Non-invasive Early Exclusion of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) After Pulmonary Embolism


Chronic thromboembolic pulmonary hypertension (CTEPH) is considered a potentially curable long-term complication of acute pulmonary embolism (PE), comprising chronic thrombotic obstruction of pulmonary arteries, which triggers small-vessel arteriopathy. The current diagnostic delay of CTEPH after PE is unacceptably long, exceeding 1 year, causing loss of quality-adjusted life years and excess mortality. Validated screening strategies for early CTEPH diagnosis are lacking. Echocardiographic screening among all PE survivors is associated with overdiagnosis and is cost-ineffective. Duliëtte Boon and Erik Klok of Leiden University Medical Center in the Netherlands and their colleagues aimed to validate a simple noninvasive screening strategy for excluding CTEPH early after acute PE while limiting the number of required echocardiograms.

In this prospective, international, multicenter management study, consecutive PE survivors were managed according to a screening algorithm starting three months after acute PE to determine whether echocardiographic evaluation of PH was required. If the “CTEPH prediction score” indicated a high pretest probability or if CTEPH specific symptoms were present, the “CTEPH rule-out criteria” were applied. These criteria consist of ECG assessment of right ventricular overload and an NT-proBNP assay. Only if these latter results could not rule out the presence of PH, patients were referred for echocardiography. In all remaining patients, echocardiographic follow-up was performed after 2 years.

A total of 424 patients were included across three European countries. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During the two-year follow-up, one patient in whom echocardiography was deemed unnecessary by the algorithm was diagnosed with CTEPH, reflecting an algorithm failure rate of 0.29% (95% CI 0%-1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients (77%) were diagnosed within 4 months after their acute PE diagnosis.

In conclusion, the InShape II algorithm for follow-up after acute PE accurately ruled out CTEPH while avoiding echocardiography in 81% of PE patients. The algorithm led to a substantially earlier detection of CTEPH than is common in current routine practice. This is the first management study to successfully validate a dedicated CTEPH screening tool, providing a valuable alternative to the follow-up algorithm proposed in the 2019 ESC Guidelines on acute PE.

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