Abstract 4145387: Cardiac Myosin inhibitors in patients with Symptomatic Hypertrophic Cardiomyopathy: An updated Systematic review and Meta-analysis of randomized trials.

Background: Current therapeutic options for relieving symptoms in hypertrophic cardiomyopathy (HCM) predominantly involve invasive interventions. In contrast, cardiac myosin inhibitors (CMI), such as aficamten and mavacamten, represent a promising pharmacological alternative to alleviate left ventricular outflow tract obstruction. However, there is limited data regarding the efficacy of this therapy. Methods: We searched Pubmed, Cochrane, and Embase databases for randomized controlled trials (RCT) comparing CMI with placebo among symptomatic HCM patients. Key outcomes assessed included: (1) improvement in at least one New York Heart Association (NYHA) functional class, (2) enhancement in the Kansas City Cardiomyopathy Questionnaire - Clinical Summary Score (KCCQ-CSS), and (3) change in N-terminal pro b-type Natriuretic Peptide (NT-proBNP) levels. Statistical analyses were performed using R Studio 4.3.2. Results: Six RCTs were included, involving 826 patients, of whom 443 (53.6%) were assigned to the CMI group. The majority of participants were male (57%), with a mean age of 57.9 years and a mean follow-up duration of 21 weeks. In the pooled analysis, CMI was associated with a significant improvement of at least one NYHA functional class (RR 2.21; 95% CI 1.75, 2.80; p<0.001; Fig 1) and KCCQ-CSS (MD 7.18; 95% CI 4.64, 9.72; p<0.01; Fig 2A). Moreover, CMI also reduced NT-proBNP levels (MR 0.22; 95% CI 0.17, 0.29; p<0.01, Fig 2B). Conclusion: This meta-analysis highlights the potential of CMI as a promising pharmacological therapy for managing symptomatic HCM, with significant improvements in NYHA functional class, quality of life and NT-proBNP levels.