Background Pulmonary arterial hypertension (PAH) is a life-limiting complication of systemic sclerosis (SSc), with median survival of 3 years. Within PAH therapy, a notable heterogeneity of response exists, leading to identification of a subset of patients termed ‘super-responders’. Although lacking a universally accepted definition, super-responders experience significantly greater benefits compared to the average population. Here, we define super-responders as patients demonstrating a 2-point improvement in their NYHA functional class. In this study, we aim to explore the impact of prostacyclin therapy on SSc-PAH and review the potential clinical and molecular markers that could predict super-responder status.

Methods This is a retrospective case series with a collection of data of four patients seen at Albany Medical Center between 2010 to 2024 with a diagnosis of SSc and PAH, who were treated with prostacyclin and showed an improvement in their functional status and pulmonary hemodynamics. After obtaining IRB approval, data was extracted that included patient demographics, time of onset of PAH, functional class, and right heart catheterization findings before and after treatment with prostacyclin.

Results Our study included 3 females and 1 male patient with a median age of 46 years. All patients received prostacyclin therapy: two subcutaneous Treprostinil, one inhaled Treprostinil, and one started subcutaneously before transitioning to oral medication. Clinically, all patients experienced a 2-point improvement in NYHA functional class within approximately a year of prostacyclin therapy. Additionally, all patients had improvements in pulmonary hemodynamics, evidenced by reductions in the mean pulmonary artery pressures (mPAP) and pulmonary vascular resistance (PVR), following prostacyclin therapy as observed via right heart catheterization (table 1). Median survival to date is 9 years.

Conclusion Our SSc-PAH patients achieved long term survival, notable improvements in functional status and even near normalization of pulmonary hemodynamics after prostacyclin therapy, indicating sustained benefits beyond mere stabilization.

Current studies speculate that prostacyclin therapy not only causes pulmonary artery vasodilation, but also influences vascular remodeling process by potentially recruiting endothelial progenitor cells (EPCs) into the pulmonary vasculature, as well as reducing the number and procoagulant activity of platelet micro-vesicles (PMVs). It will be worthwhile to investigate EPC count and PMVs as surrogate markers for prostacyclin response to address treatment response heterogeneity.