Effect of mavacamten on left ventricular myocardial volume, strain and tissue characteristics in patients with hypertrophic cardiomyopathy

Abstract Background Cardiac myosin inhibition therapy delivers pharmacologically-mediated reductions in left ventricular (LV) outflow tract obstruction that can improve clinical symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). While clinical trials of these novel therapeutics have suggested favourable cardiac remodeling [1,2], phenotypic alterations are yet to be studied in real world populations. Purpose We aimed to explore serial changes in cardiac magnetic resonance (CMR) imaging parameters of LV remodelling in patients with obstructive HCM (oHCM) completing 1-year of therapy using mavacamten. Methods 15 consecutive patients with oHCM initiated on mavacamten were recruited. All patients had CMR imaging performed prior to mavacamten initiation and completed repeat imaging at 1-year. CMR imaging was inclusive of cine, late gadolinium enhancement (LGE), and T1 mapping. Image analysis was performed using commercial software. Extracellular volume (ECV) fraction from T1 mapping was used to derive the cellular and matrix volume components of the LV myocardial mass using the equations: body surface area (BSA)-indexed cell volume = BSA-indexed LV mass * (1-ECV); BSA-indexed matrix volume = BSA-indexed LV mass * ECV. Left ventricular outflow tract (LVOT) gradients were measured by echocardiography and reported as the maximum resting or provoked gradient measured in each study. Results The study cohort had a mean age of 63.6±14.2 years (7 male, 8 female). Changes in imaging parameters from baseline CMR (median 2.4 years prior to initiation) to 1-year follow up are shown in Figure 1. LVOT gradients dropped by a mean of 74 mmHg, accompanied by reductions in both the LV ejection fraction [LVEF; absolute reduction 7.4% (p<0.001)], and right ventricular EF [RVEF; absolute reduction 8.7% (p<0.001)]. The indexed LV mass dropped by a mean of 21% (relative reduction; p=0.007), this dominantly related to regression of the intra-cellular component (mean relative reduction 16%; p=0.009). No significant changes in the matrix mass component (p=0.13) or ECV (p=0.052) were observed. Peak LV strain amplitudes were stable between the two timepoints (p=ns). CMR imaging changes for a representative patient are shown in Figure 2. Conclusions To date, this is the first real world clinical study demonstrating the effect of cardiac myosin inhibition therapy on cellular and matrix components of the hypertrophied myocardium in patients with HCM. Significant regression of LV hypertrophy was attributed to a reduction of the cellular mass component with stable markers of matrix volume. These findings offer real world evidence for reverse remodelling in HCM from myosin inhibition therapy through the regression of cellular hypertrophy. Larger scale real world cohort studies are warranted to validate these findings.Figure 1 Figure 2