The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis

Area of Science:

• Pediatric Cardiology
• Exercise Physiology
• Pharmacology

Background:

• The Fontan circulation presents unique challenges for exercise capacity.
• Udenafil has shown potential to improve exercise performance in these patients.
• Identifying patient subgroups that benefit most is crucial for targeted therapy.

Purpose of the Study:

• To conduct a post hoc analysis of the FUEL trial.
• To evaluate differential effects of udenafil on exercise performance in subgroups of Fontan patients.
• To assess treatment response based on baseline characteristics.

Main Methods:

• Subgroup analyses based on peak oxygen consumption (VO2), BNP, weight, race, gender, and ventricular morphology.
• ANCOVA modeling to assess treatment arm, subgroup, and interaction effects.
• Evaluation of exercise parameters including peak VO2, work rate at ventilatory anaerobic threshold (VAT), and ventilatory efficiency (VE/VCO2).

Main Results:

• Trends toward improved peak VO2, work rate at VAT, VO2 at VAT, and VE/VCO2 with udenafil across most subgroups.
• No significant differential response identified based on baseline characteristics.
• Participants with lower baseline peak VO2 showed a trend towards greater improvement.

Conclusions:

• Udenafil demonstrated consistent, albeit trending, improvements in exercise parameters across diverse Fontan patient subgroups.
• The lack of a differential response suggests broad applicability of udenafil's benefits.
• Further research is needed to confirm efficacy, assess long-term safety, and evaluate impact on Fontan-associated morbidities.