Construction of engineered cardiac tissue on a heart-on-a-chip device enables modeling of arrhythmogenic right ventricular cardiomyopathy

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive cardiac disorder characterized by the replacement of the right ventricular myocardium with fibrofatty tissue, with an incidence rate of approximately 1 in 5000. To advance our understanding of its pathology and facilitate drug screening, there is an urgent need for myocardial models that closely replicate human physiological conditions. In this study, we developed an engineered cardiac tissue (ECT) model on a chip using cardiomyocytes differentiated from induced pluripotent stem cells (iPSCs) derived from ARVC patients. The disease ECT model successfully recapitulated key phenotypic features of ARVC, including reduced contractility, arrhythmic events, and abnormal calcium transients. We further assessed the drug responses of the model to isoproterenol and amiodarone, confirming increased sensitivity to isoproterenol in the ARVC model, while amiodarone effectively alleviated the arrhythmic events. In conclusion, our ECT model successfully reproduced ARVC phenotypes, providing a novel platform for drug screening and pathological studies.