CONGRESS ABSTRACT

Introduction : Mavacamten, a first-in-class cardiac myosin ATPase inhibitor used as second-line option for treating hypertrophic obstructive cardiomyopathy (HOCM), was introduced in Italy in early 2024 through a compassionate use program. Aim : To illustrate 48 week (W) follow up (FU) data from compassionate use of Mavacamten in a single centre HOCM population. Methods : At baseline all patients had a peak LVOT gradient ≥ 50 mmHg, a LVEF ≥55% and were symptomatic at the highest tolerated dose of first-line drugs (NYHA II 72.7%, NYHA III 27.3%). Before starting cytochrome P450 (CYP2C19) was genotypized to select the correct starting dose and uptritation. Following compassionate use protocol, patients underwent to periodic evaluation, EKG, cardiac imaging and laboratory work-up and Mavacamten was progressively uptritated. Results : Mavacamten was started in 11 patients, with no slow metabolizer. On October 2025, all patients completed the 48W FU assessment with dramatic reduction of LVOT gradients and NT-proBNP serum levels. Maximum resting and provoked LVOT gradients decreased, respectively, from 67.0±20.4 mmHg and 82.7±26.1 mmHg at baseline to 9.18±2.9 mmHg and 16.5±15.7 mmHg at 48 W (p<0.001,Fig.1a). We integrated stress echocardiography which showed in 24W a reduction of LVOT gradients from 95.7±26.7 to 32.9±29.5 mmHg (p=0.001,Fig.1b). Alongside patients developed diastolic improvement and hypertrophic reduction with lowering interventricular septum thickness (from 21.1±3.0 to 16.8±0.8 mm, p=0.03; Fig.2). Additionaly NT-proBNP serum levels significantly decreased from 913.2±656.1 pg/mL (baseline) to 164.9±105.6 pg/mL (48 W, p<0.001; Fig.3a) and EKG showed statistically significant reduction of Sokolow-Lyon index (from 28.0±12.7 to 19.6±5.9 mm, p=0.04) and T Wave depth (from 4.40±2.9 to 0.70±0.97 mm) (Fig.3b). All patients improved their NYHA class at least of one class. Mavacamten was up-titrated to 10 mg/die (6 patients) and 15 mg/die (5 patients) without any major advers event nor dropping of systolic function (LVEF < 55%) requiring discontinuation of treatment. Conclusions : Mavacamten confirmed in a real-world small cohort of symptomatic patients significant and long-lasting efficacy throughout all 48W FU. Normalization of LVOT obstruction, followed by diastolic improvement and hypertrophic reduction offer a favorable impact on quality of life, patient physical performance and laboratory evidence, without any major adverse event.