1-043 Mavacamten in symptomatic obstructive hypertrophic cardiomyopathy: real-world insights and clinical outcomes

Introduction The treatment approach for hypertrophic cardiomyopathy (HCM) has advanced with the emergence of disease-specific therapies designed to target the underlying pathophysiology. Mavacamten, a first-in-class cardiac myosin inhibitor, received approval in the U.K. by NICE in September 2023 for use in adult patients with symptomatic obstructive HCM (oHCM). Clinical trials have shown that mavacamten reduces left ventricular outflow tract (LVOT) gradient, improves New York Heart Association (NYHA) functional class, and NT-proBNP. While randomised controlled trials have demonstrated the efficacy of cardiac myosin inhibitors, real-world data on their effectiveness and implementation are still emerging. Here we evaluated the impact of mavacamten on the first 10 patients at our Inherited Cardiac Services referral centre, with striking results. Methods All patients commencing mavacamten at a single Inherited Cardiac Services referral centre were included between the months of May and August 2024. Baseline echocardiography, standard of care biomarkers, QoL metrics and 6-minute walk test (6MWT) were assessed prior to mavacamten therapy and again following 16 weeks continuous guideline-directed treatment. Differences between groups for continuous variables were assessed using the paired student t-test. Data were analysed using SPSS (IBM SPSS Statistics, Version 28.0). Results Among the 10 prospectively studied patients, 30% were female, median age was 55 years (+/- 15 yrs) and majority were NYHA functional class III (n=6). At baseline (week 0), mean peak LVOT gradient with Valsalva was 133 mmHg (+/- 50.7 mmHg). Mean NT-proBNP was 1951pg/mL (Range 62 to 5571pg/mL) and mean patient reported QoL with Kansas City Cardiomyopathy Questionnaire (KCCQ) was 38. Following 16-weeks of guideline directed mavacamten therapy, NT pro-BNP a significant mean decrease of 1596 pg/mL was observed 95%CI: 244 to 2948: p=0.03 (figure 1A). This was complemented by a significant change in peak LVOT gradient with Valsalva, with a mean reduction of 103 mmHg [95%CI: 70 to 136: p Conclusions The data from this study add to the expanding evidence for the efficacy and safety of mavacamten in patients with oHCM, with significant improvements in NT-pro BNP, echocardiographic parameters, 6MWT and KCCQ. While real-world data often temper initial enthusiasm for new treatments, the promising results observed post licencing with mavacamten suggest that it may surpass even the most optimistic expectations. Ongoing studies are essential to further refine our understanding of mavacamten's safety and efficacy, ensuring optimal patient care and therapy delivery.