Bile Acid Pool Expansion and Hemodynamic Associations of the Secondary-to-Primary Bile Acid Ratio in Adult Fontan Circulation.

We previously reported that adults with Fontan circulation have elevated plasma bile acids, including multiple individual bile acid species, associated with frailty, impaired exercise capacity, and adverse resting and post-exercise hemodynamics. Whether the secondary-to-primary bile acid ratio provides additional insight into gut-liver-circulatory interactions in this population is unknown. We performed a secondary analysis of a previously published prospective cohort of 20 adults with Fontan circulation and 20 matched healthy controls. Primary bile acids were defined as cholic acid, chenodeoxycholic acid, and their direct conjugated, sulfated, glucuronidated, and dehydrocholic derivatives. Secondary bile acids included deoxycholic, lithocholic, ursodeoxycholic, hyodeoxycholic, and related downstream derivatives. The secondary-to-primary ratio was calculated as summed secondary-derived bile acids divided by summed primary-derived bile acids. Group comparisons used Mann-Whitney U testing. Within Fontan patients, associations with body composition, exercise performance, and resting/post-exercise hemodynamics were assessed using Spearman correlation with Benjamini-Hochberg correction. The secondary-to-primary ratio was numerically lower in Fontan patients than controls: 0.80 [0.39-1.22] vs. 1.32 [0.70-1.83]; P = 0.10. However, both primary-derived bile acids: 6333 [3473-10899] vs. 2102 [1166-3662] nM; P = 0.004, and secondary-derived bile acids: 4431 [2529-7095] vs. 2468 [1786-3660] nM; P = 0.008, were significantly increased. Within Fontan patients, higher ratio correlated with lower cardiac index/cardiac power index, and higher total peripheral resistance index. In adult Fontan circulation, bile acid pool expansion, particularly primary species, is the dominant abnormality. The secondary-to-primary ratio provides complementary compositional information and appears linked to hemodynamic burden. The ratio did not distinguish groups and should be interpreted with absolute pool size.