マバカプテン療法を受けた肥大型閉塞性心筋症患者における血行動態および症状の反応

To provide real-world data on the symptomatic and hemodynamic response of the myosin inhibitor mavacamten in patients with hypertrophic obstructive cardiomyopathy (HOCM).

Patients with HOCM up-titrated to their final mavacamten dose were included. The final dose was defined as (i) 15 mg daily (or 5 mg for poor CYP2C19 metabolizers), (ii) a dose achieving a complete hemodynamic response (LVOT gradient <30 mmHg), or (iii) a lower dose limited by adverse effects. Final evaluation was performed 12 weeks after reaching the final dose. Symptomatic response was defined as ≥1 NYHA class improvement, and incomplete hemodynamic response as residual LVOT gradient ≥30 mmHg.

40 patients (56 ± 12 years, 78% male) were included. The LVOT gradient (rest: -25 ± 32 mmHg, p < 0.001, Valsalva: -73 ± 56 mmHg, p < 0.001) and NT-proBNP levels (-785 ± 1,122 ng/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 ± 3 cm/s vs. 6 ± 2 cm/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 ± 4.9 mm vs. 19.1 ± 3.7 mm, p = 0.007) and higher LV-mass index (205 ± 63 mL/m² vs. 139 ± 31 mL/m², p = 0.038). Absolute reduction of LVOT gradients was similar in patients with and without clinical or hemodynamic response.

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.