New Concepts and Therapies of Hypertrophic Cardiomyopathy

Abstract

Heart failure (HF) and sudden cardiac death are associated with hypertrophic cardiomyopathy (HCM), a genetic disorder characterized by left ventricular hypertrophy (LVH) and myocardial disarray. The treatment options for HCM remain limited despite advances in understanding its pathophysiology. The study mostly included synthesizing evidence regarding how current therapies affect clinical and pathophysiological features of patients suffering from HCM and also to provide a comprehensive overview to explore emerging therapeutic strategies for HCM. Our first discussion focuses on the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Molecular genetics and their potential applications to the diagnosis, risk stratification, and treatment of HCM are discussed. Gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten are among the emerging therapies that promise to modulate HCM’s underlying molecular mechanisms. Aficamten and mavacamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract (LVOT) obstruction and improving symptoms. The mechanisms of action of these drugs, clinical trial outcomes, and potential implications for HCM management are discussed.
In addition, we also studied papers discussing the role of precision medicine in HCM management, including exercise prescription as part of an individualized treatment plan. To address the complex needs of patients with HCM, we emphasize the importance of multidisciplinary care and patient-centered approaches. Also, the purpose of this review is to promote additional research and collaboration in the field of HCM, including the development of novel and more effective therapeutic strategies, including cardiac myosin modulators, so that patients with sarcomeric HCM will have a better quality of life and better outcomes. Using PubMed, Web of Science, and Cochrane, we identified 41 studies and did a systematic review and meta-analysis of them. There are three types of treatments: pharmacological, invasive, and physical. There was no effect of pharmacological agents on VO2max-measured functional capacity. Invasive septal reductions increased VO2max. There were no contraindications reported and functional capacity increased mostly in structured exercise programs. Compared with those without obstruction of the LVOT at rest, patients with LVOT obstruction at rest had a greater increase in VO2max. The peak LVOT gradient was reduced with all three treatment options, but invasive therapies reduced it the most. The left ventricular ejection fraction (LVEF%) was reduced by pharmacological and invasive methods. The effects of physical exercise were not observed. Invasive procedures significantly improved symptomatic status compared to the three options. In obstructive patients with reduced VO2max, symptoms, and LVOT gradient, invasive septal reduction therapies may be considered. Exercise has emerged as a safe and effective coadjuvant therapy for functional capacity. However, pharmacological agents do not improve functional capacity, only reported The New York Heart Association (NYHA) class.