Drug Therapy and Surgery in Congenital Heart Disease With Pulmonary Hypertension

Combined Clinical and Surgical Approaches to Congenital Heart Disease Associated With Pulmonary Arterial Hypertension (PAH-CHD)

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.