Results of the FUEL Trial

被引：109

作者：

Goldberg, David J. ^{[1
]}

Zak, Victor ^{[2
]}

Goldstein, Bryan H. ^{[3
]}

Schumacher, Kurt R. ^{[4
]}

Rhodes, Jonathan ^{[5
]}

Penny, Daniel J. ^{[6
]}

Petit, Christopher J. ^{[7
]}

Ginde, Salil ^{[8
]}

Menon, Shaji C. ^{[9
]}

Kim, Seong-Ho ^{[10
]}

Kim, Gi Beom ^{[11
]}

Nowlen, Todd T. ^{[12
]}

DiMaria, Michael, V ^{[13
]}

Frischhertz, Benjamin P. ^{[14
]}

Wagner, Jonathan B. ^{[15
,16
]}

McHugh, Kimberly E. ^{[17
]}

McCrindle, Brian W. ^{[18
]}

Shillingford, M. P. H. Amanda J. ^{[19
]}

Sabati, Arash A. ^{[20
]}

Yetman, Anji T. ^{[21
]}

John, Anitha S. ^{[22
]}

Richmond, Marc E. ^{[23
]}

Files, Matthew D. ^{[24
]}

Payne, R. Mark ^{[25
]}

Mackie, Andrew S. ^{[26
]}

Davis, Christopher K. ^{[27
]}

Shahanavaz, Shabana ^{[28
]}

Hill, Kevin D. ^{[29
]}

Garg, Ruchira ^{[30
]}

Jacobs, Jeffrey P. ^{[31
]}

Hamstra, Michelle S. ^{[3
]}

Woyciechowski, Stacy ^{[1
]}

Rathge, Kathleen A. ^{[3
]}

McBride, Michael G. ^{[1
]}

Frommelt, Peter C. ^{[8
]}

Russell, Mark W. ^{[4
]}

Urbina, Elaine M. ^{[3
]}

Yeager, James L. ^{[32
]}

Pemberton, Victoria L. ^{[33
]}

Stylianou, Mario P. ^{[33
]}

Pearson, Gail D. ^{[33
]}

Paridon, Stephen M. ^{[1
]}

机构：

[1] Childrens Hosp Philadelphia, Perelman Sch Med, Div Cardiol, Philadelphia, PA 19104 USA

[2] New England Res Inst, Watertown, MA USA

[3] Cincinnati Childrens Hosp Med Ctr, Div Cardiol, Cincinnati, OH 45229 USA

[4] CS Mott Childrens Hosp, Div Cardiol, Ann Arbor, MI USA

[5] Childrens Hosp Boston, Dept Cardiol, Boston, MA USA

[6] Texas Childrens Hosp, Baylor Coll Med, Div Cardiol, Houston, TX 77030 USA

[7] Emory Univ, Sch Med, Childrens Healthcare Atlanta, Atlanta, GA USA

[8] Med Coll Wisconsin, Childrens Hosp Wisconsin, Div Cardiol, Milwaukee, WI 53226 USA

[9] Univ Utah, Div Pediat Cardiol, Salt Lake City, UT USA

[10] Sejong Gen Hosp, Dept Pediat, Bucheon Si, South Korea

[11] Seoul Natl Univ, Sch Med, Childrens Hosp, Seoul, South Korea

[12] Phoenix Childrens Hosp, Heart Ctr, Phoenix, AZ USA

[13] Univ Colorado, Sch Med, Dept Pediat, Childrens Hosp Colorado, Aurora, CO USA

[14] Vanderbilt Univ, Sch Med, Div Cardiol, Nashville, TN 37212 USA

[15] Childrens Mercy Kansas City, Div Cardiol, Kansas City, MO USA

[16] Childrens Mercy Kansas City, Div Clin Pharmacol, Kansas City, MO USA

[17] Med Univ South Carolina, Div Pediat Cardiol, Charleston, SC 29425 USA

[18] Univ Toronto, Hosp Sick Children, Div Cardiol, Toronto, ON, Canada

[19] Nemours Alfred I DuPont Hosp Children, Nemours Cardiac Ctr, Wilmington, DE USA

[20] Los Angeles Childrens Hosp, Div Cardiol, Los Angeles, CA USA

[21] Univ Nebraska, Childrens Hosp & Med Ctr, Omaha, NE 68182 USA

[22] Childrens Natl Hlth Syst, Div Cardiol, Washington, DC USA

[23] Columbia Univ, Med Ctr, Morgan Stanley Childrens Hosp, Div Pediat Cardiol, New York, NY USA

[24] Seattle Childrens Hosp, Div Cardiol, Seattle, WA USA

[25] Riley Hosp Children, Div Cardiol, Indianapolis, IN USA

[26] Stollery Childrens Hosp, Div Cardiol, Edmonton, AB, Canada

[27] Rady Childrens Hosp, Div Cardiol, San Diego, CA USA

[28] St Louis Childrens Hosp, Div Cardiol, St Louis, MO 63178 USA

[29] Duke Childrens Pediat & Congenital Heart Ctr, Durham, NC USA

[30] Cedars Sinai Med Ctr, Div Cardiol, 8700 Beverly Blvd, Los Angeles, CA 90048 USA

[31] Johns Hopkins All Childrens Hosp, Dept Surg, St Petersburg, FL USA

[32] Mezz Pharma Co Ltd, Seoul, South Korea

[33] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA

来源：

CIRCULATION | 2020年 / 141卷 / 08期

关键词：

exercise test; Fontan procedure; heart defects; congenital; phosphodiesterase; 5; inhibitor; PULMONARY VASCULAR-RESISTANCE; LONG-TERM SURVIVAL; EXERCISE CAPACITY; FONTAN OPERATION; DIASTOLIC DYSFUNCTION; SINGLE VENTRICLE; HEART-FAILURE; SILDENAFIL; ADULTS; ADOLESCENTS;

D O I：

10.1161/CIRCULATIONAHA.119.044352

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: The Fontan operation creates a total cavopulmonary connection, a circulation in which the importance of pulmonary vascular resistance is magnified. Over time, this circulation leads to deterioration of cardiovascular efficiency associated with a decline in exercise performance. Rigorous clinical trials aimed at improving physiology and guiding pharmacotherapy are lacking. Methods: The FUEL trial (Fontan Udenafil Exercise Longitudinal) was a phase III clinical trial conducted at 30 centers. Participants were randomly assigned udenafil, 87.5 mg twice daily, or placebo in a 1:1 ratio. The primary outcome was the between-group difference in change in oxygen consumption at peak exercise. Secondary outcomes included between-group differences in changes in submaximal exercise at the ventilatory anaerobic threshold, the myocardial performance index, the natural log of the reactive hyperemia index, and serum brain-type natriuretic peptide. Results: Between 2017 and 2019, 30 clinical sites in North America and the Republic of Korea randomly assigned 400 participants with Fontan physiology. The mean age at randomization was 15.5 +/- 2 years; 60% of participants were male, and 81% were white. All 400 participants were included in the primary analysis with imputation of the 26-week end point for 21 participants with missing data (11 randomly assigned to udenafil and 10 to placebo). Among randomly assigned participants, peak oxygen consumption increased by 44 +/- 245 mL/min (2.8%) in the udenafil group and declined by 3.7 +/- 228 mL/min (-0.2%) in the placebo group (P=0.071). Analysis at ventilatory anaerobic threshold demonstrated improvements in the udenafil group versus the placebo group in oxygen consumption (+33 +/- 185 [3.2%] versus -9 +/- 193 [-0.9%] mL/min, P=0.012), ventilatory equivalents of carbon dioxide (-0.8 versus -0.06, P=0.014), and work rate (+3.8 versus +0.34 W, P=0.021). 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. Conclusions: In the FUEL trial, treatment with udenafil (87.5 mg twice daily) was not associated with an improvement in oxygen consumption at peak exercise but was associated with improvements in multiple measures of exercise performance at the ventilatory anaerobic threshold.

引用

页码：641 / 651

页数：11

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