Innovative pharmacological approaches to hypertrophic cardiomyopathy: The emerging role of Aficamten

Abstract

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by left ventricular hypertrophy (LVH), which can lead to left ventricular outflow tract (LVOT) obstruction. Traditional treatments often provide limited symptom relief and may not adequately reduce the LVOT gradient. Myosin inhibitors, such as Aficamten , offer a new therapeutic approach by modulating myocardial contractility and improving symptoms. This paper evaluated the efficacy and safety of Aficamten in patients with symptomatic HCM. We conducted a comprehensive literature review of studies evaluating Aficamten for symptomatic HCM, including clinical trials and observational studies up to July 2024. Data on efficacy, safety, and patient outcomes were extracted and analyzed from a total of 10 studies involving 1,067 patients. Aficamten demonstrated substantial efficacy in reducing the LVOT gradient, with dose-dependent reductions ranging from 3.6 % to 48.6 %. It also improved symptoms, with 82.3 % of patients experiencing reduced left ventricular ejection fraction (LVEF) and notable improvements in New York Heart Association (NYHA) functional class. Exercise capacity was enhanced, as indicated by increased peak oxygen uptake. Safety profiles were generally favorable, though some serious adverse events, such as atrial fibrillation and cardiac dysfunction, were reported. Aficamten was well-tolerated overall, with manageable dose-dependent adverse effects. Aficamten represents a promising advance in the management of symptomatic HCM, offering significant reductions in LVOT gradient and improvement in symptoms and exercise capacity. Its safety profile is generally favorable, although ongoing monitoring is necessary to manage potential adverse effects. Future research should focus on long-term outcomes, comparative effectiveness, and real-world evidence.