Cardiomyocyte hypocontractility and reduced myofibril density in pediatric cardiomyopathy

Dilated cardiomyopathy amongst children (pediatric cardiomyopathy, pediatric CM) is associated with a high morbidity and mortality. Moreover, treatment based on adult heart failure therapy is often ineffective. However, the reason for high morbidity and mortality is largely unknown as data on cellular pathomechanisms are limited. Here, we assessed cardiomyocyte contractility and protein expression to define cellular pathomechanisms in pediatric CM. For this study explanted heart tissue of 11 pediatric CM and 18 controls was studied. Contractility was measured in single membrane-permeabilized cardiomyocytes and protein expression was assessed with gel electrophoresis and western blot analysis. We observed increased Ca2+-sensitivity of myofilaments which was due to hypophosphorylation of cardiac troponin I, a feature commonly observed in adult DCM. Unlike adult DCM we did not find an increase in compliant titin expression. We also found a significantly reduced maximal force generating capacity of cardiomyocytes, caused by reduced myofibril density. The limited ability of pediatric CM patients to induce cardiac remodeling might have contributed to their early disease onset and severity.