Hypertrophic cardiomyopathy (HCM)
Hypertrophic cardiomyopathy (HCM) is a disease characterized by thickening and stiffening of the left heart ventricle that results in increased contractility and impaired relaxation.
HCM may result in exertional dyspnea, fatigue, chest pain, syncope/presyncope and limited exercise capacity.
HCM is the most common inherited cardiovascular disorder, and its prevalence is likely underestimated due to the current limitations of early screening. HCM is estimated to affect at least 1 in 200 people, with obstructive (either at rest or with provocation) HCM accounting for approximately 2/3 of cases and non-obstructive HCM for approximately 1/3 of cases in clinical practice. It is a leading cause of death in young adults and athletes. HCM-related fatal and disabling events are most often attributable to sudden cardiac death, heart failure, and embolic stroke.Sudden cardiac death is the common cause of death in young HCM patients between 10 to 35 years old, while heart failure and stroke due to HCM-related atrial fillbrillation represent the common cause of death in middle-aged and elderly patients, respectively. The annual mortality rate for HCM patients in hospitals is 2% to 4%.
At present, there are no disease-specific drugs approved for HCM in China. Patients with symptomatic oHCM are generally offered pharmacotherapy with non-HCM-specific agents such as 𝛽-blockers, verapamil, diltiazem and disopyramide based on clinicians’ experience; however, these medications do not target the underlying pathology (i.e., hypercontractility) and provide only symptomatic relief with variable effectiveness and risks of significant adverse effects. For oHCM patients with a left ventricular outflow tract pressure gradient (LVOT-G) of ≥50 mm Hg either at rest or with provocation who also have severe symptoms refractory to medical therapy, septal reduction therapies (such as surgical myectomy or percutaneous alcohol septal ablation) can be effective, but these invasive procedures requires an expertise that is not widely accessible in China and carry risks of complications including death.
Aficamten is an investigational, selective, small-molecule cardiac myosin inhibitor with optimized therapeutic index and pharmacokinetic properties that may contribute to its best-in-class potential. Aficamten was designed to reduce the number of active actin-myosin cross-bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force-producing state and stabilizing it in a weak actin-binding conformation. The development program for aficamten aims to assess its potential as a treatment for improving exercise capacity and relieving symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten has received a Breakthrough Therapy Designation for the treatment of symptomatic oHCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China.
The Joint Committee of Cardiomyopathy Specialty Alliance, National Center for Cardiovascular Diseases/Cardiovascular Precision Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care. 2023 Guideline for Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. Chinese Circulation Journal, 2023, 38: 1.
Chinese Heart Failure Association of Chinese Medical Doctor Association, National Heart Failure Committee, Editorial Board of Chinese Journal of Heart Failure and Cardiomyopathy. 2022 Chinese guideline on hypertrophic cardiomyopathy. Chin J Heart Fail & Cardiomyopathy, 2022, 6(2): 80-103
Heart failure committee of Chinese medical association, Editorial board of the Chinese journal of heart failure and cardiomyopathy. 2017 Guidelines of hypertrophic cardiomyopathy management in China. Chin J Heart Fail & Cardiomyopathy. 2017; 1(2): 65-86.
Ommen SR et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. Circulation. 2020 Dec 22;142(25): e533-e557.