Cardiac myosin inhibitors in the treatment of hypertrophic cardiomyopathy (literature review)

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Abstract

The review provides information on modern drugs – cardiac myosin inhibitors (CMIs), used in the treatment of hypertrophic cardiomyopathy (HCM) and affecting myocardial hypercontractility observed in this disease. A modern understanding of the structure and function of the sarcomere is presented from the perspective of the analysis of the main structural and functional proteins, whose disorders underlie the pathology. Genetic changes and the main pathogenetic mechanisms leading to the development of HCM are discussed. Information on numerous gene mutations of sarcomere proteins and the pathogenetic events caused by them, which in turn lead to a state of myocardial hypercontractility, the development of pathological relaxation and increased energy consumption is presented. The mechanisms of action of ICMs (mavacamten and aficamten) – pharmacokinetics, pharmacodynamics, methods of administration and dosage, and specifics of prescription in different categories of patients – are described. The review presents the results of recent randomized clinical trials on evaluation of the effectiveness, safety and tolerability of the listed drugs. An analysis of data from the PIONEER-HCM, MAVERICK-HCM, EXPLORER-HCM, VALOR-HCM and REDWOOD-HCM trials devoted to the study of the effectiveness and safety of mavacamten and aficamten in patients with HCM is presented. A positive effect of ICM on the severity of left ventricular (LV) outflow tract obstruction, improvement in the functional class of heart failure, and patient well-being were noted. The tolerability of the drugs and the effect on LV systolic function, assessed by ejection fraction values, are described. The results of clinical studies have shown that ICM have a significant effect on reducing the severity of LV outflow tract obstruction, slowing the progression of heart failure and improving the quality of life of patients. Despite the noted advantages, it is necessary to continue further research to assess the safety of ICMs and study their effectiveness outside the main therapy of HCM and among different groups of patients. Mavacamten and aficamten complement the existing arsenal of therapeutic approaches in the management of patients with HCM.

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About the authors

G. A. Ignatenko

M. Gorky Donetsk State Medical University

Email: taradin@inbox.ru
ORCID iD: 0000-0003-3611-1186
Russian Federation, Donetsk

G. G. Taradin

M. Gorky Donetsk State Medical University

Author for correspondence.
Email: taradin@inbox.ru
ORCID iD: 0000-0003-3984-8482

Can. Sci. (Med.), Head of the Department of Therapy n.a. Professor A.I. Dyadyk

Russian Federation, Donetsk

L. V. Kononenko

M. Gorky Donetsk State Medical University

Email: taradin@inbox.ru
ORCID iD: 0009-0005-4560-2632
Russian Federation, Donetsk

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Supplementary files

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2. Fig. 1. Molecular structure of sarcomere with indication of the main contractile and regulatory proteins and frequency of gene mutations detection in patients with hypertrophic cardiomyopathy (N.T. Vatutin et al. [18])

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3. Fig. 2. Mechanism of ICM action

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4. Fig. 3. Pathogenetic impact points of ICM and pathophysiologic and clinical events caused by them

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