Textbook of Cardiology

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===Heart catheterization===
===Heart catheterization===
Heart catheterization is not always part of the routine diagnosis and work-up of patients with HF.  It should be considered however to exclude coronary heart disease (Class of recommendation IIa, level of evidence C, see Table 4). Coronary angiography is recommended in patients at high risk of coronary artery disease  (Class of recommendation I, level of evidence C) and in HF patients with significant valvular disease (Class of recommendation IIa, level of evidence C).
Heart catheterization is not always part of the routine diagnosis and work-up of patients with HF.  It should be considered however to exclude coronary heart disease (Class of recommendation IIa, level of evidence C, see [[Heart_Failure_Table_4|Table 4]]). Coronary angiography is recommended in patients at high risk of coronary artery disease  (Class of recommendation I, level of evidence C) and in HF patients with significant valvular disease (Class of recommendation IIa, level of evidence C).


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!colspan="5"|Table 4. Size of treatment effect
|-
|
|valign="top"|'''Class I'''
Benefit >>> Risk
|valign="top"|'''Class IIa'''
Benefit >> Risk
Additional studies with focused objectives needed
|valign="top"|'''Class IIb'''
Benefit ≥ Risk
Additional studies with broad objectives needed; additional registry data would be helpful
|valign="top"|'''Class III'''
Benefit ≥ Risk
No additional studies needed
|-
|
|Procedure/treatment should be performed/administered
|It is reasonable to perform/administer treatment
|Procedure/treatment may be considered
|Procedure/treatment should not be performed/administered since it is not helpful and may be harmful
|-
|'''Level A'''
Multiple (3-5) population risk strata evaluated
|
*Recommendation that procedure or treatment is useful/effective
*Sufficient evidence from multiple randomized trials or non-randomized trials
|
*Recommendation in favor of treatment or procedure being useful/effective
*Some conflicting evidence from multiple randomized trials or meta-analyses
|
*Recommendation’s usefulness/efficacy less well established
*Greater conflicting evidence from multiple randomized trials or meta-analyses
|
*Recommendation that procedure or treatment not useful/effective and may be harmful
*Sufficient evidence from multiple randomized trials or meta-analyses
|-
|'''Level B'''
Limited (2-3) population risk strata evaluated
|
*Recommendation that procedure or treatment is useful/effective
*Limited evidence from single randomized trial or non-randomized studies
|
*Recommendation in favor of treatment or procedure being useful/effective
*Some conflicting evidence from single randomized trial or non-randomized studies
|
*Recommendation’s usefulness/efficacy less well established
*Greater conflicting evidence from single randomized trial or non-randomized studies
|
*Recommendation that procedure or treatment not useful/effective and may be harmful
*Limited evidence from single randomized trial or non-randomized studies
|-
|'''Level C'''
Very limited (1-2) population risk strata evaluated
|
*Recommendation that procedure or treatment is useful/effective
*Only experts opinion, case studies, or standard-of-care
|
*Recommendation in favor of treatment or procedure being useful/effective
*Only diverging expert opinion case studies, or standard-of-care
|
*Recommendation’s usefulness/efficacy less well established
*Only diverging expert opinion case studies, or standard-of-care
|
*Recommendation that procedure or treatment not useful/effective and may be harmful
*Only expert opinion case studies, or standard-of-care
|}
==Etiology of heart failure==
==Etiology of heart failure==
===Coronary heart disease===  
===Coronary heart disease===  
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Deficiency of thiamine, selenium, or camitine, in states of severe cachexia.
Deficiency of thiamine, selenium, or camitine, in states of severe cachexia.


Infiltrative and storage disorders
===Infiltrative and storage disorders===
*Sarcoidosis
*[[Sarcoidosis]]
*Amyloidosis
*[[Amyloidosis]]
*Haemochromatosis  
*[[Haemochromatosis]]
*Connective tissue disease
*Connective tissue disease


===Infectious disease===
===Infectious disease===
*Chagas’ disease
*[[Chagas’ disease]]
*HIV infection
*[[HIV infection]]
*Viral, bacterial or protozoal diseases causing myocarditis.
*Viral, bacterial or protozoal diseases causing myocarditis.


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|bgcolor="99FFCC" align="center"|'''Aldosteron antagonist'''
|bgcolor="99FFCC" align="center"|'''Aldosteron antagonist'''
|bgcolor="99FFCC"|
|bgcolor="99FFCC"|
|bgcolor="9ACD32" align="center"|'''EF = 35%'''
|bgcolor="9ACD32" align="center"|'''EF < 35%'''
|bgcolor="9ACD32" align="center"|'''EF = 35%'''
|bgcolor="9ACD32" align="center"|'''EF < 35%'''
|bgcolor="9ACD32" align="center"|'''EF = 35%'''
|bgcolor="9ACD32" align="center"|'''EF < 35%'''
|-
|-
|bgcolor="99FFCC" align="center"|'''Nitrate / Hydralazine'''
|bgcolor="99FFCC" align="center"|'''Nitrate / Hydralazine'''
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|bgcolor="9ACD32" align="center"|'''Afro-American'''
|bgcolor="9ACD32" align="center"|'''Afro-American'''
|bgcolor="9ACD32" align="center"|'''Afro-American'''
|bgcolor="9ACD32" align="center"|'''Afro-American'''
|-
|bgcolor="99FFCC" align="center"|'''Ivabradine'''
|bgcolor="99FFCC"|
|bgcolor="9ACD32" align="center"|'''SR>75/min & EF<35%'''
|bgcolor="9ACD32" align="center"|'''SR>75/min & EF<35%'''
|bgcolor="9ACD32" align="center"|'''SR>75/min & EF<35%'''
|-
|-
|bgcolor="99FFCC" align="center"|'''Digoxin'''
|bgcolor="99FFCC" align="center"|'''Digoxin'''
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===Angiotensin-converting enzyme (ACE) inhibitors===  
===Angiotensin-converting enzyme (ACE) inhibitors===  
An ACE inhibitor (in addition to beta blocker) is indicated for every patient with symptomatic systolic HF and an EF ≤40 % (NYHA class II-IV). (Class I recommendation, level of evidence A) Contraindications for the use of ACE inhibitors are:
An ACE inhibitor is indicated for every patient with symptomatic systolic HF and an EF ≤40 % (NYHA class II-IV). (Class I recommendation, level of evidence A) Contraindications for the use of ACE inhibitors are:
*History of angioedema
*History of angioedema
*Bilateral renal artery stenosis
*Bilateral renal artery stenosis
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===Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists)===
===Diuretics (Loop of Henle diuretics, Thiazides, Aldosterone antagonists)===
[[Image:Henle_loop.svg|thumb|400px|'''Figure 6.''' Diuretics and site of action in the nephron.]]
Diuretics reduce preload by venous vasodilatation and by increasing diuresis. As a result, filling pressures of the heart and the lung vasculature decrease. Although the effects of diuretics on mortality and morbidity have not been studied in patients with HF (irrespective of EF), it is recommended in patients with signs and symptoms of congestion as diuretics relieve dyspnea and edema. Figure 6 depicts the nephron and the sites where different diuretics work.
Diuretics reduce preload by venous vasodilatation and by increasing diuresis. As a result, filling pressures of the heart and the lung vasculature decrease. Although the effects of diuretics on mortality and morbidity have not been studied in patients with HF (irrespective of EF), it is recommended in patients with signs and symptoms of congestion as diuretics relieve dyspnea and edema. Figure 6 depicts the nephron and the sites where different diuretics work.


===Loop of Henle diuretics===
====Loop of Henle diuretics====
Loop of Henle diuretics act on the ascending loop of Henle in the kidney tubules to inhibit sodium and chloride (and indirectly calcium and magnesium) reabsorption. This will ultimately result in increased urine production of sodium and water. Compared to thiazides, loop diuretics produce a more intense and shorter diuresis.
Loop of Henle diuretics act on the ascending loop of Henle in the kidney tubules to inhibit sodium and chloride (and indirectly calcium and magnesium) reabsorption. This will ultimately result in increased urine production of sodium and water. Compared to thiazides, loop diuretics produce a more intense and shorter diuresis.


===Thiazides===
====Thiazides====
Thiazide increases urine production by decreasing reabsorption of sodium in the distal tubule. This type of diuretic is often used in combination with loop diuretics to enhance their effects, but may be less effective in patients with a severely reduced kidney function.  
Thiazide increases urine production by decreasing reabsorption of sodium in the distal tubule. This type of diuretic is often used in combination with loop diuretics to enhance their effects, but may be less effective in patients with a severely reduced kidney function.  


===Aldosterone antagonists===
====Aldosterone antagonists====
Adding this drug is suggested for patients with moderate to severe symptomatic HF (NYHA class II to IV, refer to Table 2) and an LVEF < 35%. (Class I recommendation, level of evidence A) Contraindications:
Adding this drug is suggested for patients with moderate to severe symptomatic HF (NYHA class II to IV, refer to Table 2) and an LVEF < 35%. (Class I recommendation, level of evidence A) Contraindications:


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Possible side effects include hyperkalemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is an alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality. <cite>20</cite>
Possible side effects include hyperkalemia, hyponatremia, worsening renal function, and breast tenderness and/or enlargement. Eplerenon has less mastopathy side effects and is an alternative to spironolacton. In patients with severe heart failure, spironolactone in addition to standard therapy, reduces morbidity and mortality. <cite>20</cite>


[[Image:Henle_loop.svg|thumb|400px|'''Figure 6.''' Diuretics and site of action in the nephron.]]
====Choice and combination of diuretics====
 
===Choice and combination of diuretics===
Patients with heart failure may be treated with a thiazide diuretic, which should be switched to a loop diuretic if a suboptimal response occurs. In patients with a decreased renal function, a loop diuretic is the mainstay of treatment. Addition of a thiazide diuretic to a loop diuretic can be considered in case of a suboptimal response of loop diuretic alone, when given in sufficient doses (furosemide 250 mg twice daily), suggesting that diuretic resistance is due to distal tubular increased activity of retaining sodium. In all patients with NYHA II or more, except in those with a creatinine clearance < 20 ml/min (creatinine > 220 micromol/L), addition of an aldosterone antagonist should be considered. In special cases in which hypercapnia plays a role, metabolic alkalosis can result from diuretics, and acetazolamide, a reversible carbonic anhydrase inhibitor, is then prescribed as an alternative diuretic.  
Patients with heart failure may be treated with a thiazide diuretic, which should be switched to a loop diuretic if a suboptimal response occurs. In patients with a decreased renal function, a loop diuretic is the mainstay of treatment. Addition of a thiazide diuretic to a loop diuretic can be considered in case of a suboptimal response of loop diuretic alone, when given in sufficient doses (furosemide 250 mg twice daily), suggesting that diuretic resistance is due to distal tubular increased activity of retaining sodium. In all patients with NYHA II or more, except in those with a creatinine clearance < 20 ml/min (creatinine > 220 micromol/L), addition of an aldosterone antagonist should be considered. In special cases in which hypercapnia plays a role, metabolic alkalosis can result from diuretics, and acetazolamide, a reversible carbonic anhydrase inhibitor, is then prescribed as an alternative diuretic.  


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==Therapy of acute heart failure==
==Therapy of acute heart failure==
[[Image:acute_hf_flowchart.svg|400px|thumb|'''Figure 7.''' Flowchart acute HF.]]
When severe symptoms of heart failure quickly develop over time, it is termed acute heart failure. In Table 6, common acute HF medications and their recommended doses are summarized. In Figure 7, a flowchart for the treatment of acute HF is depicted. The mainstay of acute heart failure therapy includes diuretics, vasodilators, inotropics and vasopressors. Moreover, oxygen and morphine can be added.  
When severe symptoms of heart failure quickly develop over time, it is termed acute heart failure. In Table 6, common acute HF medications and their recommended doses are summarized. In Figure 7, a flowchart for the treatment of acute HF is depicted. The mainstay of acute heart failure therapy includes diuretics, vasodilators, inotropics and vasopressors. Moreover, oxygen and morphine can be added.  
[[Image:acute_hf_flowchart.svg|400px|thumb|'''Figure 7.''' Flowchart acute HF.]]


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|-
|-
|'''Diuretics'''
|'''Diuretics'''
|Adequate blood pressure and signs of overfilling
|colspan="2"|Adequate blood pressure and signs of overfilling
|
|-
|-
|
|
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Renal failure
Renal failure
|40 mg
|40 mg
80 mg – max 200 mg  
125 mg – max 1000 mg  
|-
|-
|
|
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Renal failure
Renal failure
|1 mg
|1 mg
2 mg – max 5 mg  
3 mg – max 25 mg  
|-
|-
|'''Vasodilators'''
|'''Vasodilators'''
|Adequate blood pressure and signs of severe overfilling
|colspan="2"|Adequate blood pressure and signs of severe overfilling
|-
|
|
*Nitroglycerine i.v.
*Nitroglycerine i.v.
|-
|
|
|20 µg/min – max 200 µg/min (guided by blood pressure)  
|20 µg/min – max 200 µg/min (guided by blood pressure)  
|-
|
|
*Nitroprusside i.v.
*Nitroprusside i.v.
|-
||Hypertensive crisis or in combination with inotropic in case of a cardiogenic shock
|
|Hypertensive crisis or in combination with inotropic in case of a cardiogenic shock
|0.3 µg/kg/min – max 5 µg/kg/min (guided by blood pressure)  
|0.3 µg/kg/min – max 5 µg/kg/min (guided by blood pressure)  
|-
|-
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|-
|-
|valign="top"|
|valign="top"|
*'''Furosemide'''
*Furosemide
|valign="bottom"|
|valign="bottom"|
Renal failure
Renal failure
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|-
|-
|valign="top"|
|valign="top"|
*'''Bumetanide'''
*Bumetanide
|valign="bottom"|
|valign="bottom"|
Renal failure
Renal failure
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|-
|-
|valign="top"|
|valign="top"|
*'''Captopril'''
*Captopril
|
|
|Start:::6.25mg
|Start 6.25mg
 
1<sup>st</sup> week:::6.25mg three times daily.
 
3-5 weeks:::12.5mg three times daily.
 
>7 weeks:::25mg three times daily.
|-
|valign="top"|
*'''Lisinopril'''
|
|Start:::2.5-5mg


1<sup>st</sup> week:::5-10mg once daily.
1<sup>st</sup> week 6.25mg three times daily.


5-7 weeks:::25mg three times daily.
3-5 weeks 12.5mg three times daily.


>7 weeks:::50 mg three times daily.
>7 weeks 25mg three times daily.
|-
|-
|valign="top"|
|valign="top"|
*'''Enalapril/quinalapril'''
*Lisinopril
|
|
|Start:::2.5-5mg
|Start 2.5-5mg


1<sup>st</sup> week:::2.5-5mg twice daily.
1<sup>st</sup> week 2.5-5mg twice daily.


3-5 weeks:::5-10mg twice daily.
3-5 weeks 5-10mg twice daily.


>7 weeks:::10-20mg twice daily.
>7 weeks 10-20mg twice daily.
|-
|-
|bgcolor="#F0F0F0 " colspan="3"|'''Beta blockers'''
|bgcolor="#F0F0F0 " colspan="3"|'''Beta blockers'''
|-
|-
|valign="top"|
|valign="top"|
*'''Metoprolol zoc (succinate)'''
*Metoprolol zoc (succinate)
|valign="top"|EF >30-45% and NYHA II-III
|valign="top"|EF >30-45% and NYHA II-III
|Start:::25mg
|Start 25mg


1<sup>st</sup> week:::50mg once daily.
1<sup>st</sup> week 50mg once daily.


3-5 weeks:::100mg once daily.
3-5 weeks 100mg once daily.


>7 weeks:::100-200mg once daily.
>7 weeks 100-200mg once daily.
|-
|-
|
|
|valign="top"|EF <30% and NYHA IV
|valign="top"|EF <30% and NYHA IV
|Start:::12.5mg
|Start 12.5mg


1<sup>st</sup> week:::25mg once daily.
1<sup>st</sup> week 25mg once daily.


3-5 weeks:::50mg once daily.
3-5 weeks 50mg once daily.


>7 weeks:::100-200mg once daily.
>7 weeks 100-200mg once daily.
|-
|-
|valign="top"|
|valign="top"|
*'''Bisoprolol'''
*Bisoprolol
|valign="top"|EF >30-45% and NYHA II-III
|valign="top"|EF >30-45% and NYHA II-III
|Start:::2.5mg
|Start 2.5mg


1<sup>st</sup> week:::3.75mg once daily.
1<sup>st</sup> week 3.75mg once daily.


3-5 weeks:::5mg once daily.
3-5 weeks 5mg once daily.


>7 weeks:::7.5-10mg once daily.
>7 weeks 7.5-10mg once daily.
|-
|-
|
|
|valign="top"|EF <30% and NYHA IV
|valign="top"|EF <30% and NYHA IV
|Start:::1.25mg
|Start 1.25mg


1<sup>st</sup> week:::2.5mg once daily.
1<sup>st</sup> week 2.5mg once daily.


3-5 weeks:::3.75mg once daily.
3-5 weeks 3.75mg once daily.


>7 weeks:::5-7.5-10mg once daily.
>7 weeks 5-7.5-10mg once daily.
|-
|-
|valign="top"|
|valign="top"|
*'''Carvedilol'''
*Carvedilol
|valign="top"|EF >30-45% and NYHA II-III
|valign="top"|EF >30-45% and NYHA II-III
|Start:::6.25mg
|Start 6.25mg


1<sup>st</sup> week:::6.25mg twice daily.
1<sup>st</sup> week 6.25mg twice daily.


3-5 weeks:::12.5mg twice daily.
3-5 weeks 12.5mg twice daily.


>7 weeks:::25mg twice daily.
>7 weeks 25mg twice daily.
|-
|-
|
|
|valign="top"|EF <30% and NYHA IV
|valign="top"|EF <30% and NYHA IV
|Start:::3.125mg
|Start 3.125mg


1<sup>st</sup> week:::3.125mg twice daily.
1<sup>st</sup> week 3.125mg twice daily.


3-5 weeks:::6.25mg twice daily.
3-5 weeks 6.25mg twice daily.


>7 weeks:::12.5-25mg twice daily.
>7 weeks 12.5-25mg twice daily.
|-
|-
|valign="top"|
|valign="top"|
*'''Nebivolol'''
*Nebivolol
|valign="top"|EF >30-45% and NYHA II-III
|valign="top"|EF >30-45% and NYHA II-III
|Start:::1.25mg
|Start 1.25mg


1<sup>st</sup> week:::2.5mg once daily.
1<sup>st</sup> week 2.5mg once daily.


3-5 weeks:::5mg once daily.
3-5 weeks 5mg once daily.


>7 weeks:::10mg once daily.
>7 weeks 10mg once daily.
|-
|-
|
|
|valign="top"|EF <30% and NYHA IV
|valign="top"|EF <30% and NYHA IV
|Start:::1.25mg
|Start 1.25mg


1<sup>st</sup> week:::2.5mg once daily.
1<sup>st</sup> week 2.5mg once daily.


3-5 weeks:::5mg once daily.
3-5 weeks 5mg once daily.


>7 weeks:::10mg once daily.
>7 weeks 10mg once daily.
|-
|-
|bgcolor="#F0F0F0 " colspan="3"|'''Aldosterone antagonist'''
|bgcolor="#F0F0F0 " colspan="3"|'''Aldosterone antagonist'''
|-
|-
|valign="top"|
|valign="top"|
*'''Spironolactone/eplerenone'''
*Spironolactone/eplerenone
|
|
|Start:::25mg s.i.d.
|Start 25mg s.i.d.


1<sup>st</sup> week:::potassium <5.0: 25mg once daily.
1<sup>st</sup> week potassium <5.0: 25mg once daily.


potassium 5.0-5.5: 12.5mg once daily.
potassium 5.0-5.5: 12.5mg once daily.
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potassium >5.5: stop
potassium >5.5: stop


3rd week:::potassium <5.0: 25mg once daily.
3rd week potassium <5.0: 25mg once daily.


potassium 5.0-5.5: 12.5mg once daily.
potassium 5.0-5.5: 12.5mg once daily.
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|-
|-
|valign="top"|
|valign="top"|
*'''Digoxin'''
*Digoxin
|
|
|Start:::0.5mg, 0.25mg and 0,25 mg, each with 6 hours in between
|Start 0.5mg, 0.25mg and 0,25 mg, each with 6 hours in between


Continue with 0.25mg once daily.
Continue with 0.25mg once daily.
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|-
|-
|valign="top"|
|valign="top"|
*'''Candesartan'''
*Candesartan
|
|
|Start:::4mg
|Start 4mg


3-5 weeks:::8mg once daily.
3-5 weeks 8mg once daily.


>7 weeks:::16mg once daily.
>7 weeks 16mg once daily.
|-
|-
|valign="top"|
|valign="top"|
*'''Valsartan'''
*Valsartan
|
|
|Start:::80mg
|Start 40mg twice daily


3-5 weeks:::160mg once daily.
3-5 weeks 80mg twice daily.


>7 weeks:::320mg once daily.
>7 weeks 160mg twice daily.
|-
|-
|colspan="3" bgcolor="#F0F0F0 "|'''Hydralazine and isosorbide dinitrate (H-ISDN)'''
|colspan="3" bgcolor="#F0F0F0 "|'''Hydralazine and isosorbide dinitrate (H-ISDN)'''
|-
|-
|valign="top"|
|valign="top"|
*'''Hydralazine'''
*Hydralazine
|
|
|Start:::25mg three times daily.
|Start 25mg three times daily.


3-5 weeks:::50mg three times daily.
3-5 weeks 50mg three times daily.


>7 weeks:::75-100mg three times daily.
>7 weeks 75-100mg three times daily.
|-
|-
|valign="top"|
|valign="top"|
*'''ISDN'''
*ISDN
|
|
|Start:::20mg twice daily
|Start 20mg twice daily


3-5 weeks:::40mg twice daily
3-5 weeks 40mg twice daily


>7 weeks:::80mg twice daily
>7 weeks 80mg twice daily
|}
|}


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===Prognosis===
===Prognosis===
The life expectancy of a patient with heart failure is determined by age, NYHA class, LVEF, normal level of sodium, systolic blood pressure, use of medication and use of ICD or CRT-D (Seattle Heart failure score). The mean yearly annual mortality is approximately 10%, varying from <6% per year when a normal LVEF is identified, to > 14% per year with an EF of <15%.  
The life expectancy of a patient with heart failure is determined by age, NYHA class, LVEF, normal level of sodium, systolic blood pressure, use of medication and use of ICD or CRT-D ([http://depts.washington.edu/shfm/app.php Seattle Heart failure score]). The mean yearly annual mortality is approximately 10%, varying from <6% per year when a normal LVEF is identified, to > 14% per year with an EF of <15%.  
Trials with medication illustrate that the (short term) benefit of medication is highest when the NYHA class is higher (Figure 9).<cite>11</cite>
Trials with medication illustrate that the (short term) benefit of medication is highest when the NYHA class is higher (Figure 9).<cite>11</cite>


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