Document Type
Article
Publication Date
8-19-2025
Identifier
DOI: 10.1161/JAHA.125.041348
Abstract
BACKGROUND: In the FUEL (Fontan Udenafil Exercise Longitudinal) trial, a positive treatment effect was identified for outcomes at the ventilatory anaerobic threshold but not for the primary outcome, oxygen consumption (Vo2 in participants with near-normal baseline exercise performance.
METHODS: Participants were divided into subgroups by baseline predicted peak Vo2 (< 80% versus ≥80%). Treatment effect was evaluated in those with a baseline peak Vo2 < 80% predicted and linear regression was performed to examine the interaction between subgroup and response to therapy for the primary and secondary outcomes.
RESULTS: Of the 379 participants with paired exercise data, 302 (80%) had a baseline peak Vo2 < 80% predicted. In this subgroup, the primary outcome of peak Vo2 improved significantly after 6 months of udenafil treatment, when compared with placebo (0.23±4.17 mL/kg per min versus -0.90±3.74 mL/kg per min; P=0.021). Secondary outcome measures, including Vo2 at ventilatory anaerobic threshold (P=0.023), work at ventilatory anaerobic threshold (P=0.032), and the myocardial performance index (P=0.007) were all significantly improved as well. A significant interaction was found between exercise subgroups and response to udenafil for peak Vo2 (P=0.036) but not for other outcomes.
CONCLUSIONS: In this post hoc subgroup analysis, after exclusion of patients with Fontan circulation with near-normal baseline peak Vo2, a positive treatment effect of udenafil was identified for the primary outcome of peak Vo2. The interaction between baseline peak Vo2 and treatment may have influenced the outcome of the FUEL trial.
REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT0274115.
Journal Title
J Am Heart Assoc
Volume
14
Issue
16
First Page
041348
Last Page
041348
MeSH Keywords
Adolescent; Child; Female; Humans; Male; Anaerobic Threshold; Double-Blind Method; Exercise Test; Exercise Tolerance; Fontan Procedure; Heart Defects, Congenital; Oxygen Consumption; Phosphodiesterase 5 Inhibitors; Pyrimidines; Sulfonamides; Time Factors; Treatment Outcome; Benzenesulfonamides
PubMed ID
40792599
Keywords
Fontan; exercise; udenafil
Recommended Citation
Goldberg DJ, Zak V, Hu C, et al. Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial. J Am Heart Assoc. 2025;14(16):e041348. doi:10.1161/JAHA.125.041348
Comments
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
Publisher's Link: https://doi.org/10.1161/jaha.125.041348