Transcriptional Active Parvovirus B19 Infection Predicts Adverse Long-Term Outcome in Patients with Non-Ischemic Cardiomyopathy

Abstract

Parvovirus B19 (B19V) is the predominant cardiotropic virus currently found in endomyocardial biopsies (EMBs). However, direct evidence showing a causal relationship between B19V and progression of inflammatory cardiomyopathy are still missing. The aim of this study was to analyze the impact of transcriptionally active cardiotropic B19V infection determined by viral RNA expression upon long-term outcomes in a large cohort of adult patients with non-ischemic cardiomyopathy in a retrospective analysis from a prospective observational cohort. In total, the analyzed study group comprised 871 consecutive B19V-positive patients (mean age 50.0 ± 15.0 years) with non-ischemic cardiomyopathy who underwent EMB. B19V-positivity was ascertained by routine diagnosis of viral genomes in EMBs. Molecular analysis of EMB revealed positive B19V transcriptional activity in n = 165 patients (18.9%). Primary endpoint was all-cause mortality in the overall cohort. The patients were followed up to 60 months. On the Cox regression analysis, B19V transcriptional activity was predictive of a worse prognosis compared to those without actively replicating B19V (p = 0.01). Moreover, multivariable analysis revealed transcriptional active B19V combined with inflammation [hazard ratio 4.013, 95% confidence interval 1.515–10.629 (p = 0.005)] as the strongest predictor of impaired survival even after adjustment for age and baseline LVEF (p = 0.005) and independently of viral load. The study demonstrates for the first time the pathogenic clinical importance of B19V with transcriptional activity in a large cohort of patients. Transcriptionally active B19V infection is an unfavourable prognostic trigger of adverse outcome. Our findings are of high clinical relevance, indicating that advanced diagnostic differentiation of B19V positive patients is of high prognostic importance.

Intramyocardial Inflammation after COVID-19 Vaccination: An Endomyocardial Biopsy-Proven Case Series

“…Although latent viral genomes of B19V were found in 10/15 (67%) cases, active B19V transcription was not confirmed in these patients. B19V is the most frequently detected viral species in the human heart, and its contribution to myocardial inflammation and thus, to long-term patient outcome, is highly dependent on its transcriptional activity [18,19]. Therefore, identified latent B19V infections are unlikely causative of the myocardial inflammation in these patients.…”

Interferon-β Suppresses Transcriptionally Active Parvovirus B19 Infection in Viral Cardiomyopathy: A Subgroup Analysis of the BICC-Trial

“…In the BICC-Trial we have shown that IFN-ß was safe in patients with myocardial enteroviral or adenoviral persistence and resulted in elimination of viral genomes and improved LVEF, whereas B19V viral persistence was barely affected in B19V positive mono-infected patients. Recent experimental and clinical data foster the important role of transcriptional active B19V [9,16].…”

“…Assessing the replicative status of the virus is the most accurate way to determine transcriptional activity of B19V in the myocardium [7,8]. Whereas latent B19V infection indicated by only viral DNA (viral genome) detection in EMBs has presumably no effect on the clinical course, it has been shown that transcriptionally active B19V characterized by viral RNA detection leads to an altered cardiac gene expression and is associated with progressive cardiac dysfunction and impaired survival [9,10].…”

Sex and autoimmunity in acute myocarditis: time for a refresh

“…In patients with cardiac HHV6 DNA copy numbers less than 500 copies/µg cardiac DNA and without signs of an active systemic HHV6 infection, steroid‐based therapy was found to be safe 12 . PVB19 may be clinically relevant only in the presence of other cardiotropic viruses, when viral load is high or with evidence of active replication 13,14 . If correlative studies of autoantibodies translate to actionable mechanistic insights, a paradigm that integrates measures of pathway‐specific immune activity may improve on the standard, decades‐old clinical and histological classifications 15 …”

“…12 PVB19 may be clinically relevant only in the presence of other cardiotropic viruses, when viral load is high or with evidence of active replication. 13,14 If correlative studies of autoantibodies translate to actionable mechanistic insights, a paradigm that integrates measures of pathway-specific immune activity may improve on the standard, decades-old clinical and histological classifications. 15 Clinical trials are underway that target specific molecular pathways.…”