Incidence of Ventricular Arrhythmias and Sudden Cardiac Death with Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

<b>Background:</b> Hypertrophic cardiomyopathy (HCM) is associated with an elevated risk of ventricular arrhythmias and sudden cardiac death (SCD) despite contemporary therapy. Cardiac myosin inhibitors directly target sarcomeric hypercontractility and have demonstrated consistent symptomatic, hemodynamic, and structural benefits in randomized controlled trials (RCTs). However, their effects on malignant ventricular arrhythmias and SCD remain uncertain. This meta-analysis aimed to evaluate the incidence of ventricular arrhythmias and SCD with cardiac myosin inhibitor therapy in HCM. <b>Methods:</b> We conducted a meta-analysis of RCTs evaluating mavacamten or aficamten in patients with HCM. PubMed was systematically searched through September 2025. Eligible trials randomized myosin inhibitors versus control and reported ventricular tachycardia (VT), ventricular fibrillation (VF), or SCD. <b>Results:</b> Seven RCTs including 1519 patients (779 myosin inhibitor; 740 control) were analyzed. Eight composite VT/VF/SCD events (1.03%) occurred in the treatment group compared with twelve (1.62%) in controls. Time-standardized incidence rates were 1.48 versus 2.36 per 100 patient-years, respectively. The pooled RR was 0.69 (95% CI 0.27-1.74; I² = 0%), indicating no statistically significant difference. Sensitivity analyses yielded concordant results despite low event counts. <b>Conclusions:</b> No statistically significant increase in ventricular arrhythmia or SCD risk was observed. However, limited events and short follow-up preclude firm conclusions regarding the arrhythmic safety of myosin inhibitors.