Abstract 13220: Distinct Disease Mechanisms Drive Pediatric and Adult Dilated Cardiomyopathy

Background: Numerous clinical studies have suggested that adult heart failure (HF) therapies are less effective in children with dilated cardiomyopathy (DCM). The mechanistic basis for this phenomenon is poorly defined. Collectively, adult HF therapeutics target a process termed adverse remodeling, a common pathway by which the adult heart responds to injury. We hypothesized that pediatric and adult DCM comprise distinct pathological entities in that children do not undergo adverse remodeling. Methods: LV specimens were obtained from donor pediatric and adult controls (24), pediatric DCM (31) and adult DCM patients (33). Pathological evidence of adverse remodeling including myocardial fibrosis, cardiomyocyte hypertrophy, and gene expression was examined using immunostaining, electron microscopy and RNA sequencing. Results: Consistent with the established pathophysiology of adult HF, adults with DCM displayed marked increases in myocardial fibrosis compared to donor controls (both p Conclusions: These findings demonstrate that children with DCM display minimal evidence of adverse remodeling; suggesting pediatric and adult DCM may represent different pathological entities. Collectively, these data provide a mechanistic basis to understand why adult HF therapeutics may not work in children, and suggest the possibility that distinct therapies may be needed for pediatric DCM.