Efficacy of sildenafil therapy in children with pulmonary hypertension secondary to congenital heart disease

Abstract

Purpose: pulmonary hypertension (PH) resulting from congenital heart disease (CHD) remains one of the most difficult childhood illness to treat. Sildenafil, a selective inhibitor of phosphodiesterase-5, is known as an effective and promising pulmonary vasodilator, with minors and insignifi cant reverse effects. Methods: we have evaluated the efficacy and the tolerability of sildenafil in chidren with advanced PH secondary CHD with shunts (simple (14 pts), mixed (35 pts) and complex (28 pts). In this monocentric, double-blind, placebocontrolled study we randomly assigned 77 pts with advanced PH (35 with repaired shunts, 31-palliative procedure and 11 inoperable pts) to placebo or Sildenafil orally, with the dose of 1-2 mg/kg/day each 8h for 6-12 months. The Sildenafil group consisted of 38 pts (mean age 19,9±5,3 months: 16 boys/22 girls) and the placebo group – 39 pts (mean age 21,7±7,8 months: 22 boys/17 girls). The study protocol included: functional class (FC) NYHA/Ross; O2 saturation; 6-min walk test; transthoracic echocardiogram (mean PAP, tricuspid annular plane systolic excursion (TAPSE), myocardial performance index (MPI or Tei index), right cardiac catheterisation, measuring pulmonary vascular resistance (PVR). In addition a special questionnaire of evidence of adverse reactions was available. Results: at the patients treated with Sildenafil was observed an improvement of FC NYHA/Ross from 3,16±0,1 to 2,15±0,1 (p<0,001); O2 sat (+3,1±0,5%) comparing with placebo (+0,6±0,3%), (p<0,001); an effort tolerance estimated by 6-minute walk test (+152,5±17,4 m at 6 months and +184,3±21,2m at 12 months of treatment), (p<0,001); the decreasing of mean PAP, with 22,0±2,22 at 6 months and with 19,03±2,3 mmHg at 12 months (p<0,001) and PVRI had decreased with 2,45±0,19 UW·m2 (p<0,001); the improvement of the systolic function, TAPSE from 16,55±0,34 to 20,7±0,64 mm/m2 (p<0,001) and global function of RV (Tei index) with 0,15±0,01(-31%) to initial (p<0,001). In placebo group the respective signs slightly changed and only PVR diminished from 6,4±0,1 to 5,7±0,3 UW/m2 (p<0,05). There was no death in the sildenafil-treated cases, contrary to 5 in the placebo group. Conclusions: Sildenafil is efficient in treating PH secondary to congenital systemic-to-pulmonary shunts, but even more effective in corrected surgical shunts. Sildenafil improves FC, tolerability at effort, O2 sat, systolic and global function of RV, diminishing PAPm and PVRI comparing with placebo. This remedy has good tolerability, with minors and insignifi cant adverse reactions and favourable impact on the quality of life.