Echocardiography in Pulmonary
Embolism
Gregory Piazza, M.D.
Beth Israel Deaconess Medical Center
January 26, 2005
Beth Israel Deaconess Medical Center
Objectives
• To present a brief overview of the
epidemiology, pathophysiology,
diagnosis, and management of acute
pulmonary embolism (PE).
• To review the role of echocardiography
in the diagnosis of PE.
• To highlight the role of
echocardiography in risk stratification of
patients with PE.
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Epidemiology
• The incidence of PE in the U.S. is
approximately 1 per 1000 per year.
• Only 1 out of every 3 cases of venous
thromboembolism (VTE), including DVT
and PE, is diagnosed.
• With approximately 450,000 cases
detected per year, a staggering 900,000
VTE cases may go undiagnosed
annually.
Lancet 1999;353:1386-1389
Lancet 2004;363:1295-1305
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Epidemiology
• In the Olmsted County registry, 30-day
mortality after PE or DVT has been
reported as high as 28%.
• The International Cooperative
Pulmonary Embolism Registry
(ICOPER) estimates a 3-month
mortality of 17.4%.
• These data suggest PE is possibly as
deadly as acute myocardial infarction.
Arch Intern Med 1999;159:445-453
Circulation 2003;108:2726-2729
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Pathophysiology
• The most common sources of PE are the
deep veins of the lower extremities and
pelvis.
• Thrombi dislodge from these veins and
embolize to the pulmonary arterial tree where
they trigger pathophysiologic changes in
hemodynamics and gas exchange.
• The size of the embolus, underlying
cardiopulmonary status, and neurohumoral
adaptations determine the hemodynamic
response to PE.
Circulation 2003;108:2726-2729
Beth Israel Deaconess Medical Center
Pathophysiology
www.benlovejoy.com/ pulmonary_embolism_main.html
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Pathophysiology
• Physical obstruction, release of vasoconstrictors, and
hypoxia lead to increased pulmonary vascular
resistance (PVR) and right ventricular (RV) afterload.
• RV pressure overload leads to chamber dilatation
and hypokinesis, tricuspid regurgitation, and eventual
RV failure.
• RV pressure overload also causes interventricular
septal flattening during systole and deviation towards
the left ventricle (LV) during diastole leading to
impaired LV filling.
• As RV pressure overload worsens, RV wall stress
and ischemia develop secondary to increased
myocardial oxygen demand and decreased supply.
Am Heart J 1995;130:1276-1282
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Pathophysiology
Pulmonary embolism
↑ PA pressure
↑ RV afterload
↑ RV wall tension
↑ RV O2 demand
RV dilatation and
dysfunction
RV ischemia +/infarction
↓ RV O2 supply
↓ RV cardiac
output
Septal shift
toward the LV
↓ coronary perfusion
↓ LV preload
↓ LV cardiac output
Am Heart J 1995;130:1276-1282
Hypotension
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Spectrum of Disease
•
1.
2.
3.
4.
A variety of clinical
syndromes may be
seen:
Normotensive with
normal RV function
Normotensive with RV
dysfunction
(submassive PE)
Cardiogenic shock
(massive PE)
Cardiac arrest
(massive PE)
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Diagnosis: History and Physical
History:
• Dyspnea (most
frequent symptom)
• Pleuritic chest pain
• Cough
• Hemoptysis
• Syncope
Physical:
• Tachypnea (most
frequent sign)
• Anxious appearance
• Tachycardia
• Fever
• Elevated JVD (most
specific sign)
• Loud P2
• Tricuspid regurgitation
• Paradoxical bradycardia
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The Diagnostic Armamentarium
•
•
•
•
•
Arterial blood gases
Electrocardiography
Chest X-ray
Plasma D-dimer
Lower extremity
ultrasound
• Echocardiography
(TTE and TEE)
• Ventilation-perfusion
lung scanning
• Spiral chest CT
• Magnetic resonance
(MR) angiography
• Contrast pulmonary
angiography
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Diagnosis: An Integrated Approach
History and Physical
Eval. clinical likelihood
Patient in ED
Electrocardiogram
Chest radiograph
Patient already
in hospital
D-dimer
Normal
No PE
Normal
High
V/Q if dye allergy or
renal insufficiency
Chest CT
Positive
Equivocal
Normal
Ultrasonography
Positive
No PE
Lancet 2004;363:1295-1305
Treat for PE
Negative
Consider
PA-gram
No PE
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Diagnosis: Transthoracic
Echocardiography
• Transthoracic echocardiography (TTE) is
insensitive in the diagnosis of acute PE.
• In a prospective study, TTE failed to diagnose
50% of patients with angiographically proven
PE.
• However, in the appropriate clinical setting,
findings of right ventricular pressure overload
may help suggest acute PE as a diagnosis.
Lancet 2004;363:1295-1305
Am J Med 2001;110:528-535
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Diagnosis: Transthoracic
Echocardiography
Apical 4- chamber
Parasternal short-axis
Parasternal long-axis
Am J Respir Crit Care Med 2002;166:1310-1319
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Echocardiographic Findings In Acute PE
• RV dilatation and hypokinesis
• Interventricular septal flattening and paradoxical
motion
• Alteration of transmitral gradients with A wave > or = E
wave
• Tricuspid regurgitation (TR)
• Pulmonary artery (PA) hypertension as estimated by
the modified Bernoulli equation
• RA dilatation
• Loss of respiratory-phasic IVC collapse with inspiration
• Patent foramen ovale
• RA, RV, or pulmonary artery thrombus
Ann Intern Med 2002;136:691-700
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RV Dilatation
• In the apical 4 chamber
view, a ratio RVEDA
(area) to LVEDA > 0.6
correlates with moderate
RV dilatation.
• A ratio > or = 1.0
correlates with major RV
dilatation.
Am J Respir Crit Care Med 2002;166:1310-1319
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RV Hypokinesis
• RV hypokinesis is frequently diagnosed in a
qualitative fashion.
• Quantitative methods, such as RV fractional area
contraction, have not proven more accurate.
• McConnell et al. noted a specific qualitative finding in
patients with RV dysfunction and acute PE compared
to patients with other causes of RV failure.
• The McConnell sign is noted when RV free-wall
hypokinesis in observed in the setting of relatively
normal RV apical contraction.
Am J Respir Crit Care Med 2002;166:1310-1319
Ann Intern Med 2002;136:691-700
Am J Cardiol 1996;78:469-473
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RV Hypokinesis
•
•
•
Am J Cardiol 1996;78:469-473
The RV free-wall endocardium was traced in the
apical 4-chamber view from base to apex at endsystole and end-diastole.
Tracings from patients with RV dysfunction from
acute PE were compared to those with RV
dysfunction from pulmonary arterial hypertension.
For PE, the McConnell sign had a sensitivity of 77%,
specificity of 94%, PPV of 71%, and NPV of 96%.
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RV Hypokinesis
Courtesy of A. Rosen
Beth Israel Deaconess Medical Center
Interventricular septal flattening and
paradoxical motion
• Right ventricular
pressure overload leads
to deviation of the
interventricular septum
towards the LV in
diastole.
• Interventricular septal
flattening is seen during
systole creating a socalled D-shaped LV.
Diastole
Systole
Am J Respir Crit Care Med 2002;166:1310-1319
Ann Intern Med 2002;136:691-700
J Am Coll Cardiol 1987;10:1201-1206
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Interventricular septal flattening and
paradoxical motion
Normal (diastole)
Acute PE (diastole)
Am J Respir Crit Care Med 2002;166:1310-1319
Beth Israel Deaconess Medical Center
Alteration of Transmitral Gradients
• In the setting of pericardial
constraint, interventricular
septal motion towards the
LV during diastole leads to
impaired LV filling.
• Diastolic impairment leads
to an A wave that is > or =
to the E wave, signifying
increased dependence on
atrial contraction for LV
filling.
Normal
PE
Am J Respir Crit Care Med 2002;166:1310-1319
Beth Israel Deaconess Medical Center
Alteration of Transmitral Gradients
Courtesy of A. Rosen
Beth Israel Deaconess Medical Center
Tricuspid Regurgitation
• RV pressure overload
frequently results in
tricuspid regurgitation
detected on color flow
and Doppler.
RV
RA
LA
Ann Intern Med 2002;136:691-700
www.geocities.com/SouthBeach/ Cove/2045/echo55.htm
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Pulmonary Hypertension
• PA systolic pressure is
estimated by using the
modified Bernoulli
equation:
P = 4V2
where P = peak pressure
gradient
V = peak velocity
of the TR jet
• Estimated RA pressure is
added to the gradient to
approximate PA systolic
pressure.
Courtesy of A. Rosen
Am J Respir Crit Care Med 2002;166:1310-1319
Ann Intern Med 2002;136:691-700
Beth Israel Deaconess Medical Center
Thrombus In The Right Main PA
Ann Intern Med 2002;136:691-700
Beth Israel Deaconess Medical Center
Diagnosis: Transesophageal
Echocardiography
• Transesophageal echocardiography (TEE)
can diagnose PE by direct visualization of the
proximal pulmonary arteries.
• Because the left main bronchus obstructs the
view of the middle portion of the left
pulmonary artery, PE is more difficult to
detect in the left PA.
• TEE may play a unique role in the diagnosis
of PE in patients with unexplained cardiac
arrest (especially pulseless electrical activity).
Ann Intern Med 2002;136:691-700
Beth Israel Deaconess Medical Center
Diagnosis: Transesophageal
Echocardiography
Long-axis transesophageal
Short-axis transgastric
Oblique transgastric
Am J Respir Crit Care Med 2002;166:1310-1319
Beth Israel Deaconess Medical Center
Diagnosis: Transesophageal
Echocardiography
Ann Intern Med 2002;136:691-700
Beth Israel Deaconess Medical Center
Case Study
• A 67 year old male with history of CAD, HTN,
and prostate cancer presents with acute
onset dyspnea and dull chest pressure.
• On exam, he is tachycardic, tachypneic,
hypoxic, but normotensive. He has elevated
neck veins and new lower extremity edema.
• His EKG reveals sinus tachycardia.
• His chest X-ray is read as “no pneumonia, no
CHF.”
• Because of high clinical suspicion for PE, he
undergoes chest CT.
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Case Study
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Case Study
• The patient is started on a weight-based
protocol of intravenous unfractionated
heparin and admitted to a telemetry floor.
• That evening, the patient’s roommate calls
the nurses station to report that the patient
has “slumped over in his chair.”
• The patient is found unresponsive and a code
is called.
• The patient is found to be in pulseless
electrical activity (PEA) and expires after
resuscitative efforts are unsuccessful.
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Risk Stratification
Risk Stratification Tools:
• History and physical
• Clinical prognostic scores
• Cardiac biomarkers including cardiac
troponin and brain-type natriuretic
peptide (BNP)
• Chest CT
• Echocardiography
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History and Physical
• ICOPER reported
several independent
clinical predictors of
increased mortality
at 3 months.
Variable
Hazard Ratio
(95% CI)
Age > 70 years 1.6 (1.1-2.3)
Cancer
2.3 (1.5-3.5)
CHF
2.4 (1.5-3.7)
COPD
1.8 (1.2-2.7)
SBP <90 mmHg 2.9 (1.7-5.0)
Lancet 1999;353:1386-9
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Cardiac Biomarkers
• Cardiac troponins and BNP have been extensively
studied in the evaluation of patients with acute PE.
• Cardiac troponins and BNP accurately identify lowrisk PE patients with negative predictive values for inhospital death ranging from 97 to 100%.
• Patients presenting with acute PE and elevated
cardiac biomarkers should undergo transthoracic
echocardiography to assess RV function.
• In patients with acute PE and normal levels of cardiac
biomarkers, echocardiography is not routinely
required as RV function will most often be normal.
Circulation 2003;108:2191-2194
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Cardiac Biomarkers
Reference
n
Biomarker
Assay
Cut-off level
Test +,%
NPV,%
PPV,%
Konstantinides et al19
106
cTnI
Centaur (Bayer)
0.07 ng/ml
41
98
14
Konstantinides et al19
106
cTnT
Elecsys (Roche)
0.04 ng/ml
37
97
12
Giannitsis et al20
56
cTnT
TropT (Roche)
0.10 ng/ml
32
97
44
Janata et al21
106
cTnT
Elecsys (Roche)
0.09 ng/ml
11
99
34
Pruszczyk et al23
64
cTnT
Elecsys (Roche)
0.01 ng/ml
50
100
25
ten Wolde et al27
110
BNP
Shionoria (CIS Bio)
21.7 pmol/L
33
99
17
Kucher et al26
73
Pro-BNP
Elecsys (Roche)
500 pg/ml
58
100
12
Kucher et al25
73
BNP
Triage (Biosite)
50 pg/ml
58
100
12
Pruszczyk et al22
79
Pro-BNP
Elecsys (Roche)
153-334 pg/ml*
66
100
23
*Age
and gender adjusted cut-off levels according to manufacturer.
Abbreviations: n, number; NPV, negative predictive value; PPV, positive predictive value; cTnI, cardiac troponin I; cTnT, cardiac troponin T; BNP, brain-type natriuretic
peptide; pro-BNP, pro-brain-type natriuretic peptide
Accuracy of cardiac biomarkers for the prediction of in-hospital
death in acute pulmonary embolism.
Circulation 2003;108:2191-2194
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Cardiac Biomarkers
↑ PVR
↑ RV pressure
Circulation 2003;108:2191-2194
RV microinfarction
↑ RV shear
stress
Myofibril
degradation
↑ Natriuretic
peptide mRNA
↑ Troponins
↑ BNP
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Chest CT Scan
• Although chest CT is used primarily for the diagnosis
of PE, RV dilatation may also be observed.
• In a study of 431 patients with acute PE diagnosed
by chest CT, multiplanar reformats of axial CT data
into CT 4-chamber views were performed.
• Right and left ventricular dimensions (RVD and LVD)
were measured. RV enlargement was defined as
RVD /LVD > 0.9.
• RV enlargement predicted 30-day death (hazard
ratio, 5.17, p = 0.005) after adjusting for pneumonia,
cancer, chronic lung disease, and age.
Circulation 2004;110:3276-3280
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Chest CT Scan
Circulation 2004;109:2401-2404
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Echocardiography
•
•
RV dysfunction on echocardiography has
been reliably established as a predictor of
adverse outcomes in PE.
The most commonly accepted quantitative
standards are:
1. RV to LV end-diastolic diameter ratio > 1
in the apical 4-chamber view
2. RV end-diastolic diameter > 30 mm
3. Paradoxical interventricular septal
systolic motion
Ann Intern Med 2002;136:691-700
Beth Israel Deaconess Medical Center
Echocardiography
• At the Karolinska Institute in Sweden, 126
consecutive patients with PE were examined
with TTE on the day of diagnosis.
• After multivariate analysis, RV dysfunction
emerged as the most powerful predictor of inhospital death.
• A 6-fold increase in relative risk was noted in
the patients with RV dysfunction compared to
those with normal RV function.
Am Heart J 1997;134:479-487
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Echocardiography
• In a cohort of 209 consecutive patients with
PE, 31% presented with a combination of
normal blood pressure and echocardiographic
evidence of RV dysfunction.
• Of these patients, 10% developed cardiogenic
shock within 25 hours and 5% died in hospital.
• None of the patients with normal RV function
died from PE.
Circulation 2000;101:2817-2822
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Echocardiography
• In ICOPER, 90-day
mortality rate was
increased in patients
with RV dysfunction.
• After multiple regression
analysis, RV dysfunction
was found to be an
independent predictor of
death at 90 days.
Lancet 1999;353:1386-1389
Beth Israel Deaconess Medical Center
Risk Stratification Algorithm
No shock
BNP ↓
Troponin ↓
Shock
BNP ↑
Troponin ↑
Echocardiography
No RV
dysfunction
Anticoagulation alone
Circulation 2003;108:2191-2194
RV dysfunction
Consider thrombolysis
or embolectomy
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Management
Primary therapy:
• Thrombolysis
• Open surgical
embolectomy
• Catheter-assisted
embolectomy
Secondary therapy:
• IV unfractionated
heparin
• Low-molecular weight
heparin (LMWH)
• Fondaparinux
• Warfarin
• IVC filter
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Management
• In patients with massive PE, primary therapy with
thrombolytics is considered a lifesaving intervention.
• Surgical or catheter-assisted embolectomy may be
considered for massive PE if thrombolysis is
contraindicated.
• For submassive PE, thrombolysis remains
controversial as no mortality benefit has been shown
in this patient population.
• However, MAPPET-3 demonstrated a reduction in
need for escalation of therapy in patients receiving
up-front t-PA (alteplase) for submassive PE.
• Normotensive patients with normal RV function are
considered low-risk and receive standard
anticoagulation.
J Thromb Thrombolysis 1995;2:227-229
N Engl J Med 2002;347:1143-1150
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Thrombolysis in PE: Pre-Lytics
*Following echo loops are courtesy of A. Kothavale
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Thrombolysis in PE: Post-Lytics
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Conclusions
• Pulmonary embolism is a common and
potentially life-threatening disorder.
• Echocardiography is insensitive in the
diagnosis of acute PE.
• In conjunction with cardiac biomarkers,
echocardiography plays a important role
in risk stratification of patient with PE.
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The End…
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