Abstract & Commentary
Synopsis: INFB therapy of heart failure patients with persistent viral genomes in the myocardium was safe, eliminated viral genomes, and improved LV function.
Source: Kühl U, et al. Circulation. 2003;107: 2793-2798.
Patients with persistent heart failure despite therapy and myocardial biopsy evidence of virus genomes have a poor prognosis. Thus, Kühl and associates from Berlin, Germany, studied 22 patients who met these criteria and had enteroviral (65%) or adenoviral (35%) genomes detected by polymerase chain reaction analysis of myocardial biopsy material. All had persistent heart failure symptoms for a mean of 44 months, and average left ventricular (LV) ejection fraction (EF) was 45%. Interferon-beta (INFB) was given subcutaneously 3 times a week for 24 weeks. Therapy was well tolerated, and no patient deteriorated. Repeat endomyocardial biopsy showed clearance of viral genomes in all of the patients. LV volumes decreased significantly, and EF increased to 53% (P < .001). LVEF normalized in 9 patients and increased > 5% in 5. These 14 patients had mild-to-moderate LV dysfunction. Those with severely impaired LV function were less likely to improve. New York Heart Association class improved in two-thirds of the patients. Biopsy results after treatment showed a decrease in CD3-positive T lymphocytes, but there was no evidence of active myocarditis on either the pre- or postspecimens. Kühl et al concluded that INFB therapy of heart failure patients with persistent viral genomes in the myocardium was safe, eliminated viral genomes, and improved LV function.
Comment by Michael H. Crawford, MD
Current supportive heart failure therapy has reduced morbidity and mortality, but adverse outcomes are still frequent. Clearly, an approach based upon eliminating the cause of myocardial dysfunction would be advantageous. This study is an attempt to pursue this line of therapy for viral myocarditis using the antiviral agent INFB. Several lines of evidence from previous studies support their approach. First, the detection of viral genomes in myocardial biopsy specimens is correlated with a worse prognosis. Second, immunosuppressive therapy often fails when viral genomes are detected. Third, lack of evidence of an inflammatory response in the myocardium correlates with the presence of viral genomes and a poor prognosis. Thus, in this pilot study of highly selected patients with persistent LV dysfunction, so spontaneous remission is not likely; patients with persistence of viral genomes on myocardial biopsy; and patients with little or no evidence of an inflammatory myocarditis, INFB therapy was generally beneficial, and no treated patient deteriorated over 6 months.
This study is remarkable for the long duration of cardiomyopathy (mean duration, 44 months) in the patients. However, most of the patients had relatively preserved LV function (mean EF, 45%) and those with more marked LV dysfunction did not improve. Thus, such therapy must be given before irreversible myocardial damage occurs, which may not always be feasible. This will be the real challenge for this approach—identifying patients early who will respond to antiviral therapy. Previous studies of the value of myocardial biopsy were not encouraging because they focused on evidence of myocarditis, which was uncommonly found. This focus on viral genome presence, if it pans out, may resurrect the myocardial biopsy. Because of the encouraging results of this pilot study, a large, randomized trial has begun. We will eagerly await the results, but in the mean time, there may be hope for some patients with viral myocardiopathy, even if they have persistent LV dysfunction for years.
Dr. Crawford, Professor of Medicine, Associate Chief of Cardiology for Clinical Programs, University of California, San Francisco, is Editor of Clinical Cardiology Alert.