|Symptomatic (NYHA class II-IV) HF: Class IIbB <cite>Esc21</cite><br />
<br />
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc22</cite><br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''<br />
|- <br />
|rowspan="7"|<br />
|rowspan="2"|Aspirin <br />
|Prevention of thrombotic cerebro- or cardio-vascular disease <br />
|75mg once/day<br />
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc23</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc25</cite><br />
<br />
Post-MI: Class Ia <cite>Esc26</cite><br />
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).<br />
|-<br />
|Pain / pyrexia <br />
|300-600mg every 4-6 hours as necessary <br />
|<br />
|-<br />
|rowspan="3"|Clopidogrel <br />
|Prevention of thrombotic events (esp. when warfarin not tolerated) <br />
|75mg once/day<br />
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc27</cite><br />
<br />
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc28</cite><br />
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.<br />
|-<br />
|Acute myocardial infarction <br />
|300mg daily initially then 75mg once/day<br />
|Post STEMI: Class IA <cite>Esc5</cite><br />
|-<br />
|Acute coronary syndrome <br />
|300mg daily initially then 75mg once/day<br />
|ACS: Class IIaC <cite>Esc29</cite><br />
|-<br />
|Prasugrel <br />
|Prevention of thrombotic events. <br />
|60mg bolus then 5-10mg once daily<br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc30</cite><br />
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.<br />
|-<br />
|Ticragelor <br />
|Prevention of thrombotic events. <br />
|180mg bolus then 90mg twice daily <br />
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite><br />
<br />
Acute phase of coronary artery syndrome: Class IB <cite>Esc30</cite><br />
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Vitamin K Antagonists'''<br />
|-<br />
|<br />
|Warfarin <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|5-10mg initially then tailored to individual (usually 3-9mg once daily at the same time)<br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|<br />
|Acenocoumarol <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|4mg initially, followed by 1-8mg daily <br />
|<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|colspan="6" bgcolor="#E6E6FA"|'''Lipid-Lowering Drugs'''<br />
|- <br />
|rowspan="3"|Statins <br />
|rowspan="3"|Simvastatin, Atorvastatin <br />
|Primary hyper-cholesterolaemia, combined hyperlipidaemia <br />
|Simvastatin: 10-20mg once daily<br />
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc31</cite><br />
<br />
Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc32</cite><br />
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)<br />
|-<br />
|Familial hyper-cholesterolaemia <br />
|Simvastatin: 40mg once daily<br />
|HeFH: Class IC <cite>Esc33</cite><br />
|-<br />
|Prevention of cardiovascular events <br />
|20-40mg once daily<br />
|Class IA <cite>Esc34</cite><br />
|-<br />
|rowspan="2"|Fibrates <br />
|Gemfibrozil <br />
|Hyperlipidaemias of types IIa, IIb, III, IV and V <br />
|Gemfibrozil: 0.9-1.2mg daily<br />
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc36</cite><br />
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity<br />
|-<br />
|Ezetimibe <br />
|Primary and familial hyper-cholesterolaemia <br />
|10mg once daily <br />
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc35</cite><br />
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis<br />
|}<br />
<br />
==References==<br />
<biblio><br />
#Esc1 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC<br />
#Esc2 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Hypertension: Class IA<br />
#Esc3 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA<br />
#Esc4 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092):Hypertension in diabetics: Class IA<br />
#Esc5 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Post STEMI: Class IA<br />
#Esc6 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Diabetic patients: Class IC<br />
#Esc7 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA<br />
#Esc8 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): LVH: Class IB<br />
#Esc9 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261) ACS: Class IIaB<br />
#Esc10 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA<br />
#Esc11 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Atrial fibrillation: Class IA; Polymorphic VT: Class IB<br />
#Esc12 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA<br />
#Acc13 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB<br />
#Esc14 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <br />
#Esc15 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Sustained VT and VF: Class IIbC<br />
#Acc16 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <br />
#Esc17 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC<br />
#Esc18 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB<br />
#Acc19 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <br />
#Acc20 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <br />
#Esc21 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF: Class IIbB<br />
#Esc22 ESC Guidelines Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC<br />
#Esc23 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Prevention in AF: Class IC; Prevention in diabetic patients: IIaB<br />
#Esc24 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA<br />
#Esc25 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA<br />
#Esc26 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Post-MI: Class Ia<br />
#Esc27 ESC and EASD Guidelines (European Heart Journal doi:10.1093/eurheart/ehl261): Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB<br />
#Esc28 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA<br />
#Esc29 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): ACS: Class IIaC<br />
#Esc30 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB<br />
#Esc31 ESC and EASD Guidelines (European Heart Journal doi:10.1093/eurheart/ehl261); Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC<br />
#Esc32 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Hypertension in diabetics: Class IA; ACS: Class IA <br />
#Esc33 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): HeFH: Class IC<br />
#Esc34 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Class IA<br />
#Esc35 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818 doi:10.1093/eurheartj/ehr158): Transplant patients (with high LDL-C): Class IIbC<br />
#Esc36 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818 doi:10.1093/eurheartj/ehr158): Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <br />
</biblio></div>NiloferThttps://www.textbookofcardiology.org/index.php?title=Cardiac_Pharmacology&diff=2428Cardiac Pharmacology2013-05-27T21:22:09Z<p>NiloferT: </p>
<hr />
<div>{{DevelopmentPhase}}<br />
<br />
__TOC__<br />
<br />
Cardiovascular disease including heart disease, arrhythmias and hypertension, is the leading cause of morbidity and mortality in the Western world. There are numerous devastating conditions affecting the heart and/or the vasculature, leading to high demand for cardiovascular drugs. This chapter focuses on some key therapeutic targets within the cardiovascular system and the drugs used to combat cardiovascular disease.<br />
<br />
==Renin-Angiotensin-Aldosterone System==<br />
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body. <br />
<br />
'''Angiotensin II causes increases in blood pressure by actions at various sites:'''<br />
<br />
*'''Adrenal Glands:''' Angiotensin II augments release of the steroid hormone aldosterone, which acts locally to augment sodium retention and potassium secretion from the kidney. The net effect of this is water retention, thus restoring fluid balance.<br />
<br />
*'''Kidneys:''' Angiotensin II also increases sodium retention via direct actions on renal proximal tubules, as well as affecting glomerular filtration rate and renal blood flow.<br />
<br />
*'''Cardiovascular System:''' Angiotensin II is a potent endogenous vasoconstrictor, causing resistance arteries and veins to constrict, raising blood pressure. Furthermore in both the blood vessels and the heart, prolonged increases in Angiotensin II encourage cell growth and resultant hypertrophy.<br />
<br />
*'''Central Nervous System:''' In the brain, Angiotensin II acts on the posterior pituitary gland, stimulating release of antidiuretic hormone (ADH, also known as Arginine Vasopressin (AVP)). ADH increases water reabsorption in the renal collecting ducts. Angiotensin II also acts on the subfornical organ within the brain to cause increased ''thirst'', encouraging water intake.<br />
<br />
Chronic activation of the RAAS system can lead to deleterious remodelling and increased inflammation in the heart, vasculature and kidneys, as well as hypertension and chronic kidney disease.<br />
<br />
==Neural Control of the Cardiovascular System==<br />
===Sympathetic (Adrenergic) Nervous System===<br />
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes. <br />
<br />
====Vasculature====<br />
The predominant receptor subtype present in blood vessels is the a1-adrenergic receptor, activation of which by catecholamine binding causes activation of the phospholipase-C (PLC), inositol triphosphate (IP3), diacylglycerol (DAG) intracellular signalling pathway. This ultimately results in myocyte contraction, vasoconstriction and consequent increases in systemic blood pressure.<br />
<br />
====Heart====<br />
Although the heart is myogenic, that is the impetus for contraction is self-initiated, the output of the heart is influenced by the central nervous system. The net effect of the sympathetic system on the heart is to increase cardiac output. The adrenergic receptors found in the heart belong to the ß-receptor subfamily and include ß1 and ß3 receptors. Catecholamine binding to ß1-receptors in the heart causes increases in cardiac output via a number of mechanisms: positive chronotropic effects, positive inotropic effects increased automaticity and conduction in both ventricular myocytes and the atrioventricular (AV) node. However ß3-receptor activation antagonises these actions, producing a negative inotropic effect and providing an inbuilt control system within the heart.<br />
<br />
Prolonged increase catecholamine levels in the circulation (e.g. when secreted from adrenal tumours or times of stress) can lead to chronic cardiovascular problems such as hypertension and arrhythmias.<br />
<br />
===Parasympathetic Nervous System===<br />
The parasympathetic system relies on the binding of the neurotransmitter acetylcholine (Ach) to muscarinic receptors, and has various roles throughout the body. <br />
<br />
====Vasculature====<br />
Although blood vessels do express muscarinic receptors, they do not receive cholinergic innervation; however application of exogenous Ach results in a swift and profound vasodilation.<br />
<br />
====Heart====<br />
Activation of muscarinic receptors (M2-subtype) in the heart by Ach released from the vagus nerve causes a reduction in cardiac output via opposite effects to adrenergic stimulation: negative chronotropic effects and decreases in AV node conduction as well as decreasing the force of atrial contractions.<br />
<br />
==Platelet/Clotting System==<br />
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar. <br />
<br />
There are several conditions in which abnormal clotting can be damaging to the body; excess clotting can lead to vascular blockage and ischaemia or stroke; less commonly, deficient clotting can lead to excess blood loss, for example in haemophilia. To combat these diseases, there are drugs that modulate the clotting process.<br />
<br />
===Anti-coagulants===<br />
Drugs that prevent clotting (anti-coagulants) are important in those with an increased risk of clotting-mediated damage such as a stroke or ischaemia.<br />
<br />
As well being an analgesic and anti-pyretic, Aspirin is an anti-thrombotic agent given in low doses to those at risk of damage from clotting (e.g. following a heart attack). Aspirin’s anti-coagulant actions come from its suppression of key pro-clotting factors such as prostaglanding and thromboxanes via irreversible inactivation of the PTGS cyclooxygenase enzyme. This suppression of factors such as thromboxane A<sub>2</sub> reduces platelet aggregation and thus prevents clot formation.<br />
<br />
P2Y<sub>12</sub> inhibitors such as clopidogrel exert their anti-coagulant effect via inhibition of the P2Y<sub>12</sub> subtype of the platelet ADP receptor. By blocking P2Y<sub>12</sub>, these drugs prevent activation of platelets and the formation of the fibrin network needed for clotting. <br />
<br />
Drugs such as abciximab and tirofiban prevent clotting via inhibition of the glycoprotein IIb/IIIa receptor preventing both platelet activation and aggregation.<br />
<br />
==Pharmacokinetics==<br />
When administering drugs to a patient, it is crucial to know several facts about the drug in order to maximise efficacy and minimise side-effects/toxicity. These include information about what dose is effective, how long the drug remains active in the body, how quickly it is broken down/removed from the body, and how easily the body can absorb/use that drug. The following table details these pharmacokinetic properties and how they are calculated:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0" <br />
|-<br />
!Property <br />
!Description <br />
!Standard units (Abbreviation) <br />
!Formula<br />
|-<br />
!Dose <br />
|Amount of active drug given to patient <br />
|align="center"|mg (D) <br />
|Drug Specific (From clinical studies)<br />
|-<br />
!Concentration <br />
|Amount of drug in a given plasma volume <br />
|align="center"|µg/ml (C) <br />
|align="center"|= D / Vd<br />
|-<br />
!EC<sub>50</sub> <br />
|The concentration of drug needed to elicit a response halfway between zero and maximal responses. <br />
|align="center"|µg/ml (EC<sub>50</sub>) <br />
|align="center"|y = bottom + (Top-Bottom)/(1+ [x/EC50] Hill Coefficient)<br />
|-<br />
!Volume of Distribution<br />
|The theoretical volume the drug would occupy if distributed uniformly throughout the tissues to elicit the current plasma concentration. <br />
|align="center"|L (Vd) <br />
|align="center"|D / C<br />
|-<br />
!Elimination Constant (Rate) <br />
|The rate at which the drug is removed from the body. <br />
|align="center"|h-1 (Ke) <br />
|align="center"|ln(2) / t1/2 or CL / Vd<br />
|-<br />
!Bioavailability <br />
|How much of the administered dose is available for actual use by the body. <br />
|no units as expressing a fraction (f) <br />
|align="center"|100 × (AUC (po)×D (iv))/(AUC (iv)×D (po))<br />
<br />
AUC = Area under curve po = oral administration iv = intravenous administration<br />
|-<br />
!Cmax or Cmin <br />
|The maximum (Cmax) / minimum (Cmin) plasma drug concentration reached following drug administration <br />
|align="center"|µg/ml (Cmax or Cmin) <br />
|Identified via direct measurement of plasma C<br />
|-<br />
!tmax <br />
|The time it takes for a drug to reach Cmax following administration <br />
|align="center"|h (tmax) <br />
|Identified via direct measurement of plasma C over time<br />
|-<br />
!Half-life <br />
|The time it takes for a drug to reach half its original concentration <br />
|align="center"|h (t1/2) <br />
|align="center"|ln(2) / Ke<br />
|-<br />
!Drug Clearance <br />
|The volume of plasma cleared of the drug over a set time <br />
|align="center"|l/h (CL) <br />
|align="center"|Vd x Ke or D / Area under curve<br />
|}<br />
<br />
==Common Drug-Drug Interactions==<br />
It is important to be aware of the interactions that can occur between concomitantly administered drugs, as they may effect efficacy and/or toxicity, or produce adverse side effects. Such interactions could for example affect drug absorption, drug bioavailability or efficacy, or combine to produce unwanted metabolites, as well as possibly having effects on clinical analyses. If a combination of two drugs decreases the effect of one or both of them, the interaction is termed an antagonistic effect; however if, conversely, a combination of two drugs enhances the effect of one or both of them, the interaction is termed a synergistic effect. Drugs that act on the cardiovascular system are high in interactivity, which is an issue as cardiovascular patients normally receive more than one drug. Some common drug—drug interactions related to cardiovascular drugs are listed below:<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Drug <br />
!Drugs that <big>↑</big> drug action <br />
!Drugs that <big>↓</big> drug action<br />
|-<br />
!Digoxin <br />
|valign="top"|<br />
*Diuretics<br />
*Antiarrhythmics<br />
*Macrolide antibiotics<br />
*Cholestyramine<br />
*Neomycin<br />
*Keto- and intraconazole<br />
*Calcium antagonists<br />
*Cyclosporine, indomethacin<br />
*HMG CoA reductase inhibitors<br />
*Benzodiazepines<br />
*Amiodarone<br />
*Verapamil <br />
|valign="top"|<br />
*Rifampicin<br />
*Antacids (liquid)<br />
|-<br />
!Warfarin <br />
|valign="top"|<br />
*Furosemide<br />
*Amiodarone<br />
*Sulfa<br />
*Macrolide and quinolone antibiotics<br />
*NSAIDs<br />
|valign="top"|<br />
*Azathioprine<br />
*Phenobarbitone<br />
*Carbamazepine<br />
*Dexamethasone<br />
*Prednisolone<br />
*Rifampicin<br />
*Vitamin K<br />
*Raloxifene<br />
|-<br />
!Clopidogrel <br />
|valign="top"|<br />
*Rifampicin<br />
*Caffeine<br />
*Methylxanthines<br />
*Phosphodiesterase inhibitors <br />
|valign="top"|<br />
*Statins<br />
*Calcium channel blockers<br />
*Warfarin<br />
*Proton pump inhibitors<br />
|-<br />
!Furosemide <br />
|<br />
|valign="top"|<br />
*NSAIDs<br />
*Phenytoin<br />
*Colesevelam<br />
|-<br />
!ACE Inhibitors <br />
|valign="top"|<br />
*NSAIDs<br />
*Probenecid<br />
*Calcium channel blockers <br />
|valign="top"|<br />
*Indomethacin<br />
*Antacids<br />
|-<br />
!ß-blockers <br />
|valign="top"|<br />
*Amiodarone<br />
*Calcium channel blockers<br />
*Diltiazem<br />
*Phenoxybenzamine <br />
|valign="top"|<br />
*Phenobarbital<br />
*Rifampicin<br />
*Cimetidine<br />
*Antacids (liquid)<br />
*NSAIDs<br />
|-<br />
!Statins <br />
|valign="top"|<br />
*Amiodarone<br />
*Verapamil<br />
*Fibrates<br />
*Amprenavir<br />
*Diltiazem <br />
|valign="top"|<br />
*Nevirapine<br />
*Rifampicin<br />
|}<br />
<br />
There are several mechanisms by which drugs are broken down by the body, usually via degradation by enzymes. One common family of enzymes involved in drug metabolismis the cytochrome P450 (CYP) family; a large, diverse group of enzymes that encourage oxidation of a variety of substrates, both endogenous (e.g. steroid hormones) and exogenous (e.g. toxins and drugs). CYP enzymes account for up to 75% of drug metabolism, aiding some drugs to form their active compounds but mostly deactivating drugs into inactive metabolites to be excreted. CYP enzymes can influence drug actions in several ways; they can increase drug metabolism (either increasing action via formation of the active by-product or decreasing action by metabolism of the active drug) or their action can be inhibited by drugs that compete for access to the CYP enzymes active site, preventing the normal interaction between drug and enzyme. Many drugs exert their interactions with other drugs viainterference with the CYP system. For example, if Drug A is metabolised by CYP and Drug B inhibits CYP activity, co-administration will result in a decreased bioavailability of Drug A. In humans there are 18 families and 43 subfamilies of the CYP group of enzymes, which target different substrates. Some CYP enzymes important in cardiovascular medicine, their cardiovascular-drug substrates and some of their interactions are shown in the table below: <br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
!Enzyme <br />
!Substrates (e.g.) <br />
!Inhibitors (e.g.) <br />
!Inducers (e.g.)<br />
|-<br />
!CYP2C19 <br />
|valign="top"|<br />
*Clopidogrel<br />
*Propranolol<br />
*Warfarin <br />
|valign="top"|<br />
*Moclobemide<br />
*Chloramphenicol<br />
*Many anti-convulsants (Valproate)<br />
*Proton pump inhibitors (Omeprazole)<br />
|valign="top"|<br />
*Rifampicin<br />
*Carbamazepine<br />
*Prednisone<br />
|-<br />
!CYP3A4 <br />
|valign="top"|<br />
*Donepezil<br />
*Statins (Atorvastatin)<br />
*Ca-channel blockers (Nifedipine)<br />
*Amiodarone<br />
*Dronedarone<br />
*Quinidine<br />
*PDE5 Inhibitors (Sildenafil)<br />
*Kinins<br />
*Caffeine<br />
*Eplerenone<br />
*Propranolol<br />
*Salmeterol<br />
*Warfarin<br />
*Clopidogrel <br />
|valign="top"|<br />
*Protease inhibitors (Ritonavir)<br />
*Macrolides (Clarithromycin)<br />
*Chloramphenicol<br />
*Nefazodone<br />
*Some Ca-channel blockers (Verapamil)<br />
*Cimetidine<br />
*Some azole anti-fungals (Ketaconazole)<br />
*Grapefruit juice <br />
|valign="top"|<br />
*Some anti-convulsants (Carbamazepine)<br />
*Baribiturates (Phenobarbital)<br />
*St. John’s Wort<br />
*Some reverse transcriptase inhibitors (Efavirenz)<br />
*Some Hypoglycaemics (Pioglitazone)<br />
*Glucocorticoids<br />
*Modafinil<br />
|-<br />
!CYP2C9 <br />
|valign="top"|<br />
*Fluvastatin<br />
*Angiotensin receptor II agonists (losartan)<br />
*Warfarin<br />
*Torasemide <br />
|valign="top"|<br />
*Some azole anti-fungals (Fluconazole)<br />
*Amiodarone<br />
*Antihistamines (Cyclizine)<br />
*Chloramphenicol<br />
*Fluvastatin<br />
*Fluvoxamine<br />
*Probenecid<br />
*Sertraline <br />
|valign="top"|<br />
*Rifampicin<br />
*Secobarbital<br />
|-<br />
!CYP2D6 <br />
|valign="top"|<br />
*ß-blockers (Propranolol)<br />
*Class I anti-arrythmics (Flecainide)<br />
*Donepezil<br />
|valign="top"|<br />
*SSRIs (Fluoxetine)<br />
*Quinidine<br />
*Sertraline<br />
*Terbinafine<br />
*Amiodarone<br />
*Cinacalcet<br />
*Ritonavir<br />
*Antipsychotics (Haloperidol)<br />
*Antihistamines (Promethazine)<br />
*Metoclopramide<br />
*Ranitidine<br />
*Mibefradil <br />
|valign="top"|<br />
*Rifampicin<br />
*Dexamethasone<br />
*Glutethimide<br />
|}<br />
<br />
In addition to drug-drug interactions, the actions of many drugs are also affected by food or drink. For example, care should be taken with alcohol consumption with many kinds of drugs, as it can put stress on the liver which is already working hard to metabolise drugs in the body. Grapefruit juice too can cause issues, as it is known to inhibit CYP3a. For more information of interactions between drugs and food/drinks see this guide: [http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/EnsuringSafeUseofMedicine/GeneralUseofMedicine/UCM229033.pdf General Use of Medicine]<br />
<br />
{| class="wikitable" border="0" cellpadding="0" cellspacing="0"<br />
|-<br />
|+Cardiovascular Drugs<br />
|- <br />
!Drug Type <br />
!Examples (generic name)<br />
!Indications <br />
!Typical Dosage <br />
!Side Effects (Prevalence %)<br />
|-<br />
|colspan="5" bgcolor="#E6E6FA"|:'''Anti-hypertensives''' <br />
|-<br />
|rowspan="2"|Diuretics <br />
|rowspan="2"|Furosemide<br />
|Oedema<br />
|Furosemide: 20-40mg once daily<br />
|rowspan="2" valign="top"|Mild gastro-intestinal disturbances, pancreatitis, hepatic encephalopathy, postural hypotension, temporary increase in serum-cholesterol and triglyceride concentration, hyperglycaemia, acute urinary retention, electrolyte disturbances, metabolic alkalosis, blood disorders, hyperuricaemia, visual disturbances, tinnitus and deafness, and hypersensitivity reactions (including rash, photosensitivity, and pruritus).<cite>Esc1</cite><br />
|-<br />
|Resistant Hypertension<br />
|Furosemide: 40-80mg once daily<br />
|-<br />
|rowspan="4"|ACE Inhibitors <br />
|rowspan="4"|Captopril, Monopril <br />
|Hypertension <br />
|Captopril: 12.5mg twice daily <br />
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.<cite>Esc2</cite><cite>Esc3</cite><cite>Esc4</cite><cite>Esc5</cite><cite>Esc6</cite><cite>Esc7</cite><br />
|-<br />
|Heart Failure <br />
|Captopril: 12.5mg 3 times daily <br />
|-<br />
|Prophylaxis Following MI <br />
|Captopril: 6.25mg once daily <br />
|-<br />
|Diabetic nephropathy <br />
|Captopril: 75-100mg once daily<br />
|-<br />
|rowspan="3"|Angiotensin Receptor Blockers <br />
|rowspan="3"|Losartan, Candesartan<br />
|Hypertension <br />
|Losartan: 50mg once daily <br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;<cite>Esc5</cite><cite>Esc8</cite><cite>Esc9</cite><cite>Esc10</cite><br />
|-<br />
|Left ventricular hypertrophy <br />
|Losartan: 12.5-150mg daily<br />
|- <br />
|Diabetic nephropathy <br />
|Losartan: 50mg daily<br />
|-<br />
|rowspan="3"|Alpha Blockers <br />
|rowspan="3"|Prazosin, Doxazosin <br />
|Hypertension <br />
|Prazosin: 1-10mg 2-3 times daily <br />
|rowspan="3" valign="top"|Drowsiness, hypotension (notably postural hypotension) (10-70% initially), syncope (1%), asthenia, dizziness, depression, headache (8-18%), dry mouth, gastro-intestinal disturbances, oedema, blurred vision (<5%), intra-operative floppy iris syndrome, rhinitis (<4%), erectile disorders (including priapism), tachycardia and palpitations (7-14%), gastrointestinal side-symptoms (4-5%), hypersensitivity reactions including rash, pruritus and angioedema.<br />
|-<br />
|Congestive Heart Failure <br />
|Prazosin: 4-20mg daily<br />
|-<br />
|Raynaud’s Syndrome <br />
|Prazosin: 1-2mg daily<br />
|- <br />
|rowspan="4"|Beta Blockers <br />
|rowspan="4"|Atenolol, Propranolol <br />
|Hypertension <br />
|Atenolol: 25-50mg daily<br />
|rowspan="4" valign="top"|Gastro-intestinal disturbances (2-4%); bradycardia, heart failure, hypotension, conduction disorders, peripheral vasoconstriction, bronchospasm, dyspnoea; headache, fatigue, sleep disturbances (2-5%), paraesthesia, dizziness (2-5%), vertigo, psychoses; sexual dysfunction; purpura, thrombocytopenia; visual disturbances; exacerbation of psoriasis, alopecia; rarely rashes and dry eyes.<cite>Esc11</cite><cite>Esc12</cite><cite>Esc13</cite><cite>Esc14</cite><cite>Acc15</cite><br />
|-<br />
|Angina <br />
|Atenolol: 100mg once/twice daily<br />
|-<br />
|Arrhythmias <br />
|Atenolol: 50-100mg daily <br />
|-<br />
|Migraine <br />
|Atenolol: 50-200mg daily <br />
|-<br />
|rowspan="3"|Calcium Channel Blockers <br />
|rowspan="3"|Nifedipine, Verapamil, Diltiazem<br />
|Hypertension <br />
|Nifedipine: 20-30mg once daily<br />
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;<cite>Esc16</cite><cite>Esc17</cite><br />
|-<br />
|Raynaud’s Syndrome <br />
|Nifedipine: 5-20mg 3 times daily<br />
|-<br />
|Angina (prophylaxis) <br />
|Nifedipine: 5-20mg 3 times daily<br />
|-<br />
|colspan="5" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''<br />
|- <br />
|Class I (sodium channel blockers)<br />
|Flecainide, Lidocaine, Procainamide<br />
|Ventricular Arrhythmias <br />
|Flecainide: 50-100mg twice daily<br />
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.<cite>Esc18</cite><cite>Acc19</cite><br />
|-<br />
|Class II (Beta blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
|-<br />
|Class III (Potassium channel blockers) <br />
|Amiodarone, Sotalol <br />
|Ventricular, Arrhythmias <br />
|Amiodarone: 200mg 2-3 times daily <br />
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes<cite>Esc20</cite><cite>Esc21</cite><cite>Acc22</cite><br />
|-<br />
|Class IV (Calcium channel blockers) <br />
|(See above) <br />
|(See above) <br />
|(See above) <br />
|(See above)<br />
|-<br />
|rowspan="2"|<br />
|rowspan="2"|Digoxin <br />
|Supra-ventricular Arrhythmias <br />
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily <br />
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.<cite>Acc23</cite><cite>Esc24</cite><cite>Esc25</cite><br />
|-<br />
|Heart Failure <br />
|62.5-125 µg daily <br />
|-<br />
|colspan="5" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''<br />
|- <br />
|rowspan="7"|<br />
|rowspan="2"|Aspirin <br />
|Prevention of thrombotic cerebro- or cardio-vascular disease <br />
|75mg once/day<br />
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).<cite>Esc26</cite><cite>Esc27</cite><cite>Esc28</cite><cite>Esc29</cite><br />
|-<br />
|Pain / pyrexia <br />
|300-600mg every 4-6 hours as necessary <br />
|-<br />
|rowspan="3"|Clopidogrel <br />
|Prevention of thrombotic events (esp. when warfarin not tolerated) <br />
|75mg once/day <br />
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.<cite>Esc30</cite><cite>Esc31</cite><cite>Esc32</cite><cite>Esc33</cite><cite>Esc34</cite><br />
|-<br />
|Acute myocardial infarction <br />
|300mg daily initially then 75mg once/day<br />
|-<br />
|Acute coronary syndrome <br />
|300mg daily initially then 75mg once/day<br />
|-<br />
|Prasugrel <br />
|Prevention of thrombotic events. <br />
|60mg bolus then 5-10mg once daily <br />
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.<cite>Esc35</cite><cite>Esc36</cite><br />
|-<br />
|Ticragelor <br />
|Prevention of thrombotic events. <br />
|180mg bolus then 90mg twice daily <br />
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%), constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.<cite>Esc37</cite><cite>Esc38</cite><br />
|-<br />
|colspan="5" bgcolor="#E6E6FA"|'''Vitamin K Antagonists'''<br />
|-<br />
|<br />
|Warfarin <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|5-10mg initially then tailored to individual (usually 3-9mg once daily at the same time)<br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|<br />
|Acenocoumarol <br />
|Prevention of thrombotic/ embolic events (esp. after prosthetic valve insertion) <br />
|4mg initially, followed by 1-8mg daily <br />
|valign="top"|Haemorrhage, nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, rash, ‘purple toes’, skin necrosis (increased risk in patients with protein C or protein S deficiency)<br />
|-<br />
|colspan="5" bgcolor="#E6E6FA"|'''Lipid-Lowering Drugs'''<br />
|- <br />
|rowspan="3"|Statins <br />
|rowspan="3"|Simvastatin, Atorvastatin <br />
|Primary hyper-cholesterolaemia, combined hyperlipidaemia <br />
|Simvastatin: 10-20mg once daily <br />
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)<cite>Esc39</cite><cite>Esc40</cite><cite>Esc41</cite><cite>Esc42</cite><br />
|-<br />
|Familial hyper-cholesterolaemia <br />
|Simvastatin: 40mg once daily <br />
|-<br />
|Prevention of cardiovascular events <br />
|20-40mg once daily<br />
|-<br />
|rowspan="2"|Fibrates <br />
|Gemfibrozil <br />
|Hyperlipidaemias of types IIa, IIb, III, IV and V <br />
|Gemfibrozil: 0.9-1.2mg daily <br />
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity<cite>Esc43</cite><br />
|-<br />
|Ezetimibe <br />
|Primary and familial hyper-cholesterolaemia <br />
|10mg once daily <br />
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis<cite>Esc44</cite><br />
|}<br />
<br />
==References==<br />
<biblio><br />
#Esc1 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC<br />
#Esc2 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Hypertension: Class IA<br />
#Esc3 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA<br />
#Esc4 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092):Hypertension in diabetics: Class IA<br />
#Esc5 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Post STEMI: Class IA<br />
#Esc6 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Diabetic patients: Class IC<br />
#Esc7 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA<br />
#Esc8 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Hypertension: Class IA<br />
#Esc9 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Hypertension in diabetics: Class IA <br />
#Esc10 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): LVH: Class IB<br />
#Esc11 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261) ACS: Class IIaB<br />
#Esc12 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA<br />
#Esc13 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Atrial fibrillation: Class IA; Polymorphic VT: Class IB<br />
#Esc14 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA<br />
#Acc15 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB<br />
#Esc16 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA<br />
#Esc17 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <br />
#Esc18 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Sustained VT and VF: Class IIbC<br />
#Acc19 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <br />
#Esc20 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC<br />
#Esc21 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB<br />
#Acc22 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <br />
#Acc23 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <br />
#Esc24 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF: Class IIbB<br />
#Esc25 ESC Guidelines Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC<br />
#Esc26 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Prevention in AF: Class IC; Prevention in diabetic patients: IIaB<br />
#Esc27 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA<br />
#Esc28 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA<br />
#Esc29 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Post-MI: Class Ia<br />
#Esc30 ESC and EASD Guidelines (European Heart Journal doi:10.1093/eurheart/ehl261): Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB<br />
#Esc31 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA; Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA<br />
#Esc32 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA<br />
#Esc33 ESC Guidelines(European Heart Journal (2012) 33, 2569-2619 doi:10.1093/eurheartj/ehs215): Post STEMI: Class IA<br />
#Esc34 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): ACS: Class IIaC<br />
#Esc35 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA<br />
#Esc36 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB<br />
#Esc37 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA<br />
#Esc38 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB<br />
#Esc39 ESC and EASD Guidelines (European Heart Journal doi:10.1093/eurheart/ehl261); Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC<br />
#Esc40 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Hypertension in diabetics: Class IA; ACS: Class IA <br />
#Esc41 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): HeFH: Class IC<br />
#Esc42 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818 doi:10.1093/eurheartj/ehr158): Transplant patients (with high LDL-C): Class IIbC<br />
#Esc43 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818 doi:10.1093/eurheartj/ehr158): Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <br />
#Esc44 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): HeFH: Class IC<br />
</biblio></div>NiloferT