Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension
Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension
The purpose of this study is to test the hypothesis that treating PAH-CHD patients
 preoperatively with PAH drugs and keeping them on treatment for six months after surgery
 reduces the risk of immediate postoperative death and the risk of residual PAH at six months
 following operation to <10%.
Pulmonary arterial hypertension (PAH) is a complicating factor in the management of
 congenital heart disease (CHD) with intracardiac or extracardiac communications. In children
 with moderate to severe PAH, the risk of serious complications following the surgical repair
 of shunts (including right cardiac failure and death) is 15-20% or even higher, and the risk
 of late, postoperative residual PAH is ~25%. We therefore intend to conduct a study aimed at
 reducing the risk of severe immediate postoperative complications and the risk of residual
 PAH at six months following surgery to less than 10% in children with moderate PAH (primary
 objective). The study is also aimed at promoting a statistically significant reduction in
 pulmonary artery pressure and pulmonary vascular resistance at six month after surgery,
 compared with baseline in children with moderate or severe PAH (secondary objective). We
 hypothesized that these goals could be achieved by treating patients preoperatively and for
 six months postoperatively with sildenafil, either singly or combined with bosentan. Both
 drugs have been approved for treatment of PAH on the basis of randomized clinical trials.
 Preoperative and postoperative (on treatment) hemodynamic evaluation will be based on
 noninvasive and invasive diagnostic procedures. As an additional objective, we intend to
 analyze possible abnormalities in genes that have been shown to be associated with PAH-CHD,
 and inflammatory mediators as well. The idea is to investigate whether changes in these
 markers correlate with the clinical profile and response to treatments.
Inclusion Criteria:

 -  Potentially operable patients with congenital cardiac septal defects (bi-ventricular
 physiology) and PAH, must have at least three of the following severity criteria: age
 > 18 months; absence of congestive heart failure (pulmonary congestion); Down
 syndrome; bidirectional shunting across the septal defect; periods of systemic
 (peripheral) oxygen saturation < 90%.

 Exclusion Criteria:

 -  Patients with complex cardiac anomalies for whom there are no possibilities of
 complete repair. Patients with uni-ventricular physiology.