Abstract 4144685: External validation and comparison with REVEAL 2.0 of the 6-strata system for risk stratification in PAH: are we reinventing the wheel?

Background: A recent study from the French Pulmonary Hypertension Network showed that stroke volume index (SVI) or mixed venous oxygen saturation (SvO2) may improve risk stratification at follow-up in pulmonary arterial hypertension (PAH) patients with intermediate-risk (according to the European 4-strata system). This resulted in a refined 6-strata system, associated with a discrimination improvement. Research Questions: This 6-strata system has not been externally validated and compared with the U.S. based REVEAL 2.0 risk score. Aims: To externally validate the refined 6-strata system and compare its performance with the current REVEAL 2.0 risk score. Methods: A harmonized dataset from 8 PAH randomized controlled trials generated in collaboration with the FDA was used for this analysis. The REVEAL 2.0 and the refined 6-strata was calculated for individual patients at first follow-up. The outcome assessed was 1-year all-cause death. Discrimination capacities using C-index and 95% confidence interval were calculated. Results: A total of 1,692 PAH patients were included: median age 50 (37, 62) years, mPAP 50 (39, 60) mmHg, PVR 9.0 (6.1, 13.1) WU, 6MWD 393 (330, 441) m, NTproBNP 1,933 (148, 1882) pg/mL. Of these, 99% and 76% of patients classified as strata 1 and 2 (low-risk) by the 6-strata system respectively, were classified as low-risk by REVEAL 2.0. Similarly, majority of patients within the strata 3/4 and 5/6 were classified as intermediate and high risk by REVEAL 2.0, respectively. ( Figure 1 ). C-index were 0.73, 95%CI [0.68, 0.78], 0.75, 95%CI[0.70, 0.80] and 0.78, 95%CI[0.73, 0.83] for the 4-strata, 6-strata and REVEAL 2.0 risk scores, respectively. There were no significant survival differences at 1-year between patients from strata 1 to 4 ( Figure 2 ). Conclusion: This is the first external validation of the modified 6-strata system. Although the discrimination capacities with the 6-strata is higher than with the 4-strata, yet it does not add incremental information regarding 1-year survival compared to REVEAL 2.0 risk score.