The cardiac myosin inhibitor mavacamten reduces even extreme left ventricular outflow gradient in obstructive hypertrophic cardiomyopathy already after one week of treatment

Mavacamten is a selective, allosteric and reversible cardiac myosin inhibitor indicated for the treatment of symptomatic (NYHA II-III class) adult patients with obstructive [≥ 50 mmHg resting or provokable left ventricular outflow tract (LVOT) peak gradient] hypertrophic cardiomyopathy (HOCM).

Ten patients with HOCM [5 men (50%), mean age: 57±11 years) were treated with mavacamten. In 9 patients the resting or provoked gradient was >100 Hgmm. In addition to recording the main demographic, clinical parameters, complete standard and 2D-speckle tracking echocardiographic examination was performed in the patients after 1 week (1W) and 16 weeks (16W) of treatment.

After 1W from initiation of mavacamten therapy, the resting peak LVOT gradient decreased by an average of -38 mmHg, from 113±36 mmHg to 75±36 mmHg (p=0.0028); which decreased further at 16W (mean difference -89 Hgmm, p=0.0002). The LVOT gradient provoked by the Valsalva maneuver decreased by -49 mmHg at 1W, from 150±43 mmHg to 107±50 mmHg (p=0.001), which further decreased at 16W (mean difference -107 Hgmm, p=0,0001). As the LVOT gradient decreased, patients' NTpBNP levels decreased at 1W by -690 pg/ml (p=0,0244), from 1270 (IQR: 636-2247) pg/ml to 756 (IQR: 377-1343) pg/ml, which further decreased at 16W (mean difference: -1103 pg/ml; p=0,0078). The ejection fraction and global longitudinal strain remained unchanged at 1W (EF: +0,7 %; p=0,6537; GLS: +0,5%; p=0.4303) and at 16W (EF: -2%; p=0.4499; GLS: 0%; p=0.9885). As the gradient decreased, the global work index and global constitutive work decreased at 1W (GWI: 2026±365 vs. 1675±382 mmHg%; p=0.0009; GCW: 2618±395 vs. 2091±468 mmHg%; p=0.0062) and at 16W (mean difference, GWI: : -406mmHg%; p=0,0062; GCW: -572 mmHg%; p=0,0018). Left atrial volume values showed a favorable regression trend at 1W (LAV: 137±30 vs. 124±25 ml; p=0.1513; LAVI: 71±13 vs. 64±12 ml/m2; p=0.1528) which became significant at 16W (mean difference, LAV: -35 ml; p=0,01; LAVI: -17 ml/m2, p=0,0092).

The direct myosin inhibitor mavacamten effectively reduces even extreme (>100 Hgmm) LVOTO gradients and has a beneficial effect on other structural and functional cardiac parameters. It has an effect even in the short term.