External validation of a refined four-stratum risk assessment score from the French pulmonary hypertension registry

Abstract

IntroductionContemporary risk assessment tools categorise patients with pulmonary arterial hypertension (PAH) as low, intermediate, or high-risk. A minority of patients achieve low-risk status with most remaining intermediate-risk. Our aim was to validate a 4-strata risk assessment approach categorising patients as low, intermediate-low, intermediate-high, or high risk, as proposed by the COMPERA Registry investigators.MethodsWe evaluated incident patients from the French PAH Registry and applied a 4-strata risk method at baseline and at first reassessment. We applied refined cut-points for 3 variables: World Health Organization functional class, 6-minute walk distance, and N-terminal pro-brain natriuretic peptide. We used Kaplan-Meier survival analyses and Cox proportional hazards regression to assess survival according to a 3-strata and 4-strata risk approach.ResultsAt baseline (n=2879), the 4-strata approach identified 4 distinct risk groups and performed better than a 3-strata method for predicting mortality. The 4-strata model discrimination was higher than the 3-strata method when applied during follow-up and refined risk categories among subgroups with idiopathic PAH, connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. Using the 4-strata approach, 53% of patients changed risk category from baseline compared to 39% of patients when applying the 3-strata approach. Those who achieved or maintained a low-risk status had the best survival, whereas there were more nuanced differences in survival for patients who were intermediate-low and intermediate-high.ConclusionsThe 4-strata risk assessment method refined risk prediction, especially within the intermediate risk category of patients, performed better at predicting survival and was more sensitive to change than the 3-strata approach.

Risk Stratification of Patients with Pulmonary Arterial Hypertension: The Role of Echocardiography

“…Recent data suggested that stroke volume index at first follow-up following the diagnosis of PAH can discriminate between two survival phenotypes within the intermediate-risk category [ 36 ]. Additionally, a four-strata approach described by COMPERA investigators computes rounded average risk scores using refined cut-off levels for WHO FC, 6MWD, and BNP/NT-proBNP and provides better discrimination compared to the conventional three-strata approach using the same variables [ 37 , 38 ]. Another recent study identified a subgroup of intermediate-risk patients with 6MWD ≥ 270 m and TAPSE/PASP ≥ 0.24 mm/mmHg who had significantly better survival compared to other patients in the same risk group [ 28 ].…”

“…The current study presents a new four-strata approach that allows for better discrimination by incorporating more objectively obtained clinical echocardiographic parameters into the existing COMPERA model. While both TAPSE and degree of TR were used to further stratify intermediate-risk patients, the approach that combined both parameters had the highest discriminatory power, with a C-statistic (0.81) exceeding that of conventional three-strata approaches (COMPERA score C-statistic = 0.62, French Pulmonary Hypertension Registry model C-statistic = 0.64, Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 score C-statistic = 0.73) [ 5 , 6 , 41 ], and, more importantly, that of novel four-strata risk scores (COMPERA 2.0 score C-statistic = 0.73, Yogeswaran et al model C-statistic = 0.72) [ 28 , 37 , 38 ]. A recent study of 102 PAH patients showed that TAPSE/TR velocity and TAPSE/PASP have the potential for dichotomizing intermediate-risk patients into two risk categories [ 42 ].…”

Lack of concordance between the different exercise test measures used in the risk stratification of patients with pulmonary arterial hypertension

“… 9 This model was validated in the French registry cohort. 10 According to this evidence, in the recent 2022 guideline this risk assessment has been included in four strata for the follow‐up of patients with PAH.…”

The original and two new derivative versions of the COMPERA 2.0 risk assessment model: useful tools for guiding balloon pulmonary angioplasty

“…According to the previously described cutoff points for WHO, 6MWD and NT-proBNP (Additional file 3 : Tables S1 and S2) [ 7 , 8 ], we assigned 1 to 4 points to each variable. The risk score for each patient was calculated as follows: sum of all points/number of variables.…”

“…Immediately after, Hoeper et al developed COMPERA 2.0 risk score, by using 3 noninvasive variables, namely World Health Organization functional class (WHO-FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP)/brain natriuretic peptide (BNP) [ 7 ]. The authors reported that the 4-stratum (4-S) model outperformed the 3-stratum (3-S) model in predicting prognosis and reflecting treatment response, which was further externally validated by Boucly et al [ 8 ].…”