JACC Basic to Translational Science · Nov 2026

Human Living Myocardial Slice Model for Load-Dependent Pharmacologic Testing in Hypertrophic Cardiomyopathy

By Taichman RB, Smolyak JN, Chittams J et al.

Experimental platforms capable of testing pharmacologic compounds on myocardial contractility will facilitate development of targeted cardiac therapeutics. We sought to develop a human living myocardial slices (hLMS) platform for interrogation of load-dependent myocardial mechanics in hypertrophic cardiomyopathy (HCM) and to study impact of pharmacologic intervention on myocardial work under physiologic loading conditions. hLMS from non-failing donor hearts or HCM myectomy tissue were used to generate biomimetic work loops in either glucose-only fuel or glucose with ketones. Following baseline measurements, slices were loaded with drug (isoproterenol, mavacamten, sotagliflozin, or empagliflozin) or vehicle (DMSO) and work loop analysis was repeated. 120 hLMS from 32 individuals (16 non-failing, 16 HCM) were analyzed. Baseline clinical characteristics predicted work. Ketones and isoproterenol increased work. Mavacamten, sotagliflozin, and empagliflozin decreased work. This platform enables assessment of myocardial mechanics across controlled loading conditions, rigorous phenotyping of human myocardium, and interrogation of direct pharmacologic effects.

doi.org/10.1016/j.jacbts.2026.101753 Open access Interventions