Targeting the Sarcomere: Myosin Inhibitors as the Revolutionary Game Changer in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) represents the most common inherited cardiac disease and a leading cause of heart failure, arrhythmias, and sudden cardiac death in young individuals. For decades, management of HCM has relied on symptom control with β-blockers, calcium channel blockers, disopyramide, or invasive septal reduction in advanced cases. The identification of pathogenic sarcomere variants and the recognition of hypercontractility as a central disease mechanism have paved the way for cardiac myosin inhibitors (CMIs), the first truly disease-specific pharmacological therapy for HCM. Indeed, CMIs represent a revolutionary therapeutic paradigm that redefines the standard of care by translating molecular discovery into clinical application. This review provides a guide to the mechanistic basis of sarcomere modulation, summarizes the clinical evidence for mavacamten and aficamten, and critically evaluates the evolving roles of both medications in obstructive and non-obstructive HCM.

• Publication year

  2026

• Venue

  Reviews in cardiovascular medicine

• Publication date

  2026-01-01

• Fields of study

  Medicine

• Identifiers
  DOI 10.31083/RCM47341PMID 41659088PMCID 12873663
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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• Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy.

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• Sacubitril/valsartan for the treatment of non‐obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (SILICOFCM)

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• Efficacy and Safety of aficamten in Symptomatic Non-Obstructive Hypertrophic Cardiomyopathy: Results From the REDWOOD-HCM Trial, Cohort 4.

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• Aficamten for Symptomatic Obstructive Hypertrophic Cardiomyopathy.

  2024influential reference
• Cardiac Myosin Inhibition in Heart Failure With Normal and Supranormal Ejection Fraction: Primary Results of the EMBARK-HFpEF Trial.

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• Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy

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• Assessing the Applicability of Cardiac Myosin Inhibitors for Hypertrophic Cardiomyopathy Management in a Large Single Center Cohort

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• Cardiac Myosin Inhibitors for Managing Obstructive Hypertrophic Cardiomyopathy: JACC: Heart Failure State-of-the-Art Review.

  2023cited by this paper
• The biochemically defined super relaxed state of myosin—A paradox

  2023cited by this paper
• Mavacamten: a first-in-class myosin inhibitor for obstructive hypertrophic cardiomyopathy

  2023cited by this paper
• Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial.

  2023influential reference
• Phase 2 Study of Aficamten in Patients With Obstructive Hypertrophic Cardiomyopathy.

  2023cited by this paper
• Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.

  2022cited by this paper
• Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy.

  2022cited by this paper
• Cardiac myosin super relaxation (SRX): a perspective on fundamental biology, human disease and therapeutics

  2021cited by this paper
• Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes.

  2020cited by this paper
• Mavacamten Favorably Impacts Cardiac Structure in Obstructive Hypertrophic Cardiomyopathy: EXPLORER-HCM CMR Substudy Analysis.

  2020cited by this paper
• Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial.

  2020cited by this paper
• Evaluation of Mavacamten in Symptomatic Patients With Nonobstructive Hypertrophic Cardiomyopathy.

  2020cited by this paper
• 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

  2020cited by this paper
• Letter by Maron et al Regarding Article, "Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights From the Sarcomeric Human Cardiomyopathy Registry (SHaRe)".

  2019cited by this paper
• Mavacamten Treatment for Obstructive Hypertrophic Cardiomyopathy

  2019cited by this paper
• Mavacamten

  2018influential reference
• Clinical Course and Quality of Life in High-Risk Patients With Hypertrophic Cardiomyopathy and Implantable Cardioverter-Defibrillators

  2018cited by this paper
• Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy

  2018cited by this paper
• Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers

  2018cited by this paper
• Clinical outcomes associated with sarcomere mutations in hypertrophic cardiomyopathy: a meta-analysis on 7675 individuals

  2017cited by this paper
• A small-molecule inhibitor of sarcomere contractility suppresses hypertrophic cardiomyopathy in mice

  2016cited by this paper
• The myosin mesa and a possible unifying hypothesis for the molecular basis of human hypertrophic cardiomyopathy.

  2015cited by this paper
• Genetic advances in sarcomeric cardiomyopathies: state of the art

  2015cited by this paper
• 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).

  2014cited by this paper
• Hypertrophic cardiomyopathy

  2013cited by this paper
• Genetics and Clinical Destiny: Improving Care in Hypertrophic Cardiomyopathy

  2010cited by this paper
• Assessment of Diastolic Function With Doppler Tissue Imaging to Predict Genotype in Preclinical Hypertrophic Cardiomyopathy

  2002cited by this paper
• Hypertrophic cardiomyopathy.

  1994cited by this paper

• No citing papers are available for this paper.