Relevance of cardiac parvovirus B19 in myocarditis and dilated cardiomyopathy: review of the literature

Abstract

Over the last decade, parvovirus B19 (B19V) has frequently been linked to the pathogenesis of myocarditis (MC) and its progression towards dilated cardiomyopathy (DCM). The exact role of the presence of B19V and its load remains controversial, as this virus is also found in the heart of healthy subjects. Moreover, the prognostic relevance of B19V prevalence in endomyocardial biopsies still remains unclear. As a result, it is unclear whether the presence of B19V should be treated. This review provides an overview of recent literature investigating the presence of B19V and its pathophysiological relevance in MC and DCM, as well as in normal hearts. In brief, no difference in B19V prevalence is observed between MC/DCM and healthy control hearts. Therefore, the question remains open whether and how cardiac B19V may be of pathogenetic importance. Findings suggest that B19V is aetiologically relevant either in the presence of other cardiotropic viruses, or when B19V load is high and/or actively replicating, which both may maintain myocardial (low-grade) inflammation. Therefore, future studies should focus on the prognostic relevance of the viral load, replicative status and virus co-infections. In addition, the immunogenetic background of MC/DCM patients that makes them susceptible to develop heart failure upon presence of B19V should be more thoroughly investigated.

Immunosuppression in inflammatory cardiomyopathy and parvovirus B19 persistence

“…Parvovirus B19 (B19V) infection is acquired in childhood and persists lifelong in approximately 70% of healthy adults and may belong to a cardiac bioportfolio without clinical significance . However, B19V DNA is also found in the majority of chronic inflammatory cardiomyopathy patients with low copy numbers, questioning whether this finding contributes to the disease and influences treatment implications . Current European Society of Cardiology and American Heart Association recommendations support an anti‐inflammatory treatment regime in inflammatory cardiomyopathy patients when active cardiac infection is excluded .…”

“…Current European Society of Cardiology and American Heart Association recommendations support an anti‐inflammatory treatment regime in inflammatory cardiomyopathy patients when active cardiac infection is excluded . Whether this precaution holds true for patients with B19V persistence, which does not principally represents an active infection, is under discussion . To gain insights into immunosuppressive treatment effects of B19V‐negative and ‐positive patients with endomyocardial biopsy (EMB)‐proven inflammatory cardiomyopathy, we compared the changes in systolic left ventricular ejection fraction (LVEF, %), B19V viral genome copy numbers (B19V DNA) and grade of inflammation of 51 consecutive B19V‐positive patients [33 men (65%), mean age 45.1 ± 14.8 years, 9 (11.6%) with > 500 DNA copies/μg DNA] and 17 virus‐negative patients with inflammatory cardiomyopathy [12 men (70.6%), mean age 45.6 ± 13.9 years] during a 6‐month course with prednisolone and azathioprine regimen in addition to standard heart failure medication in a single‐centre observational investigation.…”

Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity

“…Based on the hypothesis that the detection of viral genomes indicates active infection, immunosuppression is avoided in cardiotropic viral genome‐positive patients. The implication is that immunosuppression is withheld in most of these patients, because in ~70% of those patients, a B19V persistence can be detected . Thus, for this clinical scenario, there is an unmet need to develop new immunomodulatory or antiviral therapy strategies that do not carry the risk of viral stimulation due to global immune suppression as it is known for cortisone.…”

“…The implication is that immunosuppression is withheld in most of these patients, because in~70% of those patients, a B19V persistence can be detected. 15,46,47 Thus, for this clinical scenario, there is an unmet need to develop new immunomodulatory or antiviral therapy strategies that do not carry the risk of viral stimulation due to global immune suppression as it is known for cortisone. The antiviral and anti-inflammatory properties of telbivudine [24][25][26][27] inspired us to evaluate its potential to treat B19V-associated inflammatory cardiomyopathy.…”

Antenatal Investigation of Ductus Venosus Velocity as a Method of Detecting the Fetal Heart Failure, Caused by Parvovirus B19 Infection

“…Virus B19 enters the endothelium cells utilizing a globoside and its coreceptors a5 pi-integrin and Ku80 and after connection with a receptor pass to the state of persistent infection in the endothelium of various organs, including heart. In consequence, numerous copies of the viral genome of B19 are determined in the endothelium of intramyocardial arterioles, capillaries and post-capillary venules, initiating inflammation process indu ced by the continuous expression of pro-inflammatory cytokines (TNFa, interleukins (IL): IL-6, IL-8, IL-2)), IgG, soluble interleukin 2 receptor, leukotrienes and prostaglandins [6]. The direct cytopathic effect of parvovirus, apoptosis, activation of innate and adaptive immune response lead to endothelial dysfunction, followed by ventricular remodeling and development of dilated cardiomyopathy.…”