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Circulation. 2011 Mar 22;123(11):1185-93. doi: 10.1161/CIRCULATIONAHA.110.981746. Epub 2011 Mar 7.

Impact of oral sildenafil on exercise performance in children and young adults after the fontan operation: a randomized, double-blind, placebo-controlled, crossover trial.

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  • 1Division of Cardiology, The Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104, USA.



Children and young adults with single-ventricle physiology have abnormal exercise capacity after the Fontan operation. A medication capable of decreasing pulmonary vascular resistance should allow improved cardiac filling and improved exercise capacity.


This study was a double-blind, placebo-controlled, crossover trial conducted in children and young adults after Fontan. Subjects were randomized to receive placebo or sildenafil (20 mg three times daily) for 6 weeks. After a 6-week washout, subjects crossed over for an additional 6 weeks. Each subject underwent an exercise stress test at the start and finish of each phase. After taking sildenafil, subjects had a significantly decreased respiratory rate and decreased minute ventilation at peak exercise. At the anaerobic threshold, subjects had significantly decreased ventilatory equivalents of carbon dioxide. There was no change in oxygen consumption during peak exercise, although there was a suggestion of improved oxygen consumption at the anaerobic threshold. Improvement at the anaerobic threshold was limited to the subgroup with single left or mixed ventricular morphology and to the subgroup with baseline serum brain natriuretic peptide levels ≥100 pg/mL.


In this cohort, sildenafil significantly improved ventilatory efficiency during peak and submaximal exercise. There was also a suggestion of improved oxygen consumption at the anaerobic threshold in 2 subgroups. These findings suggest that sildenafil may be an important agent for improving exercise performance in children and young adults with single-ventricle physiology after the Fontan operation. Clinical Trial Registration- URL: Unique identifier: NCT00507819.

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