Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients.

Heinz-Peter Schultheiss,Heiko Pietsch,Felicitas Escher,Christian Baumeier,Friedrich Fruhwald,Ganna Aleshcheva,Thomas Bock

doi:10.3390/jcm10091928

Abstract

Human parvovirus B19 (B19V) is the predominant cardiotropic virus associated with dilated inflammatory cardiomyopathy (DCMi). Transcriptionally active cardiotropic B19V infection is clinically relevant and triggers adverse long-term mortality. During the study; we evaluated whether antiviral treatment with the nucleoside analogue telbivudine (LTD) is effective in suppressing transcriptional active B19V in endomyocardial biopsies (EMBs) of B19V positive patients and improving clinical outcomes. Seventeen B19V-positive patients (13 male; mean age 45.7 ± 13.9 years; mean left ventricular ejection fraction (LVEF) 37.7 ± 13.5%) with positive B19V DNA and transcriptional activity (B19V mRNA) in EMBs were treated with 600 mg/d LTD over a period of six months. Patients underwent EMBs before and after termination of the LTD treatment. B19V RNA copy numbers remained unchanged in 3/17 patients (non-responder) and declined or disappeared completely in the remaining 14/17 patients (responder) (p ≤ 0.0001). Notably; LVEF improvement was more significant in patients who reduced or lost B19V RNA (responder; p = 0.02) in contrast to non-responders (p = 0.7). In parallel; responder patients displayed statistically significant improvement in quality of life (QoL) questionnaires (p = 0.03) and dyspnea on exertion (p = 0.0006), reflecting an improvement in New York Heart Association (NYHA) Classification (p = 0.001). Our findings demonstrated for the first time that suppression of B19V transcriptional activity by LTD treatment improved hemodynamic and clinical outcome significantly. Thus; the present study substantiates the clinical relevance of detecting B19V transcriptional activity of the myocardium.

Highlights

Whereas latent B19V infection has presumably no effect on the course of DCMi [7,8], it was shown that transcriptionally active B19V leads to an altered cardiac gene expression in endomyocardial biopsies (EMBs)
Remains a single independent predictor for reduced cardiac capillary density in patients with cardiomyopathy. These results demonstrate the causality between B19V infection and reduced coronary blood flow leading to endothelial dysfunction and ischemia
Complaints included mostly dyspnea on exertion (88.2%), reflected in New York Heart Association (NYHA) class II/III (Table 1)

Summary

Introduction

Whereas latent B19V infection has presumably no effect on the course of DCMi [7,8], it was shown that transcriptionally active B19V leads to an altered cardiac gene expression in EMB. The presence of B19V remains a single independent predictor for reduced cardiac capillary density in patients with cardiomyopathy. These results demonstrate the causality between B19V infection and reduced coronary blood flow leading to endothelial dysfunction and ischemia. This is an explanation for why acute endothelial cell B19V-infection in myocarditis is associated with a cardiac microvascular impairment mimicking myocardial infarction [17,18,19]

Methods

Results

Conclusion