Effect van mavacamten op risicoscores voor plotse hartdood bij hypertrofische cardiomyopathie

AIMS: Obstructive hypertrophic cardiomyopathy (oHCM) is associated with both haemodynamic impairment and increased arrhythmic risk, including sudden cardiac death (SCD). Risk stratification relies on the European Society of Cardiology (ESC) HCM Risk-SCD model, complemented by cardiac magnetic resonance (CMR) assessment of myocardial fibrosis. Myosin inhibitors such as mavacamten improve obstruction and induce reverse remodelling, but their impact on arrhythmic risk score remains unknown. The objective was to analyse the impact of mavacamten on the evolution of the ESC rhythm score in patients with obstructive HCM. METHODS: Consecutive patients with symptomatic oHCM treated with mavacamten between October 2023 and June 2025 at four French referral centres for cardiomyopathies were retrospectively included. Clinical, echocardiographic, and CMR data were collected at baseline and after 6 months of therapy. Arrhythmic risk was calculated using the ESC HCM Risk-SCD model; patients with late gadolinium enhancement (LGE) ≥ 15% of left ventricular (LV) mass were reclassified into the high-risk category. RESULTS: Among 186 eligible patients, 161 were included (mean age 62 ± 14 years, 55% male). At baseline, arrhythmic risk was classified as high in 6%, intermediate in 9%, and low in 85%. After 6 months of mavacamten, significant improvements were observed in New York Heart Association class (III: 35 to 2%, P < .001), resting LV outflow tract (LVOT) gradient (45 ± 31 to 12 ± 9 mmHg, P < .001), provoked gradient (80 ± 32 to 25 ± 19 mmHg, P < .001) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. The median expected 5-year SCD risk decreased from 2.1% (1.7-3) to 1.4% (1.1-1.8) (P < .001). In high-risk patients, the score decreased from 7.7% (7.4-8.4) to 4.6% (4.5-6.0) (P = .001). European Society of Cardiology Risk-SCD reduction was entirely attributable to modifiable parameters: rest/Valsalva LVOT gradients (-33/-57 mmHg), left atrial diameter (-1.2 mm), and septal thickness (-1.5 mm, all P < .001). Mean HCM Risk Score reduction was 0.7% with heterogeneous inter-patient response, but homogeneous efficacy across centres (P = .206). Considering LGE, the proportion of patients with a high rhythmic risk fell from 16% to 15%. During a median follow-up of 19 months, no patient experienced SCD or required secondary prevention implantable cardioverter-defibrillator; two new non-sustained ventricular tachycardia episodes were recorded. CONCLUSION: Mavacamten therapy was associated with marked haemodynamic and symptomatic improvements and a reduction in the ESC-based SCD risk in obstructive HCM. While these findings need to be confirmed and were not paralleled by a reduction in arrhythmic events, they suggest that myosin inhibition may influence arrhythmic risk stratification. Prospective studies with longer follow-up are required to determine whether such favourable remodelling translates into true arrhythmic protection.