Systematic Review of PCR Proof of Parvovirus B19 Genomes in Endomyocardial Biopsies of Patients Presenting with Myocarditis or Dilated Cardiomyopathy

Abstract

Background: Diverse viral infections have been associated with myocarditis (MC) and dilated cardiomyopathy (DCM). In this meta-analysis, we summarize the published results on the association of parvovirus B19 (B19V) genomes with human MC/DCM versus controls. Methods: n = 197 publications referring to B19V and MC or DCM were retrieved using multiple PubMed search modes. Out of these, n = 29 publications met the inclusion criteria with data from prospective analyses on >10 unselected patients presenting with MC or DCM (dataset: MA01). Data retrieved simultaneously from both controls and MC/DCM patients were available from n = 8 from these publications (dataset: MA02). Results: In the dataset MA01 B19V genomes were detected in 42.6% of the endomyocardial biopsies (EMB) in this cohort by PCR. In the dataset MA02 comprising n = 638 subjects, there was no statistically significant different rate of B19V positivity in myocardial tissues comparing controls (mean: 38.8 + 24.1%) versus the MC/DCM-patients (45.5 + 24.3%; p = 0.58). There was also no statistical difference between the positivity rate of B19V genomes in myocardial tissues of MA01 (46.0 + 19.5%) and the two patient groups of MA02 (p > 0.05). Conclusions: This systematic review reveals that the mean rate of PCR detected B19V genomes in patients presenting with MC/DCM does not differ significantly from the findings in control myocardial tissues. These data imply pathogenetically insignificant latency of B19V genomes in a proportion of myocardial tissues, both in MC-/DCM-patients and in controls. More information (i.e., replicative status, viral protein expression) is pertinent to achieve a comprehensive workup of myocardial B19V infection.

Advanced detection strategies for cardiotropic virus infection in a cohort study of heart failure patients

“…Our study revealed the presence of actively replicating B19V among 12.5% (2/16) of patients with DCM and 20% (1/5) of patients with eosinophilic myocarditis, while it was not detected in patients with a clinical diagnosis of lymphocytic myocarditis (viral or non-viral). The prevalence of B19V among patients with DCM or myocarditis in our cohort is considerably lower than the prevalence quoted in previous reports 18 , 47 . A recent meta-analysis demonstrated that the prevalence of B19V in endomyocardial biopsies of patients with myocarditis or DCM (45.5%) was not significantly different than its prevalence in control tissues (37.5%), which supports the notion of B19V being a bystander virus as opposed to a causative agent for such conditions 47 , 68 .…”

“…The prevalence of B19V among patients with DCM or myocarditis in our cohort is considerably lower than the prevalence quoted in previous reports 18 , 47 . A recent meta-analysis demonstrated that the prevalence of B19V in endomyocardial biopsies of patients with myocarditis or DCM (45.5%) was not significantly different than its prevalence in control tissues (37.5%), which supports the notion of B19V being a bystander virus as opposed to a causative agent for such conditions 47 , 68 . It is noteworthy that of all three patients in our cohort positive for B19V (2 DCM and 1 eosinophilic myocarditis), at least one additional actively replicating virus was detected within the same tissue.…”

“…Although EBV has been implemented in rare cases of acute myocarditis 49 , exacerbation of coronary events 50 and heart failure 51 , definitive evidence of causation remains elusive and such studies have relied on detection of neutralizing antibodies for EBV in patient blood. Similar analyses have been conducted for B19V, with limited evidence for causation or contribution to acute and chronic cardiac disease 47 , 52 .…”

“…To confirm viral presence, PCR is often the standard used to detect viral genome in the heart 45 . However, PCR is insufficient to detect viral RNA in the heart in a manner that would affirm causation, as there is the potential for false positivity 46 due to viral presence in the blood being indistinguishable from viral presence in tissue using this method 47 . The pervasiveness of more common viruses further complicates matters.…”

New Insights into Parvovirus Research

“…In an observational study [18], a significant association of human bocaviruses to gastroenteritis is reported, thus further expanding their clinical involvement in addition to the established association with respiratory tract infections. In a systematic review and meta-analysis study [19], the significance of the detection of parvovirus B19 genomes in endomyocardial biopsies of patients presenting with myocarditis or dilated cardiomyopathy is discussed. This review should be regarded as a very useful contribution to a long debated and far from settled issue.…”