Are Guideline-recommended Risk Classification Schemes in Pulmonary Hypertension Adequately Robust to Guide the Real-world Setting?

Abstract

Background: Pulmonary hypertension is a complex syndrome that encompasses a diverse group of pathophysiologies predisposed by different environmental and genetic factors. It is not clear to which extent the universal risk classification schemes can be applied to cohorts in individual pulmonary hypertension centers with differing environmental backgrounds, genetic pools, referral networks.

Aims: To explore whether the recommended risk classification schemes could reliably be used for mortality prediction in an unselected pulmonary hypertension population of a tertiary pulmonary hypertension center.

Study design: A retrospective cross-sectional study.

Methods: We retrospectively screened our hospital database for the patients with pulmonary hypertension between 2015 and 2022. The grouping of pulmonary hypertension was made as follows in accordance with current guidelines: Group 1: patients with pulmonary arterial hypertension, Group 2: patients with pulmonary hypertension associated with left heart disease, Group 3: patients with pulmonary hypertension associated with lung disease and/or hypoxia, and Group 4: patients with pulmonary hypertension associated with pulmonary artery obstructions. Then, we compared the predicted and observed mortality rates of four different risk classification schemes (REVEAL, REVEAL-Lite, ESC/ERS and COMPERA).

Results: We identified 723 cases in our pulmonary hypertension database, the final study population consisted of 549 patients. The REVEAL, REVEAL-Lite and European Society of Cardiology/European Respiratory Society risk scores significantly underestimated the mortality risk in the low-risk stratum (5.3% vs. 1.9%, P < 0.001; 5.3% vs. 2.9%, P = 0.015 and 6.3% vs. 1%, P < 0.001, respectively) and overestimated the mortality risk in the high-risk stratum (11.8% vs. 25.8%, P < 0.001; 10.4% vs. 25.1%, P < 0.001 and 13.2% vs. 30%, P < 0.001, respectively). Although the COMPERA 4-strata model significantly underestimated the risk in low- and intermediate-low risk strata (4.9% vs. 1.5%, P < 0.001 and 6.8% vs. 2.8%, P = 0.001, respectively), it was accurate in intermediate-high and high-risk groups (10.1% vs. 8.7%, P = 0.592 and 15.6% vs. 22%, P = 0.384, respectively). The analyses limited only to group 1 pulmonary hypertension patients gave similar results.

Conclusion: The established risk classification schemes may not perform as good as expected in unselected pulmonary hypertension populations and this may have important implications on management decisions. Tertiary centers should not uncritically accept the published risk prediction models and consider modifying current risk scores according to their own patient characteristics.

Figure 1

One-year mortality rates according to different risk-scoring systems. For the COMPERA risk score, green, yellow, orange, and red bars indicate low, low-to-intermediate, intermediate-to-high, and high-risk status, respectively. For others, green, yellow, and red bars indicate low, intermediate, and high-risk status, respectively. The shaded background indicates 1-year mortality risk levels, where green, yellow, and red indicate low (< 5%), intermediate (5-20%), and high (> 20%) risk status, respectively. COMPERA, Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; ESC/ERS, the European Society of Cardiology/European Respiratory Society; REVEAL, Registry to Evaluate Early, and Long-Term Pulmonary Arterial Hypertension Disease Management.

Figure 2

Kaplan-Meier curves for 1-year survival according to the risk strata. a, REVEAL risk score; b, REVEAL Lite score; c; COMPERA (Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension) risk classification; d, ESC/ERS (the European Society of Cardiology/European Respiratory Society) risk score.