Primary pulmonary hypertension is a very rare occlusive disease of unknown cause involving moderate and small pulmonary arteries, causing right ventricular failure or fatal syncope 2 to 5 years after detection. The prevalence is 1:5 in men and women, and the average age at diagnosis is 35 years, with the younger the patient the worse the prognosis. Almost all cases have endocardial hyperplasia and the narrowing of the lumen caused by it. More advanced cases have multiple mid-layer hypertrophy and hyperplasia, irreversible plexiform damage and necrotizing arteritis (reticulopathy). The same clinical course of vascular damage is seen in some patients with cirrhosis and in some patients taking the appetite suppressant drug dexfenflu-ramine-phentermine (fen-phen) in combination, which is no longer available in the United States. Progressive exertional dyspnea is present in more than 95% of cases, and precordial pain on exertion and syncope are rare. Many patients have Raynaud’s phenomenon and arthralgia, usually appearing several years before the onset of significant primary pulmonary hypertension. Diagnosis and treatment The diagnosis of primary pulmonary hypertension can be considered based on the clinical presentation, but all known causes of pulmonary heart disease must be excluded, especially treatable pulmonary heart disease (e.g., pulmonary embolism). Physical examination may reveal some degree of manifestation of pulmonary heart disease. To rule out other causes of pulmonary hypertension, echocardiography, ventilation/perfusion scans, pulmonary function tests, and cardiac catheterization are often required. If there is a disproportionate segmental or large perfusion defect on the ventilation/perfusion scan, a pulmonary angiogram should be performed. This scan presentation will not be seen in primary pulmonary hypertension but is suggestive of chronic thrombotic occlusion of the pulmonary arteries as a result of unresolved pulmonary embolism. Thromboendarterectomy may be performed in some cases. Pulmonary capillary microscopy may reveal chronic appendage thrombosis, even in those with negative arteriograms. The need for open-chest biopsy is controversial. Some patients respond to vasodilators (e.g., prostacyclin, nifedipine) with dramatic reductions in pulmonary artery pressure. However, the effect of vasodilators should first be demonstrated by cardiac catheterization, and the imprudent application of these drugs has resulted in significant deterioration or death. Long-term oral nifedipine is increasingly being administered at doses determined by experience during cardiac catheterization. Continuous sedation of prostacyclin (a vasodilator and platelet aggregation inhibitor) with a portable micropump via an inserted catheter for more than 1 year has proven to be effective, improving quality of life and reducing emergency lung transplantation. To prevent recurrent thromboembolism or in situ thrombosis in silence and venous depression due to right heart failure, if not contraindicated, long-term oral coumarin anticoagulation is usually administered to maintain a prothrombin time of 1.5 to 1.75 times normal (INR, 2 to 3 – see Section 131 Laboratory Tests for Bleeding). Surgical procedures for unilateral or bilateral lung transplantation for primary pulmonary hypertension are seen to be well established.