Abstract 4367432: Impaired Peak VO ₂ at 3 Months Post-Acute Pulmonary Embolism is Independently Associated with Subsequent Development of Chronic Thromboembolic Pulmonary Hypertension

Introduction: Exercise limitation, commonly assessed by peak VO 2 , affects over 50% of acute pulmonary embolism (APE) survivors. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but potentially fatal complication of APE. The association between post-APE exercise limitation and CTEPH development remains unclear. Research Question: To determine the relationship between peak VO 2 measured at 3 months post-APE and subsequent CTEPH, as well as pulmonary vascular disease (PVD) severity. Methods: From a prospective registry of 846 consecutive hospitalized APE patients, we analyzed 319 individuals who underwent cardiopulmonary exercise testing at 3 months and had no prior pulmonary hypertension. Patients were stratified by peak VO 2 tertiles. We used Kaplan-Meier analysis and Firth logistic regression to assess the relationship between peak VO 2 and CTEPH. Patients who underwent right heart catheterization (RHC) during follow-up were re-stratified by peak VO 2 tertiles to evaluate associations with PVD severity. Between-group comparisons were performed using ANOVA or Kruskal-Wallis tests. Results: The cohort had a mean age of 60.8±13 years (45.8% male). Peak VO 2 tertiles: tertile 1, >17.9 ml/min/kg; tertile 2, 14.3-17.9 ml/min/kg; tertile 3, <14.3 ml/min/kg. During a median follow-up of 36 months, 87 patients underwent RHC and 50 developed CTEPH. Cumulative CTEPH incidence was significantly lower in tertile 1 versus tertiles 2 and 3 combined (11.9% vs. 23.3%, log-rank p=0.022), but not among individual groups (11.9% vs. 24.6% vs. 22.2%, p=0.072). Tertiles 2 and 3 showed independent CTEPH associations (OR 3.23, 95% CI 1.19-9.45, p=0.021; OR 3.17, 95% CI 1.07-10.12, p=0.037). Among 87 catheterized patients, hemodynamic parameters demonstrated consistent deterioration across declining peak VO 2 tertiles, with significant reductions in peak VO 2 , cardiac output, mixed venous oxygen saturation, and tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure (PAP) ratio (p<0.001, p=0.001, p<0.001, and p=0.007, respectively), alongside increases in mean PAP, NT-proBNP, pulmonary vascular resistance, and residual pulmonary vascular obstruction (p=0.010, p<0.001, p<0.001, and p=0.055, respectively). Conclusion: Impaired peak VO 2 at 3 months post-APE independently associated with subsequent CTEPH and correlated with PVD severity, establishing peak VO 2 as a valuable biomarker for early identification and management of post-APE PVD.