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<0.01)(Figure). In contrast, pediatric DCM had minimal evidence of fibrosis compared to both aged-matched controls and adults with DCM. Examination of cardiomyocyte hypertrophy and capillary density demonstrated less extensive cardiomyocyte hypertrophy and capillary rarefaction in pediatric compared to adult DCM patients. Electron microscopy revealed similar sarcomere thickness and length between control and pediatric DCM specimens. RNA sequencing demonstrated that genes associated with adverse remodeling were not up-regulated in pediatric DCM specimens.
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.
Author Disclosures: M.D. Patel: None. C. Schneider: None. G. Bajpai: None. J. Mohan: None. C. Canter: None. J. Towbin: None. K. Lavine: None.
- © 2016 by American Heart Association, Inc.