Abstract 15584: Metabolomic Signature of Fontan Circulation

Abstract

Introduction: Patients born with a range of cardiac defects, not amenable to biventricular repair are palliated with establishment of Fontan circulation. Although majority of patients with Fontan circulation survive childhood, eventually they experience multi-system dysfunction, mainly frailty, impaired exercise capacity, blunted exercise-augmented hemodynamics, progressive liver fibrosis, and shortened survival. Fontan circulation associated biochemical abnormalities have not been well described. Materials and Methods: Twenty adult patients with Fontan circulation and 20 age- and sex-matched healthy subjects underwent a non-targeted metabolomics assessment using an LC-QTOF-MS system to detect potential Fontan-related biomarkers. These study participants were also investigated for markers of frailty, cardiopulmonary exercise testing, and resting as well as exercise-augmented hemodynamic evaluation. Results: A total of 1679 known plasma metabolites were detected in electrospray positive and negative modes among which 37 metabolites were significantly different (T-Test Unpaired (p<0.05) followed by a multiple testing correction of p values (Benjamini-Hochberg)). These metabolites belonged to several classes of compounds including lipids, bile acids, amino acids, and derivatives. Several bile acids such as chenodeoxycholic acid glycine conjugate, glycoursodeoxycholic acid, and deoxycholic acid glycine conjugate were upregulated in patients with Fontan while 8-hydroxyguanine, N-arachidonoyl glycine, uracil, and cysteine were down-regulated in comparison to healthy subjects. Conclusion: In-depth plasma metabolomic analysis demonstrated metabolic pathways activation involved in bile acid formation, markers of oxidative stress, damage of DNA, whereas lower concentrations of several amino acids in patients with Fontan.