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(Circulation. 2005;111:3274-3280.)
© 2005 American Heart Association, Inc.

Pediatric Cardiology

Beneficial Effect of Oral Sildenafil Therapy on Childhood Pulmonary Arterial Hypertension

Twelve-Month Clinical Trial of a Single-Drug, Open-Label, Pilot Study

Tilman Humpl, MD; Janette T. Reyes, RN, MN (ACNP); Helen Holtby, MBBS; Derek Stephens, MSc; Ian Adatia, MBChB

From the Departments of Critical Care Medicine (T.H., I.A.), Anesthesia (H.H.), and Population Health Sciences (D.S.), and the Division of Cardiology (T.H., J.T.R., I.A.), Hospital for Sick Children and University of Toronto Medical School, Toronto, Canada.

Correspondence to Ian Adatia, University of California San Francisco Children’s Hospital, 505 Parnassus Ave, Room M-655, San Francisco, CA 94143-0106. E-mail iadatia{at}pedcard.ucsf.edu

Received May 10, 2004; revision received February 23, 2005; accepted March 4, 2005.

Background— Pulmonary arterial hypertension (PAH) is a progressive and fatal disease. Sildenafil is a type 5 phosphodiesterase inhibitor and pulmonary vasodilator. Therefore, we hypothesized that sildenafil would improve distance walked in 6 minutes and hemodynamics in children with PAH.

Methods and Results— After baseline assessment of hemodynamics by cardiac catheterization and distance walked in 6 minutes, we administered oral sildenafil at 0.25 to 1 mg/kg 4 times daily to 14 children (median age, 9.8 years; range, 5.3 to 18). Diagnoses were primary (n=4) and secondary (n=10) PAH. We repeated the 6-minute walk test at 6 weeks and at 3, 6, and 12 months (n=14) and cardiac catheterization (n=9) after a median follow-up of 10.8 months (range, 6 to 15.3). During sildenafil therapy, the mean distance walked in 6 minutes increased from 278±114 to 443±107 m over 6 months (P=0.02), and at 12 months, the distance walked was 432±156 m (P=0.005). A plateau was reached between 6 and 12 months (P=0.48). Mean pulmonary artery pressure decreased from a median of 60 mm Hg (range, 50 to 105) to 50 mm Hg (range, 38 to 84) mm Hg (P=0.014). Median pulmonary vascular resistance decreased from 15 Wood units m² (range, 9 to 42) to 12 Wood Units m² (range, 5 to 29) (P=0.024).

Conclusions— Oral sildenafil has the potential to improve hemodynamics and exercise capacity for up to 12 months in children with PAH. Confirmation of these results in a randomized, controlled trial is essential.

Key Words: heart defects, congenital • hypertension, pulmonary • pediatrics • pharmacology • phosphodiesterase inhibitors

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