Long-Term Effects of Mavacamten on Electromechanical Dispersion and Deformation in Obstructive Hypertrophic Cardiomyopathy

Regional electromechanical abnormalities have long been known to characterize hypertrophic cardiomyopathy (HCM), particularly in the presence of left ventricular outflow tract obstruction, contributing considerably to left ventricular (LV) diastolic dysfunction and—potentially—arrhythmic propensity.1,2 Mavacamten—a first-in-class allosteric cardiac myosin inhibitor—has recently shown substantial symptomatic benefit in patients with obstructive HCM, associated with marked and sustained decrease in LV outflow tract gradients, improved diastolic function,3 and normalization of electrocardiographic abnormalities.4 Data from the EXPLORER-HCM trial has shown initial evidence of favorable cardiac remodeling including reduced LV mass, consistent with the disease-modifying effects observed in transgenic mice. Based on these pleiomorphic effects, we postulated that improved electromechanical dispersion might contribute to the long-term benefits of mavacamten. To date, the effects of mavacamten on LV regional deformation have not been assessed, as speckle tracking imaging was not routinely included in trials. We performed echocardiographic LV global longitudinal strain (GLS) analysis at baseline and after 3-year mavacamten therapy, as well as an assessment of regional electromechanical dispersion using speckle tracking imaging and QT dispersion analysis.