Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p<0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to <50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.