BACKGROUND: Patients with Fontan circulation are frail and experience multisystem dysfunction including impaired exercise capacity, low resting and exercise-augmented cardiac output, and progressive liver fibrosis. However, common underlying biochemical abnormalities or disease-specific biomarkers have not been well-described. OBJECTIVES: We wish to investigate Fontan and their matched healthy subjects using a nontargeted, followed by targeted metabolomic analysis. METHODS: Patients with Fontan circulation were compared to age- and sex-matched healthy controls with regard to body composition, markers of frailty, cardiopulmonary exercise testing, and resting and exercise-augmented hemodynamics. Subsequently, the study participants underwent a nontargeted metabolomics assessment, followed by targeted plasma bile acid (BA) analysis. RESULTS: Twenty Fontan patients (28.8 ± 9.8 years of age
35% women) and 20 healthy controls (29.7 ± 6.0 years of age
30% women) were enrolled. Fontan patients had significantly lower skeletal muscle mass, took longer to complete the 5 times sit-to-stand test
achieved lower %VO CONCLUSIONS: Elevated BAs are associated with worsening Fontan physiology. These findings warrant further exploration.