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Updated: Jul 12, 2025

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
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Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

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The Efficacy of Cardiac Myosin Inhibitors Versus Placebo in Patients With Symptomatic Hypertrophic Cardiomyopathy: A

Mohammad Yassen1, Khalid Changal2, Joshua Busken3

  • 1Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio.

The American Journal of Cardiology
|October 26, 2023
PubMed

Insights

Cardiac myosin inhibitors significantly improve symptoms and reduce outflow tract gradients in hypertrophic cardiomyopathy (HCM). While effective, these drugs may decrease left ventricular ejection fraction (LVEF), requiring further investigation.

Area of Science:

  • Cardiology
  • Pharmacology
  • Clinical Trials

Background:

  • Hypertrophic cardiomyopathy (HCM) is a significant cause of morbidity.
  • Current treatments for symptomatic HCM have limitations.
  • Cardiac myosin inhibitors represent a novel therapeutic class.

Approach:

  • A meta-analysis of 4 randomized controlled trials (RCTs) involving 463 patients was conducted.
  • The study assessed the impact of cardiac myosin inhibitors (mavacamten, aficamten) on left ventricular outflow tract (LVOT) gradients and functional capacity.
  • Co-primary outcomes included changes in resting and Valsalva LVOT gradients and New York Heart Association (NYHA) class improvement.

Key Points:

  • Cardiac myosin inhibitors significantly reduced resting (MD -62.48%) and Valsalva (MD -54.21%) LVOT gradients compared to placebo.
  • A significantly higher proportion of patients achieved NYHA class improvement ≥1 with cardiac myosin inhibitors (OR 3.43).
  • Secondary outcomes showed significant reductions in NT-proBNP (MD -69.41%) and troponin I (MD -44.19%), but also a reduction in LVEF (MD -6.31%).

Conclusions:

  • Cardiac myosin inhibitors demonstrate significant clinical and symptomatic benefits for patients with symptomatic HCM.
  • The observed reduction in LVEF warrants careful consideration and monitoring.
  • Larger-scale, long-term trials are necessary to fully elucidate the risk-benefit profile and confirm these findings.

Keywords:
aficamtencardiomyopathymavacamtenmyosin inhibitors

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