{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:28:05Z","timestamp":1779359285303,"version":"3.51.4"},"reference-count":56,"publisher":"Georg Thieme Verlag KG","issue":"07","funder":[{"name":"Italian Ministry of University and Research","award":["PRIN-2022 Prot. 2022S74XWB; 549901_2023_Madonna_Ateneo - Fondi di Ateneo 2023"],"award-info":[{"award-number":["PRIN-2022 Prot. 2022S74XWB; 549901_2023_Madonna_Ateneo - Fondi di Ateneo 2023"]}]},{"name":"European Union\u2014Next-Generation EU through the Italian Ministry of University and Research","award":["PNRR\u2014M4C2-I1.3 Project PE_00000019 \u201cHEAL ITALIA,\u201d CUP I53C22001440006"],"award-info":[{"award-number":["PNRR\u2014M4C2-I1.3 Project PE_00000019 \u201cHEAL ITALIA,\u201d CUP I53C22001440006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts. As for hemodynamic effects, after a period of compensation, the right ventricle dilates and fails, which results in retrograde and anterograde right heart failure. Little is known on the pathophysiology of post-PE dyspnea, which has been reported in highly comorbid with lung and heart diseases, so that a \u201ctwo-hit\u201d hypothesis can be put forward: it might be caused by the acute myocardial damage caused by pulmonary embolism in the context of preexisting cardiac and\/or respiratory diseases. More than one-third of PE survivors develops PPES, with only a small fraction (3\u20134%) represented by CTEPH. A value of \u22483% is a plausible estimate for the incidence of CTEPD. Growing evidence supports the role of CTEPD as a hemodynamic phenotype intermediate between post-PE dyspnea and CTEPH, but it still remains to be ascertained whether it constantly underlies exercise-induced pulmonary hypertension and if it is a precursor of CTEPH. Further research is needed to improve the understanding and the management of CTEPD and post-PE dyspnea.<\/jats:p>","DOI":"10.1055\/a-2418-7895","type":"journal-article","created":{"date-parts":[[2024,9,19]],"date-time":"2024-09-19T23:00:13Z","timestamp":1726786813000},"page":"634-642","source":"Crossref","is-referenced-by-count":3,"title":["Not Just CTEPH: A Narrative Review on the Spectrum Approach to Postpulmonary Embolism Conditions"],"prefix":"10.1055","volume":"125","author":[{"given":"Filippo","family":"Biondi","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mattia","family":"Alberti","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Montemaggi","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"D'Alleva","sequence":"additional","affiliation":[{"name":"Cardiac Intensive Care and Interventional Cardiology Unit, Santo Spirito Hospital, Pescara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalinda","family":"Madonna","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Surgical, Medical and Molecular Pathology and Critical Area, University of Pisa, Pisa, 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heart","volume":"15","author":"R Naeije","year":"2013","journal-title":"Curr Hypertens Rep"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1152\/advances.2001.25.1.53","article-title":"Toward consistent definitions for preload and afterload","volume":"25","author":"J M Norton","year":"2001","journal-title":"Adv Physiol Educ"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"795","DOI":"10.21037\/atm.2020.04.10","article-title":"Understanding ventriculo-arterial coupling","volume":"8","author":"M I Monge Garc\u00eda","year":"2020","journal-title":"Ann Transl Med"},{"issue":"02","key":"ref7","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1002\/ehf2.14233","article-title":"Adaptive versus maladaptive right ventricular remodelling","volume":"10","author":"Z A Rako","year":"2023","journal-title":"ESC Heart Fail"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.ijcard.2016.08.138","article-title":"Simple 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Delcroix","year":"2016","journal-title":"Circulation"},{"issue":"01","key":"ref41","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s12931-020-01462-5","article-title":"The pathophysiology of 'happy' hypoxemia in COVID-19","volume":"21","author":"S Dhont","year":"2020","journal-title":"Respir Res"},{"issue":"05","key":"ref42","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1164\/ajrccm.154.5.8912753","article-title":"Value of perfusion lung scan in the diagnosis of pulmonary embolism: results of the Prospective Investigative Study of Acute Pulmonary Embolism Diagnosis (PISA-PED)","volume":"154","author":"M Miniati","year":"1996","journal-title":"Am J Respir Crit Care Med"},{"issue":"02","key":"ref43","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.thromres.2015.05.018","article-title":"Accuracy of X-ray with perfusion scan in young patients with suspected pulmonary embolism","volume":"136","author":"J van Es","year":"2015","journal-title":"Thromb Res"},{"issue":"04","key":"ref44","doi-asserted-by":"crossref","first-page":"199","DOI":"10.4103\/atm.atm_42_23","article-title":"The diagnostic accuracy of perfusion-only scan in the diagnosis of pulmonary embolism in the era of COVID-19: a single-center study of 434 patients","volume":"18","author":"T B Cengiz","year":"2023","journal-title":"Ann Thorac Med"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e149S","DOI":"10.1378\/chest.11-2301","article-title":"Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines","volume":"141","author":"C Kearon","year":"2012","journal-title":"Chest"},{"issue":"03","key":"ref46","doi-asserted-by":"crossref","first-page":"e12110","DOI":"10.1002\/pul2.12110","article-title":"Direct oral anticoagulants in patients with chronic thromboembolic pulmonary hypertension and the presence of recent thrombus during pulmonary endarterectomy","volume":"12","author":"I Jeong","year":"2022","journal-title":"Pulm Circ"},{"issue":"08","key":"ref47","doi-asserted-by":"crossref","first-page":"e0160064","DOI":"10.1371\/journal.pone.0160064","article-title":"Comparison of the non-VKA oral anticoagulants apixaban, dabigatran, and rivaroxaban in the extended treatment and prevention of venous thromboembolism: systematic review and network meta-analysis","volume":"11","author":"A T Cohen","year":"2016","journal-title":"PLoS One"},{"issue":"03","key":"ref48","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1161\/01.CIR.10.3.343","article-title":"Pulmonary arteriosclerosis and cor pulmonale due to recurrent thromboembolism","volume":"10","author":"P J Barnard","year":"1954","journal-title":"Circulation"},{"issue":"04","key":"ref49","first-page":"273","article-title":"Pulmonary endarterectomy for patients with chronic thromboembolic disease","volume":"19","author":"\u015e Olgun Y\u0131ld\u0131zeli","year":"2018","journal-title":"Anatol J Cardiol"},{"issue":"03","key":"ref50","doi-asserted-by":"crossref","first-page":"1800458","DOI":"10.1183\/13993003.00458-2018","article-title":"Exercise right heart catheterisation before and after pulmonary endarterectomy in patients with chronic thromboembolic disease","volume":"52","author":"S Guth","year":"2018","journal-title":"Eur Respir J"},{"issue":"02","key":"ref51","doi-asserted-by":"crossref","first-page":"128","DOI":"10.21037\/acs-2021-pte-17","article-title":"Pulmonary thromboendarterectomy in chronic pulmonary disease\u2014the Royal Papworth Hospital experience","volume":"11","author":"D P Jenkins","year":"2022","journal-title":"Ann Cardiothorac Surg"},{"issue":"04","key":"ref52","doi-asserted-by":"crossref","first-page":"S130","DOI":"10.1016\/j.healun.2019.01.307","article-title":"Pulmonary endarterectomy in CTED: the pavia experience","volume":"38","author":"M Pin","year":"2019","journal-title":"J Heart Lung Transplant"},{"issue":"01","key":"ref53","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12890-016-0180-x","article-title":"Case report: subjective loss of performance after pulmonary embolism in an athlete- beyond normal values","volume":"16","author":"D Dumitrescu","year":"2016","journal-title":"BMC Pulm Med"},{"issue":"02","key":"ref54","doi-asserted-by":"crossref","first-page":"180","DOI":"10.21037\/acs-2021-pte-185","article-title":"Pulmonary endarterectomy: technique and pitfalls","volume":"11","author":"S Guth","year":"2022","journal-title":"Ann Cardiothorac Surg"},{"issue":"06","key":"ref55","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1161\/CIRCINTERVENTIONS.112.971077","article-title":"Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension","volume":"5","author":"H Mizoguchi","year":"2012","journal-title":"Circ Cardiovasc 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