Preclinical and clinical advances in pulmonary hypertension associated with systemic sclerosis

Systemic sclerosis (SSc) is a chronic, severe autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Pulmonary (arterial) hypertension (P(A)H) is a common complication and leading cause of death. This review highlights preclinical and clinical advances of recent years that contribute to our understanding of pathomechanisms, risk stratification, treatment and potential targets in SSc-P(A)H.

As SSc-PH emerges from a complex interplay of immune dysregulation, endothelial injury, metabolic reprogramming and fibroproliferative remodeling, an integrated approach to early detection, combining refined cardiac imaging metrics, circulating and omics-based biomarkers, and clinical stratifiers such as age and timing of symptom onset, is increasingly feasible. Recent literature highlights mechanistic targets for therapy and also practical tools for sharpening screening algorithms to reduce unnecessary right heart catheterization. Exercise testing and detailed right heart phenotyping yield promise for early disease diagnosis. Four randomized controlled trials in PAH provide (indirect) evidence on efficacy and safety of activin signaling inhibitor, Sotatercept in SSc-PAH.

Recent years have brought major preclinical and clinical advances improving diagnosis and management of SSc-P(A)H. Large-scale multi-omics analyses, and novel treatment targets offer further advances in the field.