A Natural History Study of Novel Biomarkers in Pulmonary Arterial Hypertension

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PAH (i.e. Group 1 PAH) is a rare disorder associated with poor survival. Endothelial dysfunction resulting from 1) genetic susceptibility, and 2) a triggering stimulus that initiates pulmonary vascular injury, the two-hit hypothesis, appears to play a central role both in the pathogenesis and progression of PAH. Inflammation appears to drive this dysfunctional endothelial phenotype, propagating cycles of injury and repair in genetically susceptible patients with idiopathic PAH (IPAH) and patients with disease-associated PAH. However, despite mounting evidence of vascular inflammation in patients with PAH, detailed phenotypic studies are lacking on the temporal evolution of this process and its contribution to right ventricular (RV) and pulmonary vascular remodeling. The protocol was initially approved by the NHLBI IRB in October 2012. Subsequently IRB approval was sought and obtained at collaborating sites and various amendments were brought into alignment at all institutions by summer 2013. Referrals are being received from multiple sites. To date 51 subjects have been screened for this study and 14 have been enrolled. We hypothesize that a detailed characterization of the temporal evolution of vascular inflammation and neurohormonal activation in PAH and its impact on RV and pulmonary vascular function will add prognostic value to traditional measures of disease severity and suggest novel therapeutic targets for future research.