Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants

• Type of Material: Article
• Authors: Michael v. Di Maria, University of Colorado, Aurora; David J. Goldberg, University of Pennsylvania; Victor Zak, Healthcore; Chenwei Hu, Healthcore; Adam M. Lubert, University of Cincinnati; Andrea Dragulescu, Hospital for Sick Children, Toronto; Andrew S. Mackie, University of Alberta; Andrew McCrary, Duke University; Angela Weingarten, Vanderbilt Heart and Vascular Institute; Anitha Parthiban, Baylor College of Medicine; Benjamin Goot, Medical College of Wisconsin; Bryan H. Goldstein, University of Cincinnati; Carolyn Taylor, Medical University of South Carolina; Christopher Lindblade, University of Arizona; Christopher Petit, Emory University; Chirstopher Spurney, Children's National Hospital; David Harrild, Boston Children's Hospital; Elaime M. Urbina, University of Cincinnati; Eleanor Schuchardt, University of California San Diego; Gi Beom Kim, Seoul National University; Ja Kyoung Yoon, Sejong Hospital Cardiovascular Center; Jamie N. Colombo, Washington University, St. Louis; Matthew Files, University of Washington; Megan Schoessling, Medical College of Wisconsin; Peter Ermis, Baylor College of Medicine; Pierre Wong, University of Southern California; Ruchira Garg, Smidt Heart Institute; Sara Swanson, Children's Hospital and Medical Center; Shaji Menon, University of Utah; Shubika Srivastava, Nemours; Thor Thorsson, University of Michigan; Tiffanie R. Johnson, Riley Children's Hospital; Usha S. Krishnan, Columbia University; Stephen M. Paridon, University of Pennsylvania; Peter C. Frommelt, Medical College of Wisconsin
• Language: English
• Date: 2022-11-15
• Publisher: Wolters Kluwer Health, Inc.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022, Wolters Kluwer Health
• Final Published Version (URL): https://doi.org/10.1161/CIRCIMAGING.121.013676
• Title of Journal or Parent Work: Circulation: Cardiovascular Imaging
• Volume: 15
• Issue: 11
• Start Page: e013676
• Grant/Funding Information: This study is supported by grants (HL135680, HL135685, HL135683, HL135689, HL135646, HL135665, HL135678, HL135682, HL135666, HL135691, HL068270) from the NHLBI, NIH.
• Keywords: Fontan; echocardiography; Echocardiography; Exercise; phosphodiestherase-5-inhibitor; cardiopulmonary exercise test; Congenital Heart Disease
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

Background: The FUEL trial demonstrated statistical improvements in exercise capacity following 6 months of treatment with udenafil (87.5 mg po BID). The effect of udenafil on echocardiographic measures of single ventricle (SV) function in this cohort has not been studied. Methods: The 400 enrolled participants were randomized 1:1 to udenafil or placebo. Protocol echocardiograms were obtained at baseline and 26 weeks after initiation of udenafil/placebo. Linear regression compared change from baseline indices of SV systolic, diastolic and global function, atrioventricular valve (AVV) regurgitation and mean Fontan fenestration gradient in the udenafil cohort vs placebo, controlling for ventricular morphology (left ventricle vs. right ventricle/other) and baseline value. Results: The udenafil participants (n=191) had significantly improved between baseline and 26 weeks visits compared to placebo participants (n=195) in myocardial performance index (p=0.03, adjusted mean difference (SE) of changes between groups −0.03(0.01)), AVV inflow peak E (p=0.009, 3.95 (1.50)), and A velocities (p=0.034, 3.46 (1.62)), and annular DTI-derived peak e’ velocity (p=0.008, 0.60(0.23)). There were no significant differences in change in SV size, systolic function, AVV regurgitation severity or mean fenestration gradient. Participants with a dominant LV had significantly more favorable baseline values of indices of SV size and function (lower volumes and areas, E/e’ ratio, systolic:diastolic time and AVV regurgitation, and higher annular s’ and e’ velocity). Conclusions: FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort.