CORRESPONDENCE index ([(1− global extracellular volume fraction)× LV mass]/body surface index) decreased with mavacamten (− 14.1 [9.5] g/m2) versus no change in placebo (− 1.0 [6.5] g/m2; mean between-group difference,− 13.1 g/m2 [95% CI,− 18.7 to− 7.5]; P= 0.0002). Mavacamten was associated with a greater reduction in maximum LV wall thickness than placebo (Figure). In both groups, baseline mean LV ejection fraction was elevated and remained normal through week 30 despite a mild reduction observed with mavacamten (Figure). In the CMR substudy, LV ejection fraction reduction with mavacamten was similar to that assessed by echocardiogram in the EXPLORER-HCM population (− 6.6%[6.39%] and–3.9%[7.7%]). There was no LV ejection fraction of< 50% by CMR. Of the 9 patients in EXPLORER-HCM (7 mavacamten, 2 placebo) with a transient decrease in LV ejection fraction of< 50%(median 48%) by echocardiogram, 4 2 were in the CMR substudy (1 mavacamten, 1 placebo) and both were asymptomatic at time of the measure. Myocardial contractile fraction ([LV stroke volume/LV myocardial volume)× 100; LV myocardial volume= LV mass/[1.05 g/mL]), another parameter of LV systolic function, was similar in both groups at baseline (mavacamten, 61.0%[17.9%]; placebo, 60.1%[17.3%]) and remained unchanged at week 30 (mean between-group difference, 2.4%[95% CI,− 4.5 to 9.3]; P= 0.7043). A greater reduction in maximum left atrial volume index was observed with mavacamten versus placebo (mean between-group difference,− 10.3 mL/m2 [95% CI,− 16.0 to− 4.6]; P= 0.0004; Figure). There was little fibrosis at baseline with no notable within-or between-group changes in late gadolinium enhancement (Figure) and extracellular volume fraction (mean change [SD] global extracellular volume fraction, 0.02 [0.07] in the mavacamten group; 0.00 [0.03] in the placebo group). There was a 50% greater reduction in hs-cTnI and 80% greater reduction in NT-proBNP with mavacamten versus placebo (P< 0.01). Change in LV mass index was positively correlated with change in hs-cTnI (n= 31; Rho= 0.75 [95% CI, 0.53–0.87]). The CMR substudy is the first to show favorable impact of a pharmacological agent on cardiac remodeling in HCM. Mavacamten was associated with significant reductions in absolute intracellular myocardial mass index as well as LV mass index, maximum LV wall thickness, and left atrial volume index—all predictors of poor prognosis in obstructive hypertrophic cardiomyopathy. 5 Importantly, there were no changes in fibrosis or myocardial contractile fraction observed during 30 weeks, and contractile function remained normal. Reductions in hypertrophy and left atrial volumes were observed concurrent with reductions in levels of plasma