Taking A Deep Dive into Precision Medicine for Obstructive Hypertrophic Cardiomyopathy - Episode 1

Role of Small-Molecule Myosin Inhibitors in oHCM Treatment

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James L. Januzzi, MD, provides insight on the pathophysiology of obstructive hypertrophic cardiomyopathy (oHCM) and comments on small-molecule myosin inhibitors as an emerging therapeutic option.

This is a video synopsis of a discussion involving James L. Januzzi, MD, discussing the emergence of new treatments for obstructive hypertrophic cardiomyopathy (HCM). HCM, affecting approximately one in 500 individuals, is a common disorder of the heart muscle. Over the past few decades, there has been an increased understanding of its causes, leading to the development of cardiac myosin inhibitors.

Mutations in the sarcomere, the contractile apparatus of the muscle, are common in individuals with HCM, contributing to myocardial hypercontractility. These mutations result in excessive availability of myosin heads, increasing the strength of contraction but also leading to difficulties in relaxation, tissue injury, and fibrosis. Consequently, abnormal contractility may cause diastolic impairments and left ventricular outflow tract obstruction, potentially leading to arrhythmias and sudden death.

To address this hypercontractile state, cardiac myosin inhibitors were developed to block the excessive availability of myosin heads. By inhibiting myosin ATPase via selective binding, these drugs reduce the number of myosin heads available for engagement, ultimately restoring a normal or close-to-normal contractile state. This intervention aims to reduce left ventricular outflow tract obstruction, wall stress, and improve relaxation. Long-term benefits may include a reduction in myocardial injury and fibrosis, with an overall improvement in prognosis.

This class of medication, known as small molecule myosin inhibitor, represents a promising example of precision care in cardiology, offering hope for improved outcomes for individuals with obstructive HCM.

Video synopsis is AI-generated and reviewed by HCPLive® editorial staff.