Effect of mavacamten on left ventricular diastolic function and left atrial remodelling in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Obstructive hypertrophic cardiomyopathy (HCM) is characterized by dynamic left ventricular outflow tract (LVOT) obstruction, leading to disabling symptoms. Mavacamten, a selective cardiac myosin inhibitor, improves obstruction and symptoms. Its beneficial effects on left ventricular diastolic indices have been documented, whereas its impact on left atrial strain has only recently been explored.

AIM: To assess the effect of mavacamten on diastolic function, left atrial remodelling and ventricular filling pressures in patients with obstructive HCM.

METHODS: In this prospective, single-centre study, 55 symptomatic patients with obstructive HCM (mean age 68±12 years, 40% male) were evaluated before and after individualized mavacamten titration. Echocardiographic, clinical and biomarker parameters were collected at baseline and after stabilization: left atrial end-systolic volume (LAESV), E/E' ratio, E/A ratio, peak atrial longitudinal strain (PALS) and peak atrial contraction strain (PACS), LVOT gradients, left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and NYHA class.

RESULTS: After a mean titration of 5 months (final median maintenance dose 5mg/day), NYHA class improved from 2.5 to 1.4 (P<0.001) and NT-proBNP decreased from 1431 to 158pg/mL (P<0.001). LVOT gradients dropped at rest (65.0mmHg [41.0-89.0] to 12.0mmHg [6.0-18.0], P<0.001) and after Valsalva (101.0mmHg [78.0-126.0] to 19.0mmHg [10.0-28.0]; P<0.001). Indexed LAESV declined from 50.8 to 39.9mL/m2 (P<0.001) and E/E' from 14.2 to 9.5 (P<0.001). E/A ratio remained unchanged. PALS and PACS worsened (PALS: 20.0% to 18.0%, P=0.003; PACS: 11.0% to 8.0%, P=0.002).

CONCLUSIONS: In this prospective, observational study, mavacamten initiation was associated with improvements in diastolic parameters and reductions in left atrial volume, together with favourable changes in clinical and haemodynamic measures in patients with obstructive HCM. The observed decrease in atrial strain parameters may reflect persistent atrial mechanical dysfunction or delayed functional recovery. Further studies with longer follow-up and controlled designs are needed to clarify the long-term effects on atrial remodelling.