Myocardial and Pericardial Disease: Difference between revisions

Myocardial and Pericardial Disease (view source)

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 Hereditary amyloidosis has been increasingly recognized in the last decade, and results from mutations in the gene for thransthyretin. Some mutations are clinically limited to the myocardium. Its incidence increases with increasing age, with a predilection for men, but its prognosis is better than that of the AL type. Senile systemic amyloidosis results from deposition of normal wild-type transthyretin. This form of amyloidosis is clinically predominated by an infiltrative cardiomyopathy, but progression is slow and prognosis is better than of other acquired forms.
-*Cardiac amyloidosis
+* '''Cardiac amyloidosis'''
+:Cardiac amyloidosis is a progressive infiltrative cardiomyopathy. The primary form carries the highest cardiac involvement of approximately one third to half of patients, where deposits may be present even in the absence of clinical symptoms. Secondary amyloidosis is less frequently accompanied by cardiac infiltration, approximately 5% of cases, and is less likely associated with ventricular dysfunction due to a smaller size and more favourable location of the depositions. Familial amyloidosis is associated with clinical signs of cardiac involvement in a quarter of patients, typically presenting after the after of 35 with a distinct involvement of the cardiac conduction system. In senile amyloidosis, extense of deposits may vary widely; from solitarily atrial involvement up to extensive ventricular infiltration.
+:: ''Clinical manifestations''
+:::Apart from the occurrence of cardiac disease in the presence of known AL amyloidosis or connective tissue disease or other chronic inflammatory disorder, ardiac amyloidosis should be considered in case of:
+::::* restrictive cardiomyopathy of unknown origin
+::::* Left ventricular hypertrophy with a converse low-voltage ECG
+::::* Congestive heart failure of unknown origin, not responding to contemporary medical management.
+:: ''Clinical diagnosis''
+::: Diagnostic testing should include a 12-lead ECG, possibly with Holter monitoring, and routine echocardiography. Specific characteristics are a low-voltage 12-lead ECG with increase septal and posterior wall ventricular thickness.
+:: ''Physical examination''
+:::A physical examination may reveal an elevated jugular venous pressure, and signs of systemic edema. Auscultation frequently reveals an apical murmur due to mitral regurgitation, and a third heart sound, but the presence of a fourth heart sound may exclude amyloidosis, as atrial infiltration causes impaired atrial contraction.
+:: ''Electrocardiography''
+::: Routine 12-lead ECG shows low voltage in the limb leads, and a pseudoinfarct pattern in approximately 50% of patients. Furthermore, conduction abnormalities occur frequently, as does atrial fibrillation.
+:: ''Echocardiography''
+::: Thickening of the left ventricular wall with diastolic dysfunction are early echocardiografic features of the disease. In advancing disease, wall thickening increases resulting in a restrictive cardiomyopathy. “Sparkling” myocardium is a distinct characteristic of cardiac amyloidosis, referring to an increased echogenicity of the myocardium. However, only a minority of patients has this pattern. Doppler evaluation shows a restrictive pattern with E dominance and a short deceleration time.
+::: Furthermore, intracardiac thrombus is frequently present, which is associated with atrial fibrillation and left ventricular diastolic dysfunction.
+::: The thickening of the ventricular wall caused by amyloidosis may be misinterpreted as hypertrophy on echocardiography. An important distinctive characteristic of amyloidosis is the voltage-to-mass ratio. Unlike normal hypertrophic myocardium, the increased ventricular mass in amyloidosis is associated with a decrease in electrocardiographic voltage.
+:: ''Management''
+::: Few treatments for cardiac amyloidosis exist, and available treatments are dependent on the type of amyloidosis present. Hence, typing of the disease is pertinent. AL amyloidosis may be treated with chemotherapy using alkylating agents alone or in combination with bone marrow transplantation. Heart transplantation in combination with bone marrow transplantation after high-dose chemotherapy was shown to be result in approximately a third of treated patients surviving over 5 years, but as the great majority of patients with AL amyloidosis has severe non-cardiac amyloidosis most of patienst are not suitable transplant candidates. Patients with other types of amyloidosis frequently have less affected hearts, and progression of the disease is slow. AA amyloidosis may respond to anti-inflammatory and imunosupressive drugs that reduce production of the acute-phase reactant protein. If heart failure is present, it is usually more prone to routine medical options to reduce symptoms. If needed, heart transplantation can be performed successfully. In patients where transthyretine is the amyloidogenic protein, liver transplantation may be curative as tranthyretine is produced in the liver, but the cardiac disease may progress regardless in some patients.
+::: Overall, caution should be taken in prescribing digitalis, nifedipine, verapamil and ACE-inhibitors to cardiac amyloidosis patients. There is a high susceptibility to digitalis intoxication, nifedipine-induced hemodynamic deterioration, verapamil-induced left ventricular dysfunction, and ACE-inhibitor induced profound hypotension.
+::: If atrial fibrillation is present, or systolic ventricular function is severely impaired anticoagulation is indicated to prevent intracardiac thrombi.
+::: In selected patients with conduction disorders, pacemaker implantation may be considered. If ventricular function is severely impaired, ICD implantation may be considered.
+:: ''Prognosis and outcome''
+::: Prognosis of especially AL amyloidosis is poor.
+* '''Sarcoidosis'''
+:Sarcoidosis is a multisystem inflammatory conditions caharacterized by the formation of non-caseating granulomas, most frequently affecting the lungs and lymphatic system whereas myocardial involvement is seen in one quarter of cases only. Genetic factors are suggested as there was found to be aggregation of cases within families.
+:: ''Pathophysiology''
+::: Non-caseating granulomas may infiltrate the myocardium, leading to fibrotic scarring of the myocardium. Involvement of the myocardium may be patchy, resulting in a relatively high likelihood of false-positive results from biopsy. Cardiac sarcoidosis must me differentiated from chronic active myocarditis and giant cell myocarditis.
+:: ''Clinical diagnosis''
+::: Patients may present with syncope, heart block or congestive heart failure. Sudden cardiac death may well be a devastating initial manifestation of the disease due to malignant ventricular arrhythmias, but both atrial and ventricular presentations are common. Symptoms of heart failure may result from direct myocardial involvement, but can also be due to extensive pulmonary fibrosis; cor pulmonale. Physical examination may include signs of extracardiac sarcoidosis, a right sided third heart sound, and both S3 and S4, as well as murmurs of tricuspid regurgitation or mitral regurgitation.
+::: Initial consideration of the diagnosis is often based on chest radiographs showing bilateral hilar lymfadenopathy. CMR is emerging as a highly sensitive and specific test for sarcoidosis, and nuclear imaging techniques may show regional perfusion defect due to the granulomatous inflammation on SPECT, or focal uptake on PET CT. electrocardiography is useful to assess the extent of conduction system involvement. Echocardiography shows left ventricular dilatation with hypokinesis, right ventricular enlargement and hypertrophy and possibly left ventricular aneurysm formation.
+::: Minimal evaluation of a patients suspected of cardiac sarcoidosis consists of a 12-lead ECG, Holter monitoring and echocardiography.
+:: ''Management''
+::: Early detetction of the disease is critical for its clinical course. Immunosuppression using corticosteroids to halt the progression of inflammation is the treatment of choice in sarcoidosis, to which myocardial dysfunction, conduction disturbances and arrhthmias may all respond. Most important is the differentiation of sarcoidosis from giant cell myocarditis, which is a more aggressive disorder requiring intensive medical and mechanical support and frequently necessitates heart transplantation. Pacemaker or ICD implantation is indicated in patients with conduction disorders or malignant arrhythmias, as medical treatment is usually ineffective.
+==== Storage diseases ====
+'''''Hemochromatosis'''''
+Hemochromatosis is defined as a disorder of the iron metabolism, resulting in accumulation of iron in parenchymal tissues. In particular cardiac, liver, gonadal and pancreatic involvements are typical for hemochromatosis, in which the toxicity of redox-active iron results in organ dysfunction. Typically, hemochromatosis therefore leads to a combination of heart failure, cirrhosis, impotence, diabetes and arthritis. Although several organ systems are usually involved, cardiac complications predominate as its presenting features, which are dependent on the site and amount of cardiac depositions. DCM is the typical phenotype of cardiac involvement, but a restrictive pattern may be present.
+The most frequent, adult-onset, form of hemochromatosis was found arise from mutations in the HFE-gene, coding for a transmembrane protein involved in iron uptake in the liver and the intestine. Less frequently, mutations in the transferrine 2-encoding gene may result in hemochromatosis. The juvenile form of hemochromatosis results from mutations in the genes encoding hepcidin and hemojuvelin. The disease may also be acquired and result from ineffective erythropoiesis secondary to a defect in haemoglobin synthesis, chronic liver disease, chronic excessive oral or parenteral intake of iron, or from multiple blood transfusions.
+Three stages of the natural history of adult-onset hemochromatosis can be differentiated. The first stage, the biochemical stage, is characterized by an iron overload which remains confined to the plasma compartment. Transferrin saturation is increased. The second phase, the deposition phase, is characterized by iron accumulation in parenchymal tissues, accommodated by an increase in serum ferritine levels. The third and final stage is that of organ dysfunction.
+Juvenile hemochromatosis is a more rapidly progressing disease, which leads to early organ dysfunction, around the age of 30, and in frequently characterized by premature death due to severe cardiac complications.
+The invariably present symptoms of heart failure, may frequently be accompanied by arrhythmias, especially ventricular extrasystoles, supraventricular tachycardia, and atrial fibrillation or flutter; either due to atrial iron depositions, or ventricular dysfunction resulting in increased ventricular pressure. Furthermore conduction system involvement may lead to AV block or sick sinus syndrome.
+: ''Diagnostic features''
+:: Symptoms at initial presentation may vary.  Echocardiography may show increased left ventricular wall thickness, ventricular dilatation, and ventricular dysfunction. CMR imaging represents a sensitive mean and may aid in early detection of the disease. Electrocardiographic characteristics include ST-segment and T wave abnormalities as well as supraventricular arrhythmias, but occur as the disease advances. Biochemical testing reveals increased elevated transferrine saturation, increase plasma iron levels with low or normal iron binding capacity.
+: ''Management''
+:: Repeated phlebotomy is the cornerstone of hemochromatosis treatment, although chelating agents such as deferoxamine may be considered. Early detection of the disease is critical, as depletion of iron overload may result in complete reversal of symptoms at this stage. Evidence was found that a threshold exists beyond which permanent damage is pertinent, at which stage iron depletion does not result in recovery of function. At end-stage disease, heart transplantation is a viable option with good survival rates. Importantly, screening of first degree relatives is pertinent to ensure early detection of hereditary forms of hemochromatosis.