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

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.

Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities

“…According to the 2018 global hypertrophic cardiomyopathy burden statistics, HCM affected 6.3 billion people or 88% of the world's population ( 178 ). Auspiciously, HCM treatment has progressed from limited palliative pharmacotherapy and occasional high-risk surgery to more definitive screening tools and highly efficient interventional therapies, resulting in a 0.5% annual reduction in morbidity and mortality ( 180 – 183 ).…”

Multilevel modelling for decision support in hypertrophic cardiomyopathy in the SMASH-HCM project

“…Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Its estimated clinical prevalence approaches 1:200 in the general population [1]. It is estimated that 15-20 million people suffer from it worldwide [2].…”

“…Unlike more common heart diseases, HCM is not only a disease of the old, but people of all ages can be affected by it [3]. HCM can cause progressive dyspnea, angina, heart failure (HF) with or without left ventricular (LV) systolic dysfunction, atrial fibrillation (AF), and -the most feared consequence -sudden cardiac death (SCD) [1]. More than one-third of the sudden deaths in competitive athletes are accounted for by HCM, which is more than for any other single disease [2].…”