Abstract Body (Do not enter title and authors here): Introduction
Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by asymmetric myocardial hypertrophy, which can obstruct left ventricular outflow. Recently, myosin inhibitors have emerged as a novel therapeutic targeting cardiac muscle hypercontractility.
Objective
To assess the efficacy and safety of myosin inhibitors mavacamten and aficamten in patients with oHCM.
Methods
We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing mavacamten or aficamten to placebo in patients with symptomatic oHCM. Outcomes included improvement in peak oxygen consumption (pVO2) and NYHA function≥1 class (NYHA-FC), change in Kansas City Cardiomyopathy Questionnaire (KCCQ), peak left ventricular outflow tract gradient at rest (rLVOT) and with Valsalva maneuver (vLVOT) and treatment-emergent and serious adverse events. Random effects models generated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I²statistics.
Results
Search identified 5 randomized controlled trials including 767 patients (mavacamten 30.4%, aficamten 22.2%, placebo 47.4%) with mean follow-up of 22 weeks. Compared to placebo, myosin inhibitors were associated with improvement of ≥1 NYHA-FC (RR 2.33; 95%CI 1.92-2.82), rLVOT (MD -38.53; 95%CI [-46.06]-[-30.99]), vLVOT (MD -47.29; 95%CI [-58.03]-[-36.55]), pVO2 (MD 1.66; 95%CI 1.12-2.19), and KCCQ (MD 7.79; 95%CI 5.63-9.94) (Figure1). Other outcomes were similar with drug and placebo.

Conclusion
Cardiac myosin inhibitors are an effective and safe short-term treatment for symptomatic oHCM.