Introduction
One in 500 members of the general public has hypertrophic cardiomyopathy (HCM), a widespread inherited cardiovascular illness that is the leading cause of sudden mortality for young people, particularly athletes, and an annual mortality of 1% overall. Nonetheless, it is thought to be more common now according to modern diagnostic methods (such as genetic testing and imaging).1–3 HCM is histologically characterised by myocyte enlargement, disorganisation and myocardial fibrosis.4 While a number of therapies have proven safe and beneficial in managing HCM, no medication has been proven to alter the disease’s course or reduce the maximum wall thickness.3 Myosin inhibitors, however, have the ability to influence pathogenesis and alleviate symptoms related to HCM by modifying the contractile mechanics of the cardiomyocyte.5
Cardiac hypertrophy is caused by increased cardiac stress and afterload; the pathogenesis of the condition, however, is linked to myocardial remodelling.6 Patients with HCM are at risk for atrial fibrillation, heart failure and stroke.7 The most important predictor of heart failure in patients with HCM is left ventricular outflow tract (LVOT) obstruction, which is brought on by asymmetric hypertrophy of the cardiac septum.7 8 The various mechanisms that cause the left ventricular outflow obstruction include actin-myosin cross-bridging, which causes cardiac hypercontractility, prolonged mitral valve leaflets and protrusion of the hypertrophic ventricular septum into the LVOT.9 A well-defined management approach is required due to the substantial morbidity and mortality associated with this illness. In contrast to other areas of cardiology, the care of patients with HCM is still inadequately addressed, despite modern therapies and techniques.10 The different treatment options include beta-blockers (BB), calcium channel blockers (CCB), antiarrhythmics, ACE inhibitors/angiotensin receptor blockers, diuretics and oral anticoagulants, and the surgical options are myomectomy or septal ablation.11 Many patients experience insufficient relief of heart failure symptoms due to unsatisfactory gradient reduction or off-target adverse medication effects caused by the present pharmacological therapy.8 The sarcomere proteins are mutated genetically to produce structural abnormalities in cardiac myocytes and myofibrils, which causes aberrant force generation and electrical activity in the heart.8 Cardiac myosin inhibitors have lately surfaced as a potentially ground-breaking therapeutic option intended to improve heart failure symptoms in patients with obstructive HCM. They do this by reducing LVOT gradients and heart contractility.12–15 Because these medications, mavacamten and aficamten, inhibit the formation of actin-myosin cross-bridges, they improve symptoms, quality of life, LVOT gradients and biomarkers, suggesting the potential for sarcomere-targeted therapy in the treatment of obstructive HCM.8 16
The goal of this systematic review and meta-analysis is to emphasise the function of cardiac myosin inhibitors in the management of HCM. These medications are undergoing several clinical studies, and by compiling the data into one comprehensive analysis, we want to provide a certain assessment of their effectiveness in treating HCM and further update the evidence. Future studies on mavacamten and aficamten and their roles in HCM will benefit from the direction and guidance this review offers.