Udenafil improves measures of exercise performance at the ventilatory anaerobic threshold in individuals with Fontan physiology. This finding comes from the FUEL trial, which was presented at the AHA Scientific Sessions 2019.

In children born with single-ventricle congenital heart disease, the Fontan operation connects the inferior vena cava to the pulmonary artery. Individuals with this physiology usually experience a decline in cardiovascular efficiency and exercise performance during adolescence and into adulthood. Investigators in the phase III FUEL trial tested the use of udenafil, a phosphodiesterase type 5 inhibitor. A total of 400 participants with Fontan physiology (mean age 15.5 years) were recruited from 30 centres in North America and South Korea and were randomly assigned to receive udenafil (87.5 mg twice daily) or placebo.

The primary end point (between-group difference in change in O2 consumption at peak exercise) was not significantly different between the udenafil and placebo groups (+2.8% versus –0.2%; P = 0.071). However, analyses performed during submaximal exercise at the ventilatory anaerobic threshold indicated improvements in the udenafil group compared with the placebo group in O2 consumption, ventilatory equivalents of CO2 and work rate. No significant changes were observed in the myocardial performance index or in the serum level of B-type natriuretic peptide.

“These findings indicate that therapy with udenafil improves cardiovascular physiology at moderate levels of exercise in the cohort of patients who have undergone total cavopulmonary connection,” conclude the investigators. “Ongoing surveillance is needed to determine the effect of chronic treatment with udenafil on the long-term clinical course of those living with single-ventricle congenital heart disease.”