Assessment of Structural and Functional Pulmonary Vascular Disease in Patients with PAH

Pulmonary arterial hypertension (PAH) is a life threatening disease characterized by a progressive increase in pulmonary blood pressure that often leads to right ventricular (RV) failure and death (McLaughlin et al., 2009). A review of the clinical trial data for the three classes of drugs approved for the treatment of PAH (prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors) has shown that all agents have similar efficacy on the 6-min walking distance over 12 to 16 weeks, which was the primary endpoint in the randomized clinical trials. However, the improvement in the distance walked during the 6-min walking test in the patients receiving active therapy that led to drug approval ranged from 3 to 17% from baseline. With respect to hemodynamics (which provides direct information about the status of the pulmonary circulation) these treatments are unimpressive, producing only a minimal reduction in the pulmonary arterial (PA) pressure. Presently, it remains speculative how these different drugs act on the pulmonary vasculature of patients with PAH and little is known about their long-term efficacy (Rich, 2006). Likewise, recent metaanalysis reported that the pooled effect of all treatment strategies shows a significant reduction of 39% (2-62%, p=0.041) in all-cause mortality (Galie et al., 2009). The benefits were confined only to patients with advanced disease for only 16 weeks, regardless of which class of drug was used. However, the mechanism by which mortality decrease remains unknown because it was unrelated to a specific class of drug, the dose of the drug, or the effects of the drug on 6-minute walking distance or hemodynamics (Macchia et al., 2010).