Cardiac Assessment by PV Loop in IPAH and Scleroderma PAH

Overview

This observational study is being done to understand why people with scleroderma can develop pulmonary arterial hypertension (high blood pressure in the lungs, abbreviated PAH) and a weak heart muscle (heart failure). The study will also help the investigators understand why people with PAH from an unknown cause (called idiopathic PAH, or IPAH) can also develop a weakened heart muscle. The response of the right side of the heart or right ventricle (RV) to standard PAH therapy in scleroderma-associated PAH and in IPAH will be assessed. Blood and tissue samples will be collected from research participants during participants' normal standard of care procedures. People with scleroderma-associated PAH or idiopathic cause (IPAH) who need a right heart catheterization may join this study.

Patients with scleroderma associated pulmonary hypertension (with or without interstitial lung disease) have a worse prognosis compared to patients with idiopathic pulmonary arterial hypertension (IPAH). The investigators have discovered through a previous protocol that patients with scleroderma associated pulmonary hypertension (SSc-PAH) have intrinsic right ventricular (RV) contractile dysfunction compared with patients with idiopathic pulmonary hypertension (IPAH) despite similar afterload imposed by the pulmonary vasculature. Patients with scleroderma or presumed/known IPAH who are clinically referred for right heart catheterization (RHC) will undergo, in addition to a clinically indicated RHC, state-of-the-art Pressure-Volume (P/V) Loop Assessment and RV biopsy for research purposes. The investigators will also do a standard pathologic assessment of the RV tissue (H\&E, special staining, electron microscopy), microvascular density measurements using immunohistochemistry techniques and isolated skinned myocyte experiments. Additional experiments will include proteomics, genomics/genetics, and RV protein and microRNA expression. The investigators will compare these findings in both groups (IPAH and SSc-PAH), before and after standard treatment for 6 months, in order to fully understand the differences in how the RV adapts to pressure overload and reasons for impaired RV function in SSc-PAH as well as identifying potential therapeutic targets.