Post–Pulmonary Embolism Syndrome: An Update Based on the Revised AWMF-S2k Guideline

Abstract

In survivors of acute pulmonary embolism (PE), the post-PE syndrome (PPES) may occur. In PPES, patients typically present with persisting or progressive dyspnea on exertion despite 3 months of therapeutic anticoagulation. Therefore, a structured follow-up is warranted to identify patients with chronic thromboembolic pulmonary disease (CTEPD) with normal pulmonary pressure or chronic thromboembolic pulmonary hypertension (CTEPH). Both are currently understood as a dual vasculopathy, that is, secondary arterio- and arteriolopathy, affecting the large and medium-sized pulmonary arteries as well as the peripheral vessels (diameter < 50 µm). The follow-up algorithm after acute PE commences with identification of clinical symptoms and risk factors for CTEPH. If indicated, a stepwise performance of echocardiography, ventilation–perfusion scan (or alternative imaging), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level, cardiopulmonary exercise testing, and pulmonary artery catheterization with angiography should follow. CTEPH patients should be treated in a multidisciplinary center with adequate experience in the complex therapeutic options, comprising pulmonary endarterectomy, balloon pulmonary angioplasty, and pharmacological interventions.

Keywords

pulmonary embolism - chronic thromboembolic pulmonary hypertension - chronic thromboembolic pulmonary disease - pulmonary endarterectomy - balloon pulmonary angioplasty

Publikationsverlauf

Eingereicht: 16. September 2023

Angenommen: 13. Dezember 2023

Artikel online veröffentlicht:
26. März 2024

• References

• 1 Humbert M, Kovacs G, Hoeper MM. et al. ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2023; 61 (01) 2200879
• 2 Delcroix M, Torbicki A, Gopalan D. et al. ERS statement on chronic thromboembolic pulmonary hypertension. Eur Respir J 2021; 57 (06) 1-37
• 3 Klok FA, van der Hulle T, den Exter PL, Lankeit M, Huisman MV, Konstantinides S. The post-PE syndrome: a new concept for chronic complications of pulmonary embolism. Blood Rev 2014; 28 (06) 221-226
• 4 Boon GJAM, Huisman MV, Klok FA. Determinants and management of the post-pulmonary embolism syndrome. Semin Respir Crit Care Med 2021; 42 (02) 299-307
• 5 Nijkeuter M, Hovens MM, Davidson BL, Huisman MV. Resolution of thromboemboli in patients with acute pulmonary embolism: a systematic review. Chest 2006; 129 (01) 192-197
• 6 Valerio L, Mavromanoli AC, Barco S. et al; FOCUS Investigators. Chronic thromboembolic pulmonary hypertension and impairment after pulmonary embolism: the FOCUS study. Eur Heart J 2022; 43 (36) 3387-3398
• 7 Ende-Verhaar YM, Cannegieter SC, Vonk Noordegraaf A. et al. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature. Eur Respir J 2017; 49 (02) 49
• 8 Quadery SR, Swift AJ, Billings CG. et al. The impact of patient choice on survival in chronic thromboembolic pulmonary hypertension. Eur Respir J 2018; 52 (03) 1800589
• 9 Klok FA, Ageno W, Ay C. et al. Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society. Eur Heart J 2022; 43 (03) 183-189
• 10 de Perrot M, Gopalan D, Jenkins D. et al. Evaluation and management of patients with chronic thromboembolic pulmonary hypertension: consensus statement from the ISHLT. J Heart Lung Transplant 2021; 40 (11) 1301-1326
• 11 Konstantinides SV, Meyer G. The 2019 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2019; 40 (42) 3453-3455
• 12 Klok FA, Couturaud F, Delcroix M, Humbert M. Diagnosis of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Eur Respir J 2020; 55 (06) 55
• 13 Held M, Grün M, Holl R. et al. Cardiopulmonary exercise testing to detect chronic thromboembolic pulmonary hypertension in patients with normal echocardiography. Respiration 2014; 87 (05) 379-387
• 14 Kahn SR, Hirsch AM, Akaberi A. et al. Functional and exercise limitations after a first episode of pulmonary embolism: results of the ELOPE prospective cohort study. Chest 2017; 151 (05) 1058-1068
• 15 Fernandes TM, Alotaibi M, Strozza DM. et al. Dyspnea postpulmonary embolism from physiological dead space proportion and stroke volume defects during exercise. Chest 2020; 157 (04) 936-944
• 16 Guérin L, Couturaud F, Parent F. et al. Prevalence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism. Prevalence of CTEPH after pulmonary embolism. Thromb Haemost 2014; 112 (03) 598-605
• 17 Ende-Verhaar YM, Meijboom LJ, Kroft LJM. et al. Usefulness of standard computed tomography pulmonary angiography performed for acute pulmonary embolism for identification of chronic thromboembolic pulmonary hypertension: results of the InShape III study. J Heart Lung Transplant 2019; 38 (07) 731-738
• 18 Boon G, Ende-Verhaar YM, Beenen LFM. et al. Prediction of chronic thromboembolic pulmonary hypertension with standardised evaluation of initial computed tomography pulmonary angiography performed for suspected acute pulmonary embolism. Eur Radiol 2022; 32 (04) 2178-2187
• 19 Guth S, D'Armini AM, Delcroix M. et al. Current strategies for managing chronic thromboembolic pulmonary hypertension: results of the worldwide prospective CTEPH registry. ERJ Open Res 2021; 7 (03) 7
• 20 Brenot P, Jaïs X, Taniguchi Y. et al. French experience of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension. Eur Respir J 2019; 53 (05) 53
• 21 Jenkins DP, Madani M, Mayer E. et al. Surgical treatment of chronic thromboembolic pulmonary hypertension. Eur Respir J 2013; 41 (03) 735-742
• 22 Bunclark K, Newnham M, Chiu YD. et al. A multicenter study of anticoagulation in operable chronic thromboembolic pulmonary hypertension. J Thromb Haemost 2020; 18 (01) 114-122
• 23 Humbert M, Simonneau G, Pittrow D. et al. Oral anticoagulants (NOAC and VKA) in chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2022; 41 (06) 716-721
• 24 Jenkins D, Madani M, Fadel E, D'Armini AM, Mayer E. Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017; 26 (143) 26
• 25 Kawakami T, Matsubara H, Shinke T. et al. Balloon pulmonary angioplasty versus riociguat in inoperable chronic thromboembolic pulmonary hypertension (MR BPA): an open-label, randomised controlled trial. Lancet Respir Med 2022; 10 (10) 949-960
• 26 Grünig E, MacKenzie A, Peacock AJ. et al. Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial. Eur Heart J 2021; 42 (23) 2284-2295
• 27 Nagel C, Nasereddin M, Benjamin N. et al. Supervised exercise training in patients with chronic thromboembolic pulmonary hypertension as early follow-up treatment after pulmonary endarterectomy: a prospective cohort study. Respiration 2020; 99 (07) 577-588
• 28 Kim NH, Delcroix M, Jais X. et al. Chronic thromboembolic pulmonary hypertension. Eur Respir J 2019; 53 (01) 53
• 29 Held M, Kolb P, Grün M. et al. Functional characterization of patients with chronic thromboembolic disease. Respiration 2016; 91 (06) 503-509
• 30 Meyer FJ, Borst MM, Buschmann HC. et al. Exercise testing in respiratory medicine: DGP recommendations. Pneumologie 2018; 72 (10) 687-731
• 31 Linnemann B, Blank W, Doenst T. et al . Diagnostics and Therapy of Venous Thrombosis and Pulmonary Embolism. The revised AWMF S2k Guideline. Vasa. 2023 Oct; 52(S111): 1–146. PMID: 37904504. DOI: 10.1024/0301-1526/a001089