Among 104 obstructive hypertrophic cardiomyopathy (oHCM) patients meeting 2024 ACC/AHA criteria for invasive septal reduction therapy (SRT), aficamten — a selective cardiac myosin inhibitor — eliminated guideline eligibility in virtually all participants. Resting left ventricular outflow tract (LVOT) gradients fell by a least-squares mean of 41 mmHg and Valsalva gradients by 56 mmHg. NT-proBNP (a heart stress biomarker) dropped 77%, cardiac troponin I fell 38%, and 95.2% of patients improved by at least one NYHA functional class. These gains were sustained over a median follow-up reaching 3.5 years, with only two instances of ejection fraction dropping below 50% — both managed by dose reduction.
This finding matters because septal reduction therapy — either surgical myectomy or alcohol septal ablation — carries procedural risks including heart block, stroke, and mortality, and requires specialized centers. A durable pharmacological alternative would represent a genuine paradigm shift in HCM management, not merely incremental progress. Aficamten joins mavacamten in this drug class, but the near-complete SRT conversion rate and multi-year durability data here are striking. Critically, this is an open-label extension without a placebo arm, meaning symptom improvements carry placebo susceptibility, and patient selection may favor responders. The 315-patient cohort, while meaningful, remains modest. As a preprint posted on medRxiv and not yet peer-reviewed, these results require independent scrutiny before reshaping clinical guidelines — but they strongly reinforce the case for myosin inhibition as first-line therapy before invasive intervention.
