In patients with single ventricle congenital heart disease (SV-CHD) who underwent a Fontan operation, treatment with udenafil "was not associated with a statistically significant improvement in oxygen consumption at peak exercise," according to results from the FUEL trial presented Nov. 17 during AHA 2019 in Philadelphia, PA and simultaneously published in Circulation.

David J. Goldberg, MD, et al., looked at 400 patients with SV-CHD who underwent a Fontan operation with a mean age of 15.5 from 30 sites in North America and the Republic of Korea. Patients were randomized to receive 85.7 mg twice daily of udenafil vs. placebo and were assessed over a six-month period.

Results showed that the primary outcome – the between-group difference in change in oxygen consumption at peak exercise – increased in the udenafil group by 44 ±245 mL/min (2.8 percent) and declined in the placebo group by 3.7 ±228 mL/min (-0.2 percent), but "the difference did not reach statistical significance" (p=0.071).

In terms of secondary outcomes, ventilatory anaerobic threshold analysis showed improvements in the udenafil group vs. the placebo group in oxygen consumption, ventilatory equivalents of carbon dioxide, and work rate. There was no difference in change of myocardial performance index, the natural log of the reactive hyperemia index, or serum brain-type natriuretic peptide level.

The authors conclude that although their study "was not associated with a statistically significant improvement in oxygen consumption at peak exercise [it] did demonstrate statistically significant improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold."

Moving forward, they explain that more studies are warranted "to determine if udenafil is selectively beneficial for subpopulations within the larger cohort with SV-CHD, and to evaluate the long-term tolerability and safety of treatment."

In a related editorial comment, Marc Gewillig, MD, and Alexander Van de Bruaene, MD, add that "the current study again underscores that manipulating the Fontan circuit is extremely challenging." They note that "priorities in pre-Fontan management may need to be redefined."

Keywords: AHA19, AHA Annual Scientific Sessions, Heart Defects, Congenital, Fontan Procedure, Carbon Dioxide, Hyperemia, Anaerobic Threshold, Sulfonamides, Pyrimidines, Oxygen Consumption, Natriuretic Peptides

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