Identification of metabolomic profile related to adult Fontan pathophysiology

Autor: Noriko Motoki, Hirohiko Motoki, Masafumi Utsumi, Shoko Yamazaki, Haruka Obinata, Kohta Takei, Satoshi Yasukochi
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Cardiology: Heart & Vasculature, Vol 37, Iss , Pp 100921- (2021)
Druh dokumentu: article
ISSN: 2352-9067
DOI: 10.1016/j.ijcha.2021.100921
Popis: Background: Metabolic disorders are important pathophysiologies that can cause multiple organ dysfunction and worsen prognosis in Fontan patients. This study aimed to comprehensively evaluate the metabolomic profile of adult Fontan patients and characterize its pathophysiology in relation to 2 control groups. Methods and Results: We performed metabolomic analysis of 31 plasma samples using capillary electrophoresis time-of-flight mass spectrometry. This observational cross-sectional study compared plasma metabolites of 14 heterogeneous adult Fontan patients with those of control groups, including 9 patients with congenital heart disease after biventricular repair and 8 normal healthy controls. Fontan patients exhibited significant differences in intermediate metabolite concentrations related to glycolysis, the tricarboxylic acid (TCA) cycle, and the urea cycle. The plasma concentrations of lactic acid, 2-oxoglutarate, isocitric acid, malic acid, cis-aconitic acid, arginine, citrulline, and the ratio of ornithine/citrulline showed significantly differences among the groups. Multiple logistic regression analysis with a stepwise selection-elimination method identified 2-oxoglutaric acid (odds ratio [OR] 1.98, 95% confidence interval [CI] 1.05–3.76) and cis-aconitic acid (OR 2.69, 95% CI 1.04–6.99) as independently associated with Fontan patients. After adjustment for the covariates of age and gender, 2-oxoglutaric acid (OR 1.97, 95% CI 0.98–3.93) and cis-aconitic acid (OR 3.88, 95% CI 0.99–15.2) showed remarkable relationships with Fontan patients. Conclusions: The present findings suggest that abnormalities in the TCA cycle and amino acid metabolism are distinguishing features in the pathophysiology of Fontan patients. Future metabolomic studies will assist in developing biomarkers for the early prediction of “silent” Fontan pathophysiologies.
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