• Dyspnoea score
• Exercise capacity (six-minute walk)
• NYHA/WHO functional class
• Change of acropachy
• Blood gas test
• Pulmonary artery pressure (measured by echocardiogram or catheter)

• 1. Change of acropachy
• 2. Blood gas test
• 3. Pulmonary artery pressure (measured by echocardiogram or catheter)

• Other echocardiographic changes:
• Systolic pulmonary arterial pressure
• Change of right to left shunt expressed by time-velocity integral (TVI) from the defect
• Change of left to right shunt expressed by TVI from the defect
• Right ventricular (RV) acceleration time (ms)
• RV ejection time (ms)
• Ratio of RV ejection time/RV acceleration time
• Pulmonary arterial valve TVI
• Change of diameters of both left and right ventricles
• Change of diameters of both left and right atrium
• Doppler mitral valve (MV) TVI
• Blood gas test

• Other echocardiographic changes:
• Systolic pulmonary arterial pressure
• Change of right to left shunt expressed by time-velocity integral (TVI) from the defect
• Change of left to right shunt expressed by TVI from the defect
• Right ventricular (RV) acceleration time (ms)
• RV ejection time (ms)
• Ratio of RV ejection time/RV acceleration time
• Pulmonary arterial valve TVI
• Change of diameters of both left and right ventricles
• Change of diameters of both left and right atrium
• Doppler mitral valve (MV) TVI
• Blood gas test
• Dyspnoea score
• Exercise capacity (six-minute walk)
• NYHA/WHO functional class

The purpose of this study is to determine whether a larger dose of the aldosterone antagonist spironolactone combined with an ACE inhibitor (captopril) and a beta-blocker (carvedilol) is effective in reverse pulmonary artery remodeling in patients with pulmonary arterial hypertension (PAH)secondary to congenital heart disease

The pathogenesis of PAH involves multiple mechanisms. However, three common factors are thought to cause the increased pulmonary vascular resistance that characterizes this devastating disease: vasoconstriction, pulmonary vascular proliferation and remodeling, and thrombosis in situ. Advances in our knowledge of the molecular mechanisms involved in PAH suggest that endothelial dysfunction with chronic impaired production of vasoactive mediators plays a key role. Reduced production of vasoactive mediators, such as nitric oxide (NO) and prostacyclin, along with prolonged overexpression of vasoconstrictors such as endothelin-1 (ET-1), not only affect vascular tone but also promote vascular remodeling. Thus, these substances represent logical pharmacological targets. Animal studies showed ET-1 could stimulate aldosterone secretion in different species, both in vivo and in vitro. This stimulation involves the ET-B alone and both ET-A and ET-B receptor subtypes in rats and humans. Animal studies also showed spironolactone combined with ACE inhibitor could normalize blood pressure, prevents upregulation of vascular ET-1, restore nitric oxide (NO)-mediated endothelial dysfunction. Beta-blockers have ability to reduce dp/dt in pulmonary artery, as well as left ventricle, thus prevent further damage to the dysfunctional endothelium. Furthermore, we observed from our practice that the aforementioned therapy could lower pulmonary artery pressure in patents with pulmonary hypertension secondary to left ventricular dysfunction. Thus, we hypothesize spironolactone combined with ACE inhibitor and beta-blocker has the ability to reverse remodeling of pulmonary artery in PAH patients.

Inclusion Criteria:

• A mean pulmonary artery pressure higher than 25 mm Hg or, when estimated by echocardiography, pulmonary artery pressure more than half the systemic artery pressure
• Congenital systemic-to-pulmonary shunts