Functional and haemodynamic heterogeneity of post-acute pulmonary embolism patients with persistent symptoms

Background The prognosis of acute pulmonary embolism (APE) survivors follows a broad continuum, from full recovery through residual symptoms with or without chronic thromboembolic disease (CTEPD), to established chronic thromboembolic pulmonary hypertension (CTEPH), with symptomatic burden varying considerably across this spectrum. Patients with persistent symptoms at 3 months are at particularly high risk of CTEPD, yet the functional and haemodynamic heterogeneity of this population remains poorly characterised. Whilst transthoracic echocardiography (TTE) provides a non-invasive means of estimating pulmonary hypertension (PH) probability at follow-up, whether TTE-based PH probability meaningfully reflects the degree of objective functional and haemodynamic impairment across this continuum has not been systematically evaluated. This study therefore aims to characterise this heterogeneity in symptomatic APE survivors stratified by TTE-based PH probability at 3 months. Methods Consecutive APE survivors reporting persistent symptoms at 3-month follow-up were screened. Those who underwent TTE and cardiopulmonary exercise testing at 3 months and received right heart catheterisation (RHC) during follow-up were included. Post-APE patients with confirmed CTEPH were further stratified by TTE-based PH probability into non-high and high groups. Functional and haemodynamic parameters were compared across four groups: non-pulmonary vascular disease (PVD) controls, post-APE patients without CTEPH, post-APE CTEPH with non-high PH probability, and post-APE CTEPH with high PH probability. Results Of 772 patients adjudicated as having unexplained persistent symptoms at 3 months, 92 post-APE patients and 46 non-PVD controls were included. Over a median follow-up of 31 months, 60 CTEPH diagnoses were confirmed in the symptomatic cohort. Kaplan-Meier analysis demonstrated significantly different CTEPH incidence across the 3 PH probability groups (p < 0.001) (Figure 1-A). Scatterplot analyses revealed progressive deterioration in both percentage predicted and absolute peak oxygen uptake (VO₂) against haemodynamic parameters across the four groups (Figure 1-B, C), a pattern confirmed on comparisons with significant overall between-group differences and a significant trend towards worsening impairment from non-PVD controls through to post-APE CTEPH with high PH probability (Table 1). Conclusion Symptomatic APE survivors demonstrate significant functional and haemodynamic heterogeneity, with progressive impairment across the post-APE continuum. TTE-based PH probability at 3 months effectively stratifies CTEPH incidence and reflects the degree of objective functional and haemodynamic compromise in those who subsequently develop CTEPH, supporting its role as a risk stratification as well as risk screening tool in this population.