Background
Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by dynamic left ventricular outflow tract (LVOT) obstruction leading to heart failure symptoms and reduced quality of life. Septal reduction therapies (SRT) such as transcoronary ablation of septal hypertrophy (TASH) represent established interventional strategies, whereas the cardiac myosin inhibitor Mavacamten has recently emerged as a targeted pharmacological option. However, direct real-world comparisons between both approaches remain limited.
Methods
We conducted a single-center, non-randomized, observational and comparative cohort study using longitudinal collected registry data to evaluate outcomes in symptomatic (NYHA class II–III) adults with obstructive HCM treated either with TASH (n = 113) or Mavacamten (n = 99).
Baseline demographic, clinical, genetic, and echocardiographic parameters were collected. Functional, laboratory, and echocardiographic outcomes were evaluated at 6- and 12-month follow-up. The composite endpoint of major adverse cardiac events (MACE) included cardiovascular death, heart failure hospitalization, new SRT, heart transplantation, LVAD implantation, atrioventricular block requiring pacemaker, or LVEF decrease to < 40%.
Results
Baseline characteristics were balanced between groups (mean age 59 ± 13 years, 54 % male, 52 % NYHA III). Genetic testing was available in 41 %, revealing pathogenic variants in 47 % (predominantly MYBPC3 and MYH7). Both therapies significantly reduced LVOT gradients over time (p < 0.001 for both; Friedman test). The magnitude of gradient reduction from baseline to 12 months was greater with Mavacamten (ΔLVOT −74 ± 54 mmHg) than with TASH (ΔLVOT −64 ± 56 mmHg; p = 0.418; Welch t-test), supported by a non-significant group × time interaction (p = 0.677). NT-proBNP levels declined in both groups (p < 0.001), with a more pronounced and sustained decrease under Mavacamten (median Δ −1080 pg/mL vs −570 pg/mL; p < 0.001). NYHA functional class improved similarly in both cohorts: the proportion of patients in NYHA II increased from 45 % to > 80 % at 12 months (p < 0.001). During 12-month follow-up, the cumulative incidence of MACE was significantly lower with Mavacamten compared with TASH (log-rank p = 0.003). Event-free survival at one year was 96 % in the Mavacamten group versus 84 % following TASH, mainly driven by more atrioventricular conduction disturbances and procedural complications in the interventional cohort.
Conclusions
Both TASH and Mavacamten substantially improved symptoms, LVOT obstruction, and biomarker profiles in patients with oHCM. While TASH achieved durable mechanical gradient relief, it was associated with higher rates of MACE mainly driven by complete heart block. Mavacamten provided comparable symptomatic improvement, a stronger biomarker response, and favorable short-term safety. These findings support myosin inhibition as an effective non-invasive alternative to SRT and underscore the need for prospective head-to-head trials to refine patient selection and optimize treatment pathways.
