Diastolic dysfunction and thin filament dysregulation resulting from excitation-contraction uncoupling in a mouse model of restrictive cardiomyopathy

► The RCM mutation R193H in troponin I decreased myocardial and myocyte compliance. ► R193H troponin I elevated end diastolic pressures. ► Sarcomere relaxation and Ca2+ decay were uncoupled in isolated R193H myocytes. ► Altered Ca2+ handling proteins compensated for R193H Ca2+ sensitive myofilaments.