Baseline clinical profile of patients with obstructive hypertrophic cardiomyopathy in the Italian Mavacamten early access program

BACKGROUND Obstructive hypertrophic cardiomyopathy (oHCM) has recently seen the introduction of mavacamten, a disease-specific therapy that alleviates obstruction and symptoms with potential effects on disease expression. Since most patients remain symptomatic with conventional therapies, mavacamten constitutes an efficacious treatment strategy METHODS: The early access program (EAP) for mavacamten treatment ran from September 2023 to September 2024. We collected clinical and echocardiographic data prospectively RESULTS: 337 patients with oHCM (53% male, mean age 61.4 ± 12.3 years) were receiving mavacamten treatment from 54 centers in Italy. The EAP cohort was older and showed a more advanced cardiac phenotype, showing lower left ventricular ejection fraction (LVEF) (66 ± 6% vs 74 ± 6% in EXPLORER-HCM cohort, p < 0.0001) and higher left atrial volume index (51.1 ± 16.4 ml/m2 vs 40.5 ± 12.3 ml/m2, p < 0.0001. Only 74 (22%) patients in the EAP group were candidates for septal reduction therapy (SRT). Echocardiographic parameters like LVEF, maximal wall thickness and LAVI as well as pharmacologic therapy showed no difference between subgroups, while LVOT obstruction gradient was higher in SRT candidates (40 vs 63 mmHg, p < 0.0001).. CONCLUSION The compassionate use program for mavacamten in Italy demonstrated significant engagement. The Italian oHCM cohort were older and exhibited more advanced disease stages compared to those in the EXPLORER-HCM trial. Only one-quarter of the patients were eligible for SRT, they did not show a more severe biomarker or echocardiographic parameters compared to those without indication. Mavacamten provides an additional option for oHCM patients unresponsive to standard therapy, especially those symptomatic but ineligible for SRT.