FIG 75.3 Mechanisms of acute right ventricular failure and pulmonary hypertensive crisis LVEDV, Left ventricular end-diastolic volume; PAP, pulmonary arterial pressure, PBF, pulmonary blood flow; PVR, pulmonary vascular resistance; RV, right ventricular; RVEDP, right ventricular enddiastolic pressure; RVEDV, right ventricular end-diastolic volume; V/Q, ventilation/perfusion (Modified from Abman SH, Hansmann G, Archer SL, et al Pediatric pulmonary hypertension: guidelines from the American Heart Association and American Thoracic Society Circulation 2015;132[21]:2037–2099.) The incidence of life-threatening postcardiopulmonary bypass pulmonary hypertensive crises has markedly decreased, from 20% in the 1980s to only 2% to 5% 25 years later.24 This change reflects improved surgical techniques, treatments to lessen the impact of cardiopulmonary bypass, and, most importantly, earlier age at operation before the pulmonary vasculature has been injured However, the pathophysiology nevertheless remains relevant for complex patients, particularly for those with the Fontan circulation Risk factors for pulmonary hypertensive crisis include patient age, type of cardiac lesion, and presence of other genetic syndromes such as trisomy 21 Basic strategies for preventing pulmonary hypertensive crisis include avoidance of triggering stimuli such as acidosis and hypercarbia Inhaled pulmonary vasodilators including nitric oxide and iloprost have been shown to reduce pulmonary artery pressures postoperatively and, in the case of nitric oxide, shorten length of stay.24,25 Other commonly used pulmonary vasodilators include sildenafil, milrinone, and levosimendan Advanced strategies such as extracorporeal membrane oxygenation are indicated only for bridging a situation that may be expected to recover Pulmonary Hypertension Associated With Bronchopulmonary Dysplasia or Chronic Lung Disease Patients with pulmonary hypertension associated with prematurity and bronchopulmonary dysplasia (BPD) represents another significant population with pulmonary hypertension in childhood Infants born at less than 28 weeks’ gestation seem to have the highest risk Other risk factors include low gestational age, small for gestational age, oligohydramnios, duration of oxygen therapy, and duration of mechanical ventilation.26 Early pulmonary hypertension in premature infants has also been shown as a risk factor for severe BPD and mortality.27 The incidence of pulmonary hypertension is loosely associated with the severity of BPD, with an estimated incidence of 4% in mild BPD and up to 33% in severe BPD.28 Recent estimates suggest that between 25% and 40% of neonates with BPD have some evidence of pulmonary hypertension Histologic findings suggest an arrested alveolar development, or loss of alveoli, and a disruption in angiogenesis causing increased vascular tone and altered vasoreactivity In contrast, preservation of vascular growth and endothelial survival may promote growth and may sustain the architecture of the distal air space Echocardiography is the most frequently used screening technique for pulmonary hypertension associated with BPD Current guidelines recommend screening when an infant is diagnosed with moderate or severe BPD or for patients with worsening pulmonary status Cardiac catheterization is reserved for those with severe pulmonary hypertension, primarily to evaluate for comorbidities and assess pulmonary vasoreactivity An evaluation for concomitant conditions should be undertaken just as it is required in older patients Evaluation should assess for the presence of pulmonary vein stenosis, atrial communications, left ventricle diastolic dysfunction, and aortopulmonary collaterals The mainstay of treatment for BPD associated pulmonary hypertension includes oxygen to avoid hypoxemic vasoconstriction Recently, other pulmonary vasodilators have been used with limited clinical data in this population Specifically, sildenafil has limited clinical studies showing benefit Pulmonary vasodilators may be considered after careful evaluation and exclusion of fixed pulmonary vascular resistance Congenital Diaphragmatic Hernia This entity is characterized by pulmonary hypoplasia, with structural as well as functional anomalies, leading to a high pulmonary vascular resistance and pulmonary hypertension A combination of compression of the lungs during fetal life, limited flow of blood to the lungs, and intrinsic pulmonary developmental arrest is responsible for the parenchymal pulmonary hypoplasia.29–32 In addition, a dysregulation of the expression of the receptors for endothelin-1 has been documented, which has been shown to decrease local nitric oxide and vascular relaxation.33 Evidence of altered autonomic innervation has also been seen in human lung specimens, which may contribute to hyperreactivity of the pulmonary vasculature All these factors lead to the elevated pulmonary vascular resistance characteristic of congenital diaphragmatic hernia The degree of pulmonary vascular resistance is a strong prognostic indicator for survival.34 The clinical management includes surgical repair in the early neonatal phase, followed by supportive care over the long term With newer options for treatment, such as high-frequency oscillatory ventilation, intravenous infusion of prostaglandin, inhaled nitric oxide, and extracorporeal membrane oxygenation, better neonatal survival is achieved,35–37 but the number of patients with chronic lung disease, or recurrent or residual pulmonary hypertension, is also increasing There are no controlled clinical trials on the use of vasodilators in long-term survivors with elevated pulmonary arterial pressures Maximal exercise capacity was shown to be mildly decreased when a cohort of patients with this problem was compared with normal controls.38 Pulmonary Venoocclusive Disease This is a very rare condition that affects mainly, but not exclusively, children and young adults Multiple possible factors for its development have been proposed, including infections, genetic changes, toxic exposure, and autoimmune disorders.39–45 The clinical presentation is very similar to idiopathic pulmonary