Impact of mitral valvular and subvalvular abnormalities on response to mavacamten in obstructive hypertrophic cardiomyopathy

Background Left ventricular outflow tract (LVOT) obstruction is present in two thirds of patients with hypertrophic cardiomyopathy (HCM) and is a major determinant of symptoms. In addition to myocardial hypercontractility and hypertrophy, structural abnormalities of the mitral valvular and subvalvular apparatus are frequently observed in obstructive HCM. Mavacamten, a cardiac myosin inhibitor, reduces LVOT obstruction and improves symptoms but the impact of mitral valvular and subvalvular abnormalities on response to mavacamten is unclear. Purpose to analyse the effectiveness of mavacamtem according to the presence or not of mitral apparatus abnormalities Methods We conducted a multicenter study across four French centers including all patients with obstructive HCM treated with mavacamten at least for 6 months. Clinical, echocardiographic, and treatment data were collected. Mitral valvular and subvalvular apparatus abnormalities were carefully analysed: presence of systolic anterior motion (SAM), papillary muscle (PM) hypertrophy, PM bifidity, PM accessory and apical or anterior displacement of a PM. Results Between November 2023 and December 2025, 112 patients were treated with mavacamten (45% women, median age was 63 [48; 72] years, NYHA II in 55% and III in 45% patients). Concomitant medical therapy included beta-blockers (87%) calcium channel blockers (12%) and disopyramide (6%). Among these patients, 100 (89%) had a systolic anterior movement including 44 (39%) with direct contact between septum and mitral valve and 85 (76%) had at least one subvalvular abnormality: 37 (33%) had anterior or apical displacement of a PM, 66 (59%) patients had PM hypertrophy, 24 (21%) had bifid PM, and 21 (19%) had accessory PM. At 6 months, mavacamten treatment was associated with a significant reduction in LVOT gradient at rest, decreasing from 39 [25, 70] to 10 [6, 16] mmHg (p < 0.001) and at Valsalva, decreasing from 66 [49, 87] to 14 [10, 28] mmHg (p<0.001) and 82 (73%) patients had a complete response to mavacamten with an LVOT gradient below 30 mmHg. Clinical improvement was observed, with at least one NYHA class improvement in 74% of patients. No significant difference in treatment response regarding changes in LVOT gradient at Valsalva and NYHA at 6 months was observed according to the presence of mitral subvalvular apparatus abnormalities (Table 1). There was no difference in treatment efficacy based on the LVOT gradient at Valsalva according to the initial severity of SAM. Conclusion Mitral valvular and subvalvular apparatus abnormalities did not influence the hemodynamic and clinical response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy.Sub valvular apparatus