Comparison of pulmonary arterial risk assessment tools to predict mortality or morbidity in treatment naive and previously diagnosed patients

Abstract Background Pulmonary arterial hypertension (PAH) risk stratification (1-year prediction of risk) is crucial and should be the most accurate to ensure appropriate aggressiveness of the treatment choices. According to the European guidelines, several risk tools can be used both at baseline and/or follow-up assessment. Yet, a comparison of risk tools performances only in treatment-naïve or only previously diagnosed patients is still missing. Aims To compare the available risk assessment tools performances to predict 1-year mortality but also 1-year clinical worsening in treatment-naïve and previously diagnosed PAH patients. Methods Eight PAH trials (AMBITION, ARIES1, ARIES2, FREEDOM, GRIPHON, PATTENT, PHIRST and SERAPHIN) provided by the FDA were harmonized and treatment-naïve patients were separated from previously diagnosed patients. Outcomes were 1-year mortality and 1-year clinical worsening (i.e., morbidity) either from baseline assessment or at follow-up. Kaplan-Meier and log-rank tests were performed for each of the following risk tools: European 4-strata, REVEAL2.0, REVEAL Lite, noninvasive FRENCH. In each subgroup, their C-indices were calculated and compared using a total of 100 bootstrap samples from the original data, providing a robust method for comparing across the different tools. Results Among the 4,122 patients included, 1,701 (41%) were treatment-naïve and 2,411 (59%) were previously diagnosed patients. Compared to treatment naïve patients, previously diagnosed patients were younger (p<0.001), with lower level of natriuretic peptide (p=0.013), higher 6MWD (p<0.001) and higher mPAP (p<0.001). At 1-year, the mortality rate was the same in the 2 subgroups (5.6% 5.1%, p=0.05) but clinical worsening occurred more often among previously diagnosed patients (19% vs 8.4%, p<0.001). Each of the risk tools were able to predict both 1-year mortality or morbidity in each subgroup, especially among previously diagnosed or at follow-up, with fair to good C-index (Figure 1). Forrest plots of 95%CI for the C-index differences among the 100 bootstrap samples showed that REVEAL 2.0 was the best performer, followed by REVEAL Lite (Figure 2). Conclusions In this large dataset, we showed that all PAH risk tools were able to predict not only 1-year mortality but also 1-year morbidity, both in treatment naïve and previously diagnosed patients. REVEAL 2.0 depicted the higher C-index.Figure 1.C-index for PAH risk toolsFigure 2.Forrest plots of 95%CI