Incremental value of cardiopulmonary exercise testing in intermediate-risk pulmonary arterial hypertension

Background: Risk assessment in pulmonary arterial hypertension (PAH) is essential for prognostication. However, the majority of patients end-up in an intermediate risk status, offering insufficient guidance in clinical practice. The added value of cardiopulmonary exercise testing in this setting remains undefined. Methods: Two independent cohorts with idiopathic PAH at intermediate risk were used to develop (n = 124) and externally validate (n = 143) the prognostic model. Cross-validation on the overall population was used to strengthen the results of the analysis. Risk assessment was based on the simplified version of the ESC/ERS guidelines score. Discrimination and calibration were assessed. Results: A risk score was constructed based on the beta-coefficient of the cross-validated model, including the stroke volume index (SVI) and the peak oxygen uptake (VO₂ peak). Patients were grouped based on cutoff values of the risk score allowing the highest discrimination in the overall cohort. Group 1, score ≤2 (101 patients) with VO₂ peak ≥14 ml/kg/min and SVI >30 ml/m²; Group 2, score between 2 and 5 (112 patients) with VO₂ peak between 9 and 14 ml/kg/min, and SVI between 20 and 50 ml/m²; Group 3, score >5 (46 patients) with VO₂ peak <10 ml/kg/min and SVI <30 ml/m². The event-free survival rates at 1, 2 and 3 years, were 96%, 83% and 79% for Group 1, respectively; 82%, 67% and 52% for Group 2; 69%, 50% and 41% for Group 3. Conclusions: Combinations of VO₂ peak and SVI may provide important information to further stratify intermediate-risk prevalent patients with idiopathic PAH.