Fontan and Baudet1 initially described the Fontan operation, which involved applying right ventricular exclusion to a patient with tricuspid atresia. The results of patients with univentricular physiology have improved over the years due to a variety of successive advancements in surgical procedures.2–4 Total cavopulmonary connection (TCPC) as a contemporary approach was established. However, despite the improvements in outcomes, Fontan patients still face significant challenges.5–7 Although patients can have a good function status with a well-functioning Fontan circulation, numerous complications will occur, which affect their life expectancy.8–10 The complications include heart failure, protein-losing enteropathy (PLE), plastic bronchitis (PB), Fontan-associated liver disease (FALD), arrhythmias, and thrombosis. Patients who suffer from Fontan failure will pose challenges to management.11 Therefore, the long-term outcome of the Fontan procedure is still being understood.

The aim of our study was to estimate the early and long-term outcomes of Fontan patients and to investigate the risk factors for adverse outcomes.

In this study, we evaluated the clinical outcomes of patients undergoing the Fontan procedure. The primary findings were as follows: (1) The early mortality rate was 5.5%, with significant associations observed with asplenia, one-stage TCPC, and prolonged CPB time. (2) The incidence of Fontan failure was 9.0%, which was significantly influenced by the presence of heterotaxy and elevated pulmonary artery pressure.

Most of our patients underwent extracardiac conduit TCPC, whereas the lateral tunnel technique was less frequently utilized. Although computational fluid dynamics simulation models have not demonstrated a clear advantage of the extracardiac conduit over the lateral tunnel,12 the extracardiac approach offers the benefit of avoiding aortic cross clamping and intra-atrial suturing. In our cohort, 35.4% of procedures were performed without cross clamping, which theoretically may reduce the incidence of arrhythmias. A recent meta-analysis by Ben Ali et al.13 supports this notion, indicating that the extracardiac conduit Fontan procedure preserves sinus node function and significantly reduces the incidence of long-term postoperative arrhythmias. Furthermore, studies have demonstrated more favorable long-term survival and exercise outcomes with the extracardiac conduit.14,15 However, the adequacy of conduit size remains a critical concern due to its lack of growth potential. Both oversized and undersized conduits are associated with significant morbidity and mortality. The modified Fontan procedure, utilizing a direct TCPC (dTCPC) with entirely autologous vessels, appears to offer a promising solution. As previously reported,16 we have investigated this novel approach in selected patients, yielding favorable long-term outcomes and potential for growth.

Following multiple modifications to the Fontan procedure, both early and late postoperative mortality rates have significantly declined. In our cohort, the early mortality rate was 5.5%. One-stage TCPC was performed in 18.25% of cases but accounted for 40.9% of early deaths. The overall early mortality rate for one-stage TCPC was 12.3% (9/73), with most of these procedures (84.9%) performed within the first decade. Over time, staging of the Fontan palliation has been recognized as an optimal strategy to reduce mortality at Fontan completion, particularly in high-risk patients. Staged TCPC allows for gradual ventricular unloading, thereby improving hemodynamics. However, significant interstage mortality remains a concern,17 and the rate of final Fontan completion remains suboptimal even with a staged approach. Patients deemed unsuitable for eventual Fontan completion are often left with a bidirectional cavopulmonary shunt for extended periods. Post-Fontan completion, long-term survival rates were comparable between one-stage and staged TCPC.

Consistent with previous studies,18 we identified asplenia as a significant predictor of early mortality, strongly associated with heterotaxy in our cohort (14/17). Patients with complex anatomical variations, such as direct hepatic venous return to the atrium, often required additional surgical interventions. Furthermore, asplenia was associated with decreased long-term survival.19

With advancements in management strategies, the prospective survival of Fontan patients has steadily improved, surpassing earlier expectations. In our cohort, the overall survival rates post-Fontan surgery were 97.5%, 92.6%, and 90.0% at 5, 10, and 15 years, respectively. Despite these improvements, postoperative complications remain a significant challenge, necessitating lifelong management. Fontan failure represents the most common cause of death, with notable complications including PLE, PB, FALD, arrhythmias, significant AVVR, and thromboembolism.

The Fontan population continues to grow, driven by advancements in surgical techniques. However, Fontan circulation is not a definitive treatment and is associated with chronic multisystem morbidity. Risk stratification remains challenging, and sudden adverse events can occur unpredictably. A survey conducted by Elder et al.20 revealed that cardiologists were only marginally able to predict which Fontan patients were at risk for major adverse events over a one-year period. While risk factors for adverse events in Fontan patients have been extensively studied, consensus remains elusive. Late mortality and failure risk factors included significant AVVR, heterotaxy, high pulmonary arterial pressure, morphologic right ventricle. The risk factors for long-term outcomes vary in different studies. In our study, heterotaxy and elevated pulmonary artery pressure were associated with late Fontan failure. However, Fontan failure is difficult to predict with many patients seemingly clinically well with normal ventricular function. Significant differences in cardiac diagnoses further complicate risk stratification, underscoring the need for international collaboration to achieve robust risk assessment.

This study has several limitations that must be acknowledged. First, it was conducted at a single center, which may limit the generalizability of the findings. Second, the retrospective nature of the study introduces inherent biases related to patient selection and data availability.

The early mortality rate was 5.5% while the overall survival rates after Fontan surgery were 97.5%, 92.6%, 90.0% at 5, 10, 15 years, respectively. Staging Fontan palliation reduced early mortality but did not show any benefit on long-term outcome. Asplenia and long CPB time were the other risk factors for early mortality. Heterotaxy was associated with late Fontan failure.

The current study was approved by the Institutional Review Board and Hospital Research Ethics Committee of Guangdong Provincial People's Hospital (GDREC2019338H).

This work was supported by the National Natural Science Foundation of China (grant number 82300268, 2024), Science and Technology Planning Project of Guangdong Province, China (No. 2019B020230003), Science and Technology Projects in Guangzhou, China (202206010049), Guangdong Special Funds for Science and Technology Innovation Strategy, China (Stability Support for Scientific Research Institutions Affiliated to Guangdong Province, No. KD022023019).

The authors declare no conflict of interest.