Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance
Background Fontan circulation (FC) in complex congenital heart disease is characterized by altered hemodynamics and associated with Fontan‐associated liver disease. Patients with FC may exhibit abnormalities in cholate clearance due to abnormal perfusion. We aimed to compare cholate clearance in adu...
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| Format: | Article |
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Wiley
2025-04-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.039479 |
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| author | Yuli Y. Kim Annique Nyman Yuan‐Shung Huang Alexis Z. Tomlinson Michael P. McRae Greg T. Everson Sumeet Vaikunth Benjamin Rosenthal Jack Rychik Maarouf A. Hoteit |
| author_facet | Yuli Y. Kim Annique Nyman Yuan‐Shung Huang Alexis Z. Tomlinson Michael P. McRae Greg T. Everson Sumeet Vaikunth Benjamin Rosenthal Jack Rychik Maarouf A. Hoteit |
| author_sort | Yuli Y. Kim |
| collection | DOAJ |
| description | Background Fontan circulation (FC) in complex congenital heart disease is characterized by altered hemodynamics and associated with Fontan‐associated liver disease. Patients with FC may exhibit abnormalities in cholate clearance due to abnormal perfusion. We aimed to compare cholate clearance in adults with FC to healthy controls and explore associations between cholate clearance and clinical features. Methods and Results This is a prospective cohort study of patients with FC ≥18 years of age between 2019 and 2022. Systemic and portal hepatic clearance of cholate was assessed using a dual cholate clearance assay (HepQuant Shunt), measuring systemic and portal hepatic filtration rates (HFRs). Systemic HFR/portal HFR ratio (SHUNT%) was calculated. Participants with FC and healthy controls were compared using the Fisher exact test and Wilcoxon test. Univariable regression and multivariable analyses determined associations with clinical variables. There were 35 participants with FC (54% women; median age 29.0 years [interquartile range, 24.0–36.0], 91% White) and 26 controls. In addition to lower platelet counts and higher aspartate aminotransferase to platelet ratio index, and Fibrosis‐4 indices, FC participants had lower systemic HFR and portal HFR. SHUNT% was comparable with controls but ranged from 8% to 76%, with 8 (23%) having SHUNT% >30%. In those with FC, increase in SHUNT% was associated with elevated Fontan pressure, higher aortopulmonary collateral flow, decreased oxygen saturation, elevated NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, thrombocytopenia, and Fibrosis‐4 ≥1.45. Conclusions Cholate clearance, as defined by systemic and portal HFR, is impaired in those with FC. Features of worse Fontan physiology correlate with higher SHUNT%, supporting the hypothesis that hemodynamic derangements play a role in progression of Fontan‐associated liver disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03726229. |
| format | Article |
| id | doaj-art-fa1c37b888084cae8628f0ca0d4cf09c |
| institution | DOAJ |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-fa1c37b888084cae8628f0ca0d4cf09c2025-08-20T03:07:50ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-04-0114710.1161/JAHA.124.039479Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate ClearanceYuli Y. Kim0Annique Nyman1Yuan‐Shung Huang2Alexis Z. Tomlinson3Michael P. McRae4Greg T. Everson5Sumeet Vaikunth6Benjamin Rosenthal7Jack Rychik8Maarouf A. Hoteit9Division of Cardiology Hospital of the University of Pennsylvania Philadelphia PADivision of Cardiology Children’s Hospital of Philadelphia Philadelphia PAData Science and Biostatistics Unit, Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia Philadelphia PAData Science and Biostatistics Unit, Department of Biomedical and Health Informatics Children’s Hospital of Philadelphia Philadelphia PAHepQuant LLC Denver COHepQuant LLC Denver CODivision of Cardiology Hospital of the University of Pennsylvania Philadelphia PADivision of Hepatology Hospital of the University of Pennsylvania Philadelphia PADivision of Cardiology Children’s Hospital of Philadelphia Philadelphia PADivision of Hepatology Hospital of the University of Pennsylvania Philadelphia PABackground Fontan circulation (FC) in complex congenital heart disease is characterized by altered hemodynamics and associated with Fontan‐associated liver disease. Patients with FC may exhibit abnormalities in cholate clearance due to abnormal perfusion. We aimed to compare cholate clearance in adults with FC to healthy controls and explore associations between cholate clearance and clinical features. Methods and Results This is a prospective cohort study of patients with FC ≥18 years of age between 2019 and 2022. Systemic and portal hepatic clearance of cholate was assessed using a dual cholate clearance assay (HepQuant Shunt), measuring systemic and portal hepatic filtration rates (HFRs). Systemic HFR/portal HFR ratio (SHUNT%) was calculated. Participants with FC and healthy controls were compared using the Fisher exact test and Wilcoxon test. Univariable regression and multivariable analyses determined associations with clinical variables. There were 35 participants with FC (54% women; median age 29.0 years [interquartile range, 24.0–36.0], 91% White) and 26 controls. In addition to lower platelet counts and higher aspartate aminotransferase to platelet ratio index, and Fibrosis‐4 indices, FC participants had lower systemic HFR and portal HFR. SHUNT% was comparable with controls but ranged from 8% to 76%, with 8 (23%) having SHUNT% >30%. In those with FC, increase in SHUNT% was associated with elevated Fontan pressure, higher aortopulmonary collateral flow, decreased oxygen saturation, elevated NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, thrombocytopenia, and Fibrosis‐4 ≥1.45. Conclusions Cholate clearance, as defined by systemic and portal HFR, is impaired in those with FC. Features of worse Fontan physiology correlate with higher SHUNT%, supporting the hypothesis that hemodynamic derangements play a role in progression of Fontan‐associated liver disease. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03726229.https://www.ahajournals.org/doi/10.1161/JAHA.124.039479congenital heart diseaseFontanFontan‐associated liver diseasesingle ventricle |
| spellingShingle | Yuli Y. Kim Annique Nyman Yuan‐Shung Huang Alexis Z. Tomlinson Michael P. McRae Greg T. Everson Sumeet Vaikunth Benjamin Rosenthal Jack Rychik Maarouf A. Hoteit Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease congenital heart disease Fontan Fontan‐associated liver disease single ventricle |
| title | Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance |
| title_full | Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance |
| title_fullStr | Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance |
| title_full_unstemmed | Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance |
| title_short | Alterations in Liver Perfusion in Adults With Fontan Circulation as Assessed by Dual Cholate Clearance |
| title_sort | alterations in liver perfusion in adults with fontan circulation as assessed by dual cholate clearance |
| topic | congenital heart disease Fontan Fontan‐associated liver disease single ventricle |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.039479 |
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