Randomized Controlled Trial

. 2022 Nov;15(11):e013676.

doi: 10.1161/CIRCIMAGING.121.013676. Epub 2022 Nov 15.

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

Michael V Di Maria¹, David J Goldberg², Victor Zak³, Chenwei Hu³, Adam M Lubert⁴, Andreea Dragulescu⁵, Andrew S Mackie⁶, Andrew McCrary⁷, Angela Weingarten⁸, Anitha Parthiban⁹, Benjamin Goot¹⁰, Bryan H Goldstein^{4

11}, Carolyn Taylor¹², Christopher Lindblade¹³, Christopher J Petit¹⁴, Christopher Spurney¹⁵, David M Harrild¹⁶, Elaine M Urbina⁴, Eleanor Schuchardt¹⁷, Gi Beom Kim¹⁸, Ja Kyoung Yoon¹⁹, Jamie N Colombo²⁰, Matthew D Files²¹, Megan Schoessling¹⁰, Peter Ermis⁹, Pierre C Wong²², Ruchira Garg²³, Sara K Swanson²⁴, Shaji C Menon²⁵, Shubhika Srivastava²⁶, Thor Thorsson²⁷, Tiffanie R Johnson²⁸, Usha S Krishnan²⁹, Stephen M Paridon², Peter C Frommelt¹⁰; Pediatric Heart Network

Affiliations

¹ Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO (M.V.D.M.).
² Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA (D.J.G., S.M.P.).
³ Healthcore, Watertown, MA (V.Z., C.H.).
⁴ Cincinnati Children's Hospital, Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine, OH (A.M., B.H.G., E.M.U.).
⁵ Hospital for Sick Children, Toronto, Ontario, Canada (A.D.).
⁶ Stollery Children's Hospital, University of Alberta, Edmonton, Canada (A.S.M.).
⁷ Duke University, Durham, NC (A.M.C.).
⁸ Vanderbilt Heart and Vascular Institute, Nashville, TN (A.W.).
⁹ Texas Children's Hospital, Baylor College of Medicine, Houston, TX (A.P., P.E.).
¹⁰ Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI (B.G., M.S., P.C.F.).
¹¹ UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, PA (B.H.G.).
¹² Shawn Jenkins Children's Hospital, Medical University of South Carolina, Charleston, SC (C.T.).
¹³ Phoenix Children's Hospital, University of Arizona, Phoenix, AZ (C.L.).
¹⁴ Children's Heart Center, Emory University School of Medicine, Atlanta, GA (C.J.P.).
¹⁵ Children's National Hospital, Washington, DC (C.S.).
¹⁶ Boston Children's Hospital, MA (D.M.H.).
¹⁷ Rady Children's Hospital, University of California San Diego, CA (E.S.).
¹⁸ Seoul National University Children's Hospital, Seoul National University College of Medicine, South Korea (G.B.K.).
¹⁹ Sejong Hospital Cardiovascular Center, Department of Pediatrics, Bucheon, South Korea (J.K.Y.).
²⁰ St. Louis Children's Hospital, Washington University School of Medicine, St Louis, MO (J.N.C.).
²¹ Seattle Children's Hospital, University of Washington, Seattle, WA (M.D.F.).
²² Children's Hospital of Los Angeles, Keck School of Medicine of USC, Los Angeles, CA (P.C.W.).
²³ Smidt Heart Institute, Cedars-Sinai, Los Angeles, CA (R.G.).
²⁴ Children's Hospital and Medical Center, Omaha, NE (S.K.S.).
²⁵ Primary Children's Hospital, University of Utah, Salt Lake City, UT (S.C.M.).
²⁶ Nemours, AI DuPont, Wilmington, DE (S.S.).
²⁷ C.S. Mott Children's Hospital, University of Michigan Congenital Heart Center, Ann Arbor, MI (T.T.).
²⁸ Riley Children's Hospital (Prairieland), Indianapolis, IN (T.R.J.).
²⁹ Columbia University Irving Medical Center, Morgan Stanley Children's Hospital of New York, NY (U.S.K.).

PMID: 36378780
PMCID: PMC9674374
DOI: 10.1161/CIRCIMAGING.121.013676

Randomized Controlled Trial

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

Michael V Di Maria et al. Circ Cardiovasc Imaging. 2022 Nov.

. 2022 Nov;15(11):e013676.

doi: 10.1161/CIRCIMAGING.121.013676. Epub 2022 Nov 15.

Authors

Affiliations

¹ Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, CO (M.V.D.M.).
² Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA (D.J.G., S.M.P.).
³ Healthcore, Watertown, MA (V.Z., C.H.).
⁴ Cincinnati Children's Hospital, Heart Institute, Department of Pediatrics, University of Cincinnati College of Medicine, OH (A.M., B.H.G., E.M.U.).
⁵ Hospital for Sick Children, Toronto, Ontario, Canada (A.D.).
⁶ Stollery Children's Hospital, University of Alberta, Edmonton, Canada (A.S.M.).
⁷ Duke University, Durham, NC (A.M.C.).
⁸ Vanderbilt Heart and Vascular Institute, Nashville, TN (A.W.).
⁹ Texas Children's Hospital, Baylor College of Medicine, Houston, TX (A.P., P.E.).
¹⁰ Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, WI (B.G., M.S., P.C.F.).
¹¹ UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, PA (B.H.G.).
¹² Shawn Jenkins Children's Hospital, Medical University of South Carolina, Charleston, SC (C.T.).
¹³ Phoenix Children's Hospital, University of Arizona, Phoenix, AZ (C.L.).
¹⁴ Children's Heart Center, Emory University School of Medicine, Atlanta, GA (C.J.P.).
¹⁵ Children's National Hospital, Washington, DC (C.S.).
¹⁶ Boston Children's Hospital, MA (D.M.H.).
¹⁷ Rady Children's Hospital, University of California San Diego, CA (E.S.).
¹⁸ Seoul National University Children's Hospital, Seoul National University College of Medicine, South Korea (G.B.K.).
¹⁹ Sejong Hospital Cardiovascular Center, Department of Pediatrics, Bucheon, South Korea (J.K.Y.).
²⁰ St. Louis Children's Hospital, Washington University School of Medicine, St Louis, MO (J.N.C.).
²¹ Seattle Children's Hospital, University of Washington, Seattle, WA (M.D.F.).
²² Children's Hospital of Los Angeles, Keck School of Medicine of USC, Los Angeles, CA (P.C.W.).
²³ Smidt Heart Institute, Cedars-Sinai, Los Angeles, CA (R.G.).
²⁴ Children's Hospital and Medical Center, Omaha, NE (S.K.S.).
²⁵ Primary Children's Hospital, University of Utah, Salt Lake City, UT (S.C.M.).
²⁶ Nemours, AI DuPont, Wilmington, DE (S.S.).
²⁷ C.S. Mott Children's Hospital, University of Michigan Congenital Heart Center, Ann Arbor, MI (T.T.).
²⁸ Riley Children's Hospital (Prairieland), Indianapolis, IN (T.R.J.).
²⁹ Columbia University Irving Medical Center, Morgan Stanley Children's Hospital of New York, NY (U.S.K.).

PMID: 36378780
PMCID: PMC9674374
DOI: 10.1161/CIRCIMAGING.121.013676

Abstract

Background: The FUEL trial (Fontan Udenafil Exercise Longitudinal) 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 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 single ventricle systolic, diastolic and global function, atrioventricular valve regurgitation, and mean Fontan fenestration gradient in the udenafil cohort versus placebo, controlling for ventricular morphology (left ventricle versus 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]), atrioventricular valve inflow peak E (P=0.009, 3.95 [1.50]), and A velocities (P=0.034, 3.46 [1.62]), and annular Doppler tissue imaging-derived peak e' velocity (P=0.008, 0.60[0.23]). There were no significant differences in change in single ventricle size, systolic function, atrioventricular valve regurgitation severity, or mean fenestration gradient. Participants with a dominant left ventricle had significantly more favorable baseline values of indices of single ventricle size and function (lower volumes and areas, E/e' ratio, systolic:diastolic time and atrioventricular valve 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.

Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT02741115.

Keywords: Fontan, echocardiography; adolescents; anaerobic threshold; cardiopulmonary exercise test; phosphodiestherase-5-inhibitor.

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Figures

**Figure 1.**
This schematic of a heart with Fontan circulation includes echocardiographic measurements grouped by type.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

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Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical