Pulmonary arterial hypertension.

PURPOSE OF REVIEW: The prevalence of pulmonary arterial hypertension is rising worldwide. Significant progress in our understanding of the pathobiology of pulmonary arterial hypertension has resulted in a shift from vasodilator therapy to the development of specific drugs targeting seminal molecular derangements of this disorder. This review highlights the recent advances in treatment and provides directions for the future care.

RECENT FINDINGS: Induction of endothelin-1 and decreased transcription of nitric oxide and prostacyclin leads to pulmonary vasoconstriction that triggers several downstream molecular events which result in pulmonary vascular remodeling. Treatment with endothelin receptor antagonists, prostanoids and phosphodiesterase-5 inhibitors that prevent breakdown of cGMP have all demonstrated benefits in prospective, randomized, controlled trials of pulmonary arterial hypertension patients. Future strategies will combine these therapies to explore whether targeting more than one pathway provides synergistic long-term benefit.

SUMMARY: Treatment guidelines developed by the American College of Chest Physicians aim to ensure that evidence-based approaches are practiced. Because of genetic heterogeneity in treatment effects and outcomes among patients, pharmacogenetics which will study polymorphisms that modulate the response to treatment will enable physicians to deliver cost-effective, tailored treatments for all pulmonary arterial hypertension patients in the future.