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