Failure of the Fontan Circulation

Fontan-type surgery is the final step in the sequential palliative surgical treatment of infants born with a univentricular heart. The resulting long-term haemodynamic changes promote liver damage, leading to Fontan-associated liver disease (FALD), in virtually all patients with Fontan circulation. Owing to the lack of a uniform definition of FALD and the competitive risk of other complications developed by Fontan patients, the impact of FALD on the prognosis of these patients is currently debatable. However, based on the increasing number of adult Fontan patients and recent research interest, the European Association for The Study of the Liver and the European Reference Network on Rare Liver Diseases thought a position paper timely. The aims of the current paper are: (1) to provide a clear definition and description of FALD, including clinical, analytical, radiological, haemodynamic, and histological features; (2) to facilitate guidance for staging the liver disease; and (3) to provide evidence- and experience-based recommendations for the management of different clinical scenarios.

Fontan pathway stenosis is a well-known complication after palliation. Percutaneous stenting is effective for angiographic/hemodynamic relief of Fontan obstruction, but its clinical impact in adults remains unknown.

This was a retrospective cohort of 26 adults undergoing percutaneous stenting for Fontan obstruction from 2014 to 2022. Procedural details, functional capacity, and liver parameters were reviewed at baseline and during follow-up.

Median age was 22.5 years (interquartile range [IQR] 19-28.8 y); 69% were male. After stenting, Fontan gradient significantly decreased (2.0 ± 1.9 vs 0 [IQR 0-1] mm Hg; P < 0.005), and minimal Fontan diameter increased (11.3 ± 2.9 vs 19.3 [IQR 17-20] mm; P < 0.001). One patient developed acute kidney injury periprocedurally. During a follow-up of 2.1 years (IQR 0.6-3.7 y), 1 patient had thrombosis of the Fontan stent and 2 underwent elective Fontan re-stenting. New York Heart Association functional class improved in 50% of symptomatic patients. Changes in functional aerobic capacity on exercise testing were directly related to pre-stenting Fontan gradient (n = 7; r = 0.80; P = 0.03) and inversely related to pre-stenting minimal Fontan diameter (r = −0.79; P = 0.02). Thrombocytopenia (platelet count < 150 10⁹/L) was present in 42.3% of patients before and in 32% after the procedure (P = 0.08); splenomegaly (spleen size > 13 cm) was present in 58.3% and 58.8% (P = 0.57), respectively. Liver fibrosis (aspartate transaminase to platelet ratio index and Fibrosis-4) scores were unchanged after the procedure compared with baseline.

Percutaneous stenting in adults is safe and effective in relieving Fontan obstruction, resulting in subjective improvement in functional capacity in some. A subset of patients demonstrated improvement in markers of portal hypertension, suggesting that Fontan stenting could improve Fontan-associated liver disease in select individuals.

Une sténose dans le circuit de Fontan est une complication connue à la suite d’un traitement palliatif. La mise en place d’une endoprothèse percutanée est efficace pour la résolution angiographique et hémodynamique de l’obstruction du circuit de Fontan, mais ses répercussions cliniques chez l’adulte n’ont pas encore été élucidées.

Il s’agit d’une étude de cohorte rétrospective menée auprès de 26 adultes chez qui une endoprothèse percutanée a été mise en place entre 2014 et 2022 pour traiter une obstruction du circuit de Fontan. Les détails de l’intervention, les capacités fonctionnelles et les paramètres hépatiques ont été examinés au début de l’étude et durant le suivi.

L’âge médian était de 22,5 ans (intervalle interquartile [IIQ] : 19,0-28,8 ans); 69 % des sujets étaient des hommes. Après l’implantation de l’endoprothèse, le gradient de pression dans le circuit de Fontan a diminué de façon significative (2,0 ± 1,9 vs 0 mmHg [IIQ : 0-1]; p < 0,005), et le diamètre minimal de la voie de Fontan a augmenté (11,3 ± 2,9 vs 19,3 mm [IIQ : 17-20]; p < 0,001). Un patient a présenté une lésion rénale aiguë en période périopératoire. Au cours d’un suivi de 2,1 ans (IIQ : 0,6-3,7 ans), un patient a subi une thrombose de l’endoprothèse, et on a procédé à une nouvelle implantation non urgente d’une endoprothèse chez deux patients. Chez 50 % des patients symptomatiques, la classe fonctionnelle de la New York Heart Association a été améliorée. Les modifications de la capacité aérobie fonctionnelle lors des tests d'effort étaient directement liées au gradient de pression dans le circuit de Fontan avant l’implantation de l’endoprothèse (n = 7 ; r = 0,80 ; p = 0,03) et inversement liées au diamètre minimal de la voie de Fontan avant l’implantation de l’endoprothèse (r = −0,79 ; p = 0,02). Une thrombocytopénie (numération plaquettaire < 150 x 10⁹/L) a été observée chez 42,3 % des patients avant l’intervention et chez 32 % des patients après l’intervention (p = 0,08); une splénomégalie (taille de la rate > 13 cm) a été observée chez 58,3 % et 58,8 % (p = 0,57), respectivement. À la suite de l’intervention, les indicateurs de fibrose hépatique (indice du rapport aspartate aminotransférase/plaquettes et score Fibrosis-4) sont restés inchangés par rapport au début de l’étude.

La mise en place d’une endoprothèse percutanée chez l’adulte est un traitement sûr et efficace de l’obstruction du circuit de Fontan et, chez certains patients, elle entraîne une amélioration subjective de la capacité fonctionnelle. Une amélioration des marqueurs de l’hypertension portale a été notée dans un sous-ensemble de patients, ce qui indique que la mise en place d’une endoprothèse dans le circuit de Fontan pourrait améliorer l’état de certains patients présentant une maladie du foie associée à l'intervention de Fontan.

The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown.

The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients.

We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses.

A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]).

Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

Fontan physiology results in multiorgan dysfunction, most notably affecting the liver and kidney. We evaluated the utility of Model for End-Stage Liver Disease Excluding INR (MELD-XI) score, a score evaluating the function of both liver and kidney to identify Fontan patients at increased risk for morbidity and mortality post–heart transplant.

The Pediatric Heart Transplant Society database was queried to identify Fontan patients listed for heart transplant between January 2005 and December 2018. MELD-XI scores were calculated at listing and heart transplant. A multivariable analysis was conducted to identify risk factors for post–heart transplant mortality. Demographic, clinical characteristics, and survival differences were evaluated and compared between the high and low MELD-XI score cohorts. The impact of changing MELD-XI scores during the waitlist period on post–heart transplant outcomes was also evaluated.

Of 565 Fontan patients who underwent transplantation, 524 (93%) had calculable MELD-XI scores at the time of heart transplant: 421 calculable at listing and 392 calculable at listing and at heart transplant. On multivariable analysis, only MELD-XI score (squared) (hazard ratio, 1.007), history of protein-losing enteropathy (hazard ratio, 2.1), and ventricular assist device use at transplant (hazard ratio, 3.4) were risk factors for early phase post–heart transplant mortality. Patients with high MELD-XI scores at heart transplant had inferior survival post–heart transplant (P = .02); those in the high MELD-XI score cohort at wait listing and heart transplant tend to have the worst post–heart transplant survival; however, this was not significant (P = .42).

The MELD-XI, an easily calculated score, serves as a valuable aid in identifying pediatric Fontan patients at increased risk for post–heart transplant mortality.

Recently, many studies reported that congenital heart disease (CHD) causes liver disease. Especially, Fontan-associated liver disease (FALD) is an important late complication involving liver dysfunction, such as cirrhosis and hepatocellular carcinoma (HCC), in patients who have undergone the Fontan procedure. A previous report showed that cirrhosis and/or HCC in patients, who have undergone the Fontan procedure, were not rare late complications and were associated with high mortality rates. Moreover, low platelet counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, total bilirubin, and elevated international normalized ratio of prothrombin time could be the risk markers for FALD. This article reviewed recent articles that associate CHD with liver disease.