Independent associations and incremental prognostic value of follow-up peak oxygen uptake in symptomatic post-acute pulmonary embolism patients
B L Yang, S Y Song, W Fang, C M XiongAbstract
Background
Persistent symptoms following acute pulmonary embolism (APE) are associated with a heightened risk of chronic thromboembolic pulmonary hypertension (CTEPH), yet reliable tools for early identification of at-risk patients remain limited. Cardiopulmonary exercise testing (CPET) provides objective assessment of functional capacity and may offer prognostic value in this population; however, its independent association with subsequent CTEPH development and incremental value over established risk stratification tools has not been systematically evaluated. This study therefore aims to determine the independent associations and incremental prognostic value of peak oxygen uptake (VO₂) at 3 months in symptomatic APE survivors.
Methods
Consecutive APE survivors with persistent symptoms at 3 months who underwent CPET at follow-up were included and randomly divided into training and validation cohorts. In the training cohort, % pred peak VO₂ was evaluated both as a continuous variable and dichotomised by functional limitation (% pred < 80%) and by the optimal threshold for subsequent CTEPH development identified via receiver operating characteristic (ROC) analysis. Kaplan-Meier (KM) analysis compared cumulative CTEPH incidence between groups, and stepwise logistic regression evaluated the independent association of % pred peak VO₂ with subsequent CTEPH diagnosis. Sensitivity analyses were conducted in the total cohort and in patients with ventilation/perfusion (V/Q) mismatch at 3 months. Incremental value over TTE-based PH probability was assessed by comparing ROC-derived discriminatory performance between models.
Results
In total, 441 patients were included and allocated to training (n = 221) and validation (n = 220) cohorts, with comparable baseline parameters across all 3 groups. ROC analysis identified 60% pred peak VO₂ as the optimal threshold for subsequent CTEPH development (AUC: 0.65; sensitivity: 51.6%; specificity: 73.2%). KM analysis demonstrated significantly higher CTEPH incidence in patients below this threshold (p = 0.005) (Figure 1-A). Stepwise logistic regression confirmed that % pred peak VO₂ < 60%, as well as its continuous form, was independently associated with subsequent CTEPH development, with findings consistent across sensitivity analyses (Table 1). In the validation cohort, the addition of % pred peak VO₂ < 60% to a model based on intermediate-high PH probability on TTE alone significantly improved discriminatory performance for identifying underlying CTEPH (AUC: 0.77 vs 0.84; p = 0.003) (Figure 1-B).
Conclusion
In symptomatic APE survivors, % pred peak VO₂ at 3 months is independently associated with subsequent CTEPH development and provides significant incremental value beyond TTE-based PH probability. These findings support the integration of CPET into structured follow-up protocols for early identification of patients at heightened risk of CTEPH following APE.For image description, please refer to the figure legend and surrounding text.Figure 1For image description, please refer to the figure legend and surrounding text.