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

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 treatme...

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Main Authors: Heinz-Peter Schultheiss, Thomas Bock, Heiko Pietsch, Ganna Aleshcheva, Christian Baumeier, Friedrich Fruhwald, Felicitas Escher
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/10/9/1928
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spelling doaj-a9031a1ccab243e6a0efd6f779911e1d2021-04-29T23:04:25ZengMDPI AGJournal of Clinical Medicine2077-03832021-04-01101928192810.3390/jcm10091928Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive PatientsHeinz-Peter Schultheiss0Thomas Bock1Heiko Pietsch2Ganna Aleshcheva3Christian Baumeier4Friedrich Fruhwald5Felicitas Escher6Institute of Cardiac Diagnostics and Therapy, 12203 Berlin, GermanyInstitute of Cardiac Diagnostics and Therapy, 12203 Berlin, GermanyInstitute of Cardiac Diagnostics and Therapy, 12203 Berlin, GermanyInstitute of Cardiac Diagnostics and Therapy, 12203 Berlin, GermanyInstitute of Cardiac Diagnostics and Therapy, 12203 Berlin, GermanyDepartment of Cardiology, Medical University Graz, 8036 Graz, AustriaInstitute of Cardiac Diagnostics and Therapy, 12203 Berlin, GermanyHuman 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) (<i>p</i> ≤ 0.0001). Notably; LVEF improvement was more significant in patients who reduced or lost B19V RNA (responder; <i>p</i> = 0.02) in contrast to non-responders (<i>p</i> = 0.7). In parallel; responder patients displayed statistically significant improvement in quality of life (QoL) questionnaires (<i>p</i> = 0.03) and dyspnea on exertion (<i>p</i> = 0.0006), reflecting an improvement in New York Heart Association (NYHA) Classification (<i>p</i> = 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.https://www.mdpi.com/2077-0383/10/9/1928parvovirus B19dilated inflammatory cardiomyopathytelbivudine
collection DOAJ
language English
format Article
sources DOAJ
author Heinz-Peter Schultheiss
Thomas Bock
Heiko Pietsch
Ganna Aleshcheva
Christian Baumeier
Friedrich Fruhwald
Felicitas Escher
spellingShingle Heinz-Peter Schultheiss
Thomas Bock
Heiko Pietsch
Ganna Aleshcheva
Christian Baumeier
Friedrich Fruhwald
Felicitas Escher
Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients
Journal of Clinical Medicine
parvovirus B19
dilated inflammatory cardiomyopathy
telbivudine
author_facet Heinz-Peter Schultheiss
Thomas Bock
Heiko Pietsch
Ganna Aleshcheva
Christian Baumeier
Friedrich Fruhwald
Felicitas Escher
author_sort Heinz-Peter Schultheiss
title Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients
title_short Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients
title_full Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients
title_fullStr Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients
title_full_unstemmed Nucleoside Analogue Reverse Transcriptase Inhibitors Improve Clinical Outcome in Transcriptional Active Human Parvovirus B19-Positive Patients
title_sort nucleoside analogue reverse transcriptase inhibitors improve clinical outcome in transcriptional active human parvovirus b19-positive patients
publisher MDPI AG
series Journal of Clinical Medicine
issn 2077-0383
publishDate 2021-04-01
description 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) (<i>p</i> ≤ 0.0001). Notably; LVEF improvement was more significant in patients who reduced or lost B19V RNA (responder; <i>p</i> = 0.02) in contrast to non-responders (<i>p</i> = 0.7). In parallel; responder patients displayed statistically significant improvement in quality of life (QoL) questionnaires (<i>p</i> = 0.03) and dyspnea on exertion (<i>p</i> = 0.0006), reflecting an improvement in New York Heart Association (NYHA) Classification (<i>p</i> = 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.
topic parvovirus B19
dilated inflammatory cardiomyopathy
telbivudine
url https://www.mdpi.com/2077-0383/10/9/1928
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