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Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy

  • Myocardial Disease (A Abbate and G Sinagra, Section Editors)
  • Published:
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Abstract

Purpose of review

Pharmacological treatment options for hypertrophic cardiomyopathy (HCM) are currently limited and comprise non-disease specific therapies such as β-blockers, non-dihydropyridine calcium channel blockers, and disopyramide. These agents that offer a variable degree of symptomatic relief, often suboptimal, are often limited by side-effects and fail to address the key molecular abnormalities of the disease.

Recent findings

Mavacamten is a novel, first-in-class, allosteric inhibitor of cardiac myosin ATPase, which reduces actin-myosin cross-bridge formation, thereby reducing myocardial contractility and improving myocardial energetic consumption in experimental HCM models. Following a successful Phase 2 study, the recently published phase III, placebo-controlled, randomized EXPLORER-HCM trial demonstrated the efficacy and safety of mavacamten in reducing left ventricular outflow tract obstruction and ameliorating exercise capacity, New York Heart Association functional class and health status in patients with obstructive HCM.

Summary

Mavacamten represents the first agent specifically developed for HCM successfully tested in a Phase III trial, to be registered soon for clinical use, representing a radical change of paradigm in the pharmacological treatment of HCM.

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Authors and Affiliations

  1. Cardiomyopathy Unit, Careggi University Hospital, Largo Brambilla 3, 50134, Florence, Italy

    Mattia Zampieri, Alessia Argirò, Alberto Marchi, Martina Berteotti, Mattia Targetti, Alessandra Fornaro, Alessia Tomberli & Iacopo Olivotto

  2. Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Mattia Targetti, Alessandra Fornaro, Niccolò Marchionni & Iacopo Olivotto

  3. Division of General Cardiology, Careggi University Hospital, Florence, Italy

    Mattia Targetti, Alessandra Fornaro & Iacopo Olivotto

  4. Division of Cardiac Surgery, Careggi University Hospital, Florence, Italy

    Pierluigi Stefàno

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  1. Mattia Zampieri
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  2. Alessia Argirò
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Correspondence to Mattia Zampieri.

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Conflict of interest

Dr. Olivotto is on the advisory board of EXPLORER-HCM trial and has received research funding and speakers’ fees from Myokardia.

The other authors declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Zampieri, M., Argirò, A., Marchi, A. et al. Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy. Curr Cardiol Rep 23, 79 (2021). https://doi.org/10.1007/s11886-021-01508-0

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