Update in Pulmonary Diseases

Pulmonary Hypertension: New Treatments and Outcomes

The hallmark of pulmonary arterial hypertension is an increase in pulmonary vascular resistance, which may be 20 times normal, leading to mean pulmonary artery pressures exceeding 25 mm Hg at rest and 30 mm Hg during exercise. If untreated, the condition leads to right ventricular failure and ultimately death. All layers of the pulmonary vessel walls are affected. Proliferation of the adventitia limits vascular elasticity, while hypertrophy of the medial smooth muscle promotes vasoconstriction in what is normally a high-flow, low-pressure system. Intimal proliferation and in situ thrombosis may eventually occlude the vascular lumen. Endothelial cell dysfunction is part of the disease process, and mounting evidence shows that endothelin-1, a strong endogenous vasoconstrictor, has a key pathogenic role. According to the 1998 World Health Organization (WHO) classification, subtypes of pulmonary arterial hypertension include primary pulmonary hypertension and pulmonary arterial hypertension associated with collagen vascular diseases (especially scleroderma), congenital heart disease with a left-to-right shunt, portal hypertension, HIV infection, and assorted drugs and toxins.

In the first, preclinical stage of pulmonary arterial hypertension, pulmonary vascular resistance and pulmonary arterial pressure increase but there are no symptoms. The disorder is seldom diagnosed at this stage, which corresponds to functional class I in the New York Heart Association (NYHA)/WHO classification system. In stage 2 (NYHA/WHO functional classes II and III), the pulmonary vascular bed can no longer accommodate increased blood flow during exercise, and the patient experiences progressive dyspnea on exertion. In patients with stage 3 pulmonary arterial hypertension (NYHA/WHO functional class IV), the right ventricle begins to fail, cardiac output decreases, and the patient becomes symptomatic at rest. Patients with primary pulmonary hypertension live an average of less than 3 years after diagnosis. Treatment is based in part on disease severity, which may …