Abstract

Background: Mavacamten is the first commercially available myosin inhibitor shown to improve cardiac hemodynamics and functional status in patients with obstructive hypertrophic cardiomyopathy (HCM). Mavacamten may be considered in patients who have not responded to first-line medical therapies and are being considered for septal-reduction therapy (SRT). Research Question and Aims: The efficacy of Mavacamten relative to SRT remains unknown. This study compares Mavacamten and SRT with alcohol-septal ablation (ASA) in modifying cardiac hemodynamics and functional status in patients with obstructive HCM. Methods: Patients of the Bluhm Cardiovascular Institute (BCVI) of Northwestern University in Chicago, IL, managed for HCM from January 2008 to May 2024 were sampled. Patients who had undergone ASA (N = 41) or initiated treatment with Mavacamten (N = 40) were identified. Clinical and echocardiographic data were collected and reported for individuals at baseline, at 16 weeks, and after 24 weeks following ASA or the initiation of Mavacamten, respectively. Results: Baseline demographics were similar for both groups except for age and tobacco use history (Table 1). Patients who underwent ASA were older compared to counterparts treated with Mavacamten (75 v 61, p < 0.001). Both ASA and Mavacamten were associated with a greater than 70% reduction in valsalva left-ventricular outflow tract (LVOT) gradient and mitral regurgitation. The maximal effect of ASA on LVOT gradient was observed at 16 weeks, whereas the maximal effect of Mavacamten was not appreciated until after 24 weeks. At baseline, the average left-ventricular ejection fraction (LVEF) was hyperdynamic in patients receiving Mavacamten relative to those treated with ASA. After 24 weeks, the average LVEF of patients treated with Mavacamten was reduced yet remained in the normal range. Patients who underwent ASA had a poorer NYHA functional class at baseline compared to those prescribed Mavacamten (~2.5 v 2.1, p < 0.001); however, each therapy significantly improved functional capacity, and average NYHA scores were comparable after 24 weeks (1.5 v 1.3, not significant). Conclusion: In patients with obstructive HCM, ASA and Mavacamten yield significant and comparable improvements in hemodynamics, mitral regurgitation, and functional status with lower, but normal, ejection fraction among patients on Mavacamten at the end of 24 weeks.