Extracellular Matrix From Hypertrophic Myocardium Provokes Impaired Twitch Dynamics in Healthy Cardiomyocytes.

•The goal of this study was to examine the effects of diseased extracellular matrix on the behavior of healthy heart cells.•Myocardium was harvested from a genetically engineered miniature pig carrying the hypertrophic cardiomyopathy mutation MYH7 R403Q and from a wild-type littermate.•Engineered heart tissues were created by seeding healthy human induced pluripotent stem cell–derived cardiomyocytes onto thin strips of decellularized porcine myocardium.•Engineered heart tissues made from the extracellular matrix of hypertrophic cardiomyopathy hearts exhibit increased stiffness, impaired relaxation, and increased force development.•This suggests that diseased extracellular matrix can provoke abnormal contractile behavior in otherwise healthy cardiomyocytes.