Advanced Statistical Analysis of Factors Influencing the Onset of Late Fontan Failure

All articles of this category (opens in new window) Background: Due to advances in surgical techniques, preoperative patient selection, and postoperative surveillance, most Fontan palliated patients reach adulthood. Although potential risk factors for mortality after the Fontan operation have been identified in cross-sectional studies, conventional statistics seem not to be sufficient to identify risk factors properly. In this analysis, we collected longitudinal data and used advanced statistical methods to get a better understanding of the interaction between different variables and their influence on late Fontan failure. Methods: A total of 230 consecutive datasets from a total of 630 patients who underwent Fontan palliation at DHZC between 1986 and 2021 were enrolled in the retrospective study until August 2025. Each dataset contained approximately 100 variables. Statistical analysis of the factors influencing Fontan failure included multivariate Cox regression, classification and regression trees (CART), and parametric regression with two time scales for the categorical variables main diagnosis, Fontan modification, age at Fontan procedure, and presence of heterotaxy. Results: Multivariate Cox regression revealed a higher risk for late Fontan failure in patients with hypoplastic left heart syndrome (HLHS, HR: 4.56; p = 0.001) or atrioventricular septal defect (AVSD, HR: 3.92; p = 0.006) compared with tricuspid atresia (TA). Hazard function showed that main diagnoses other than TA are associated with a higher risk for Fontan failure over time, especially if the age at Fontan procedure was higher (6 vs. 3 years of age). In the CART analysis, the combination of absence of HLHS and AVSD and age at Fontan procedure < 18 years had the longest Fontan failure-free median survival time (26.6 years). Conclusion: The preliminary results demonstrated clear statistical superiority in relation to subsequent Fontan failure for TA vs. HLHS or AVSD, and for surgery performed before 3 years of age vs. after 6 years of age. Overall, patients without HLHS or AVSD who underwent surgery during childhood or adolescence had the longest survival without Fontan failure. The final results from the total cohort might bring a more precise understanding of the risk factors for Fontan failure. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany