A systematic review of present and future pharmaco‐structural therapies for hypertrophic cardiomyopathy

• Type of Material: Article
• Authors: Mariem Sawan, Emory University; Sindhu Prabakaran, Emory University; Melroy D'souza, Emory University; Omid Behbahani-Nejad, Emory University; Matthew Evan Gold, Emory University; Byron Robinson Williams, Emory University; Ozlem Bilen, Emory University
• Language: English
• Date: 2024-01-03
• Publisher: John Wiley & Sons, Inc.​
• Publication Version: Final Published Version
• Copyright Statement: © 2024 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://onlinelibrary.wiley.com/doi/10.1002/clc.24207
• Title of Journal or Parent Work: Clinical Cardiology
• Volume: 47
• Issue: 1
• Keywords: sudden death; obstructive hypertrophic cardiomyopathy; hypertrophic cardiomyopathy; cardiomyopathy; left ventricular outflow tract obstruction; non‐obstructive hypertrophic cardiomyopathy
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence‐based, and targeted disease‐modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first‐in‐class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.