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Prospects for remodeling the hypertrophic heart with myosin modulators

Hypertrophic cardiomyopathy (HCM) is a complex but relatively common genetic disease that usually arises from pathogenic variants that disrupt sarcomere function and lead to variable structural, hypertrophic, and fibrotic remodeling of the heart which result in substantial adverse clinical outcomes...

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Detalles Bibliográficos
Autores principales: Sewanan, Lorenzo R., Shimada, Yuichi J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622926/
https://www.ncbi.nlm.nih.gov/pubmed/36330009
http://dx.doi.org/10.3389/fcvm.2022.1051564
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author Sewanan, Lorenzo R.
Shimada, Yuichi J.
author_facet Sewanan, Lorenzo R.
Shimada, Yuichi J.
author_sort Sewanan, Lorenzo R.
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description Hypertrophic cardiomyopathy (HCM) is a complex but relatively common genetic disease that usually arises from pathogenic variants that disrupt sarcomere function and lead to variable structural, hypertrophic, and fibrotic remodeling of the heart which result in substantial adverse clinical outcomes including arrhythmias, heart failure, and sudden cardiac death. HCM has had few effective treatments with the potential to ameliorate disease progression until the recent advent of inhibitory myosin modulators like mavacamten. Preclinical investigations and clinical trials utilizing this treatment targeted to this specific pathophysiological mechanism of sarcomere hypercontractility in HCM have confirmed that myosin modulators can alter disease expression and attenuate hypertrophic remodeling. Here, we summarize the state of hypertrophic remodeling and consider the arguments for and against salutary HCM disease modification using targeted myosin modulators. Further, we consider critical unanswered questions for future investigative and therapeutic avenues in HCM disease modification. We are at the precipice of a new era in understanding and treating HCM, with the potential to target agents toward modifying disease expression and natural history of this most common inherited disease of the heart.
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spelling pubmed-96229262022-11-02 Prospects for remodeling the hypertrophic heart with myosin modulators Sewanan, Lorenzo R. Shimada, Yuichi J. Front Cardiovasc Med Cardiovascular Medicine Hypertrophic cardiomyopathy (HCM) is a complex but relatively common genetic disease that usually arises from pathogenic variants that disrupt sarcomere function and lead to variable structural, hypertrophic, and fibrotic remodeling of the heart which result in substantial adverse clinical outcomes including arrhythmias, heart failure, and sudden cardiac death. HCM has had few effective treatments with the potential to ameliorate disease progression until the recent advent of inhibitory myosin modulators like mavacamten. Preclinical investigations and clinical trials utilizing this treatment targeted to this specific pathophysiological mechanism of sarcomere hypercontractility in HCM have confirmed that myosin modulators can alter disease expression and attenuate hypertrophic remodeling. Here, we summarize the state of hypertrophic remodeling and consider the arguments for and against salutary HCM disease modification using targeted myosin modulators. Further, we consider critical unanswered questions for future investigative and therapeutic avenues in HCM disease modification. We are at the precipice of a new era in understanding and treating HCM, with the potential to target agents toward modifying disease expression and natural history of this most common inherited disease of the heart. Frontiers Media S.A. 2022-10-18 /pmc/articles/PMC9622926/ /pubmed/36330009 http://dx.doi.org/10.3389/fcvm.2022.1051564 Text en Copyright © 2022 Sewanan and Shimada. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Sewanan, Lorenzo R.
Shimada, Yuichi J.
Prospects for remodeling the hypertrophic heart with myosin modulators
title Prospects for remodeling the hypertrophic heart with myosin modulators
title_full Prospects for remodeling the hypertrophic heart with myosin modulators
title_fullStr Prospects for remodeling the hypertrophic heart with myosin modulators
title_full_unstemmed Prospects for remodeling the hypertrophic heart with myosin modulators
title_short Prospects for remodeling the hypertrophic heart with myosin modulators
title_sort prospects for remodeling the hypertrophic heart with myosin modulators
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9622926/
https://www.ncbi.nlm.nih.gov/pubmed/36330009
http://dx.doi.org/10.3389/fcvm.2022.1051564
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