Effect of Mavacamten and Disopyramide on Left Ventricular Mechanical Dispersion and Life-threatening Arrhythmia in Obstructive Hypertrophic Cardiomyopathy

Abstract Aims Disopyramide and mavacamten both decrease left ventricular outflow tract gradients in obstructive hypertrophic cardiomyopathy (HCM). Yet, their effects on myocardial mechanics remain unclear. This study aimed to compare the effects of mavacamten and disopyramide on left ventricular mechanical dispersion (LVMD) and its association with life-threatening ventricular arrhythmias. Methods and Results Consecutive subjects (n=120) with obstructive HCM treated with either Mavacamten or disopyramide from 2018 to 2024 were identified. Echocardiographic speckle-tracking strain imaging with myocardial work indices and LVMD quantification was performed at baseline and follow-up. Patients were followed up for life-threatening ventricular arrhythmias: sustained ventricular tachycardia (VT) or sudden cardiac arrest (SCA), up to 2 years. Propensity matching was performed for age and sex to compare the groups. Mavacamten significantly reduced LVMD (85.1 ± 26.4 ms vs. 64.3 ± 16.7 ms, p=0.013) and global wasted work (GWW) (268 mmHg% (185-378) vs 150 mmHg% (124-262), p=0.006) and increased global work efficiency (GWE) (87% (82-92) vs 90% (86-94), p=0.038). None of the favorable effects were observed with disopyramide. The median follow-up duration was 12 (range 6-24) months. LVMD at follow-up was significantly associated with the outcome events (area under curve: 0.784, 95% CI [0.622-0.945], p<0.001). LVMD <72 ms at follow-up was associated with improved event-free survival (X26.4, log-rank p=0.011). Mavacamten and global work indices were independent determinants of LVMD at follow-up. Conclusion Mavacamten, but not disopyramide decreased LVMD, GWW and increased GWE in obstructive HCM. LVMD <72 ms at follow-up is promising for assessing the risk for life-threatening ventricular arrhythmias.