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

Authors :
Olukayode Garuba
Jason Christensen
Lanier Jackson
Michael DiMaria
Salil Ginde
Jon A Detterich
Peter Sassalos
Bryan H. Goldstein
Carol Prospero
Marcus S. Schamberger
Angela Weingarten
Reid C. Chamberlain
Emilie M Jean-st-michel
David A. White
Shabana Shahanavaz
Chen Quin Eric Lam
Gayatri Ranganathan
Rahul H. Rathod
Adam L. Ware
Michael Khoury
David J. Goldberg
Christopher J. Petit
Michele Mietus-Snyder
Stephen M. Paridon
Usha Krishnan
Victor Zak
Elaine M. Urbina
edward j woodford
Ja Kyoung Yoon
Colin Conner
Source :
Circulation. 142
Publication Year :
2020
Publisher :
Ovid Technologies (Wolters Kluwer Health), 2020.

Abstract

Introduction: In 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. Methods: Endothelial function (Framingham reactive hyperemia index, FRHI; area under the curve to max occlusion, AUC Max ) 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. Results: Paired 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 (FRHI: 0.39 ± 0.37 vs. 0.29 ± 0.31, p=0.056; AUC Max : 6.53 ± 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. Conclusions: In 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.

Details

ISSN :
15244539 and 00097322
Volume :
142
Database :
OpenAIRE
Journal :
Circulation
Accession number :
edsair.doi...........1a38c7ae5e6af1cb2b5b080f615e8e25
Full Text :
https://doi.org/10.1161/circ.142.suppl_3.15417