An evidence-based approach to the management of pulmonary arterial hypertension.

PURPOSE OF REVIEW Evidence-based therapies and guidelines for pulmonary arterial hypertension are critiqued. RECENT FINDINGS Morbidity and mortality in pulmonary arterial hypertension reflects failure of right ventricular compensation for increased afterload caused by obstructive pulmonary arterial remodeling. This predominantly reflects excessive proliferation/impaired apoptosis of smooth muscle and endothelial cells, rather than vasoconstriction. To exclude confounding effects of cardiac output and left ventricular end-diastolic pressure, the diagnosis of pulmonary arterial hypertension should require a pulmonary vascular resistance >3 Wood-units, not simply a mean pulmonary arterial pressure >25 mmHg. A 'positive' response (20% fall in pulmonary arterial pressure/pulmonary vascular resistance PAP/PVR) to acute, selective, pulmonary vasodilators (e.g. inhaled nitric oxide), occurs in 20% of patients, portends a favorable prognosis and justifies a trial of calcium channel blockers. Randomized controlled trials support treatment of NYHA class III pulmonary arterial hypertension with oral endothelin antagonists or phosphodiesterase-5 inhibitors. Prostacyclin analogues (inhaled/subcutaneous) are useful adjunctive therapies. Intravenous epoprostenol remains the therapeutic mainstay for class IV PAH. Emerging antiproliferative-proapoptotic therapies that merit investigator-initiated clinical trials include: statins, Imatinib, NONO-ates, anti-survivin, potassium channel modulation, and dichloroacetate. SUMMARY The diagnostic criteria for pulmonary arterial hypertension should be revised to include PVR. Sildenafil's efficacy and price recommend it as a first-line oral therapy. New pulmonary arterial hypertension-regression therapies and therapeutic combinations offer the potential for cure of pulmonary arterial hypertension.