Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population

Background and aims: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world (RW) HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment. Methods: We collected information on HOCM patients followed-up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.e. gradient >=30 mmHg at rest or >=50 mmHg after Valsalva maneuver or exercise) despite pharmacological or non-pharmacological therapy. Results: Pharmacological or non-pharmacological therapy resolved LVOTO in 1,044 (61.2%) of the 1,706 HOCM patients under active follow-up, whereas 662 patients (38.8%) had persistent LVOTO. Compared to the EXPLORER-HCM trial population, these RW HOCM patients were older (62.1+-14.3 vs 58.5+-12.2, p=0.02), had a lower body mass index (26.8+-5.3 vs 29.7+-4.9 kg/m2 p<0.0001) and a more frequent history of atrial fibrillation (21.5% vs 9.8%, p=0.027). At echocardiography, they had lower left ventricular ejection fraction (LVEF, 66+-7% vs 74+-6%, p<0.0001), higher LVOT gradients at rest (60+-27 vs 52+-29 mmHg, p=0.003), and larger left atrial volume (49+-16 vs 40+-12 mL/m2 , p<0.0001). Overall, 324 (48.9%) would have been eligible for enrollment in the EXPLORER-HCM trial and 339 (51.2%) for treatment with mavacamten according to European guidelines. Conclusions: RW HOCM patients differ from the EXPLORER-HCM population for their older age, lower LVEF and larger atrial volume, potentially reflecting a more advanced stage of the disease. About half of RW HOCM patients were found eligible to mavacamten.