achieved in total PAH population, sub-analysis within CTD-PAH patients showed failure to achieve short-term primary endpoints (2-4). In addition, current PH registries, such as REVEAL and ASPIRE, showed that patients with SSc-PAH had worse prognosis than those with other PH subgroups (5, 6). Recent meta-analysis on prognosis of patients with SSc-PAH reported that 1-, 2-, and 3-year survival rates were 82%, 67%, and 56%, respectively, even in modern treatment era (7). Furthermore, a recent striking report has demonstrated that survival in SSc-PAH had not improved at all after availability of oral pulmonary vasodilators, whereas survival in patients with idiopathic or heritable PAH had improved remarkably (8). Precipitating factors for poor prognosis of SSc-PAH still remain unclear, but at least two mechanisms can be speculated: poor responsiveness to pulmonary vasodilators and potential emergence of unfavorable effects by use of pulmonary vasodilators. The histology of pulmonary vasculature in patients with SSc-PAH is unique and is characterized by concentric intimal fibrosis with less prominent hypertrophy of vascular smooth muscle cells (9), which is a main target of pulmonary vasodilators. On the other hand, pathophysiological conditions of SSc-PAH are highly complex, since SSc affects not only pulmonary arteries, but also other organ systems, including lung interstitium, myocardium, gastrointestinal tract, and peripheral vasculature (10). Therefore, upon introduction of pulmonary vasodilators, it is necessary to consider their potential beneficial or harmful effects on the entire SSc lesions.