A comparative analysis of risk stratification tools in SSc-associated pulmonary arterial hypertension: a EUSTAR analysis
Authors: Bjørkekjær Hilde Jenssen , Bruni Cosimo , Broch Kaspar , Brunborg Cathrine , Carreira Patricia E , Airò Paolo , Simeón-Aznar Carmen Pilar , Truchetet Marie-Elise , Giollo Alessandro , Balbir-Gurman Alexandra , Martin Mickael , Denton Christopher P , Gabrielli Armando , Del Galdo Francesco , Vonk Madelon C , Fretheim Håvard , Bitter Helle , Midtvedt Øyvind , Andreassen Arne , Høie Sverre , Tanaka Yoshiya , Riemekasten Gabriela , Müller-Ladner Ulf , Matucci-Cerinic Marco , Castellví Ivan , Siegert Elise , Hachulla Eric , Molberg Øyvind , Distler Oliver , Hoffmann-Vold Anna-Maria ,   EUSTAR Collaborators, Guiducci Serena , Iannone Florenzo , Rednic Simona , Allanore Yannick , Montecucco Carlomaurizio , Kumánovics Gábor , Iudici Michele , Moroncini Gianluca , Andréasson Kristofer , Idolazzi Luca , Henes Jörg , Pflugfelder Johannes , da Silva José António Pereira , Hughes Michael , Riccieri Valeria , Balanescu Andra , Gheorghiu Ana Maria , Bergmann Christina , Cantatore Francesco Paolo , De Langhe Ellen , Ani Branimir , Müller Carolina de Souza , Solanki Kamal , Rosato Edoardo , Maurer Britta , Saketkoo Lesley Ann , Limonta Massimiliano , Hsu Vivien M , Chung Lorinda S , Levy Yair , Sfikakis Petros , Oliveira Susana , Kuwana Masataka 
Published: January 2025

Abstract

Objectives
The 2022 European Society of Cardiology and European Respiratory Society (ESC/ERS) guidelines for pulmonary arterial hypertension (PAH) recommend risk stratification to optimize management. However, the performance of generic PAH risk stratification tools in patients with SSc-associated PAH remains unclear. Our objective was to identify the most accurate approach for risk stratification at SSc-PAH diagnosis.

Methods
In this multicentre, international cohort study from the European Scleroderma Trials and Research (EUSTAR) group database, we screened 11 risk stratification tools upon SSc-PAH diagnosis. We compared the performance of the three top-ranked tools to predict mortality with the ESC/ERS three-strata model, the currently recommended tool for baseline risk assessment. We also assessed the impact of incorporating SSc-specific characteristics into the tools. Kaplan–Meier analyses and Cox regression with area under the ROC curve (AUC) were conducted.

Results
The ESC/ERS three-strata model had a lower ability to predict mortality than the ESC/ERS four-strata model, ‘SPAHR updated’ and ‘REVEAL Lite 2’. The ESC/ERS four-strata model divided ‘intermediate-risk’ patients into two groups with significantly different long-term survival rates and is the easiest applicable tool. Incorporating SSc-specific characteristics did not significantly improve the predictive ability of any model, but a low diffusing capacity of the lung for carbon monoxide (DLCO) was an independent predictor of mortality.

Conclusion
Considering its ability to predict mortality, risk segregation capabilities and clinical applicability, this study provides a rationale for using the simplified ESC/ERS four-strata model at SSc-PAH diagnosis as an alternative to the comprehensive ESC/ERS three-strata model. We propose considering DLCO as an individual prognostic marker in SSc-PAH.