Myocardial parvovirus B19 persistence: lack of association with clinicopathologic phenotype in adults with heart failure

Abstract

Background: Multiple viruses have been isolated from the heart, but their significance remains controversial. We sought to determine the prevalence of cardiotropic viruses in endomyocardial biopsy (EMB) samples from adult patients with heart failure (HF) and to define the clinicopathologic profile of patients exhibiting viral positivity.

Methods and results: EMB from 100 patients (median ejection fraction, 30%; interquartile range [IQR], 20% to 45%) presenting for cardiomyopathy evaluation (median symptom duration, 5 months; IQR, 1 to 13 months) were analyzed by polymerase chain reaction for adenovirus, cytomegalovirus, enteroviruses, Epstein-Barr virus, and parvovirus B19. Each isolate was sequenced, and viral load was determined. Parvovirus B19 was the only virus detected in EMB samples (12% of subjects). No patient had antiparvovirus IgM antibodies, but all had IgG antibodies, suggesting viral persistence. The clinical presentation of parvovirus-positive patients was markedly heterogeneous with both acute and chronic HF, variable ventricular function, and ischemic cardiomyopathy. No patient met Dallas histopathologic criteria for active or borderline myocarditis. Two patients with a positive cardiac MRI and presumed "parvomyocarditis" had similar viral loads to autopsy controls without heart disease. The oldest parvovirus-positive patients were positive for genotype 2, suggesting lifelong persistence in the myocardium.

Conclusions: Parvovirus B19 was the only virus isolated from EMB samples in this series of adult patients with HF from the United States. Positivity was associated with a wide array of clinical presentations and HF phenotypes. Our studies do not support a causative role for parvovirus B19 persistence in HF and, therefore, advocate against the use of antiviral therapy for these patients.

Figure 1

Panel A. I, Amplification curve of endogenous myocardial DNA from patients H55 and H64 by GAD65 TaqMan assay. II, Amplification curves from samples that were negative for parvovirus B19. III and IV, triplicate amplification curves from samples H55, genotype 1 and sample H64, genotype 2. Inset are triplicate samples resolved by agarose gel electrophoresis stained with ethidium bromide. Panel B. Parvovirus B19 viral copies per μg myocardial DNA from endomyocardial biopsy. Subjects H16 and H55, were classified as idiopathic dilated cardiomyopathy (DCM), subject H77 had ischemic cardiomyopathy (ICM), and subjects H100 and H102 had myocarditis. A1 and A2 are myocardial autopsy samples from subjects who had no clinical or pathological evidence of heart disease. Viral load was determined by quantitative PCR. Inset is the standard curve analysis of diluted parvovirus 19 plasmid used to extrapolate parvovirus 19 viral copies in the quantitative PCR.