Heart Transplantation for the Failing Fontan

doi:10.1016/j.athoracsur.2013.05.087

The Annals of Thoracic Surgery

Volume 96, Issue 4, October 2013, Pages 1413-1419

https://doi.org/10.1016/j.athoracsur.2013.05.087 Get rights and content

Background

Patients with failing Fontan circulation are at high risk for complications after heart transplantation (HTx) because of multiple prior operations, elevated panel reactive antibody, hepatic dysfunction, coagulopathy, protein-losing enteropathy (PLE), and poor nutrition. The purpose of this review was to evaluate the outcome of HTx for these patients, including those who are status post-Fontan conversion.

Methods

Of 206 heart transplants at Ann & Robert H. Lurie Children’s Hospital of Chicago from 1990 to 2012, 22 patients had a failing Fontan. Median age at HTx was 12.2 years, median interval from initial Fontan to HTx was 7.1 years. Potential preoperative risk factors included PLE (n = 15), mechanical ventilation (n = 8), prior Fontan conversion (n = 7), renal failure (n = 3), and plastic bronchitis (n = 2) Median number of prior operations was 3. Donor branch pulmonary arteries were used in 17 patients.

Results

There were 5 early deaths (23%), due to graft failure (1), pulmonary hypertension (1), and infection (3). There were 3 late deaths (13%) at 1, 5, and 8 years. Two of 3 patients with preoperative renal failure died. Survivors who had preoperative PLE (n = 11) and preoperative plastic bronchitis (n = 2) experienced complete resolution of these pathological conditions after heart transplantation. Median length of stay was 30 days. Five of 7 Fontan conversion patients survived, and 6 of 8 preoperative ventilator-dependent patients survived. One-, 5-, and 10-year survival was 77%, 66%, and 45%, respectively.

Conclusions

The operative mortality of HTx for patients with a failing Fontan is high. Using the donor branch pulmonary arteries greatly facilitated the transplant. Because infection caused the majority of early deaths, lower intensity initial immunosuppression may be warranted. Transplantation was successful in treating PLE in all survivors. Prior Fontan conversion was not a risk factor. Preoperative mechanical ventilation was not a risk factor. Preoperative renal failure may be a relative contraindication. Earlier referral of failing Fontan patients may improve results.

Section snippets

Patients and Methods

We utilized the congenital cardiac surgical database at Ann & Robert H. Lurie Children’s Hospital of Chicago to identify patients who had HTx from 1990 to 2012. The Lurie Children’s Institutional Review Board approved this study and granted a waiver of informed consent. Of 206 patients, 22 had a previous Fontan operation. Mean age at HTx was 14.9 ± 11.8 years; median age was 12.2 years. The mean interval from initial Fontan procedure to HTx was 8.3 ± 7.7 years; median interval was 7.1 years.

Results

Among 22 patients who underwent HTx after a Fontan procedure, there were 5 early deaths (23%), due to graft failure (1), pulmonary hypertension (1), and infection (3). There were 3 late deaths (13%) at 1, 5, and 8 years. Mean donor ischemia time was 3.1 ± 1.0 hours. Median postoperative length of stay was 30.5 days. Two of 3 patients who had preoperative renal failure died. Of 7 patients who had undergone Fontan conversion, 5 survived. Six of 8 patients who were ventilator dependent

Comment

The Fontan operation was first performed in 1968. It was an atriopulmonary connection in a patient with tricuspid atresia, and it launched the surgical treatment of functionally univentricular hearts [8]. However, the absence of two distinct ventricular chambers has led to what is termed “the failing Fontan circulation” in some of these patients 3, 4. Carey and colleagues [1] reviewed 9 patients undergoing HTx for a failed Fontan in the first report on this topic. The operative mortality was

References (22)

Y. d'Udekem et al.
Predictors of survival after single-ventricle palliation: the impact of right ventricular dominance
J Am Coll Cardiol
(2012)
E.R. Griffiths et al.
Evaluating failing Fontans for heart transplantation: predictors of death
Ann Thorac Surg
(2009)
J.P. Jacobs et al.
Pediatric cardiac transplantation in children with high panel reactive antibody
Ann Thorac Surg
(2004)
J.R. Kovach et al.
Comparison of risk factors and outcomes for pediatric patients listed for heart transplantation after bidirectional Glenn and after Fontan: an analysis from the Pediatric Heart Transplant Study
J Heart Lung Transplant
(2012)
J.M. Lamour et al.
The effect of age, diagnosis, and previous surgery in children and adults undergoing heart transplantation for congenital heart disease
J Am Coll Cardiol
(2009)
T. Karamlou et al.
Impact of single-ventricle physiology on death after heart transplantation in adults with congenital heart disease
Ann Thorac Surg
(2012)
K.R. Kanter et al.
Heart transplantation in children with a Fontan procedure
Ann Thorac Surg
(2011)
K.E. Simpson et al.
Failed Fontan heart transplant candidates with preserved vs impaired ventricular ejection: 2 distinct patient populations
J Heart Lung Transplant
(2012)
J. Odim et al.
Peri-operative renal function and outcome after orthotopic heart transplantation
J Heart Lung Transplant
(2006)
R.K. Voeller et al.
Trends in the indications and survival in pediatric heart transplants: a 24-year single-center experience in 307 patients
Ann Thorac Surg
(2012)

A. Gamba et al.

Heart transplantation in patients with previous Fontan operations

J Thorac Cardiovasc Surg

(2004)

Cited by (89)

Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation
2023, Journal of the American College of Cardiology
An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited.
The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population.
A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of “failing” Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, “failing Fontan” diagnosis by treating cardiologist, or admission for heart failure.
A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade.
In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.
Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation
2023, Journal of the American College of Cardiology
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.
The majority of pediatric Fontan patients have excellent post-transplant survival
2023, Journal of Thoracic and Cardiovascular Surgery
Many pediatric Fontan patients require heart transplant, but this cohort is understudied given the difficulty in identifying these patients in national registries. We sought to characterize survival post-transplant in a large cohort of pediatric patients undergoing the Fontan.
The United Network for Organ Sharing and Pediatric Health Information System were used to identify Fontan heart transplant recipients aged less than 18 years (n = 241) between 2005 and 2022. Decompensation was defined as the presence of extracorporeal membrane oxygenation, ventilation, hepatic/renal dysfunction, paralytics, or total parenteral nutrition at transplant.
Median age at transplant was 9 (interquartile range, 5-12) years. Median waitlist time was 107 (37-229) days. Median volume across 32 center was 8 (3-11) cases. Approximately half (n = 107, 45%) of recipients had 1A/1 initial listing status. Sixty-four patients (28%) were functionally impaired at transplant, 10 patients (4%) were ventilated, and 18 patients (8%) had ventricular assist device support. Fifty-nine patients (25%) had hepatic dysfunction, and 15 patients (6%) had renal dysfunction. Twenty-one patients (9%) were dependent on total parenteral nutrition. Median postoperative stay was 24 (14-46) days, and in-hospital mortality was 7%. Kaplan–Meier analysis showed 1- and 5-year survivals of 89% (95% CI, 85-94) and 74% (95% CI, 81-86), respectively. Kaplan–Meier of Fontan patients without decompensation (n = 154) at transplant demonstrated 1- and 5-year survivals of 93% (95% CI, 88-97) and 88% (95% CI, 82-94), respectively. In-hospital mortality was higher in decompensated patients (11% vs 4%, P = .023). Multivariable analysis showed that decompensation predicted worse post-transplant survival (hazard ratio, 2.47; 95% CI, 1.16-5.22; P = .018), whereas older age at transplant predicted superior post-transplant survival (hazard ratio, 0.89/year; 95% CI, 0.80-0.98; P = .019).
Pediatric Fontan post-transplant outcomes are promising, although early mortality remains high. For nondecompensated pediatric patients at transplant without end-organ disease (>63% of cohort), early mortality is circumvented and post-transplant survival is excellent and similar to all pediatric transplantation.
Canadian Cardiovascular Society 2022 Guidelines for Cardiovascular Interventions in Adults With Congenital Heart Disease
2022, Canadian Journal of Cardiology
Interventions in adults with congenital heart disease (ACHD) focus on surgical and percutaneous interventions in light of rapidly evolving ACHD clinical practice. To bring rigour to our process and amplify the cumulative nature of evidence ACHD care we used the ADAPTE process; we systematically adjudicated, updated, and adapted existing guidelines by Canadian, American, and European cardiac societies from 2010 to 2020. We applied this to interventions related to right and left ventricular outflow obstruction, tetralogy of Fallot, coarctation, aortopathy associated with bicuspid aortic valve, atrioventricular canal defects, Ebstein anomaly, complete and congenitally corrected transposition, and patients with the Fontan operation. In addition to tables indexed to evidence, clinical flow diagrams are included for each lesion to facilitate a practical approach to clinical decision-making. Excluded are recommendations for pacemakers, defibrillators, and arrhythmia-directed interventions covered in separate designated documents. Similarly, where overlap occurs with other guidelines for valvular interventions, reference is made to parallel publications. There is a paucity of high-level quality of evidence in the form of randomized clinical trials to support guidelines in ACHD. We accounted for this in the wording of the strength of recommendations put forth by our national and international experts. As data grow on long-term follow-up, we expect that the evidence driving clinical practice will become increasingly granular. These recommendations are meant to be used to guide dialogue between clinicians, interventional cardiologists, surgeons, and patients making complex decisions relative to ACHD interventions.
Les interventions chez les adultes atteints de cardiopathie congénitale (AACC) sont axées sur des interventions chirurgicales et percutanées, tenant compte de l'évolution rapide de la pratique clinique dans ce domaine. Afin d'apporter une certaine rigueur à notre démarche et d'amplifier la propension cumulative des données probantes concernant les AACC, nous avons utilisé le processus ADAPTE; nous avons systématiquement évalué, mis à jour et adapté les lignes directrices existantes des sociétés de cardiologie canadiennes, américaines et européennes de 2010 à 2020. Nous avons appliqué cette méthode aux interventions liées à l'obstruction du débit ventriculaire droit et gauche, à la tétralogie de Fallot, à la coarctation, à l'aortopathie associée à une dysfonction de la valve aortique bicuspide, aux anomalies du canal auriculo-ventriculaire, à l'anomalie d'Ebstein, à la transposition congénitale complète corrigée, et aux patients ayant subi une intervention de Fontan. En plus des tables indexées aux évidences, des diagrammes de flux cliniques sont inclus pour chaque affection afin de faciliter une approche pratique de la prise de décision clinique. En sont exclues : les recommandations concernant les stimulateurs cardiaques, les défibrillateurs et les interventions dirigées envers les arythmies, qui font l'objet de documents distincts. De la même façon, en cas de chevauchement avec d'autres directives sur les interventions valvulaires, il est fait référence à des publications parallèles. Il y a une pénurie d’évidences de haute qualité sous forme d'essais cliniques randomisés pour appuyer les lignes directrices concernant les AACC. Nous en avons tenu compte dans la formulation de l’amplitude des recommandations formulées par nos experts nationaux et internationaux. Au fur et à mesure que les données sur le suivi à long terme s'accumulent, nous nous attendons à ce que les preuves à la base de la pratique clinique deviennent de plus en plus granulaires. Ces recommandations sont destinées à guider la discussion entre les cliniciens, les cardiologues interventionnels, les chirurgiens et les patients qui doivent prendre des décisions complexes concernant les interventions chez les AACC.
Heart Transplant Indications, Considerations, and Outcomes in Fontan Patients: Age-Related Nuances, Transplant Listing, and Disease-Specific Indications
2022, Canadian Journal of Cardiology
Citation Excerpt :
Future studies should focus attention on patient and surgical-specific risk factors, as well as mitigation strategies, including judicious application of combined heart and liver transplant.25,27,77 Most reports of HTx for PLE and/or PB show complete resolution in survivors.16,31,35,60,68,69,78 A diagnosis of PLE did not impact waitlist or post-transplant survival in most single-centre reports.
In the current era, 5%-10% of Fontan patients die or need a transplant in childhood, and approximately 50% will experience the same fate by age 40 years. Heart transplant (HTx) can be successful for selected children and adults with Fontan circulatory failure of any mechanism, with a 1-year post-transplant survival rate approaching 90% in children and 80% in the largest single-centre adult Fontan HTx experience. Protein-losing enteropathy and plastic bronchitis can be expected to resolve post-transplant, and limited data suggest patients with Fontan-associated liver disease who survive HTx can expect improvement in liver health. Early Fontan failure, within 12 months of Fontan completion, is not easily rescued by HTx, and late referrals and failure to refer adult patients remain problematic. Very little is known about the numbers of patients who are not referred, are turned down following assessment for HTx, or die on the waiting list—numbers that are needed to understand the complete picture of HTx in the Fontan population and to identify where best to focus quality-improvement efforts. Recent revisions to listing prioritization in Canada with considerations specific to the Fontan population aim to mitigate the fact that the status-listing criteria are not tailored to the congenital heart population. Transplanting high-risk children prior to Fontan completion, developing adult congenital heart disease transplant centres with expertise that can also offer combined heart-liver transplant when appropriate, and improving single-ventricle mechanical support options and criteria for both adults and children may help mitigate the early post-listing mortality.
De nos jours, les patients qui ont subi l’intervention de Fontan meurent ou doivent subir une transplantation cardiaque pendant leur enfance dans 5 à 10 % des cas ou avant l’âge de 40 ans dans environ 50 % des cas. La transplantation cardiaque (TC) peut être pratiquée avec succès chez certains enfants et adultes qui ont subi l’intervention de Fontan et qui viennent à présenter une insuffisance circulatoire, quelle qu’en soit la cause. Par exemple, dans le cadre de la plus grande expérience monocentrique portant sur la TC postérieure à l’intervention de Fontan, le taux de survie à 1 an des personnes ayant subi une transplantation était de près de 90 % chez les enfants et de 80 % chez les adultes suivis. On peut s’attendre à ce que l’entéropathie avec perte de protéines et la bronchite plastique se résolvent après la transplantation, et les données limitées dont nous disposons donnent à penser que les patients atteints d’une maladie du foie associée à la circulation de Fontan qui survivent à la TC devraient voir leur fonction hépatique s’améliorer. La TC ne permet pas de remédier facilement à l’échec rapide de l’intervention de Fontan, c’est-à-dire moins de 12 mois après sa réalisation, et l’aiguillage tardif ou l’absence d’aiguillage des patients adultes vers les services de transplantation restent problématiques. On sait très peu de choses sur le nombre de patients qui ne sont pas aiguillés vers les services de transplantation, qui ne sont pas retenus comme candidats à la TC au terme d’une évaluation de leur admissibilité ou qui meurent dans l’attente d’une TC. Des données quantitatives sont nécessaires pour se faire une idée plus complète de la question des TC chez les patients ayant subi l’intervention de Fontan et pour mieux cibler nos efforts en matière d’amélioration de la qualité. Les révisions récentes de la priorisation des inscriptions au Canada tiennent compte spécifiquement du cas des patients ayant subi l’intervention de Fontan et visent à pallier le fait que les critères d’inscription en fonction du statut des patients ne sont pas adaptés au contexte des cardiopathies congénitales. Le recours à la transplantation chez les enfants à haut risque en amont de l’intervention de Fontan, la création de centres de transplantation ayant la capacité de prendre en charge les adultes atteints de cardiopathies congénitales et possédant l’expertise nécessaire pour pratiquer une transplantation combinée cœur-foie, au besoin, et l’amélioration des options et des critères d’assistance monoventriculaire mécanique applicables chez les adultes et les enfants peuvent contribuer à limiter la mortalité précoce parmi les patients en attente de transplantation.
Heart transplantation after Fontan operation
2022, JTCVS Techniques

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Original articleCongenital heart surgeryHeart Transplantation for the Failing Fontan

Background

Methods

Results

Conclusions

Section snippets

Patients and Methods

Results

Comment

J Am Coll Cardiol

Ann Thorac Surg

Ann Thorac Surg

J Heart Lung Transplant

J Am Coll Cardiol

Ann Thorac Surg

Ann Thorac Surg

J Heart Lung Transplant

J Heart Lung Transplant

Ann Thorac Surg

J Thorac Cardiovasc Surg

Original article
Congenital heart surgery
Heart Transplantation for the Failing Fontan