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Novel Myosin-Based Therapies in Hypertrophic Cardiomyopathy

  • Heart Failure (W Tang, Section Editor)
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Current Treatment Options in Cardiovascular Medicine Aims and scope Submit manuscript

Abstract

Purpose of review

Hypertrophic cardiomyopathy is the most common genetic disease of myocardium and is recognized to have substantial clinical impact including sudden cardiac death, arrhythmias, and heart failure. Historically medical therapies have been used in hypertrophic cardiomyopathy (HCM) with limited prospective randomized data to support their effectiveness. In this review, we discuss a novel class of drug that inhibits myosin (myo-blocker) which was developed to precisely target the mechanism of HCM in detail.

Recent findings

We discuss and contextualize the clinical trial results for mavacamten, positioning it in the therapeutic landscape as well as presenting future questions and further developments to be made in this area.

Summary

Many sarcomeric mutations driving hypertrophic cardiomyopathy seem to have a primary effect of causing hypercontractility which may drive many secondary problems such as structural remodeling, arrhythmias, and further contractile deficits. Myo-blockers such as the first-in-class mavacamten are small molecules that specifically target myosin to decrease contractility and have been developed to precisely ameliorate the hypercontractile mechanism of HCM. Mavacamten has been shown in large, randomized, double-blind clinical trials to have benefit generally in improving symptoms, decreasing LV outflow tract obstruction, and promoting beneficial remodeling in HCM with obstructive physiology.

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Funding

This work was supported by following sources of funding: P.D. Soros Fellowship for New Americans, National Institute of Health/National Institute of General Medical Sciences Medical Scientist Training Program Grant (T32GM007205), and American Heart Association Predoctoral Fellowship to LRS.

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  1. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

    Lorenzo R. Sewanan PhD & Daniel L. Jacoby MD

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Correspondence to Daniel L. Jacoby MD.

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Lorenzo R. Sewanan declares that he has no conflict of interest.

Daniel L. Jacoby has received personal fees from MyoKardia/BMS and Cytokinetics. Daniel L. Jacoby has a financial stake in Propria, LLC, and is a partial holder of a patent for the use of engineered heart tissue.

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Sewanan, L.R., Jacoby, D.L. Novel Myosin-Based Therapies in Hypertrophic Cardiomyopathy. Curr Treat Options Cardio Med 23, 46 (2021). https://doi.org/10.1007/s11936-021-00921-6

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