Abstract 2161: Sildenafil Improves Ventricular Performance in Children and Young Adults After the Fontan Operation
Background: Sildenafil inhibits phosphodiesterase type 5, resulting in pulmonary vasodilation and enhanced ventricular performance in adults with structurally normal hearts. These actions may improve the physiologic and clinical status of patients with single ventricle physiology (SV) after the Fontan operation.
Objective: As part of a larger study evaluating the safety and efficacy of Sildenafil after the Fontan Operation (SAFO), we examined the impact of Sildenafil on ventricular function.
Methods: A double blind, placebo controlled, crossover trial was conducted in children and young adults after the Fontan operation. Subjects were randomized at trial entry to receive either placebo or Sildenafil for 6 weeks (Phase 1). After a 6-week washout, subjects crossed over to the opposite arm for 6 weeks (Phase 2). Sildenafil was given at a dose of 20 mg tid. An echocardiogram was performed before and after each phase. Measurements of ventricular function included: myocardial performance index (MPI), E/A ratio (surrogate for diastolic performance), and the product of systolic ejection velocity time integral and heart rate (surrogate for cardiac output). Each outcome variable was analyzed using a paired t-test to compare the mean change within each phase between the placebo and Sildenafil phases.
Results: We enrolled 28 subjects; 27 (96%) completed Phase 2. Mean age was 14.9 ± 5.1 yrs. Mean time from Fontan was 11.3 ± 3.8 yrs. SV morphology was dominant RV in 15 (54%). Among all subjects, there was a significant improvement in mean MPI during the Sildenafil phase (pre-phase: 0.42; post-phase: 0.35) compared to the placebo phase (p < 0.01). There was an indication of improved diastolic performance and increased cardiac output in response to Sildenafil, but these differences did not achieve statistical significance. There was no difference in mean MPI improvement between the RV dominant subgroup and the non-RV dominant subgroup, indicating a benefit regardless of ventricular morphology.
Conclusions: Sildenafil significantly improves ventricular performance in children and young adults after the Fontan operation. We speculate that enhanced ventricular performance may result in improved exercise performance and/or quality of life.