Real-world effectiveness, response patterns and clinical implementation of Mavacamten in obstructive hypertrophic cardiomyopathy: Insights from the SWISS-MAVA cohort.

INTRODUCTION

Mavacamten has demonstrated efficacy and safety in randomized trials for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM), but detailed real-world data in clinically complex populations remain limited.

METHODS

We evaluated the effectiveness, response patterns, safety and implementation challenges of mavacamten in a multicenter cohort (SWISS-MAVA) of adult patients with oHCM treated without CYP2C19 genotyping. The primary outcome was reduction of provocable (Valsalva) left ventricular outflow tract gradient (LVOTGval) ≤ 30 mmHg, or LVOTGval≤50 mmHg with ≥1 NYHA class improvement at last follow-up.

RESULTS

Eighty-two patients were included (age 59.5 ± 13.4 years, 63% male) and followed for 52.4 ± 21.4 weeks. Mavacamten reduced LVOTGval from 82[62 to 112] to 20[6 to 25] mmHg, NT-proBNP from 537[273-1279] to 142[77-303] ng/L, E/e' from 14.5 ± 6.6 to 10.8 ± 4.5 and left atrial volume indexed from 44.7 ± 12.5 to 37.2 ± 11.2 mL/m2 (p < 0.001). Mean left ventricular ejection fraction (LVEF) decreased (66.7 ± 5.4% to 62.6 ± 5.8%, (p < 0.001)) but remained preserved overall. The primary endpoint was achieved in 74/82 patients (90%), with 62/82 (76%) responding within 6 months. Twelve patients (15%) showed a super-hemodynamic response requiring protocol-mandated dose reduction, prolonging titration by 3.5 ± 2 months. Transient LVEF<50% occurred in 5 patients (6%; 5.9/100 patient-years), all reversible after treatment interruption; in 4/5 cases, a potential cofactor was identified. New-onset atrial fibrillation occurred in 6 patients (7.3%; 7.1/100 patient-years). Weight loss was observed in some obese/overweight responders, with transitions to lower BMI categories.

CONCLUSIONS

These data support the effectiveness and safety of mavacamten in real-world practice while highlighting clinically relevant heterogeneity in response patterns, titration burden, and adverse-event susceptibility.