Risk assessment models and survival in pulmonary arterial hypertension: A SPAHR analysis

Multicomponent improvement (MCI) is a novel endpoint for predicting survival in patients with pulmonary arterial hypertension (PAH), included in the sotatercept clinical program. For the first time, we investigated the prognostic value of MCI, European Society of Cardiology/European Respiratory Society (ESC/ERS) 4-strata risk (4SR) assessment, and the non-invasive French risk stratification score (FRS), for predicting survival in PAH patients in Sweden. All risk prediction models are based on 3 parameters: WHO-FC (World Health Organization Functional Class), NT-proBNP, and 6MWD (6-minute walk distance).

Data from the Swedish PAH & CTEPH Registry (SPAHR) collected 2008-2021 were used for the analyses. The association of MCI achievement, 4SR, and FRS calculated at 6 months, with transplant-free (TF) survival was investigated in the whole cohort, as well as categorized by age (<65 and ≥65 years). All risk prediction models are based on three parameters: WHO-FC (World Health Organization Function Class), NT-proBNP, and 6MWD (6-minute walk distance). Kaplan-Meier estimate/Log-Rank test and Cox proportional model were used for survival analyses.

The study included 411 patients (70% women) with a median [IQR] age of 66 years.²¹ At 6 months, the mean (SD) NT-proBNP decrease was 808 (603) and the mean 6MWD increase was 44 (11) meters. Median survival/follow-up time was 3.5 years [1.7, 5.4]. After adjustment for sex and comorbidities, achievement of MCI independently predicted TF-survival; one MCI-criterion met (HR 0.65; CI 0.46-0.92, p = 0.015); 2 MCI-criteria met (HR 0.45; CI 0.31-0.66, p < 0.001); all 3 MCI-criteria met (HR 0.32; CI 0.21-0.52, p < 0.001). Likewise, 4SR and FRS demonstrated a strong association with TF-survival with patients achieving lower risk scores exhibiting longer survival compared to those with higher risk scores. Patients ≥65 years more often had connective tissue disease-associated PAH, lower DLCO, more pronounced comorbidity burden, higher risk at baseline, less improvement during follow-up, and worse TF-survival then patients <65 years.

All models were found to have prognostic relevance for TF-survival. Risk prediction was incremental with the number of low-risk criteria met, while improvements in only one of 6MWD, NT-proBNP, or FC showed a modest association with survival. The risk assessment tools predicted outcome in patients across both age categories.