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Hypertrophic Cardiomyopathy Center, Heart Vascular Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA

‡Co-first authors. Authors contributed equally

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Adel Hajj Ali‡§¶

https://orcid.org/0000-0002-7166-1071

Hypertrophic Cardiomyopathy Center, Heart Vascular Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA

Department of Internal Medicine, Indiana University, Indianapolis, IN 46202, USA

‡Co-first authors. Authors contributed equally

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Milind Y Desai

*Author for correspondence: Tel.: +1 216 445 5250;

E-mail Address: desaim2@ccf.org

https://orcid.org/0000-0003-0010-9797

Hypertrophic Cardiomyopathy Center, Heart Vascular Thoracic Institute, Cleveland Clinic, Cleveland, OH 44195, USA

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Published Online:7 Nov 2023https://doi.org/10.2217/fca-2023-0056

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Abstract

Hypertrophic cardiomyopathy (HCM) is a phenotypically heterogeneous disease with a genetic basis and variable penetrance. The hallmarks of HCM include dynamic left ventricular outflow tract obstruction, typically caused by asymmetric septal hypertrophy. However, abnormal papillary muscle placement, abnormal mitral valve and subvalvular apparatus and apical hypertrophic forms have also been described. Typical medical treatment has been stagnant for decades, although there have been significant advances in surgical treatment of patients with obstructive HCM. Herein, we describe a new class of drugs targeting the specific pathophysiology of HCM.

Plain language summary

Hypertrophic obstructive cardiomyopathy is a genetic condition that leads to increased heart muscle size. This increase in heart muscle can cause blockage of appropriate blood flow out of the heart. In such cases, current medications like β-blockers, calcium channel blockers and disopyramide can be used, but do not directly target the problem of increased heart muscle size. A new medication class, cardiac myosin inhibitors, decrease the squeezing power of the increased heart muscle to allow for more appropriate blood flow out of the heart. So far, trials have been conducted with mavacamten, with upcoming trials of aficamten (another novel cardiac myosin inhibitor). Recent trials with mavacamten have shown that this medication class has been beneficial for patients in whom other medications have failed. Some trials have also shown that by taking cardiac myosin inhibitors, patients have been able to avoid or delay surgery to correct this problem. Reassuringly, short-term data for this class of medications are positive. However, given that these medications are new, continued monitoring and research is being done to evaluate their long-term effect.

Tweetable abstract

Hypertrophic cardiomyopathy (HCM) is a phenotypically heterogeneous disease with a genetic basis and variable penetrance. We describe a new class of drugs targeting the specific pathophysiology of HCM @DesaiMilindY.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 19, No. 13

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Received 25 April 2023

Accepted 13 September 2023

Published online 7 November 2023

Published in print October 2023

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Acknowledgments

M Desai acknowledges the Haslam Family endowed chair in cardiovascular medicine. The authors are solely responsible for drafting and editing this paper.

Financial disclosure

No funding was used to support this work. The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

M Desai is a consultant for Bristol Myers Squibb, Cytokinetics and Medtronic. The authors have no other competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

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Obstructive hypertrophic cardiomyopathy: a review of new therapies

Abstract

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References