Chronic diastolic stretch unmasks conduction defects in an in vitro model of arrhythmogenic cardiomyopathy

We uncover a novel mechanotransductive mechanism that unmasks conduction defects in arrhythmogenic cardiomyopathy (ACM). Using a novel dynamic bioreactor and human-induced pluripotent stem cell (hiPSC)-derived engineered heart tissue (EHT), we apply strain at distinct intervals during the cardiac cycle. Imposing mechanical strain during diastole selectively slows conduction velocity. To our knowledge, this is the first time that the effect of mechanical loading during a specific part of the cardiac cycle has been shown to cause conduction deficits in ACM.