Cause of death in a contemporary cohort of patients with pulmonary arterial hypertension

Abstract

Abstract Background In pulmonary arterial hypertension (PAH), contemporary risk tools primarily estimate all-cause mortality, offering limited insight into what patients die from. Aims We aimed to characterize causes of death across baseline risk strata and to examine baseline factors associated with PAH-related versus non-PAH–related death in a national cohort. Methods and results Adults with Group 1 PAH in the Hellenic Pulmonary Hypertension Registry (2015–2024) were classified by ESC/ERS 3-strata risk at baseline. Causes of death were adjudicated as PAH-related or non-PAH–related and further categorized. We modeled cause-specific mortality using competing-risk models with prespecified predictors. Model performance was summarized by discrimination and calibration. Among 462 patients followed for a median (IQR) of 2.2 (5.7) years, 163 deaths occurred; causes were adjudicated in 149 cases (55% PAH-related, 45% non-PAH-related). PAH-related deaths increased across risk strata, whereas the pattern of non-PAH causes did not differ significantly. Sepsis was the leading non-PAH cause. In multivariable competing-risk analyses, higher baseline risk and male sex independently aligned with PAH-related death, while older age aligned with non-PAH death. Discrimination was acceptable: AUC 0.77 (95% CI 0.70–0.83) for non-PAH death and 0.75 (95% CI 0.68–0.80) for PAH-related death. Integrated Brier score (IBS) improved versus null models, and calibration was good across the central predicted-risk distribution. Conclusion In contemporary PAH, what patients die from differs by baseline risk. PAH progression dominates in high-risk patients, whereas competing causes, especially sepsis, remain influential across strata. Cause-specific modeling may refine counseling, prevention, and resource allocation beyond all-cause risk alone.