IMMUNOSUPPRESSIVE THERAPY FOR BIOPSY-PROVEN MYOCARDITIS

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This is a clinical research study designed to determine if immunosuppressive treatment improves cardiac function in patients with myocarditis documented by endomyocardial biopsy. Patients with unexplained cardiac dysfunction will undergo cardiac biopsy. Those who are found to have active myocarditis will be asked to consent to this research and will form the study population. They will be randomized during a two year period to three treatment limbs: conventional therapy for congestive heart failure, immunosuppression with prednisone and azathioprine, or immunosuppression with cyclosporine and prednisone. Treatment will be maintained for six months, and a rigorous post-treatment follow-up program will be instituted thereafter for a minimum of six months. Before, once during and twice after therapy, extensive assessment will include endomyocardial biopsy, right heart hemodynamic study, radionuclide angiogram, 2-dimensional echocardiogram, treadmill exercise test, holter monitoring study and symptom assessment. Strict criteria are established to determine improvement, worsening and failure of treatment. Data will be examined intermittently to determine if conventional therapy or either form of immunosuppression is superior. The primary determinants of efficacy in this study are changes in maximum exercise time and resting radionuclide left ventricular ejection fraction. Several additional endpoints will be examined. The clinical trial is supplemented by an effort to improve our understanding of the pathophysiology of myocarditis in humans by means of extensive analysis of blood and myocardial samples. The analyses include immunofluorescent techniques, western immunoblotting, immunoperoxidase technique, immunohistochemistry, flow cytometry cellular cytoxicity assays, lymphocyte subtype function assays and others. The ultimate purpose of these studies is to identify the antigens recognized in human myocarditis and to characterize the lymphocyte populations involved.