Stress testing in the diagnosis and early screening of chronic thromboembolic pulmonary disease with and without pulmonary hypertension

Background: Chronic thromboembolic pulmonary disease (CTEPD) and its hemodynamic counterpart chronic thromboembolic pulmonary hypertension (CTEPH) are long-term sequelae of acute pulmonary embolism (PE), often underdiagnosed. Often, patients with CTEPD without PH may, however, develop exercise-induced PH (ExPH), a clinical condition detectable only under stress conditions. Objective: This narrative review aims at evaluating current evidence on the role of stress testing in the early diagnosis, screening and clinical management of CTEPD and CTEPH, with a particular focus on exercise-induced hemodynamic abnormalities. Methods: A literature search was conducted using PubMed, including observational studies, clinical trials and international guidelines published from 1998 to 2025 Studies investigating the use of cardiopulmonary exercise testing (CPET), exercise stress echocardiography (ESE), stress cardiac magnetic resonance imaging (MRI), the 6-min walk test (6MWT) and exercise right heart catheterization (exRHC) in both CTEPD and CTEPH were selected. Results: Non-invasive stress tests such as CPET and ESE demonstrated high sensitivity and negative predictive value in detecting ExPH, particularly in oligosymptomatic patients with persistent symptoms after PE. ExRHC remains the gold standard for confirming ExPH, defined by a mPAP/CO slope >3 mmHg/L/min with normal pulmonary arterial wedge pressure (PAWP) and elevated pulmonary vascular resistance (PVR) during exercise. Nevertheless, due to its invasive nature and limited availability, ExRHC is not suitable for first-line screening. For early evaluation, non-invasive tests such as CPET and ESE may be preferred, as they provide a broader, safer and more accessible functional assessment. Conclusion: Stress testing is a valuable tool in the functional assessment of CTEPD without PH and should be systematically integrated into post-PE screening protocols. Early use of CPET and ESE allows detection of subclinical pulmonary vascular dysfunction, guiding appropriate referral and treatment, while exercise RHC should be reserved for selected cases with inconclusive findings or complex physiology.