In a propensity-matched single-center registry of 220 adults with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced mean left ventricular outflow tract (LVOT) gradient from 85.7 to 18.4 mmHg at 12 months — a deeper reduction than alcohol septal ablation (ASA), which dropped gradient from 100.3 to 44.2 mmHg. NT-proBNP, a key heart-stress biomarker, fell more sharply with mavacamten at both follow-up points. The composite adverse clinical outcome — including cardiovascular death, hospitalization, and serious arrhythmias — occurred in 12.1% of ASA patients versus just 3.5% on mavacamten (HR 0.19; 95% CI 0.06–0.60).
These findings matter because mavacamten, a first-in-class cardiac myosin inhibitor approved in 2022, has lacked robust head-to-head comparisons against established procedural therapies like ASA. A hazard ratio of 0.19 is a striking signal, suggesting an 81% relative risk reduction in serious short-term events. Third-degree AV block — a dangerous ablation complication requiring pacemaker implantation — occurred in 6.5% of ASA patients versus zero on mavacamten, reinforcing pharmacotherapy's procedural-safety advantage.
However, critical limitations apply: this is a retrospective, observational, single-center study subject to residual confounding despite propensity matching. The 12-month window cannot address long-term durability, and mavacamten's known ejection-fraction monitoring requirements introduce treatment complexity. As a preprint not yet peer-reviewed, these results may shift substantially after independent scrutiny. Still, this represents potentially paradigm-shifting real-world evidence that could accelerate earlier pharmacologic intervention in eligible oHCM patients.
