Impact of Oral Sildenafil on Exercise Performance in Children and Young Adults After the Fontan Operation: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Study Questions:

What is the impact of oral sildenafil therapy on exercise performance in children and young adults after the Fontan operation?

Methods:

A randomized, double-blind, placebo-controlled, crossover trial was performed at a single center. A group of selected children ≥8 years and young adults with single-ventricle congenital heart disease after the Fontan procedure and good clinical status were enrolled. Subjects were randomized to sildenafil 20 mg three times daily or placebo, and crossed over after a 6-week washout period. Exercise testing was performed before and after each phase of therapy.

Results:

There was a significantly decreased respiratory rate and minute ventilation at peak exercise for patients on sildenafil. Sildenafil administration resulted in no change in the primary endpoint for the study, oxygen consumption at peak exercise. There was some suggestion of improved oxygen consumption at the anaerobic threshold for patients on sildenafil, which was limited to patients with single left- or mixed-ventricle morphology, and patients with baseline serum brain natriuretic peptide levels ≥100.

Conclusions:

The authors concluded that in a selected cohort of Fontan patients, sildenafil improves ventilatory efficiency at peak and submaximal exercise.

Perspective:

Pulmonary vasodilators are an attractive potential therapy for patients with Fontan physiology as a means of increasing pulmonary blood flow, ventricular filling, and cardiac output. This randomized controlled trial of sildenafil for children and young adults after the Fontan procedure showed benefit in some, but not all exercise parameters. This was a highly selected group of patients with good exercise capacity, as demonstrated by a mean peak oxygen consumption of 30.5 ml · kg–1/min–1. Further study in a larger sample size and longer duration of follow-up will be necessary before widespread adoption of sildenafil for this indication.

Clinical Topics: Cardiac Surgery, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Cardiac Surgery and CHD & Pediatrics, Cardiac Surgery and Heart Failure, Congenital Heart Disease, CHD & Pediatrics and Interventions, CHD & Pediatrics and Quality Improvement

Keywords: Child, Heart Diseases, Follow-Up Studies, Fontan Procedure, Purines, Anaerobic Threshold, Phosphodiesterase 5 Inhibitors, Respiratory Rate, Cardiac Output, Piperazines, Vasodilator Agents, Exercise Test


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