Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity

Abstract

AimsMyocarditis is often associated with parvovirus B19 (B19V) persistence, which can induce vascular damage. Based on the antiviral and anti‐inflammatory properties of telbivudine, we aimed to evaluate its efficacy to protect B19V‐infected endothelial cells in vitro and to treat chronic lymphocytic myocarditis patients with B19V transcriptional activity.Methods and resultsWe evaluated the endothelial‐protective potential of telbivudine in human microvascular endothelial cells‐1, which were infected with B19V. Treatment with 10 ng/mL of telbivudine decreased the B19V‐induced endothelial cell apoptosis and endothelial‐to‐mesenchymal transition. Along with this finding, telbivudine reduced the expression of transforming growth factor‐β1 and of tenascin‐C. The endothelial‐protective properties of telbivudine were also found in tumour necrosis factor‐α‐stressed human microvascular endothelial cells‐1. In addition, oxidative stress in angiotensin II‐stressed and transforming growth factor‐β1‐stressed HL‐1 cardiomyocytes and fibroblasts, respectively, was reduced upon telbivudine treatment, illustrating that telbivudine exerts multimodal protective effects. Based on these in vitro findings, four patients severely suffering from an endomyocardial biopsy‐proven myocarditis associated with B19V transcriptional activity (VP1/VP2‐mRNA positive) were treated with telbivudine (600 mg/dL) for 6 months in a single‐patient‐use approach. Follow‐up biopsies 6 months after treatment showed that VP1/VP2‐mRNA levels and CD3 cells decreased in all patients and were associated with an improvement in ejection fraction and New York Heart Association class. These findings were paralleled by a drop in tenascin‐C expression as shown via matrix‐assisted laser desorption ionization–imaging mass spectrometry.ConclusionsTelbivudine exerts endothelial‐protective effects in B19V‐infected endothelial cells and improves chronic myocarditis associated with B19V transcriptional activity. These findings will be further evaluated in the clinical exploratory trial: the PreTopic study.

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

“…31 ). B19V infection of endothelial cells can thereby induce cardiomyocyte apoptosis, as shown in vitro in B19V-infected endothelial cells co-cultured with cardiomyocytes 32 . Sustained severe cardiac inflammation, especially in the setting of acute B19V infection, might lead to cardiomyocyte necrosis 33 .…”

Update on myocarditis – what we know so far and where we may be heading

“…There is no Food and Drug Administrationapproved regimen for the treatment of acute and chronic myocarditis. 2,23,29,30,32,34,36,37,41,42,78,85,89,136,147,177,[187][188][189][190][191][192][193][194][195] Still, consideration is reserved for patients with newonset, rapidly deteriorating, advanced heart failure with suspicion of the following conditions:…”

“…16,19,77,196 Further studies to investigate the utility of novel tools for the analysis of EMB and improvement of diagnostic and prognostic assessment of myocarditis by means of transcriptomic, proteomic or genetic analysis have shown promising results. 71,86,99,100,187…”

Selected nucleos(t)ide-based prescribed drugs and their multi-target activity

“…Moreover, telbivudine has some pleiotropic immunomodulatory and anti-inflammatory properties (Rehermann and Bertoletti, 2015). Recently, it was shown that telbivudine confers endothelial-protective effects on B19V-infected endothelial cells and improves the chronic myocarditis associated with B19V transcriptional activity (Van Linthout et al, 2018).…”