Association of Fontan Pathophysiology With Plasma Bile Acids
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 h...
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Elsevier
2025-02-01
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| Series: | JACC: Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772963X24008445 |
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| author | Ashish H. Shah, MD, MD-Research Arun Surendran, MSc Pedram Hassan-Tash, BSc, MD C. Nolan Turnbull, BSc Nicole Johnston, MSc David Goodlett, BSc, PhD Jun Han, PhD Robin A. Ducas, MD James W. Tam, MD Eberhard Renner, MD Todd A. Duhamel, PhD Michel Aliani, MSc, PhD Amir Ravandi, MD, PhD Richard A. Krasuski, MD |
| author_facet | Ashish H. Shah, MD, MD-Research Arun Surendran, MSc Pedram Hassan-Tash, BSc, MD C. Nolan Turnbull, BSc Nicole Johnston, MSc David Goodlett, BSc, PhD Jun Han, PhD Robin A. Ducas, MD James W. Tam, MD Eberhard Renner, MD Todd A. Duhamel, PhD Michel Aliani, MSc, PhD Amir Ravandi, MD, PhD Richard A. Krasuski, MD |
| author_sort | Ashish H. Shah, MD, MD-Research |
| collection | DOAJ |
| description | 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 %VO2 max, and had lower resting and postexercise hemodynamic parameters. Nontargeted metabolomics assessment demonstrated elevated BAs, oxylipins, and leucine metabolites in Fontan patients. Total BA as well as 17 BA components were markedly elevated in the Fontan patients. Selective BAs were negatively associated with age, degree of frailty, cardiopulmonary function, and hemodynamic parameters. Conclusions: Elevated BAs are associated with worsening Fontan physiology. These findings warrant further exploration. |
| format | Article |
| id | doaj-art-936f86dbf0af4b25b8c435e54feb3e55 |
| institution | Kabale University |
| issn | 2772-963X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | JACC: Advances |
| spelling | doaj-art-936f86dbf0af4b25b8c435e54feb3e552025-01-19T06:26:59ZengElsevierJACC: Advances2772-963X2025-02-0142101563Association of Fontan Pathophysiology With Plasma Bile AcidsAshish H. Shah, MD, MD-Research0Arun Surendran, MSc1Pedram Hassan-Tash, BSc, MD2C. Nolan Turnbull, BSc3Nicole Johnston, MSc4David Goodlett, BSc, PhD5Jun Han, PhD6Robin A. Ducas, MD7James W. Tam, MD8Eberhard Renner, MD9Todd A. Duhamel, PhD10Michel Aliani, MSc, PhD11Amir Ravandi, MD, PhD12Richard A. Krasuski, MD13Department of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada; Institute of Cardiovascular Sciences, Albrechtsen Research Center, St. Boniface Hospital, Winnipeg, MB, Canada; Address for correspondence: Dr Ashish H. Shah, St. Boniface Hospital, Y3006-409, Tache Avenue, Winnipeg, MB R2H 2A6, Canada.Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada; Institute of Cardiovascular Sciences, Albrechtsen Research Center, St. Boniface Hospital, Winnipeg, MB, CanadaDepartment of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, CanadaInstitute of Cardiovascular Sciences, Albrechtsen Research Center, St. Boniface Hospital, Winnipeg, MB, Canada; Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB, CanadaInstitute of Cardiovascular Sciences, Albrechtsen Research Center, St. Boniface Hospital, Winnipeg, MB, Canada; Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB, CanadaDepartment of Biochemistry and Microbiology, University of Victoria, Victoria, BC, CanadaGenome BC Proteomics Centre, University of Victoria, Victoria, BC, CanadaDepartment of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, CanadaDepartment of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, CanadaDepartment of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, CanadaInstitute of Cardiovascular Sciences, Albrechtsen Research Center, St. Boniface Hospital, Winnipeg, MB, Canada; Faculty of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, MB, CanadaDepartment of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, CanadaDepartment of Internal Medicine, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada; Institute of Cardiovascular Sciences, Albrechtsen Research Center, St. Boniface Hospital, Winnipeg, MB, CanadaDivision of Adult Congenital Heart Disease, Duke University Health System, Durham, NC, USABackground: 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 %VO2 max, and had lower resting and postexercise hemodynamic parameters. Nontargeted metabolomics assessment demonstrated elevated BAs, oxylipins, and leucine metabolites in Fontan patients. Total BA as well as 17 BA components were markedly elevated in the Fontan patients. Selective BAs were negatively associated with age, degree of frailty, cardiopulmonary function, and hemodynamic parameters. Conclusions: Elevated BAs are associated with worsening Fontan physiology. These findings warrant further exploration.http://www.sciencedirect.com/science/article/pii/S2772963X24008445bile acidsFontan circulationmetabolomicspathophysiology |
| spellingShingle | Ashish H. Shah, MD, MD-Research Arun Surendran, MSc Pedram Hassan-Tash, BSc, MD C. Nolan Turnbull, BSc Nicole Johnston, MSc David Goodlett, BSc, PhD Jun Han, PhD Robin A. Ducas, MD James W. Tam, MD Eberhard Renner, MD Todd A. Duhamel, PhD Michel Aliani, MSc, PhD Amir Ravandi, MD, PhD Richard A. Krasuski, MD Association of Fontan Pathophysiology With Plasma Bile Acids JACC: Advances bile acids Fontan circulation metabolomics pathophysiology |
| title | Association of Fontan Pathophysiology With Plasma Bile Acids |
| title_full | Association of Fontan Pathophysiology With Plasma Bile Acids |
| title_fullStr | Association of Fontan Pathophysiology With Plasma Bile Acids |
| title_full_unstemmed | Association of Fontan Pathophysiology With Plasma Bile Acids |
| title_short | Association of Fontan Pathophysiology With Plasma Bile Acids |
| title_sort | association of fontan pathophysiology with plasma bile acids |
| topic | bile acids Fontan circulation metabolomics pathophysiology |
| url | http://www.sciencedirect.com/science/article/pii/S2772963X24008445 |
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