Hepatic and renal end-organ damage in the Fontan circulation: A report from the Australian and New Zealand Fontan Registry

Thomas G Wilson; Yves d'Udekem; David S Winlaw; Rachael L Cordina; David S Celermajer; Gavin R Wheaton; Andrew Bullock; Thomas L Gentles; Robert G Weintraub; Robert N Justo; Leeanne E Grigg; Dorothy J Radford; Winita Hardikar; Michael Cheung; Timothy M Cain; Padma Rao; Stephen I Alexander; Julian Ayer; Charlotte Verrall; Karin Du Plessis; Janina Chapman; Kathryn Rice; Judith Barry; Diana Zannino; Ajay J Iyengar; Australian and New Zealand Fontan Registry

doi:10.1016/j.ijcard.2018.07.118

Hepatic and renal end-organ damage in the Fontan circulation: A report from the Australian and New Zealand Fontan Registry

Int J Cardiol. 2018 Dec 15:273:100-107. doi: 10.1016/j.ijcard.2018.07.118. Epub 2018 Jul 25.

Authors

Thomas G Wilson¹, Yves d'Udekem², David S Winlaw³, Rachael L Cordina⁴, David S Celermajer⁴, Gavin R Wheaton⁵, Andrew Bullock⁶, Thomas L Gentles⁷, Robert G Weintraub⁸, Robert N Justo⁹, Leeanne E Grigg¹⁰, Dorothy J Radford¹¹, Winita Hardikar¹², Michael Cheung¹³, Timothy M Cain¹⁴, Padma Rao¹⁴, Stephen I Alexander¹⁵, Julian Ayer³, Charlotte Verrall¹⁵, Karin Du Plessis¹⁶, Janina Chapman¹⁶, Kathryn Rice⁷, Judith Barry⁷, Diana Zannino¹⁶, Ajay J Iyengar¹⁷; Australian and New Zealand Fontan Registry

Affiliations

¹ Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, Faculty of Medicine, The University of Melbourne, Victoria, Australia.
² Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, Faculty of Medicine, The University of Melbourne, Victoria, Australia; Department of Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia. Electronic address: [email protected].
³ The Heart Centre for Children, The Children's Hospital at Westmead, Sydney, Australia; Department of Paediatrics, University of Sydney, Sydney, Australia.
⁴ Department of Paediatrics, University of Sydney, Sydney, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia.
⁵ Department of Cardiology, Women's and Children's Hospital, Adelaide, Australia.
⁶ Children's Cardiac Centre, Princess Margaret Hospital for Children, Perth, Australia.
⁷ Greenlane Paediatric and Congenital Cardiac Service, Starship Children's Hospital, Auckland, New Zealand.
⁸ Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, Faculty of Medicine, The University of Melbourne, Victoria, Australia; Department of Cardiology, The Royal Children's Hospital, Melbourne, Australia.
⁹ Queensland Paediatric Cardiac Service, Lady Cilento Children's Hospital, Brisbane, Queensland, Australia.
¹⁰ Department of Cardiology, The Royal Melbourne Hospital, Melbourne, Australia.
¹¹ Adult Congenital Heart Unit, The Prince Charles Hospital, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
¹² Department of Gastroenterology, The Royal Children's Hospital, Melbourne, Australia.
¹³ Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Cardiology, The Royal Children's Hospital, Melbourne, Australia.
¹⁴ Medical Imaging Department, The Royal Children's Hospital, Melbourne, Australia.
¹⁵ The Heart Centre for Children, The Children's Hospital at Westmead, Sydney, Australia.
¹⁶ Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia.
¹⁷ Heart Research Group, Murdoch Children's Research Institute, Melbourne, Australia; Department of Paediatrics, Faculty of Medicine, The University of Melbourne, Victoria, Australia; Department of Cardiac Surgery, The Royal Children's Hospital, Melbourne, Australia.

PMID: 30060970
DOI: 10.1016/j.ijcard.2018.07.118

Abstract

Background: Hepatic and renal dysfunction have been observed in survivors of the Fontan procedure, however their incidence and associated factors remain poorly defined.

Methods: A total of 152 participants from a Registry of 1528 patients underwent abdominal ultrasound, transient elastography (FibroScan), serum fibrosis score (FibroTest), in vivo Tc-99m DTPA measurement of glomerular filtration rate (mGFR), and urine albumin-creatinine ratio (ACR).

Results: Mean age and time since Fontan were 19.8 ± 9.3 and 14.1 ± 7.6 years, respectively. Features suggestive of hepatic fibrosis were observed on ultrasound in 87/143 (61%) and no patient was diagnosed with hepatocellular carcinoma. FibroScan median kPa was ≥10 in 117/133 (88%), ≥15 in 75/133 (56%), and ≥20 in 41/133 (31%). Fifty-four patients (54/118, 46%) had a FibroTest score ≥0.49 (equivalent to ≥F2 fibrosis). FibroTest score correlated with FibroScan value (r = 0.24, p = 0.015) and ACR (r = 0.29, p = 0.002), and patients with ultrasound features of hepatic fibrosis had a higher FibroScan median kPa (19.5 vs 15.4, p = 0.002). Renal impairment was mild (mGFR 60-89 ml/min/1.73 m²) in 46/131 (35%) and moderate (mGFR 30-59 ml/min/1.73 m²) in 3/131 (2%). Microalbuminuria was detected in 52/139 participants (37%). By multivariable analysis, time since Fontan was associated with increased FibroScan median kPa (β = 0.89, 95% CI 0.54-1.25, p = 0.002) and decreased mGFR (β = -0.77, 95% CI -1.29-0.24, p = 0.005).

Conclusions: In the second decade after Fontan hepatic and renal structure and function are abnormal in a significant number of patients: close to 60% have ultrasonographic evidence of structural hepatic abnormalities, 46% have elevated serum hepatic fibrosis scores, and 57% have either reduced glomerular filtration rate or microalbuminuria. Hepatic and renal function should be monitored for potential impacts on outcomes after Fontan completion.

Keywords: Cross-sectional studies; Fontan procedure; Liver fibrosis; Renal function; Serological markers.

MeSH terms

Adolescent
Adult
Australia / epidemiology
Cross-Sectional Studies
Echocardiography / trends
Female
Fontan Procedure / adverse effects
Fontan Procedure / trends*
Glomerular Filtration Rate / physiology
Humans
Kidney / diagnostic imaging*
Kidney / physiology
Liver / diagnostic imaging*
Liver / physiology
Male
New Zealand / epidemiology
Registries*
Research Report*
Young Adult