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ESC GUIDELINES
Guidelines on the diagnosis and managementof acute pulmonary embolism
The Task Force for the Diagnosis and Management of AcutePulmonary Embolism of the European Society of Cardiology (ESC)
Authors/Task Force Members: Adam Torbicki, Chairperson (Poland)
*
,Arnaud Perrier (Switzerland), Stavros Konstantinides (Germany),Giancarlo Agnelli (Italy), Nazzareno Galie`(Italy), Piotr Pruszczyk (Poland),Frank Bengel (USA), Adrian J.B. Brady (UK), Daniel Ferreira (Portugal),Uwe Janssens (Germany), Walter Klepetko (Austria), Eckhard Mayer (Germany),Martine Remy-Jardin (France), and Jean-Pierre Bassand (France)
Full author affiliations can be found on the page dedicated to these guidelines on the ESC Web Site(www.escardio.org/guidelines)
ESC Committee for Practice Guidelines (CPG): Alec Vahanian, Chairperson (France), John Camm (UK),Raffaele De Caterina (Italy), Veronica Dean (France), Kenneth Dickstein (Norway), Gerasimos Filippatos (Greece),Christian Funck-Brentano (France), Irene Hellemans (Netherlands), Steen Dalby Kristensen (Denmark),Keith McGregor (France), Udo Sechtem (Germany), Sigmund Silber (Germany), Michal Tendera (Poland),Petr Widimsky (Czech Republic), and Jose Luis Zamorano (Spain)Document Reviewers: Jose-Luis Zamorano, (CPG Review Coordinator) (Spain), Felicita Andreotti (Italy),Michael Ascherman (Czech Republic), George Athanassopoulos (Greece), Johan De Sutter (Belgium),David Fitzmaurice (UK), Tamas Forster (Hungary), Magda Heras (Spain), Guillaume Jondeau (France),Keld Kjeldsen (Denmark), Juhani Knuuti (Finland), Irene Lang (Austria), Mattie Lenzen (The Netherlands), Jose Lopez-Sendon (Spain), Petros Nihoyannopoulos (UK), Leopoldo Perez Isla (Spain), Udo Schwehr (Germany),Lucia Torraca (Italy), and Jean-Luc Vachiery (Belgium)
Keywords
Pulmonary embolism
†
Venous thrombosis
†
Shock 
†
Hypotension
†
Chest pain
†
Dyspnoea
†
Heart failure
†
Diagnosis
†
Prognosis
†
Treatment
†
Guidelines
*
Corresponding author. Department of Chest Medicine, Institute for Tuberculosis and Lung Diseases, ul. Plocka 26, 01–138 Warsaw, Poland. Tel:
þ
48 22 431 2114,Fax:
þ
48 22 431 2414; Email: a.torbicki@igichp.edu.plThe content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only. No commercial use is authorized. No part of theESC Guidelines may be translated or reproduced in any form without written permission from the ESC. Permission can be obtained upon submission of a written request to OxfordUniversity Press, the publisher of the European Heart Journal and the party authorized to handle such permissions on behalf of the ESC.
Disclaimer.
The ESC Guidelines represent the views of the ESC and were arrived at after careful consideration of the available evidence at the time they were written. Healthprofessionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of healthprofessionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’sguardian or carer. It is also the health professional’s responsibility to verify the rules and regulations applicable to drugs and devices at the time of prescription.
&
The European Society of Cardiology 2008. All rights reserved. For permissions please email: journals.permissions@oxfordjournals.org
European Heart Journal (2008)
29
, 2276–2315doi:10.1093/eurheartj/ehn310
 
Table of contents
List of acronyms and abbreviations . . . . . . . . . . . . . . . . . .2277Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2277Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2278Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2279Predisposing factors . . . . . . . . . . . . . . . . . . . . . . . . .2279Natural history . . . . . . . . . . . . . . . . . . . . . . . . . . . .2279Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . .2280Severity of pulmonary embolism . . . . . . . . . . . . . . . . .2281Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2282Clinical presentation . . . . . . . . . . . . . . . . . . . . . . . . .2282Assessment of clinical probability . . . . . . . . . . . . . . . .2282D-dimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2283Compression ultrasonography and computed tomographic venography . . . . . . . . . . . . . . . . . . . . . .2284Ventilation–perfusion scintigraphy . . . . . . . . . . . . . . . .2284Computed tomography . . . . . . . . . . . . . . . . . . . . . . .2285Pulmonary angiography . . . . . . . . . . . . . . . . . . . . . . .2286Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . .2287Diagnostic strategies . . . . . . . . . . . . . . . . . . . . . . . . .2288Suspected high-risk pulmonary embolism . . . . . . . . . 2288Suspected non-high-risk pulmonary embolism . . . . . . 2289Prognostic assessment . . . . . . . . . . . . . . . . . . . . . . . . . . .2292Clinical assessment of haemodynamic status . . . . . . . . .2292Markers of right ventricular dysfunction . . . . . . . . . . . .2292Markers of myocardial injury . . . . . . . . . . . . . . . . . . .2293Additional risk markers . . . . . . . . . . . . . . . . . . . . . . .2294Strategy of prognostic assessment . . . . . . . . . . . . . . . .2294Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2295Haemodynamic and respiratory support . . . . . . . . . . . .2295Thrombolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2296Surgical pulmonary embolectomy . . . . . . . . . . . . . . . .2297Percutaneous catheter embolectomy and fragmentation .2297Initial anticoagulation . . . . . . . . . . . . . . . . . . . . . . . . .2298Therapeutic strategies . . . . . . . . . . . . . . . . . . . . . . . .2299High-risk pulmonary embolism . . . . . . . . . . . . . . . . 2299Non-high-risk pulmonary embolism . . . . . . . . . . . . . 2300Long-term anticoagulation and secondary prophylaxis . . .2301Venous filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2302Specific problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2303Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2303Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2304Right heart thrombi . . . . . . . . . . . . . . . . . . . . . . . . .2304Heparin-induced thrombocytopenia . . . . . . . . . . . . . . .2305Chronic thromboembolic pulmonary hypertension . . . . .2305Non-thrombotic pulmonary embolism . . . . . . . . . . . . .2306References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2307
List of acronyms and abbreviations
aPTT activated partial thromboplastin timeanti-Xa anti-factor Xa activityBNP brain natriuretic peptideCI confidence intervalCT computed tomographyCTEPH chronic thromboembolic pulmonary hypertensionCUS compression venous ultrasonographyDVT deep vein thrombosisECG electrocardiogramELISA enzyme-linked immunoabsorbent assayHIT heparin-induced thrombocytopeniaICOPER International Cooperative Pulmonary EmbolismRegistryINR international normalized ratioIVC inferior vena cavaLMWH low molecular weight heparinLV left ventricleMDCT multidetector computed tomographyNPV negative predictive valueNT-proBNP N-terminal proBNPOR odds ratioPaO
2
arterial oxygen pressurePE pulmonary embolismPIOPED Prospective Investigation On Pulmonary EmbolismDiagnosis studyPPV positive predictive valuertPA recombinant tissue plasminogen activator RV right ventricleRVD right ventricular dysfunctionSBP systolic blood pressureSDCT single-detector computed tomographyVKA vitamin K antagonistVTE venous thromboembolismV/Q scan ventilation–perfusion scintigraphy
Preamble
Guidelines and Expert Consensus Documents summarize andevaluate all currently available evidence on a particular issue with the aim of assisting physicians in selecting the best managementstrategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk/benefit ratio of particular diagnostic or therapeutic means. Guide-lines are no substitutes for textbooks. The legal implications of medical guidelines have been discussed previously.A great number of Guidelines and Expert Consensus Docu-ments have been issued in recent years by the European Societyof Cardiology (ESC) as well as by other societies and organizations.Because of the impact on clinical practice, quality criteria for thedevelopment of guidelines have been established in order tomake all decisions transparent to the user. The recommendationsfor formulating and issuing ESC Guidelines and Expert ConsensusDocuments can be found on the ESC Web Site (http:\\www.escardio.org/guidelines).In brief, experts in the field are selected and undertake a com-prehensive review of the published evidence for managementand/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, includingassessment of the risk–benefit ratio. Estimates of expectedhealth outcomes for larger societies are included, where
ESC Guidelines
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data exist. The level of evidence and the strength of recommen-dation of particular treatment options are weighed and gradedaccording to predefined scales, as outlined in
Tables 1
and
2
.The experts of the writing panels have provided disclosurestatements of all relationships they may have which might be per-ceived as real or potential sources of conflicts of interest. Thesedisclosure forms are kept on file at the European Heart House,headquarters of the ESC. Any changes in conflict of interest thatarise during the writing period must be notified to the ESC.The Task Force report was entirely supported financially by theEuropean Society of Cardiology and was developed without anyinvolvement of the industry.The ESC Committee for Practice Guidelines (CPG) supervisesand coordinates the preparation of new Guidelines and ExpertConsensus Documents produced by Task Forces, expert groupsor consensus panels. The Committee is also responsible for theendorsement process of these Guidelines and Expert ConsensusDocuments or statements. Once the document has been finalizedand approved by all the experts involved in the Task Force, it issubmitted to outside specialists for review. The document isrevised, and finally approved by the CPG and subsequentlypublished.After publication, dissemination of the message is of paramountimportance. Pocket-sized versions and personal digital assistant(PDA)-downloadable versions are useful at the point of care.Some surveys have shown that the intended end-users are some- times not aware of the existence of guidelines, or simply do not translate them into practice; this is why implementationprogrammes for new guidelines form an important componentof the dissemination of knowledge. Meetings are organized by the ESC and are directed towards its member national societiesand key opinion leaders in Europe. Implementation meetings canalso be undertaken at national level, once the guidelines havebeen endorsed by the ESC member societies and translated into the national language. Implementation programmes are neededbecause it has been shown that the outcome of disease may befavourably influenced by the thorough application of clinicalrecommendations.Thus, the task of writing Guidelines or Expert Consensus Docu-ments covers not only the integration of the most recent research,but also the creation of educational tools and implementationprogrammes for the recommendations. The loop between clinicalresearch, the writing of guidelines, and implementing them intoclinical practice can then only be completed if surveys and regis- tries are performed to verify that real-life daily practice is inkeeping with what is recommended in the guidelines. Suchsurveys and registries also make it possible to evaluate theimpact of implementation of the guidelines on patient outcomes.Guidelines and recommendations should help physicians to makedecisions in their daily practice; however, the ultimate judgementregarding the care of an individual patient must be made by thephysician in charge of that patient’s care.
Introduction
Pulmonary embolism (PE) is a relatively common cardiovascular emergency. By occluding the pulmonary arterial bed it may lead to acute life-threatening but potentially reversible right ventricular failure. PE is a difficult diagnosis that may be missed because of non-specific clinical presentation. However, early diagnosis is fun-damental, since immediate treatment is highly effective. Dependingon the clinical presentation, initial therapy is primarily aimed either at life-saving restoration of flow through occluded pulmonaryarteries (PA) or at the prevention of potentially fatal early recur-rences. Both initial treatment and the long-term anticoagulation that is required for secondary prevention must be justified ineach patient by the results of an appropriately validated diagnosticstrategy.
1
Epidemiology, predisposing factors, natural history, and thepathophysiology of PE have been described more extensively else-where.
2–5
This document focuses on currently available and vali-dated methods of diagnosis, prognostic evaluation and therapy of PE. In contrast to previous guidelines, we decided to grade also the level of evidence of diagnostic procedures. The most robustdata come from large-scale accuracy or outcome studies. Accuracystudies are designed to establish the characteristics of a diagnostic test (sensitivity and specificity) by comparing test results with areference diagnostic criterion (the so-called gold standard).Outcome studies evaluate patient outcomes when a givendiagnostic test or strategy is used for clinical decision-making. In the field of PE, the outcome measurement is the rateof thromboembolic events [deep vein thrombosis (DVT) or PE]during a 3-month follow-up period in patients left untreated byanticoagulants. The reference for comparison is the rate of DVTor PE in patients left untreated after a negative conventional................................................................................................................................................................
Table 1
Classes of recommendations
Class I Evidence and/or general agreement that agiven treatment or procedure is beneficial,useful, and effectiveClass II Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of  the given treatment or procedureClass IIa Weight of evidence/opinion is in favour of usefulness/efficacyClass IIb Usefulness/efficacy is less well established byevidence/opinionClass III Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases may beharmful
Table 2
Levels of evidence
Level of evidence A Data derived from multiple randomized clinical trials
a
or meta-analysesLevel of evidence B Data derived from a single randomized clinical trial
a
or large non-randomized studiesLevel of evidence C Consensus of opinion of the experts and/or small studies, retrospective studies, registries
a
Or large accuracy or outcome trial(s) in the case of diagnostic tests or strategies.
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