ESC GUIDELINES
Guidelines on the diagnosis and management
of acute pulmonary embolism
The Task Force for the Diagnosis and Management of Acute
Pulmonary 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: þ48 22 431 2114,
Fax: þ48 22 431 2414; Email: a.torbicki@igichp.edu.pl
The 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 the
ESC 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 Oxford
University 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. Health
professionals are encouraged to take them fully into account when exercising their clinical judgement. The guidelines do not, however, override the individual responsibility of health
professionals to make appropriate decisions in the circumstances of the individual patients, in consultation with that patient, and where appropriate and necessary the patient’s
guardian 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, 2276–2315
doi:10.1093/eurheartj/ehn310
Table of contents
List of acronyms and abbreviations . . . . . . . . . . . . . . . . . . 2277
Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2277
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2278
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2279
Predisposing factors . . . . . . . . . . . . . . . . . . . . . . . . . 2279
Natural history . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2279
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2280
Severity of pulmonary embolism . . . . . . . . . . . . . . . . . 2281
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2282
Clinical presentation . . . . . . . . . . . . . . . . . . . . . . . . . 2282
Assessment of clinical probability . . . . . . . . . . . . . . . . 2282
D-dimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2283
Compression ultrasonography and computed
tomographic venography . . . . . . . . . . . . . . . . . . . . . . 2284
Ventilation–perfusion scintigraphy . . . . . . . . . . . . . . . . 2284
Computed tomography . . . . . . . . . . . . . . . . . . . . . . . 2285
Pulmonary angiography . . . . . . . . . . . . . . . . . . . . . . . 2286
Echocardiography . . . . . . . . . . . . . . . . . . . . . . . . . . . 2287
Diagnostic strategies . . . . . . . . . . . . . . . . . . . . . . . . . 2288
Suspected high-risk pulmonary embolism . . . . . . . . . 2288
Suspected non-high-risk pulmonary embolism . . . . . . 2289
Prognostic assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . 2292
Clinical assessment of haemodynamic status . . . . . . . . . 2292
Markers of right ventricular dysfunction . . . . . . . . . . . . 2292
Markers of myocardial injury . . . . . . . . . . . . . . . . . . . 2293
Additional risk markers . . . . . . . . . . . . . . . . . . . . . . . 2294
Strategy of prognostic assessment . . . . . . . . . . . . . . . . 2294
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2295
Haemodynamic and respiratory support . . . . . . . . . . . . 2295
Thrombolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2296
Surgical pulmonary embolectomy . . . . . . . . . . . . . . . . 2297
Percutaneous catheter embolectomy and fragmentation . 2297
Initial anticoagulation . . . . . . . . . . . . . . . . . . . . . . . . . 2298
Therapeutic strategies . . . . . . . . . . . . . . . . . . . . . . . . 2299
High-risk pulmonary embolism . . . . . . . . . . . . . . . . 2299
Non-high-risk pulmonary embolism . . . . . . . . . . . . . 2300
Long-term anticoagulation and secondary prophylaxis . . . 2301
Venous filters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2302
Specific problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2303
Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2303
Malignancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2304
Right heart thrombi . . . . . . . . . . . . . . . . . . . . . . . . . 2304
Heparin-induced thrombocytopenia . . . . . . . . . . . . . . . 2305
Chronic thromboembolic pulmonary hypertension . . . . . 2305
Non-thrombotic pulmonary embolism . . . . . . . . . . . . . 2306
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2307
List of acronyms and abbreviations
aPTT activated partial thromboplastin time
anti-Xa anti-factor Xa activity
BNP brain natriuretic peptide
CI confidence interval
CT computed tomography
CTEPH chronic thromboembolic pulmonary hypertension
CUS compression venous ultrasonography
DVT deep vein thrombosis
ECG electrocardiogram
ELISA enzyme-linked immunoabsorbent assay
HIT heparin-induced thrombocytopenia
ICOPER International Cooperative Pulmonary Embolism
Registry
INR international normalized ratio
IVC inferior vena cava
LMWH low molecular weight heparin
LV left ventricle
MDCT multidetector computed tomography
NPV negative predictive value
NT-proBNP N-terminal proBNP
OR odds ratio
PaO2 arterial oxygen pressure
PE pulmonary embolism
PIOPED Prospective Investigation On Pulmonary Embolism
Diagnosis study
PPV positive predictive value
rtPA recombinant tissue plasminogen activator
RV right ventricle
RVD right ventricular dysfunction
SBP systolic blood pressure
SDCT single-detector computed tomography
VKA vitamin K antagonist
VTE venous thromboembolism
V/Q scan ventilation–perfusion scintigraphy
Preamble
Guidelines and Expert Consensus Documents summarize and
evaluate all currently available evidence on a particular issue with
the aim of assisting physicians in selecting the best management
strategies 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 Society
of Cardiology (ESC) as well as by other societies and organizations.
Because of the impact on clinical practice, quality criteria for the
development of guidelines have been established in order to
make all decisions transparent to the user. The recommendations
for formulating and issuing ESC Guidelines and Expert Consensus
Documents 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 management
and/or prevention of a given condition. A critical evaluation of
diagnostic and therapeutic procedures is performed, including
assessment of the risk–benefit ratio. Estimates of expected
health outcomes for larger societies are included, where
ESC Guidelines 2277
data exist. The level of evidence and the strength of recommen-
dation of particular treatment options are weighed and graded
according to predefined scales, as outlined in Tables 1 and 2.
The experts of the writing panels have provided disclosure
statements of all relationships they may have which might be per-
ceived as real or potential sources of conflicts of interest. These
disclosure forms are kept on file at the European Heart House,
headquarters of the ESC. Any changes in conflict of interest that
arise during the writing period must be notified to the ESC.
The Task Force report was entirely supported financially by the
European Society of Cardiology and was developed without any
involvement of the industry.
The ESC Committee for Practice Guidelines (CPG) supervises
and coordinates the preparation of new Guidelines and Expert
Consensus Documents produced by Task Forces, expert groups
or consensus panels. The Committee is also responsible for the
endorsement process of these Guidelines and Expert Consensus
Documents or statements. Once the document has been finalized
and approved by all the experts involved in the Task Force, it is
submitted to outside specialists for review. The document is
revised, and finally approved by the CPG and subsequently
published.
After publication, dissemination of the message is of paramount
importance. 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 implementation
programmes for new guidelines form an important component
of the dissemination of knowledge. Meetings are organized by
the ESC and are directed towards its member national societies
and key opinion leaders in Europe. Implementation meetings can
also be undertaken at national level, once the guidelines have
been endorsed by the ESC member societies and translated into
the national language. Implementation programmes are needed
because it has been shown that the outcome of disease may be
favourably influenced by the thorough application of clinical
recommendations.
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 implementation
programmes for the recommendations. The loop between clinical
research, the writing of guidelines, and implementing them into
clinical practice can then only be completed if surveys and regis-
tries are performed to verify that real-life daily practice is in
keeping with what is recommended in the guidelines. Such
surveys and registries also make it possible to evaluate the
impact of implementation of the guidelines on patient outcomes.
Guidelines and recommendations should help physicians to make
decisions in their daily practice; however, the ultimate judgement
regarding the care of an individual patient must be made by the
physician 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. Depending
on the clinical presentation, initial therapy is primarily aimed either
at life-saving restoration of flow through occluded pulmonary
arteries (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 in
each patient by the results of an appropriately validated diagnostic
strategy.1
Epidemiology, predisposing factors, natural history, and the
pathophysiology 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 robust
data come from large-scale accuracy or outcome studies. Accuracy
studies are designed to establish the characteristics of a diagnostic
test (sensitivity and specificity) by comparing test results with a
reference diagnostic criterion (the so-called gold standard).
Outcome studies evaluate patient outcomes when a given
diagnostic test or strategy is used for clinical decision-making. In
the field of PE, the outcome measurement is the rate
of thromboembolic events [deep vein thrombosis (DVT) or PE]
during a 3-month follow-up period in patients left untreated by
anticoagulants. The reference for comparison is the rate of DVT
or PE in patients left untreated after a negative conventional
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Table 1 Classes of recommendations
Class I Evidence and/or general agreement that a
given treatment or procedure is beneficial,
useful, and effective
Class II Conflicting evidence and/or a divergence of
opinion about the usefulness/efficacy of
the given treatment or procedure
Class IIa Weight of evidence/opinion is in favour of
usefulness/efficacy
Class IIb Usefulness/efficacy is less well established by
evidence/opinion
Class III Evidence or general agreement that the given
treatment or procedure is not useful/
effective, and in some cases may be
harmful
Table 2 Levels of evidence
Level of evidence A Data derived from multiple randomized clinical
trialsa or meta-analyses
Level of evidence B Data derived from a single randomized clinical
triala or large non-randomized studies
Level of evidence C Consensus of opinion of the experts and/or
small studies, retrospective studies, registries
aOr large accuracy or outcome trial(s) in the case of diagnostic tests or strategies.
ESC Guidelines2278
pulmonary angiogram, which is around 1–2%, with an upper limit
of the 95% confidence interval (CI) of 3% during a 3-month
follow-up.6 The advantage of outcome studies is that they are
easily carried out under normal clinical circumstances and their
results are therefore generalizable. However, they do not yield
any information on false positives and potential overtreatment.
We used the following criteria for grading levels of evidence
from diagnostic studies:
† Data derived from multiple comparisons or outcome studies or
meta-analyses are considered level of evidence A.
† Data from a single large comparison or outcome study are con-
sidered level of evidence B.
† Expert consensus and/or data derived from small comparison or
outcome studies are considered level of evidence C.
The first edition of the ESC Clinical Practice Guidelines on PE,
published in 2000, was among the documents most often down-
loaded from the Eur Heart J Web Site.7 We dedicate the
current Guidelines to Prof. Henri Denolin, former President of
the ESC, Prof. Mireille Brochier, former President of the French
Cardiac Society, Prof. Jiri Widimsky, former President of the Cze-
choslovak Cardiac Society, and Prof. Mario Morpurgo, former
Chairman of the ESC Working Group on Pulmonary Circulation,
and to other eminent cardiologists who paved the path towards
the more effective diagnosis and clinical management of acute pul-
monary embolism.
Epidemiology
PE and DVT are two clinical presentations of venous thromboem-
bolism (VTE) and share the same predisposing factors. In most
cases PE is a consequence of DVT. Among patients with proximal
DVT, about 50% have an associated, usually clinically asymptomatic
PE at lung scan.8 In about 70% of patients with PE, DVT can be
found in the lower limbs if sensitive diagnostic methods are used.5,9
The epidemiology of VTE has recently been reviewed.4 Although
DVT and PE are manifestations of a single disease, namely VTE, PE
has features that are distinct from DVT. The risk of death related
to the initial acute episode or to recurrent PE is greater in patients
who present with PE than in those who present with DVT.10
According to prospective cohort studies, the acute case fatality
rate for PE ranges from 7 to 11%.11 Also, recurrent episodes are
about three times more likely to be PE after an initial PE than
after an initial DVT (about 60% after PE vs. 20% after DVT).11
The prevalence of PE among hospitalized patients in the United
States, according to data collected between 1979 and 1999, was
0.4%.12 Though only 40–53 per 100 000 persons were diagnosed
with PE per year, the annual incidence in the United States was
estimated at 600 000 cases.13 The corresponding figures for
Europe are unavailable. Among regional registries, an analysis of
2356 autopsies performed in 1987 on 79% of all deceased inhabi-
tants from the city of Malmo, Sweden, with a population of
230 000, revealed VTE in 595 (25%), while PE was found in 431
(18.3%) of all cases.14 In 308 autopsies (13.1%), PE was considered
to be the main cause or a contributory cause of death. The inci-
dence of PE, as diagnosed by lung scintigraphy, within the same
period and population was only 48 (2%) cases in the whole
Malmo region. From autopsy, phlebography and lung scintigraphy
results, the authors estimated the incidence of VTE in the city of
Malmo at 42.5/10 000 inhabitants/year. However, recalculation
of their data indicates that the incidence of PE was 20.8/10 000
inhabitants/year.14 In a more recent community-based study
involving 342 000 inhabitants in Brittany, France, the incidences
of VTE and PE were 18.3 and 6.0/10 000/year respectively.
However, autopsy data were not available.15 The true incidence
of PE is therefore difficult to assess in view of its non-specific
clinical presentation.16
Predisposing factors
Although PE can occur in patients without any identifiable predis-
posing factors, one or more of these factors are usually identified
(secondary PE). The proportion of patients with idiopathic or
unprovoked PE was about 20% in the International Cooperative
Pulmonar