Immunosuppressive Therapy for Myocarditis
Abstract & Commentary
Synopsis: In patients with active lymphocytic myocarditis and persistent heart failure for greater than 6 months, those with circulating cardiac autoantibodies and no viral genomes detected on myocardial biopsy are the most likely to benefit from immunosuppressive therapy.
Source: Frustaci A, et al. Circulation. 2003;107: 857-863.
The role of immunosuppressive therapy in myocarditis is controversial due to the heterogeneity in the pathophysiology. Thus, Attilio Maseri’s group from Catholic University in Rome, Italy, performed a retrospective analysis of their experience in patients with active lymphocytic myocarditis and heart failure who failed conventional supportive care and were treated with immunosuppression. Their goal was to identify the virological and immunologic characteristics that defined those who responded to this therapy. The population was derived from 652 patients who underwent myocardial biopsy for a variety of reasons. Active myocarditis was observed in 112—80 with heart failure, 28 with ventricular arrhythmias, and 4 with unexplained chest pain. Among the 80 with heart failure, 41 had lymphocytic myocarditis and NYHA class III-IV heart failure for greater than 6 months unresponsive to conventional supportive care. These 41 patients were treated for 6 months with prednisone and azathioprine and constitute the study population. At 1 and 6 months, all had repeat catheterization and biopsy. At the end of this treatment, 21 were classified as responders because they decreased at least 1 NYHA clinical class and their left ventricular ejection fraction increased at least 10% compared to baseline. Follow-up continued for 1 year. Clinical, echocardiographic, and hemodynamic data were not different between the responders and the non-responders. By polymerase chain reaction on the biopsy material, viral genomes were detected in 17 of the non-responders (85%) vs 3 responders, all of whom had hepatitis C identified. Serum cardiac autoantibodies were present in 19 responders (90%) and none of the nonresponders. Frustaci and associates concluded that in patients with active lymphocytic myocarditis and persistent heart failure for greater than 6 months, those with circulating cardiac autoantibodies and no viral genomes detected on myocardial biopsy are the most likely to benefit from immunosuppressive therapy.
Comment by Michael H. Crawford, MD
The heterogeneous clinical and biopsy results of previous studies has led to a sense of therapeutic nihilism for treating patients with heart failure and suspected myocarditis with immunosuppressive agents. Current guidelines suggest that certain biopsy findings warrant a trial of immunosuppressive therapy, namely, eosinophilic, granulomatous, or giant cell myocarditis, none of which is particularly common. Also, myocarditis thought to be due to connective tissue diseases or cardiac transplant rejection responds to immunosuppressive therapy. Thus, it is not surprising that Maseri’s group found that patients with circulating cardiac autoantibodies responded to immunotherapy. These 19 patients were 46% of the 41 patients with lymphocytic myocarditis and persistent heart failure, who were 51% of the 80 patients with heart failure and biopsy evidence of myocarditis, who were 17% of the 478 patients with idiopathic heart failure who underwent biopsy at their institution. Thus, 4% of patients (19 of 478) with idiopathic heart failure are potential candidates for immunotherapy. If you add other rare cases described above that may respond to immunotherapy, perhaps 5% will be candidates. Unfortunately, that is a lot of biopsies for a small, albeit important, gain. Clearly, the ability to use circulating autoantibodies to cull out potential responders is very important. Whether biopsy still needs to be done to detect viral genomes before embarking on a trial of immunosuppressives in patients with high autoantibody titers is unclear because we don’t know if it is harmful, if not successful. Of interest is the fact that the responders in this trial were improved within a week. This suggests that a trial of immunosuppressives may not have to be long to assess efficacy. Another issue is whether one needs to wait 6 months to see which patients with suspected myocarditis are not within the 40% who will improve spontaneously. Perhaps autoantibodies should be sought earlier in the course.
Of interest, the 3 responders with viral genomes detected in their biopsies all had hepatitis C identified. None had hepatic or other systemic manifestations. When therapy ended, these 3 patients quickly deteriorated unlike the other responders, and they had histologic evidence of recurrent myocarditis. They improved clinically and histologically on resumption of immunosuppressive therapy. Thus, patients with hepatitis C virus-associated myocarditis may need to be on chronic immunosuppression. Other viruses detected in this study included enterovirus, Epstein-Barr, adenovirus, influenza A, and parvovirus B19. Of these, enterovirus and adenovirus alone or in combination had the worst prognosis. Patients with viruses other than hepatitis C detected on biopsy may respond to beta interferon.
Dr. Crawford is Professor of Medicine, Mayo Medical School; Consultant in Cardiovascular Diseases, and Director of Research, Mayo Clinic, Scottsdale, AZ.
In patients with active lymphocytic myocarditis and persistent heart failure for greater than 6 months, those with circulating cardiac autoantibodies and no viral genomes detected on myocardial biopsy are the most likely to benefit from immunosuppressive therapy.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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