It is imperative that the diagnosis of primary pulmonary hypertension not be made until potentially treatable causes of elevated pulmonary arterial pressure have been excluded. The presence of pulmonary hypertension and cor pulmonale caused by chronic pulmonary disease can be established readily by finding abnormalities in pulmonary function. In particular, interstitial lung diseases with fibrosis, such as sarcoidosis, and pneumoconioses, such as silicosis, as well as hypoxic pulmonary hypertension associated with impaired ventilation should be excluded. Cardiac catheterization and/or echocardiographic studies are necessary to search for a primary cardiac defect, and angiography or radioactive lung-scanning studies also may be indicated to detect emboli to relatively large pulmonary arteries. In performing pulmonary arteriography, the use of small amounts of contrast medium, preferentially injected selectively into the branches of the main pulmonary artery, is advisable since sudden death during catheterization has occasionally occurred. Patients having chronic emboli to the lungs are difficult to distinguish from those with primary pulmonary hypertension, but the distinction is important because anticoagulants, inferior vena caval interruption, and pulmonary embolectomy sometimes have been effective in patients with embolic disease. The lung scan and pulmonary arteriogram are typically normal in primary pulmonary hypertension, but with thromboembolic pulmonary hypertension, perfusion defects on lung scan or pulmonary arterial occlusions and filling defects on angiography often are visible. With pulmonary embolism, serial chest x-rays may show evidence of pulmonary infarction. Open lung biopsy has been used occasionally to differentiate primary pulmonary hypertension from the thromboembolic variety. Sometimes a site of origin for emboli cannot be identified in the leg veins, and other possible sources should be considered, such as right atrial thrombus, or ovarian and pelvic vein thromboses. Occasionally, pulmonary hypertension is due to parasitic disease, such as schistosomiasis or filariasis, or to multiple pulmonary artery thromboses consequent to sickle cell disease. Although the importance of accurate diagnosis is emphasized, short of open lung biopsy clinical differentiation may be impossible between the three main pathologic types of pulmonary hypertension (pulmonary venoocclusive, thromboembolic or thrombotic, and plex-ogenic pulmonary arteriopathic types), and they are frequently categorized by the clinician as primary pulmonary hypertension.

Several congenital cardiac conditions must be considered and excluded by appropriate echocardiographic or cardiac catheterization studies. Valvular pulmonic stenosis usually can be distinguished from pulmonary hypertension by identification of the delayed, soft pulmonic closure sound, but peripheral stenoses of the pulmonary arteries may be associated with an increased second heart sound. A left-to-right shunt at the pulmonary arterial, ventricular, or atrial levels should be sought. The wide, fixed splitting of the second heart sound should be helpful in identifying patients with atrial septal defect. Eisenmen-ger’s syndrome in a patient with ventricular septal defect or patent ductus arteriosus may be confused with primary pulmonary hypertension, but usually in Eisenmenger’s syndrome cyanosis, polycythemia, and clubbing are present, and at cardiac catheterization a large right-to-left shunt at the ventricular, atrial, or pulmonary arterial level can be demonstrated.

The murmurs of tricuspid or pulmonic regurgitation and the atrial gallop sounds heard in patients with primary pulmonary hypertension may be mistaken for the murmurs of rheumatic mitral and aortic valve disease, or vice versa. Before making the diagnosis of primary pulmonary hypertension, the presence of left atrial hypertension due to undetected mitral stenosis, or to a more unusual lesion such as left atrial myxoma or cor triatriatum, should be specifically sought and excluded. This can be done by echocardiography, by obtaining pulmonary arterial wedge pressure tracings, or by catheterization of the left side of the heart, with angiography if necessary.