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Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity #MMPMID30099854
Van Linthout S; Elsanhoury A; Klein O; Sosnowski M; Miteva K; Lassner D; Abou-El-Enein M; Pieske B; Kuhl U; Tschope C
ESC Heart Fail 2018[Oct]; 5 (5): 818-829 PMID30099854show ga
AIMS: Myocarditis 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 RESULTS: We 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-beta1 and of tenascin-C. The endothelial-protective properties of telbivudine were also found in tumour necrosis factor-alpha-stressed human microvascular endothelial cells-1. In addition, oxidative stress in angiotensin II-stressed and transforming growth factor-beta1-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. CONCLUSIONS: Telbivudine 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.
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ESC+Heart+Fail 2018 ; 5 (5): 818-829
