Primary pulmonary hypertension: Current therapy.

Because the causes of primary pulmonary hypertension (PPH) remains unknown, the therapeutic approach of the disease can be only empirical, based on the pathology and pathobiology of pulmonary circulation. Despite the inability to cure the disease, therapeutic advances over the past 20 years have contributed to an improvement of quality of life and prolonged survival in PPH patients. Current therapeutic approach of PPH mostly includes limitation of physical activity, long-term anticoagulation, and vasodilator therapy. Among all tested oral vasodilators, calcium-channel blockers are the most efficient long-term therapies by improving symptoms and hemodynamics in a subset of PPH patients (10% to 15%) who acutely respond to such drugs. Acute pulmonary vasodilator response to inhalation of nitric oxide can predict acute and chronic responses to oral calcium-channel blockers. A better understanding of the pathogenesis of PPH has changed the focus of medical treatments from purely chronic vasodilator therapy to the evaluation of agents, such as prostaglandins, that may reverse the proliferation of pulmonary vascular cells and result in regression of the pulmonary vascular hypertrophy and remodeling. Long-term treatment with intravenous epoprostenol (prostaglandin I(2) or prostacyclin) improves exercise capacity, hemodynamics and survival in most patients with PPH in functional class NYHA III or IV, and may be currently considered as the "gold standard" therapy for severe patients. However, response to long-term epoprostenol therapy may be incomplete, adverse effects are common, and survival remains unsatisfactory (55% at 5 years). In such patients with severe pulmonary hypertension refractory to medical therapy, atrioseptostomy and lung transplantation can be indicated.