Identification of metabolomic profile related to adult Fontan pathophysiology

Abstract

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.

Nutritional considerations for people living with a Fontan circulation: a narrative review

“…41,42 Preliminary research in adults with a Fontan circulation has noted alterations in amino acid metabolism, phospholipid metabolism, and the tricarboxylic cycle. [43][44][45] Together, the gut microbiome and metabolites play an important role in ensuring essential functions are performed including the production of vitamins and amino acids, regulation of the immune system, and maintaining the epithelial barrier of the gastrointestinal system. 46,47 Over the course of a person's life, environmental factors of diet and medication usage have a role in influencing the composition of the gut microbiome.…”

Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy

“…Another recent metabolomics study suggests differences in 2-oxoglutarate, isocitric acid, malic acid, and cis-aconitic acid that could reflect alterations of the Krebs cycle [ 163 ]. The authors suggest Krebs cycle activation might be necessary to increase cardiac output to counteract hypoxia in Fontan patients.…”

Metabolomics: A New Tool in Our Understanding of Congenital Heart Disease

“…In complex CHD, such as single ventricle hearts, which have been surgically palliated with the Fontan technique, abnormalities in the tricarboxylic acid cycle and amino acid metabolism were identified as distinguishing the metabolomic profiles of these patients [ 22 ].…”