Beneficial Effect of Oral Sildenafil Therapy on Childhood Pulmonary Arterial Hypertension

Abstract

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 m 2 (range, 9 to 42) to 12 Wood Units m 2 (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.