A Single–centre Experience With Compassionate Use Program With Mavacamten in a Real–world Population of Patients With Hypertrophic Cardiomyopathy: Mid–term Outcome and Role of Exercise Echocardiography

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.