Non-invasive early exclusion of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: the InShape II study

Abstract

Background The current diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism (PE) is unacceptably long, 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 cost-ineffectiveness. We aimed to validate a simple screening strategy for excluding CTEPH early after acute PE, limiting the number of performed echocardiograms. Methods In this prospective, international, multicentre management study, consecutive patients were managed according to a screening algorithm starting 3 months after acute PE to determine whether echocardiographic evaluation of pulmonary hypertension (PH) was indicated. If the ‘CTEPH prediction score’ indicated high pretest probability or matching symptoms were present, the ‘CTEPH rule-out criteria’ were applied, consisting of ECG reading and N-terminalpro-brain natriuretic peptide. Only if these results could not rule out possible PH, the patients were referred for echocardiography. Results 424 patients were included. Based on the algorithm, CTEPH was considered absent in 343 (81%) patients, leaving 81 patients (19%) referred for echocardiography. During 2-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% to 1.6%). Overall CTEPH incidence was 3.1% (13/424), of whom 10 patients were diagnosed within 4 months after the PE presentation. Conclusions The InShape II algorithm accurately excluded CTEPH, without the need for echocardiography in the overall majority of patients. CTEPH was identified early after acute PE, resulting in a substantially shorter diagnostic delay than in current practice.

Identification of chronic thromboembolic pulmonary hypertension on CTPAs performed for diagnosing acute pulmonary embolism depending on level of expertise

“…It has been hypothesized that CTEPH might either present as acute-on-chronic PE or develop in the course of acute PE. [4,32] Particularly in the setting of pre-existing conditions that may also contribute to signs of PH, e.g. COPD or chronic heart failure, it should be emphasized that CTPA findings itself are not diagnostic for CTEPH.…”

“…The InShape II algorithm for follow-up after acute PE is an alternative strategy aimed at selecting specific PE patients at high risk of developing CTEPH who require further diagnostic testing. [32,33] This risk stratification starts with assessment of the pre-test probability based on the CTEPH prediction score, combined with evaluation of the presence of symptoms suggestive of CTEPH and the application of the CTEPH rule-out criteria. [34][35][36] Replacing the 'simple' RV/LV diameter ratio with more comprehensive CTPA assessment in the CTEPH prediction score will likely result in improved diagnostic accuracy of the algorithm.…”

Chronic thromboembolic pulmonary hypertension: diagnosis, operability assessment and patient selection for pulmonary endarterectomy

“…We therefore, propose in Figure 1 to apply a dedicated CTEPH screening algorithm three months after the diagnosis of an acute PE, based on the InShape II study results (25). Pretest probability of CTEPH is assessed by calculating the 'CTEPH prediction score' (Table 1) (26).…”

“…Pretest probability of CTEPH is assessed by calculating the 'CTEPH prediction score' (Table 1) (26). Only patients with >6 points or those with symptoms that might be associated with CTEPH (i.e., exertional dyspnea, edema, newly developed palpitations, syncope or chest pain) are subjected to the CTEPH rule-out criteria, that is, assessment of the presence of any of the three ECG criteria of RV pressure overload (Figure 2), or an abnormal age-dependent and gender-dependent NT-proBNP level (25). If one of these rule-out criteria is present, the patient is referred for a TTE.…”

Why, Whom, and How to Screen for Chronic Thromboembolic Pulmonary Hypertension after Acute Pulmonary Embolism

“…3). 46 Follow-up results will ultimately determine the sensitivity of the algorithm and are expected by late 2020.…”