Current PAH therapies consist of prostacyclin analogues, endothelin receptor antagonists (ETRA) and phosphodiesterase type V (PDE V) inhibitors (13). All have been shown to be effective in improving exercise capacity as measured by the 6 MWD in short term (12 - 16 week) randomized, placebo-controlled clinical trials. However, the clinical response is highly variable and mortality remains high (14). Moreover, the majority of subjects enrolled in these trials have had IPAH. Over the past 10 years, the Johns Hopkins Pulmonary Hypertension Program and Scleroderma Center have worked closely to address the daunting clinical challenge of PAH associated with scleroderma or systemic sclerosis (PAH-SSc). Previous work from our group (15;16) and others (17-19) has clearly demonstrated a markedly worse prognosis in PAH-SSc compared with IPAH despite similar treatments. An intriguing and consistent finding when comparing these two groups is that whereas mPAP is, on average, lower in PAH-SSc, markers of RV dysfunction (e.g. CO and RAP) are similar, raising the possibility of maladaptive RV response to pressure overload and/or intrinsic myocardial disease. Current PAH therapies target pathways that have been implicated in the remodeling of the pulmonary vasculature (PV). However, there is no clear evidence that these therapies have altered PV and/or RV remodeling or offered significant beneficial effects in patients with PAH-SSc in whom mortality remains exceedingly high. In addition, their effects on RV dysfunction and RV-PV interaction remain poorly characterized.