Abstract 15417: Impact of Udenafil on Vascular Function in Fontan Circulation: Results From the FUEL Trial

• Published in: Circulation (New York, N.Y.) Vol. 142; no. Suppl_3 Suppl 3; p. A15417
• Main Authors: Goldstein, Bryan H, Goldberg, David J, Paridon, Stephen, Lam, Chen Quin Eric, Ranganathan, Gayatri, Jean-st-michel, Emilie M, Rathod, Rahul, Krishnan, Usha S, Chamberlain, Reid, Jackson, Lanier, Ware, Adam, Detterich, Jon A, Ginde, Salil, Sassalos, Peter, Schamberger, Marcus S, Petit, Christopher, Shahanavaz, Shabana, Garuba, Olukayode D, woodford, edward j, Weingarten, Angela, Mietus-Snyder, Michele, White, David A, DiMaria, Michael, Conner, Colin, Christensen, Jason, Khoury, Michael, Yoon, Ja Kyoung, Prospero, Carol, zak, victor, Urbina, Elaine M
• Format: Journal Article
• Language: English
• Published: by the American College of Cardiology Foundation and the American Heart Association, Inc 17.11.2020
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.142.suppl_3.15417

IntroductionIn the Pediatric Heart Network double-blind Fontan Udenafil Exercise Longitudinal (FUEL) trial, treatment with udenafil (Mezzion Pharma Co Ltd) for 6 months was associated with modest improvements in exercise capacity and ventricular performance (NCT02741115). Measures of vascular function, which have been related to Fontan exercise capacity, were also obtained but have not been explored in detail. MethodsEndothelial function (Framingham reactive hyperemia index, FRHI; area under the curve to max occlusion, AUCMax) and arterial stiffness (augmentation index, AI) were assessed with peripheral arterial tonometry. The primary outcome was the effect of udenafil vs. placebo on vascular function. Secondary outcomes included baseline, and 26-week change from baseline, measures of vascular function in subgroups of the udenafil arm, stratified by exercise response. Exercise response was defined by longitudinal change in peak oxygen consumption and categorized by 1) any positive change vs. other and 2) tertile of change. ResultsPaired measures of vascular function were analyzed in 164 (82%) and 167 (84%) udenafil and placebo participants, respectively. There were no baseline differences between groups, including the use of vasoactive medications. Overall, there were no differences in change in measures of vascular function between treatment groups. In subgroup analysis, exercise responders demonstrated better baseline endothelial function (FRHI0.39 ± 0.37 vs. 0.29 ± 0.31, p=0.056; AUCMax6.53 ± 2.91 vs. 5.63 ± 2.21, p=0.023) and suggestion of a 26-week reduction in arterial stiffness (AI-1.42 ± 10.3 vs. 1.69 ± 11.7, p=0.075). Analysis by tertile of exercise response showed that AI was significantly improved in the top tertile of exercise responders (-3.27 ± 8.4 vs. 2.62 ± 12.4 vs. 0.35 ± 11.1, p=0.022) compared with the lower tertiles. ConclusionsIn the FUEL trial, treatment with udenafil was not associated with significant changes in measures of vascular function. Udenafil-treated participants with evidence of exercise responsiveness to therapy manifest better baseline endothelial function and a significant improvement in arterial stiffness. Vascular function may play a role in PDE-5 responsiveness in Fontan circulation.