Associated Pediatric Pulmonary Hypertensive Diseases Pulmonary Vascular Disease in Congenital Heart Disease Congenital heart disease is one of the most common secondary causes of pulmonary vascular disease in children Consequently, with the increasing number of children with congenital heart disease who survive to adulthood, the population of patients with pulmonary vascular disease due to congenital heart defects outnumbers those with idiopathic pulmonary hypertension A patient with congenital heart disease can develop pulmonary hypertension by several different mechanisms due to a wide variety of congenital lesions Pulmonary hypertension can occur in unrepaired heart disease, after appropriate complete repair, after incomplete repair or palliation, and acutely during the postoperative recovery after cardiopulmonary bypass Pulmonary Vascular Disease in Unrepaired Congenital Heart Disease Unrepaired congenital heart disease can result in pulmonary vascular disease through several pathophysiologic mechanisms These include excessive pulmonary blood flow (at normal or increased pressure), decreased pulmonary artery capacitance due to an underdeveloped pulmonary arterial bed, and postcapillary obstruction The development of pulmonary vascular disease is also influenced by predisposing genetic syndromes such as Downs or Noonan syndrome Any congenital heart defect that is associated with excessive pulmonary blood flow can result in pulmonary hypertension This includes the most common types of congenital heart disease, such as atrial septal defects, ventricular septal defects, and a patent ductus arteriosus, as well as rarer diseases such as common arterial trunk An increase in the pulmonary blood flow can cause shear stress on the pulmonary arteries, altering the endothelin and nitric oxide pathways, predisposing to an elevated pulmonary vascular resistance The timing of the development of pulmonary hypertension depends on the degree of excessive blood flow, the pressure of the shunted blood, and its oxygen content Unrestrictive interarterial shunts will develop pulmonary vascular disease faster than ventricular or atrial shunts, due to exposure to both systolic and diastolic systemic arterial pressure Ventricular shunts develop pulmonary vascular disease faster than do atrial shunts because they are exposed to systolic systemic pressure, whereas atrial level shunts are exposed only to increased flow and not increased pressure Evaluating surgical candidacy in unrepaired congenital heart disease may require cardiac catheterization and pulmonary vasodilator testing (Fig 75.1) FIG 75.1 Management of patients with congenital heart disease associated with pulmonary hypertension and congenital shunt lesions The indication for invasive diagnoses and eligibility for surgery/operability by comprehensive left and right heart catheterization includes basic evaluation and AVT, the latter especially in the gray zone of forecast uncertainty ASD, Atrial septal defect; AVT, acute vasodilkative testing; PDA, patent ductus arteriosus; PH, pulmonary hypertension; pre op, preoperatively; PVR, pulmonary vascular resistance; PVRi, PVR index; Qp, pulmonary blood flow; Qs, systemic blood flow; SVR, systemic vascular resistance; VSD, ventricular septal defect; WU, Wood units (Modified from Kozlik-Feldmann R, Hansmann G, Bonnet D, Schranz D, Apitz C, Michel-Behnke I Pulmonary hypertension in children with congenital heart disease (PAHCHD, PPHVD-CHD) Expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK Heart 2016;102:ii42–ii48.) Eisenmenger syndrome is seen when there is severe systemic cyanosis as a result of an unrepaired or incompletely repaired shunt (at the atrial, ventricular, or arterial level) that has right-to-left shunting due to persistent elevations in the pulmonary vascular resistance As undiagnosed congenital heart disease becomes less common and there is improvement in earlier surgical repair, this syndrome is becoming less prevalent The natural history of Eisenmenger syndrome is quite variable but eventually results in severe cyanosis and cardiac failure In one study, half of a cohort of patients with unrepaired ventricular septal defect was alive 20 years after the diagnosis.5 Other symptoms include progressive shortness of breath, polycythemia, headache, and hemoptysis Therapeutic options are limited and include supplemental oxygen therapy, anticoagulation, vasodilator therapy, and endothelin receptor antagonists.6–12 Bosentan and sildenafil have both been shown to increase functional capacity.13,14 Lung and heart-lung transplantation may be offered but have high 1- and 5-year mortalities Oral contraceptives should be prescribed for females because pregnancy in such patients has a high incidence of maternal and perinatal death and so should be actively discouraged and avoided.15 Pulmonary vascular disease can develop if, during fetal life, the pulmonary arteries are either very hypoplastic or absent This occurs primarily with tetralogy of Fallot with pulmonary atresia The severity of this disease is highly dependent on the presence and size of the native pulmonary arteries and the presence of major aortopulmonary collaterals Small true pulmonary arteries have higher pulmonary vascular resistances and, if there are aortopulmonary collaterals, may be exposed to higher flow and pressure The degree of pulmonary vascular disease will depend on the growth potential of the pulmonary arteries and establishing adequate pulmonary blood flow after surgical repair Finally, “downstream” obstruction can cause pulmonary artery hypertension Obstruction may occur at the level of the pulmonary veins, left atrium (e.g., cor triatriatum), mitral valve, or atrial septum in functionally single ventricle lesions These conditions all cause elevation in the pulmonary venous pressure that