Decreases in Left Atrial Strain with Mavacamten Therapy and Associations with Atrial Fibrillation

BACKGROUND In obstructive hypertrophic cardiomyopathy (oHCM), the cardiac myosin inhibitor (CMI) mavacamten improves left ventricular outflow tract (LVOT) obstruction and functional capacity. Symptoms and exertional capacity in oHCM are also influenced by left atrial function, commonly assessed by left atrial strain (LAS). Current data regarding effects of CMIs on LAS are mixed. OBJECTIVES To assess changes in LAS in patients on mavacamten and correlate strain patterns to atrial fibrillation (AF) development. METHODS Serial echocardiograms were obtained following mavacamten initiation. We remeasured 2D and Doppler-derived measurements and obtained strain measurements. We examined temporal changes in LAS and related parameters, including those determining atrial preload and afterload, along with ventricular changes affecting atrial function. RESULTS We included 434 echocardiograms from 65 patients. After 24 weeks of therapy, LVOT gradient, global longitudinal strain, and LV ejection fraction all decreased. LA volume index (p < 0.001), mitral regurgitation severity (p = 0.01), and E/e' velocities (p = 0.01) also decreased. All three components of LAS worsened (p < 0.001). Seven patients with baseline AF had recurrences, and four others had new-onset AF. LAS predicted AF as a time-dependent variable. CONCLUSIONS Decreases in LAS seen with mavacamten may be downstream effects of alterations to other hemodynamic parameters, a decline in atrial function, or a combination thereof. LAS reductions may therefore represent harmful effects on the left atrium or neutral byproducts of other changes, although the association between LAS and AF is notable and may highlight prognostic implications of strain measurements in this population.