Abstract 4145506: Cardiac Myosin Inhibitors Improve Hemodynamics and Symptom Burden in Symptomatic Hypertrophic Cardiomyopathy: An Updated Meta-Analysis

Introduction: Cardiac myosin inhibitors (CMI), including mavacamten and more recently aficamten, are emerging therapies in the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) that facilitate ventricular relaxation by reducing myosin-actin crossbridge formations. We performed an updated, contemporary pooled analysis to study to study the clinical efficacy of CMI in patients with HCM. Methods: We searched PubMed database from its inception to May 25, 2024 using the search terms “mavacamten” or “aficamten” and “hypertrophic cardiomyopathy” for literature search. Random effects model with Mantel–Haenszel method was used to pool data. The following outcomes were analyzed: change in peak VO 2 , valsalva LVOT gradient, Kansas City Cardiomyopathy questionnaire (KCCQ) clinical summary scale (CSS), improvement in NYHA functional class (FC), and LVEF decline. Results: We identified five randomized controlled studies which compared CMI with placebo. Pooled analysis included 741 patients of whom 389 received either mavacamten or aficamten and 352 received placebo. Median follow up time was 24 weeks. When compared to placebo, CMI decreased valsalva LVOT gradient (mean difference -41.08 mmHg, 95% CI -48.41 – -33.75 mmHg, p<0.001), improved KCCQ CSS (mean difference 6.83, 95% CI 3.59-10.06, p<0.001), increased peak VO 2 (mean difference 1.19 mL/kg/min, 95% CI 0.21-2.17 mL/kg/min, p=0.02). Patients receiving CMIs were more likely to experience ≥1 NYHA FC improvement (RR 2.18, 95% CI 1.67-2.84, p<0.001) (Figure 1). CMIs were associated with a temporary decline in LVEF (RR 3.30, 95% CI 1.25-8.73, p=0.02). However, LVEF normalized in all patients with temporary decline by the end of follow-up. Conclusion: This is the largest pooled analysis assessing the efficacy of CMI in patients with HCM. Evidence from this analysis suggests that CMIs improved hemodynamic measures and symptom burden in patients with HCM.