Abstract
Objectives: To evaluate the circulating metabolome of interstage infants with single ventricle heart disease (SVHD) and determine whether metabolite levels were associated with pulmonary vascular inadequacy. Background: Infants with SVHD experience morbidity related to pulmonary vascular inadequacy. Metabolomic analysis involves a systems biology approach to identifying novel biomarkers and pathways in complex diseases. The metabolome of infants with SVHD is not well understood and no prior study has evaluated the relationship between metabolite levels and pulmonary vascular readiness for staged SVHD palliation. Methods: Prospective cohort study of 52 infants with SVHD undergoing Stage 2 palliation and 48 healthy infants. Targeted metabolomic phenotyping (n=175 metabolites) performed by tandem mass spectrometry on SVHD pre-Stage 2, post-Stage 2, and control serum samples. Clinical variables were extracted from the medical record. Results: Random Forest analysis readily distinguished between cases and controls (Figure), and pre-op and post-op samples. Seventy-four of 175 metabolites differed between SVHD and controls. Twenty-seven of 39 metabolic pathways were altered including pentose phosphate and arginine metabolism. Seventy-one metabolites differed in SVHD patients between timepoints. Thirty-three of 39 pathways were altered post-operatively including arginine and tryptophan metabolism. We found trends towards increased pre-operative methionine metabolites in patients with higher pulmonary vascular resistance and higher post-operative tryptophan metabolites in patients with greater post-operative hypoxemia. Conclusions: The circulating metabolome of interstage SVHD infants differs significantly from controls and is further disrupted after Stage 2. Several metabolites showed promising trends towards association with adverse outcomes. Metabolic dysregulation may be an important factor in early SVHD pathobiology.
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