Management of dyspnea in advanced pulmonary arterial hypertension

Abstract

Pulmonary hypertension leads to progressive increase in pulmonary vascular resistance, heart failure, and death. Pulmonary arterial hypertension (PAH) is a subset of pulmonary hypertension affecting small pulmonary arteries and not associated with underlying heart or lung disease. Dyspnea and exercise intolerance are hallmarks of PAH and are used to monitor disease progression. This review focuses on recent advances in the pathophysiology and treatment of dyspnea in PAH. The etiological classification of pulmonary hypertension and World Health Organization functional class clinical classification, as used to guide management, have recently been revised. Dyspnea and PAH disease progression are best assessed by cardiopulmonary exercise testing and the six-minute walk test. Understanding of the molecular pathogenesis of PAH has led to new classes of treatments, including prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors. Prostanoids have the longest track record in treatment of PAH but a short half-life and cumbersome delivery systems limit their utility. More convenient endothelin receptor antagonists are becoming mainstream in PAH management. Phosphodiesterase-5 inhibitors improve exercise capacity and quality of life, although long-term outcome data are pending. Combination therapy with different medication classes appears promising for progressive disease. Establishing the cause and clinical severity of pulmonary hypertension is critical for management. The pathophysiology of dyspnea in PAH is complex and related to pulmonary vascular resistance. Although disease-specific treatments are now available, a cure for PAH remains elusive and trials of combination treatments to improve symptoms and outcomes are ongoing.