1. Echocardiography in Pulmonary Embolism
Gregory Piazza, M.D.
Beth Israel Deaconess Medical Center
January 26, 2005
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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.
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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.
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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.
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Pathophysiology
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:
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Pathophysiology
↑ PA pressure
↑ RV afterload
↑ RV wall tension
↑ RV O2 demand
RV dilatation and dysfunction
RV ischemia +/- infarction
↓ RV O2 supply
↓ coronary perfusion
Hypotension
↓ RV cardiac output
Septal shift toward the LV
↓ LV preload
↓ LV cardiac output
Pulmonary embolism
RV plays a central role
Am Heart J 1995;130:
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Spectrum of Disease
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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10. Diagnosis: History and Physical
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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11. 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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12. Diagnosis: An Integrated Approach
History and Physical
Eval. clinical likelihood
Electrocardiogram
Chest radiograph
Patient already in hospital
Patient in ED
D-dimer
High
Normal
Chest CT
V/Q if dye allergy or renal insufficiency
Positive
Equivocal
Ultrasonography
Negative
No PE
Treat for PE
Consider PA-gram
No where does echo appear
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13. 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.
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Am J Med 2001;110:
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14. Diagnosis: Transthoracic Echocardiography
Apical 4- chamber Parasternal short-axis Parasternal long-axis
Main views for the RV
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15. 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
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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.
Often times, readers call RV dil if RV > LV but it is more exact than this
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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.
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Am J Cardiol 1996;78:
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RV Hypokinesis
The RV free-wall endocardium was traced in the apical 4-chamber view from base to apex at end-systole 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%.
Am J Cardiol 1996;78:
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RV Hypokinesis
Courtesy of A. Rosen
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20. 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 so-called D-shaped LV.
Diastole
Systole
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21. Interventricular septal flattening and paradoxical motion
Normal (diastole) Acute PE (diastole)
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22. 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
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23. Alteration of Transmitral Gradients
Courtesy of A. Rosen
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24. Tricuspid Regurgitation
RV pressure overload frequently results in tricuspid regurgitation detected on color flow and Doppler. RV RA LA
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Cove/2045/echo55.htm
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25. 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
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26. Thrombus In The Right Main PA
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27. 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).
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28. Diagnosis: Transesophageal Echocardiography
Long-axis transesophageal Short-axis transgastric Oblique transgastric
Main views for the RV
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29. Diagnosis: Transesophageal Echocardiography
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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.
This case is meant to illustrate that not all patients with PE are equal. There are clearly subgroups of patients at higher risk for adverse events. This realization has led to greater interest in risk stratification.
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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.
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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 low-risk PE patients with negative predictive values for in-hospital 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.
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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
cTnT
Elecsys (Roche)
0.04 ng/ml 37 97 12
Giannitsis et al20 56
TropT (Roche)
0.10 ng/ml 32 44
Janata et al21
0.09 ng/ml 11 99 34
Pruszczyk et al23 64
0.01 ng/ml 50
100 25
ten Wolde et al27
110
BNP
Shionoria (CIS Bio)
21.7 pmol/L 33 17
Kucher et al26 73
Pro-BNP
500 pg/ml 58
Kucher et al25
Triage (Biosite)
50 pg/ml
Pruszczyk et al22 79
pg/ml* 66 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.
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37. Myofibril degradation ↑ Natriuretic peptide mRNA
Cardiac Biomarkers
↑ RV pressure
↑ PVR
RV micro-infarction
↑ 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.
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Chest CT Scan
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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 > in the apical 4-chamber view
2. RV end-diastolic diameter > 30 mm
3. Paradoxical interventricular septal systolic motion
Ann Intern Med 2002;136:
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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 in-hospital 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:
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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:
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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:
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44. Risk Stratification Algorithm
No shock
Shock
BNP ↓
Troponin ↓
BNP ↑
Troponin ↑
RV dysfunction
No RV dysfunction
Anticoagulation alone
Consider thrombolysis or embolectomy
Echocardiography
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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.
Define massive and submassive PE
J Thromb Thrombolysis 1995;2:
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47. Thrombolysis in PE: Pre-Lytics
*Following echo loops are courtesy of A. Kothavale
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52. 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…
Thanks For Listening...
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