Cause-specific outcomes in systemic sclerosis-associated, systemic lupus erythematosus-associated, and idiopathic pulmonary hypertension with significant pre-capillary components: a competing risk analysis.

BACKGROUND: Connective tissue disease-associated pulmonary hypertension (CTD-PH) comprises subtypes with divergent prognoses, yet its established endpoint, transplant-free survival (TFS), aggregates death and lung transplantation and cannot reveal whether subtypes differ in death, transplantation, or both. We decomposed TFS into its competing components in systemic sclerosis-associated (SSc-PH), systemic lupus erythematosus-associated (SLE-PH), and idiopathic PH (iPH).

METHODS: We analyzed 197 patients with right heart catheterization-confirmed precapillary PH (pulmonary vascular resistance > 2 Wood units) in a single-center Korean registry (2010-2025): SSc-PH (n = 15), SLE-PH (n = 17), iPH (n = 165). Cumulative incidence functions (CIF) for death and transplantation were estimated with bootstrap confidence intervals; cause-specific and subdistribution hazards and post-transplant follow-up were examined.

RESULTS: Over a median follow-up of 3.2 years, 28 deaths and 16 transplantations occurred. Five-year cumulative incidence of transplantation was 66.2% in SSc-PH versus 7.8% in iPH (difference 58.4 points, 95% CI 27.5-90.0), whereas death incidence, counting only deaths before transplantation, did not differ (- 5.5 points, - 18.9 to 21.6); no SLE-PH patient underwent transplantation. Because transplantation removes patients from the mortality risk set, transplant-censored survival was optimistically biased in SSc-PH: counting post-transplant deaths raised 5-year death incidence from 9.6% to 26.7%, though all-cause mortality did not differ across groups (log-rank p = 0.44).

CONCLUSIONS: In CTD-PH, TFS comprises markedly different events by subtype-predominantly transplantation in SSc-PH, exclusively death in SLE-PH. Mortality in SSc-PH could not be reliably characterized rather than being genuinely low. Cause-decomposed, subtype-specific reporting is needed; neither TFS nor transplant-censored survival alone captures these differences. These hypothesis-generating findings require confirmation in larger multicenter cohorts. Key Points • In CTD-PH, transplant-free survival decomposes into markedly different events by subtype: predominantly lung transplantation in SSc-PH and exclusively death in SLE-PH. • The 5-year cumulative incidence of transplantation was 58 percentage points higher in SSc-PH than iPH, whereas the cumulative incidence of death, which counts only deaths occurring before transplantation, did not differ. • Overall survival that censors transplantation is optimistically biased in SSc-PH; counting post-transplant deaths raised the 5-year death incidence from 9.6% to 26.7% and revealed additional post-transplant infection deaths.