Abstract 16026: Divergent Metabolic Programming in Pediatric and Adult Non-Ischemic Dilated Cardiomyopathy

IntroductionAlthough abnormalities of mitochondrial function and beta-oxidation with depletion of tissue ATP stores are recognized features of end-stage heart failure (HF) in adults, cardiac metabolic adaptations in children with HF are poorly understood. The purpose of the current study was to understand age-related metabolic responses to HF secondary to non-ischemic dilated cardiomyopathy (DCM).MethodsA cross-sectional investigation using explanted human DCM hearts and non-failing (NF) donor controls from children and adults in the University of Colorado Heart Tissue Bank (pediatric16 DCM/ 16 NF, adult16 DCM/16 NF). RT-qPCR was used to assess expression of metabolic regulatory factors, metabolic enzymes (beta oxidation and glycolysis pathways), and mitochondrial biogenesis programs. Enzymatic activity of CPTI and CPTII were assessed from tissue samples, and lipidomic (including acyl-CoA content) and metabolomic analyses (acyl-carnitines, ATP, phosphocreatine, TCA intermediates) were performed in a subset of the cohorts.ResultsDivergent responses to heart failure were observed in children versus adults in most aspects of the metabolic pathways studied. While beta-oxidation (ex. TFPα and β, both 2-fold, p