Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.
com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
►► Additional material is
published online only. To view
please visit the journal online
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Department of Medicine,
Medical College of Wisconsin,
Milwaukee, Wisconsin, USA
Correspondence to
Dr Paul Anthony Bergl,
Medical College of Wisconsin,
Milwaukee, WI 53226-0509,
USA; p​ bergl@​mcw.e​ du
Received 10 May 2019
Revised 6 July 2019
Accepted 22 July 2019
© Author(s) (or their
employer(s)) 2019. No
commercial re-use. See rights
and permissions. Published
by BMJ.
To cite: Dabbouseh NM,
Patel JJ, Bergl PA. Heart
Epub ahead of print:
[please include Day Month
Year]. doi:10.1136/
heartjnl-2019-314776
Role of echocardiography in managing acute
pulmonary embolism
Noura M Dabbouseh, Jayshil J Patel, Paul Anthony Bergl‍ ‍
ABSTRACT
The role of echocardiography in acute pulmonary
embolism (PE) remains incompletely defined.
Echocardiography cannot reliably diagnose acute PE,
and it does not improve prognostication of patients
with low-risk acute PE who lack other clinical features
of right ventricular (RV) dysfunction. Echocardiography,
however, may yield additional prognostic information in
higher risk patients and can aid in distinguishing acute
from chronic RV dysfunction. Specific echocardiographic
markers of RV dysfunction have the potential to enhance
prognostication beyond existing risk models. Until
these markers are subjected to rigorous prospective
studies, the therapeutic utility and economic value of
echocardiography in acute PE are uncertain.
Introduction
Outcomes from acute pulmonary embolism (PE)
have been steadily improving over the last two
decades; all-cause mortality rates now approximate
5%–7%, perhaps owing to improved risk stratifi-
cation and more appropriate use of advanced ther-
apies like thrombolysis.1–3 Nonetheless, among
patients who present with haemodynamic insta-
bility, shock or cardiac arrest, 30-day all-cause
mortality remain 14%–22%.4 5 Conversely, the
lowest risk patients, who comprise between 20%
and 50% of all patients with acute PE, have a short-
term mortality of less than 1%.4 6 7 With this wide
range of risk and therapeutic approaches to acute
PE constantly evolving,8 risk-modelling in acute PE
has become highly relevant.
Right ventricular (RV) dysfunction secondary
to acute PE remains a source of cardiopulmonary
morbidity and mortality.2 9 Varying degrees of acute
RV dysfunction and injury (elevations of cardiac
biomarkers and/or imaging findings) can be iden-
tified in at least half of hospitalised patients with
acute PE.4–7 Myriad studies have corroborated
echocardiography’s usefulness in risk stratifying
acute PE.10 However, few studies examining echo-
cardiography’s role in PE prognosis have diligently
adjusted for other markers of RV injury or dysfunc-
tion and only recently have risk models incorpo-
rated cardiac biomarkers and/or CT evidence of RV
dysfunction.6 11 In addition, professional society
guidelines, such as from the European Society of
Cardiology (ESC) and American College of Chest
Physicians, have cautioned against routine use of
echocardiography in acute PE.12 13
Professional guidelines cannot account for all
potential scenarios in which echocardiography
might aid in clinical decision-making. Critically
appraising the literature can inform nuanced deci-
sions about ordering echocardiography in acute
PE. In this narrative review, we will synthesise the
Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776
Review
available literature on echocardiography’s role in
diagnosing and prognosticating outcomes in acute
PE. Further, we will discuss potential echocardio-
graphic markers of risk and echocardiography’s
impact on management decisions and healthcare
utilisation in acute PE.
Echocardiography and the diagnosis of
acute pulmonary embolism
The test performance characteristics of multi-
detector computed tomographic (MDCT) angi-
ography have made this the test of choice for
diagnosing acute PE.12 Because of its non-inva-
sive nature, ubiquity and ability to be performed
bedside, echocardiography may seem an appealing
alternative to MDCT.Indeed, investigators have
long sought to clarify echocardiography’s role in
Medical Center. Protected by copyright.
diagnosing acute PE.14
In a recent systematic review and meta-analysis,
22 studies were identified that investigated test
performance characteristic for echocardiography in
suspected PE.14 Multiple imaging modalities were
considered potential ‘gold standards’, including
MDCT, ventilation-perfusion scanning, surgery
or autopsy. Among the combined studied popula-
tion, the prevalence of acute PE was 40.8%. Only
enlarged RV end-diastolic diameter was at least
80% sensitive for acute PE (95% CI 61% to 92%)
leading the authors to assert that echocardiography
lacks sensitivity to rule out PE.14
Two findings of this meta-analysis merit further
consideration. First, in suspected acute PE, multiple
echocardiographic signs are highly specific: right-
heart thrombus (online supplementary video 1),
McConnell’s sign (online supplementary videos
2–4), paradoxical septal movement (online supple-
mentary videos 5 and 6 and RV free wall hypokinesis
(table 1). These clinical signs retain high specificity
even in point-of-care examinations performed by
non-cardiologists.14 Second, the overall echocardio-
graphic impression of ‘right heart strain’, an incom-
pletely specified but frequently studied finding, has
a modest positive likelihood ratio of 3.12 when
acute PE is suspected.14
Patients with haemodynamic instability or
cardiac arrest might also benefit from focused echo-
cardiography when acute PE is suspected and ‘gold
standard’ imaging is not feasible (figure 1).15 Echo-
cardiography may play a role in diagnosing PE in
pregnant patients or other situations warranting
avoidance of radiation. However, formal validated
diagnostic assessment for thromboembolism, such
as with venous ultrasonography, is recommended.12
Early echocardiography is recommended to
confirm RV dysfunction as the cause of hypoten-
sion in patients with known or suspected acute PE,
  1

Review
Table 1  Potentially valuable echocardiographic findings in the diagnosis of suspected PE (adapted from Fields et al14
Echocardiographic finding Pooled specificity (citation)
Right heart thrombus 0.99 (95% CI 0.96 to 1.0)
McConnell’s sign 0.97 (95% CI 0.95 to 0.99)
Paradoxical septal movement 0.95 (95% CI 0.93 to 0.97)
RV free wall hypokinesis 0.91 (95% CI 0.88 to 0.94)
RV end-diastolic diameter (dilation) 0.80 (95% CI 0.61 to 0.92)
Overall impression of RV strain 0.83 (95% CI 0.74 to 0.90)
PE, pulmonary embolism; RV, right ventricle.
although based largely on low quality evidence and opinion.12 15
Interpretation of bedside echocardiography by non-cardiologists
in such scenarios retains high accuracy and reproducibility,16 17
thereby extending echocardiography’s role in prompt diagnosis.
Distinguishing acute pulmonary embolism from
other causes of right ventricular failure
In limited scenarios, echocardiography can elucidate the aeti-
ology of RV dysfunction, usually by way of exclusion of other
causes. Primary RV failure due to infarction or acute PE cannot
usually be differentiated by echocardiography. However, indi-
rect evidence of left atrial (LA) hypertension, such as LA enlarge-
ment, mitral valve disease or left ventricular (LV) systolic or
diastolic dysfunction, could implicate left-sided heart disease as
the culprit for RV dysfunction in the proper clinical context.18
Additionally, while less reliable in severe pulmonary hyper-
tension, non-invasive echocardiography-based estimates of
Figure 1  A patient underwent echocardiogram for evaluation after
cerebrovascular accident. McConnell’s sign was incidentally noted.
Panel A is a still frame during diastole and Panel B is a still frame during
systole. Note only the apex demonstrates any significant contraction
or motion. Acute PE was diagnosed on MDCT ordered after this study.
Bottom images: Paradoxical septal motion in acute PE. Mid systole still
frames of the same patient’s heart before (Panel C) and after (Panel
D) she suffered haemodynamically significant pulmonary embolus
resulting in intraoperative cardiac arrest. Note the RV enlargement
and paradoxical septal motion: left ventricle geometry has changed
from round to D-shaped after acute PE, which was highly suggested by
these echo findings and later confirmed on MDCT. MDCT, multidetector
computed tomography; PE, pulmonary embolism; RV, right ventricle.
2 Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776
Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
Estimated positive likelihood ratio Estimated negative likelihood ratio
5.0 0.96
7.3 0.80
5.2 0.78
4.2 0.68
4.0 0.25
3.1 0.57
pulmonary vascular resistance (PVR) have been validated,19
which aids further in distinguishing precapillary and postcapil-
lary pulmonary hypertension.
Similarly, certain echocardiographic findings of the RV vary
with acute versus chronic pressure overload (table 2).20 Lower
magnitude (less negative) RV free wall longitudinal strain, lower
RV fractional area change (FAC) and higher RV end diastolic
area appear more suggestive of acute PE than chronic pulmo-
nary arterial hypertension (PAH).21 Patients with acute PE may
also have significantly lower magnitudes of global circumferen-
tial peak systolic strain (PSS) and global LV longitudinal PSS.20
Other significant findings favouring acute PE over chronic PAH
also include lower indexed RV end diastolic area, end systolic
area, LV indexed end diastolic volume and stroke volume index.
Medical Center. Protected by copyright.
Although global RV longitudinal PSS does not reliably differ-
entiate the two, LV PSS, global circumferential PSS and LV
PSS dyssynchrony are more markedly abnormal in acute PE.20
Other potential echocardiographic findings that suggest acute
PE (rather than chronic PAH) include lower RV outflow tract
systolic excursion, lower estimated pulmonary artery systolic
pressures and less severe tricuspid regurgitation.22 23 Despite
its high specificity in populations suspected of having acute PE,
McConnell’s sign cannot reliably determine the chronicity of RV
dysfunction.21 23
Echocardiography in risk stratifying and
prognosticating outcomes of acute pulmonary
embolism
Integrating echocardiography into risk stratification for acute
PE has garnered attention for over two decades.24 The prog-
nostic value of echocardiographic RV dysfunction in acute PE
has been demonstrated repeatedly.10 The American Society of
Echocardiography broadly advises echocardiography for risk
stratification,25 but other professional societies do not recom-
mend routinely incorporating echocardiography into PE risk
assessment.12 13
The ESC guidelines classify PE into three strata based on early
mortality risk: (1) high risk, as defined by arterial hypotension
or shock, (2) intermediate risk, as defined by a simplified Pulmo-
nary Embolism Severity Index (sPESI) score >1 and (3) low
risk, as defined by absence of hypotension and sPESI score of
0.12 The ESC definitions of high-risk and intermediate-risk PE
align with the older classifications of ‘massive’ and ‘submassive’
PE as defined by the American Heart Association (AHA),26 but
the ESC guidelines further specify intermediate-high and inter-
mediate-low risk profiles as outlined in table 3. Although the
ESC approach identifies echocardiographic RV dysfunction as
a potential marker of intermediate-high risk, it does not require
its presence.
Given the known high mortality in high-risk ‘massive’
PE,1 3–5 contemporary risk stratification has focused on
predicting outcomes in haemodynamically stable acute PE. At
 Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
Review

Table 2  Findings helpful for distinguishing acute PE from chronic pulmonary hypertension as cause of RV dysfunction
Echocardiographic finding Responses suggesting acute PE Responses suggesting chronic pulmonary hypertension
RV free wall longitudinal strain Lower magnitude (less negative) is seen, approximately Typical values of strain are −14% at the apex, −20% at the
−10 to −15%.21 mid wall and −23% at the base.21
RV FAC FAC is usually less 30% with values<20% suggesting FAC may be less than 30%, but values exceeding 35%
acute PE.20 21 23 suggest chronic pulmonary hypertension.20
Estimated PASP Estimated PASP is not expected to exceed 60–65 mm Hg PASP exceeding 85 mm Hg is possible and may be found
and almost never exceeds 80 mm Hg.23 in nearly 20% of patients with long-standing pulmonary
hypertension.23
TR severity By vena contracta, TR is typically <0.5 cm.23 Vena contracta width exceeding 0.6 cm more likely represents
chronic elevation in right-sided pressures.23
FAC, fractional area change; PASP, pulmonary artery systolic pressure; PE, pulmonary embolism; RV, right ventricle; TR, tricuspid regurgitation.

least 16 other risk prognostic models have been validated for this
purpose, including the original Pulmonary Embolism Severity
Index (PESI), sPESI, eStiMaTe and the Bova score.6 11 27 Many
models build from (s)PESI and incorporate additional markers
of RV injury or dysfunction, such as cardiac biomarker eleva-
tion, echocardiography and/or CT findings.27 In general, these
enhanced models improve prognostication marginally, but few
have been tested prospectively to ascertain their role in clinical
decision-making.27
Prognostic value of echocardiography in specific
patient populations
ESC guidelines for diagnosing RV dysfunction (RV free wall
hypokinesis and RV-to-LV end-diastolic ratio >0.9), only 18% of
haemodynamically stable patients referred for echocardiography
had RV dysfunction.28 In prospective studies in which every
haemodynamically stable patient underwent an echocardiogram,
fewer than one in four patients had RV dysfunction.7 29 30
Low-risk patients
In a large study of multiple prospective cohorts, RV dysfunc-
tion (by CT and/or echocardiography) was identified in 41%
of low-risk patients (sPESI of 0).4 Even among these patients,
mortality was only 1.2%, which approximated the mortality

Medical Center. Protected by copyright.

Unselected patients among all low-risk patients (0.5%, no test of statistical signifi-
Echocardiographic RV dysfunction is infrequently identified cance reported).4 Similarly, in a large prospective study of haemo-
among unselected haemodynamically stable patients with acute dynamically stable patients, incorporating echocardiographic
PE. In a retrospective cohort study strictly applying the AHA/ findings into risk modelling of low-risk patients did not enhance

Table 3  AHA/historical and ESC categories of PE risk

ESC risk category12 Historical classification26 Definition12 Approximate proportion Approximate 30 day all- Risk of complicated
of patients with acute cause mortality course (all-cause death,
PE1–6 haemodynamic collapse or
recurrent PE)
High Massive ►► Shock 3%–12%1 3 5 9%–22%1 3 5 Insufficient data
►► Hypotension with
systolic blood
pressure < 90 mm
Hg or
►► Systolic pressure drop
of > 40 mm Hg

Intermediate-high Submassive ►► Absence of shock Insufficient data 5.3%–7.7%4 7 17.5% (95%CI 8.8% to
►► sPESI score > 1 29.9%)7
►► Presence of both
RV dysfunction on
imaging (CT and/or
echocardiography)
and elevated cardiac
biomarkers

Intermediate-low ►► Absence of shock 6.0%–7.1%4 7 10.0% (95%CI 7.5% to

►► sPESI score > 1 13.1%)7
►► Presence of either
RV dysfunction on
imaging (CT and/or
echocardiography)
or elevated cardiac
biomarkers

Low Low ►► Absence of shock 20%–50%2 4 6 0.3%–0.5%4 7 1.6% (95%CI 0.5% to 3.75%)7
or hemodynamic
instability
►► sPESI score = 0
AHA, American Heart Association; ESC, European Society of Cardiology; PE, pulmonary embolism; RV, right ventricle; sPESI, simplified Pulmonary Embolism Severity Index.

Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776 3

 Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
Review
prediction of death, haemodynamic collapse or recurrent PE.30
In low-risk patients with low levels of natriuretic peptides, the
risk of death or complications is <1%, thereby eliminating any
additive value of performing echocardiography.6 26

Patients with CT evidence of RV dysfunction (intermediate-risk

patients)
CT and echocardiographic evidence of RV dysfunction are often
considered equivalent.11 12 31 Yet studies comparing both modali-
ties suggest distinct risk profiles and unreliable interchangeability.
In one analysis of emergency room patients, RV dysfunction on
both imaging modalities conferred a higher rate of deteriora-
tion (30% in first 5 days) than for either modality alone (20%
for echocardiography, 3% for CT, p=0.002, Fisher’s exact test).
Moreover, there was relatively poor agreement between the CT
and echocardiographic diagnosis of RV dysfunction. Of note,
only 40% of the enrolled patients in this study underwent formal Figure 2  Example of TAPSE and s’ in a patient with normal RV
echocardiography, which implies selection bias.32 Other prospec- function (panels A and B) and in patients with acute RV dysfunction
tive studies have affirmed that intermediate-risk PE patients with due to PE (panels C and D). PE, pulmonary embolism; RV, right ventricle;
CT evidence of RV dysfunction may experience more compli- TAPSE, tricuspid annular plane systolic excursion.
cations when echocardiographic evidence of RV dysfunction is
also present.30 An additional prospective study demonstrated
that patients were far more likely to have RV dysfunction by evidence of RV dysfunction, echocardiographic RV dysfunction
CT (94% of patients with RV dysfunction) than by echocardiog- and cardiac biomarkers; echocardiographic findings were not
raphy (38% of patients with RV dysfunction) or troponin eleva- associated with increased risk after adjusting for biomarkers,

Medical Center. Protected by copyright.

tion (7% of patients with RV dysfunction). While CT evidence
of RV dysfunction correlated poorly with echocardiography and
outcomes, the degree of clot burden on CT was significantly
associated with increased risk of echocardiographic RV dysfunc-
tion, short-term clinical deterioration and use of thrombolysis,
but not death.33 Thus, the combined presence of CT-based and
echocardiographic RV dysfunction may suggest higher risk of
adverse outcome but may not have management implications
(see below).
Patients with biochemical evidence of RV strain or injury
(intermediate-risk patients)
Cardiac biomarkers aid in risk stratifying acute PE6 12 24 26 29 with
elevated troponin and/or natriuretic peptides portending worse
prognosis.6 11 27 29 In the absence of biomarker elevation, echo-
cardiography is unlikely to enhance risk prediction.6 12 Among
recently validated risk prediction models for haemodynamically
stable patients with acute PE that incorporate biomarkers (Bova
score and eStiMaTe), echocardiographic RV dysfunction is not
required as an input variable.6 11 In fact, derivation of eStiMaTe
adjusted for all relevant markers of RV dysfunction, namely CT
sPESI and presence of lower extremity clot.6 Together, these
data strongly argue against using echocardiography in patients
with non-elevated biomarkers, and they suggest that the mere
presence of RV dysfunction may not meaningfully enhance prog-
nostication among patients with elevated biomarkers.
Prognostic utility of select echocardiographic
findings
No contemporary risk prediction model has incorporated
specific high-risk echocardiographic markers. As these markers
reflect the severity of RV dysfunction, they offer an advantage
over CT, which can only infer RV dysfunction from dilation
on static images, and biomarkers, which may be influenced by
numerous patient characteristics and comorbidities. Several
markers are backed by compelling data suggesting a potential
role in prognostication, particularly among intermediate-high
risk PE patients (table 4).
Tricuspid annular plane systolic excursion (TAPSE)
TAPSE, or the M-mode-derived basal-to-apical longitudinal
displacement of the lateral tricuspid annulus during systole,

Table 4  Selected echocardiographic parameters predicting adverse outcome from acute PE

Echocardiographic finding Technical considerations Summary of relationship with PE outcomes
TAPSE Though reproducible and easy to measure routinely, is Strongly and independently associated with risk of death and/
angle dependent and can be affected by tethering; less or decompensation in multiple studies, though cut-off value
accurate in setting of regional wall motion abnormalities. varies (between 15 and 18 mm).35 37 44
Right heart thrombi Highly specific for acute PE but also highly insensitive, Associated with increased short-term all-cause mortality
particularly in the setting of poor acoustic windows, risk, particularly in patients with haemodynamic instability
which are less forgiving for low quality 2D images than or RV dysfunction. Unlikely to impact risk in low-risk patients
Doppler-derived measurements. incidentally found to have right-heart thrombus.28 39–41
RV overload defined as at least two of the following: No consensus definition for elevated EDD in PE literature, Only in patients with sPESI >0, echocardiographic evidence of
elevated EDD, free wall hypokinesis, PA systolic pressure though elevated RV/LV ratio frequently studied. RV overload increased the risk of complicated course.30
>30 Hypokinesis frequently a subjective assessment.
RV speckle-tracking (strain) imaging High quality apical windows with good endocardial Predictor of complicated course in haemodynamically stable
definition needed; RV shape is complex; differences patients.21 43
between software vendors; not angle dependent and
captures regional dysfunction.
EDD, end-diastolic diameter; PE, pulmonary embolism; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion; sPESI, simplified Pulmonary Embolism Severity Index.

4 Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776


has been validated as a highly reproducible measure of RV
systolic function34 and consistent indicator of adverse PE-re-
lated outcomes (figure 2). In prospective observational studies,
TAPSE<15–16 mm independently predicts PE-related mortality
and rescue thrombolysis, ever after adjustment for other echo-
cardiographic findings of RV dysfunction.35 36 TAPSE>18 mm
virtually excludes PE-related mortality,35 37 and TAPSE is a
better predictor of acute PE-related outcomes than RV/LV ratio
in normotensive patients.35 Declining TAPSE correlates highly
with elevations in natriuretic peptides in acute PE;35 36 whether
TAPSE retain its prognostic utility after adjusting for other
markers of RV dysfunction is unknown.
Right heart thrombus
Right heart thrombus is found in approximately 2%–4% of
patients who undergo echocardiography in the context of acute
PE.28 38–40 No prospective study has captured the true incidence
among all PE patients, but right heart thrombus is rarely found
in normotensive patients who lack echocardiographic evidence
of RV dysfunction (1.0%) and is far more common in hypoten-
sive patients (up to 20%).28 39
The presence of right heart thrombus clearly increases the
risk of short-term mortality in acute PE, with mortality rates
approaching 20%,38 39 41 but the risk of adverse outcomes appears
to be restricted to patients with haemodynamic instability or RV
dysfunction,39 who comprise the majority of patients with right
heart thrombus.28 39 A 2017 meta-analysis of prospective and
retrospective cohort studies in acute PE reported an OR of 3.0
(95%CI 2.2 to 4.1) for all-cause mortality within 30 days of
identification of right heart thrombus.41 Associations between
right heart thrombus and mortality remain significant even after
adjustment for demographics, major cardiovascular comorbidi-
ties and sPESI score40 or adjustment through propensity score
matching.39 In normotensive patients and in low-risk patients by
ESC guidelines (no haemodynamic instability, no RV dysfunc-
tion), the presence of right heart thrombus has no impact on
mortality.28 39 41 Morphology, size or mobility of the intracardiac
thrombus has no effect on mortality; the sPESI score best strati-
fies risk in this population.39
Other common findings
RV enlargement is typically defined as RV/LV end diastolic
ratio >0.9 or 1.0, either in isolation or combination with other
markers. Progressive increases in RV/LV end diastolic ratio
reflect increased risk of adverse outcome.42 Reduced RV FAC,
reduced velocity on tissue Doppler measurement of tricuspid
annular systolic excursion velocity (s’) and elevated PVR also
may independently predict in-hospital complications and
death.43 Of note, while diminished s’ velocity in acute PE can
predict a complicated course, it may have inferior performance
compared with TAPSE.44
Novel markers of risk
Emerging literature suggests a role for three-dimensional (3D)
based RV function assessment and RV strain (figure 3)in strati-
fying PE risk. In a small prospective study, 3D-derived RV ejec-
tion fraction and mid-free wall longitudinal strain had the highest
discrimination for complicated outcome in haemodynamically
stable PE patients. These measures remained independently asso-
ciated with 6-month adverse outcome, even after multivariate
analysis adjusting for cardiac biomarkers and other commonly
obtained echocardiographic values.45 In another prospec-
tive single-centre study of haemodynamically stable patients,
Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776
Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
Review
Figure 3  Example of normal global longitudinal strain in a normally
functioning RV in a patient with acute PE. Note the software is ‘tricked’
into measuring ‘LV apical’ strain, and this strain is then plotted on
a bullseye as an assessment of RV function. LV, left ventricle; PE,
pulmonary embolism; RV, right ventricle.
abnormal RV free wall and global wall strain independently
predicted PE-related death or escalation of therapies.43
Therapeutic implications of echocardiography
Barring contraindications, thrombolysis is universally recom-
mended for the highly morbid, high-risk (massive) acute PE.12 13 26
In contemporary registries, haemodynamically unstable patients
who had received thrombolysis had a reduced risk of dying (OR
0.66, 95% CI 0.45 to 0.97).46 Because of the time-sensitive
Medical Center. Protected by copyright.
nature of thrombolysis, early echocardiogram is warranted to
identify RV dysfunction-induced cardiogenic shock.12 15
The role for thrombolysis is less clear for non-high-risk acute
PE. Several large randomised controlled trials have compared
systemic thrombolysis plus anticoagulation to anticoagulation
alone8 with the largest of these trials (PEITHO) enrolling 1005
adults.31 In PEITHO, patients with acute PE, CT-based or echo-
cardiographic RV dysfunction and troponinemia were enrolled.
Though haemodynamic decompensation was higher in those
treated with anticoagulation alone, there was no difference
in death from any cause, even at 6 years.9 More than 85% of
patients in PEITHO had echocardiographic RV dysfunction, and
all would be considered intermediate-high risk per ESC defini-
tions. Because of the harms associated with thrombolysis, such
as major extracranial bleeding (6.3% vs 1.2% in controls) and
stroke (2.4% vs 0.2% in controls), treating all intermediate-high
risk patients with echocardiographic RV dysfunction could result
in net harm. In PEITHO, the number needed to treat to prevent
haemodynamic decompensation was 29, while the number
needed to harm to cause one major bleed was 19.31
Catheter-directed thrombolysis (CDT) is emerging as an
alternative method to deliver thrombolytic with a lower risk
of bleeding.8 The only prospective trial of CDT randomised
63 haemodynamically stable acute PE patients with echocar-
diographic RV dysfunction to undergo CDT or anticoagulation
alone; the primary outcome was RV/LV ratio from baseline to
24 hours. In the CDT group, the RV/LV ratio from baseline
to 24 hours was 1.28 (±0.19) to 0.99 (±0.17) compared with
1.20 (±0.14) to 1.17 (±0.20) in the heparin group (p=0.001).
Despite improvements in this echocardiographic surrogate or
RV dysfunction, there were no differences in mortality, haemo-
dynamic decompensation or major bleeding.47
Echocardiography is a key step in deciding on advanced ther-
apies in acute PE. However, echocardiographic RV dysfunction,
even in intermediate-high risk patients, is not a compelling
indication for systemic thrombolysis,8 31 and improvement in
echocardiographic surrogates has not definitively translated to
improved clinical outcomes.8 47 Though speculative, daunting
echocardiographic findings may incline clinicians towards
5

Review
aggressive treatments with perceived beneficence at the expense
of increased bleeding and harm.48
Echocardiography and healthcare utilisation
Despite its limitations as a diagnostic modality and variable
utility in prognosis, echocardiography is ordered in approx-
imately of 40%–45% of acute PE hospital admissions in
developed nations.40 48 Common predictors of early echocar-
diography include cardiovascular comorbidities, such as heart
failure, diabetes mellitus or atrial fibrillation, and markers of
clinical severity including hypoxemia, tachycardia and organ
Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
failures.40 48 Larger hospital size and attending physicians special-
ising in cardiology or pulmonary-critical care also are associated
with increased use of echocardiography in acute PE.48
Early echocardiography in acute PE is associated with longer
lengths of stay,48–50 greater use of ICU care,48 higher costs of
hospitalisation48 50 and uncertain effects on mortality.48–50 At
least one retrospective study using propensity score matching
found that patients undergoing inpatient echocardiography
had a lower in-hospital mortality (OR 0.75%, 95% CI 0.68
to 0.83, p<0.001) despite having longer hospital stays and
higher costs.50 Other studies have found no association between

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Figure 4  Proposed clinical decision pathway for integrating echocardiography into management of acute PE. LV, left ventricle; PE, pulmonary
embolism; RV, right ventricle; sPESI, simplified Pulmonary Embolism Severity Index; TAPSE, tricuspid annular plane systolic excursion.
6 Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776

echocardiography use and risk-adjusted mortality in acute
PE48 49 but have shown positive correlations between frequency
of echocardiography and thrombolysis (OR 5.58, 95% CI 4.40
to 7.09) and major bleeding (OR 1.37, 95% CI 1.24 to 1.51).48
Unfortunately, these studies cannot ascertain whether increased
resource utilisation represents inappropriate cautiousness in the
presence of abnormal echocardiographic findings (ie, treating
the image, not the patient) or appropriately reserving echocardi-
ography for the sickest patients. Moreover, they cannot directly
measure the incremental benefit per cost (ie, value) or impact on
patient outcomes.
Conclusion
Despite decades of research, echocardiography’s role in prognos-
ticating and managing acute PE remains uncertain. For high-risk
patients with massive PE, echocardiography is widely embraced,
and it confirms the aetiology of haemodynamic instability. For
low-risk patients with haemodynamic stability, echocardiography
rarely yields actionable findings and does not enhance prognosti-
cation. While echocardiography can help predict outcomes in a
subset of intermediate-risk PE patients, existing risk models and
biomarker testing offer less costly and more rapid prognostica-
tion. That said, among patients with high-risk clinical features
or comorbidities, selected echocardiographic markers might be
useful for risk stratification. Thus, we suggest the clinical deci-
sion pathway detailed in figure 4 based on our critical appraisal
of the literature.
Several questions around echocardiography still merit further
investigation. First, the prognostic utility of echocardiographic
markers has not been rigorously studied with adjustment for
biochemical markers of RV injury. On the other hand, among
validated risk models in acute PE, none incorporates high-yield
echocardiographic markers that might identify a subset of inter-
mediate-risk patients who merit more intensive monitoring or
therapy. Thus, studies should seek to incorporate high-risk echo-
cardiographic findings into existing risk stratification models,
particularly for intermediate-high risk patients.
Because of the widespread use of MDCT, incidentally discov-
ered PE has increasingly presented clinicians with treatment
dilemmas.13 To our knowledge, the use of echocardiography
in aiding therapeutic decision-making in incidental PE has not
been systematically studied and could also be an area for future
research. In addition, as studies have focused on echocardiog-
raphy within 24–72 hours of initial presentation, whether echo-
cardiography provides additive prognostic information after
clinical deterioration (eg, worsening hypoxemia, syncope, falling
blood pressure) remains unstudied. Further, future work should
explore potential benefits of serial echocardiography of interme-
diate-high risk patients with a focus on the most easily measur-
able and reproducible makers of risk, such as TAPSE.
Contributors  NMD contributed to the overall design and organisation of the
manuscript, collected and analysed the available literature, drafted the manuscript,
provided critical revisions and approved of the final version. JJP contributed to the
design and organisation of the manuscript, suggested and appraised literature,
drafted sections of the manuscript, critically revised the remainder of the manuscript
and approved of the final version. PAB initiated this review, helped in collecting and
analysing the available literature, shared in drafting the manuscript, contributed
critical revisions, provided final edits and approved of the final version.
Funding  The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests  None declared.
Patient consent for publication  Not required.
Provenance and peer review  Commissioned; externally peer reviewed.
Dabbouseh NM, et al. Heart 2019;0:1–8. doi:10.1136/heartjnl-2019-314776
Heart: first published as 10.1136/heartjnl-2019-314776 on 22 August 2019. Downloaded from http://heart.bmj.com/ on August 23, 2019 at Dahlgren Memorial Library, Georgetown University
Review
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