Hemodynamic and symptomatic response in real-world patients with hypertrophic obstructive cardiomyopathy and myosin inhibitor therapy

Aims To provide real-world data on the symptomatic and hemodynamic response of the myosin inhibitor mavacamten in patients with hypertrophic obstructive cardiomyopathy. Methods Patients who were up-titrated on mavacamten to either complete hemodynamic response (maximum outflow tract [LVOT] gradient < 30mmHg) or the maximum dose of 15mg were included and a final assessment was conducted 12 weeks after reaching the final dose. Symptomatic response was defined by at least one NYHA class improvement and incomplete hemodynamic response was defined by residual LVOT gradient ≥ 30mmHg. Results 40 patients (56 ± 12 years, 78% male) were included. The LVOT gradient (rest: -25 ± 32mmHg, p <0.001, Valsalva: -73 ± 56mmHg, p <0.001) and NT-proBNP levels (-785 ± 1,122ng/l, p <0.001) significantly decreased during a mean follow up of 184 ± 83 days. 78% had a symptomatic response and 93% were complete hemodynamic responders. Patients with no improvement in NYHA class had a lower e´ lat. (9 ± 3cm/s vs. 6 ± 2cm/s, p=0.034) and less often baseline therapy with beta-blockers. Patients with incomplete hemodynamic response had a significantly higher baseline septum thickness (26.3 ± 4.9mm vs 19.1 ± 3.7mm, p=0.007) and higher LV-mass index (205 ± 63mL/m² vs. 139 ± 31mL/m², p=0.038). Absolute reduction of LVOT gradients was similar in patients with and without clinical or hemodynamic response. Conclusion Clinical and hemodynamic response to mavacamten was high in this real-world cohort and comparable to pivotal trial results. Incomplete response might be related to more severe baseline disease, which needs further study.