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Updated: Jul 12, 2025

Evaluation of Cardiac Contractility Modulation Therapy in 2D Human Stem Cell-Derived Cardiomyocytes
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Aficamten-A Second in Class Cardiac Myosin Inhibitor for Hypertrophic Cardiomyopathy

Jay Patel1, Andy Wang, Sihari S Naidu

  • 1From the Department of Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY.

Cardiology in Review
|October 26, 2023
PubMed

Insights

Hypertrophic cardiomyopathy (HCM) involves heart muscle thickening, often causing outflow obstruction. Novel cardiac myosin inhibitors show promise for treating obstructive HCM, with one approved and another in trials.

Area of Science:

  • Cardiology
  • Genetics
  • Pharmacology

Background:

  • Hypertrophic cardiomyopathy (HCM) is an under-recognized genetic heart disease characterized by left ventricular thickening, reduced compliance, and myocardial fibrosis.
  • A significant majority of HCM patients develop dynamic left ventricular outflow tract obstruction.
  • Medical management has evolved from negative inotropic agents to targeted therapies.

Purpose of the Study:

  • To review the evolving medical management of obstructive hypertrophic cardiomyopathy (oHCM).
  • To discuss novel cardiac myosin inhibitors as a therapeutic class for oHCM.
  • To focus on aficamten, a second-generation cardiac myosin inhibitor in Phase III trials.

Main Methods:

  • Review of existing literature and clinical trial data on HCM management.
  • Analysis of the mechanism of action for cardiac myosin inhibitors.
  • Evaluation of clinical outcomes associated with mavacamten and aficamten.

Main Results:

  • Mavacamten, a cardiac myosin inhibitor, is FDA-approved for symptomatic obstructive HCM.
  • Cardiac myosin inhibitors target cardiac contractility at the sarcomere level.
  • Aficamten is currently undergoing Phase III clinical evaluation.

Conclusions:

  • Cardiac myosin inhibitors represent a significant advancement in oHCM treatment.
  • Aficamten shows potential as a novel therapy for oHCM patients.
  • Continued research and clinical trials are crucial for understanding the full potential of these therapies.

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