arterial hypertension, with shortness of breath, chest pain, syncope, hypoxemia, and later signs of right-sided cardiac failure Histologic findings include intimal fibrosis of the pulmonary veins, leading to narrowing and occlusion of affected vessels.46,47 From the hemodynamic aspect, there is elevated pulmonary arterial pressure, with a raised pulmonary capillary wedge pressure, but normal left atrial pressure The chest radiograph typically shows enlargement of the pulmonary trunk, pulmonary edema with prominent Kerley B lines, and pleural effusions On computed tomography (CT), the disease manifests with thickened interlobular septa, enlarged lymph nodes, and ground-glass opacities.48 Definitive diagnosis requires lung biopsy, a high-risk procedure in end-stage patients Cardiac catheterization, with testing for vasodilation, may be indicated, but acute pulmonary edema has been described.49 Therapy includes supplemental oxygen and diuresis, as well as anticoagulation.50 There are also reports on the use of immunosuppressive therapy with corticosteroids51 and azathioprine,52 but this approach should be limited to patients with suspected or proven collagen vascular disease Lung transplantation is most likely the only option for treatment, but the long waiting time for organs may limit the final outcome Alveolar Capillary Dysplasia This is a relatively rare cause of persistent pulmonary hypertension of the newborn, but its incidence is most likely underestimated A retrospective study on neonates treated with extracorporeal membrane oxygenation in the United Kingdom between 1997 and 2000 identified a total of nine patients with such irreversible lung dysplasia.53 The etiology is still uncertain, with familial cases suggesting a possible genetic mutation.54,55 The histologic findings include muscularization of the pulmonary arterioles, a deficiency in the number of alveolar units and pulmonary capillary vessels with thickening of the interalveolar septa, anomalous pulmonary veins accompanying the pulmonary arteries and bronchi, and dilated lymphatics.56–58 The newborn usually presents with severe hypoxemia, without response to treatment with oxygen or pulmonary vasodilators Open lung biopsy has been recommended if a neonate with persistent pulmonary hypertension shows no clinical improvement after 72 hours despite maximal medical therapy Cardiac catheterization may be helpful to complete the diagnostic work-up.59 Currently the disease is incurable, with a maximum reported survival time of approximately 3 months, albeit sometimes with a phase of mild improvement with the administration of vasodilating agents.60,61 Pulmonary Hypertension Associated With Pulmonary Venous Obstruction Pulmonary venous obstruction induces both pulmonary arterial and pulmonary venous hypertension The condition may be related to anatomic abnormalities of the pulmonary veins and congenital heart disease, as described earlier, or less frequently may be congenital Pulmonary vein stenosis has also been seen in cases of BPD believed to be due to the disruption of angiogenesis that is characteristic of BPD Although rare, this is likely an underdiagnosed phenomenon Diagnosis of Pulmonary Hypertension Diagnostic Approach The diagnosis of pulmonary hypertension can be elusive because early signs and symptoms are often subtle and nonspecific Once pulmonary hypertension has been diagnosed, testing has several purposes Patients require assessment of ventricular function, disease severity, and functional capacity A complete workup for secondary causes of pulmonary hypertension should also be performed Presenting Symptoms Despite multiple associated diseases, patients with pulmonary hypertension develop similar symptoms In the early stages, pulmonary hypertension is asymptomatic until cardiac function becomes affected Progressive dyspnea with activity that progresses over months is the most frequent symptom Chest pain and syncope with exertion may become evident with more severe pulmonary hypertension and impaired right ventricular function Peripheral edema and hepatomegaly develop in later stages Syncope is a concerning symptom and has been associated with mortality risk independent of the degree of pulmonary artery pressure elevation or right ventricular dysfunction Patients with pulmonary hypertension associated with left heart disease or pulmonary venous obstruction may present with pulmonary edema Grading the limitations in exercise using the World Health Organization classification is useful for monitoring patient's response to therapy (see Table 75.3) Physical Findings Depending on the degree of pulmonary artery pressure elevation, a patient may exhibit few if any physical signs A loud second heart sound is present in most patients with elevated pulmonary artery pressures Murmurs due to tricuspid regurgitation or pulmonary insufficiency may also be heard In later stages, signs of right heart failure such as jugular venous distension, hepatomegaly, peripheral edema, or ascites become evident Chest Radiography