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Acute Pulmonary

Diagnosis and

Robert Sidlow, MD

November 8, 2010
Why care?
 PE is the most common
preventable cause of death in
hospitalized patients
 ~600,000 deaths/year
 80% of pulmonary emboli occur
without prior warning signs or
 2/3 of deaths due to pulmonary
emboli occur within 30 minutes of
 Death due to massive PE is often
 Diagnosis can be difficult
 Early treatment is highly effective

At least 90% of pulmonary
emboli originate from major leg
Natural History of VTE
 40-50% of pts with DVT develop PE, often
 PE presents 3-7 days after DVT
 Fatal within 1 hour after onset of respiratory
symptoms in 10%
 Shock/persistent hypotension in 5-10% (up to 50% of
patients with RV dysfunction)
 Most fatalities occur in untreated pts
 Perfusion defects completely resolve in 75% of
all patients (who survive)
Diagnosis: Clinical Presentation
 Dyspnea, tachypnea, or pleuritic chest pain most
 Pleuriticpain = distal emboli pulmonary infarction
and pleural irritation
 Isolated dyspnea of rapid onset= central PE with
hemodynamic sequlea
 Retrosternal angina like sxs= RV ischemia
 Syncope=rare presentation, but indicates
severely reduced hemodynamic reserve
 Sxs can develop over weeks
 In pts with pre-existing CHF or COPD,
worsening dyspnea may indicate PE
Diagnosis: Chest X-Ray
 Usually abnormal, but non-specific
 Study of 2,322 patients with PE:
 Cardiac enlargement (27%)
 Normal (24%)
 Pleural effusion (23%)
 Elevated hemidiaphragm (20%)
 Pulmonary artery enlargement (19%)
 Atelectasis (18%)
 Parenchymal pulmonary infiltrates (17%)

Chest Radiographs in Acute Pulmonary Embolism: Results From the International Cooperative
Pulmonary Embolism Registry. Chest July 2000 118:3338; 10.1378/chest.118.1.33
Diagnosis: ECG
 Usually non-specific ST/T waves changes
and tachycardia
 RV strain patterns suggest severe PE
 InvertedT waves V1-V4
 QR in V1
 Incomplete RBBB
 S1Q3T3
S1Q3T3 and T wave changes
Diagnosis:Other tests
 Most patients with PE have a normal pulse
 A-a gradient is insensitive and non-specific
Clinical Diagnosis of PE
 In summary, clinical signs, symptoms and
routine tests do not allow for the exclusion
or confirmation of acute PE but may
increase the index of its suspicion
 Consider PE in cases of unexplained
tachycardia or syncope
Diagnosis-Probability Assessment

 Implicit clinical judgement is fairly
accurate: “Do you think this patient has a
 Validated prediction rules standardize
clinical judgement
 Wells
 Geneva
Proportion with PE
 D-Dimer
 Fibrindegradation product
 ELISA tests are highly sensitive (>95%)
 Non specific (~40%): cancer, sepsis,
inflammation increase d-dimer levels
 SnNOut
 Negativeresult excludes PE safely in PE-
unlikely patients (using Clinical probability
Spiral CT
• Direct visualization of emboli.
• Both parenchymal and mediastinal
structures can be evaluated.
• Offers differential diagnosis in 2/3 of cases
with a negative scan.
•Dye load and large radiation dose
•Optimally used when incorporated into a
validated diagnostic decision tree
3 month
VTE rate 0.5% (all non fatal) 1.3%

This algorithm allowed for a management decision in 98% of
patients presenting with symptoms suggestive of PE
Diagnosis- Summary
 History and physical examination
 Then 1,2,3 approach:
1. Clinical decision score
2. D-Dimer test
3. Chest CT
3’. (V/Q scan remains a valid option for patients
with contraindication to CT)
Clinical Management
After disembarking from a 10 hour airline
flight, a 69 year old man w/o past medical
hx presents to the ER with acute dyspnea.
BP is 120/80 (baseline) and pulse is 120
BPM. Wells score = 5 (intermediate), D-
Dimer is positive.
Spiral CT shows bilateral pulmonary emboli
in >50% of arterial tree.
Congratulations! You’ve made the

What’s next?
Question: For the hemodynamically stable
patient, how can we differentiate between
patients who are going to do well with
anticoagulation alone versus those with
worse prognosis who might benefit from
more aggressive therapy?
Poor Prognostic Signs
 Hypotension (not caused by arrhythmia,
sepsis, or hypovolemia)
 SBP <90 mm Hg = 53% 90-day all cause
 SBP drop of 40 mm Hg for at least 15 minutes
= 15% in–hospital mortality
 Syncope= bad
 Shock= really bad
Poor Prognosis: myocardial injury

 Troponin levels correlate with in-hospital
mortality and clinical course in PE
 Troponins do not necessarily mean “MI”
 Significantly increased mortality in patients with
troponin level >0.1 ng/ml (O.R.= 6)
 Normal troponin has very high NPV (99-100%)
Prognostic value of troponins in acute pulmonary embolism: a meta analysis. Circulation
Poor Prognosis: myocardial
 Brain natriuretic peptide
 Elevated levels related to worse outcomes.
 Low levels can identify patients with a good
prognosis (NPV 94-100%)

Prognostic role of brain natriuretic peptide in acute pulmonary embolism.
Circulation 2003;107:2545-2547
CT evidence of RV dysfunction
 RV dilation
 RV/LV short axis >1= pulmonary
 RV/LV short axis >1.5= severe PE
 Leftward septal bowing
Graph of mean values of the RV/LV ratio relative to clinical outcome.

van der Meer R W et al. Radiology 2005;235:798-803

©2005 by Radiological Society of North America
Transverse contrast-enhanced CT scan shows maximum minor axis measurements of the
right ventricle (A) and left ventricle (B).

van der Meer R W et al. Radiology 2005;235:798-803

©2005 by Radiological Society of North America
Echocardiograms before and after Thrombolysis
Echocardiography-RV Dilation
RV dysfunction-Echocardiogram

Arch Intern Med. 2005;165:1777-1781
RV Dysfunction- Echocardiogram

Arch Intern Med. 2005;165:1777-1781
Summary-Elements of PE Risk Stratification
High Risk PE
Approved thrombolytic regimens for
pulmonary embolism

 Streptokinase 250 000 IU as a loading dose
over 30 min, followed by 100 000 IU/h over 12–
24 h
 Accelerated regimen: 1.5 million IU over 2 h
 Urokinase 4400 IU/kg as a loading dose over 10
min, followed by 4400 IU/kg/h over 12–24 h
 Accelerated regimen: 3 million IU over 2 h
 rtPA 100 mg over 2 h or 0.6 mg/kg over 15 min
(maximum dose 50 mg)
Catheter Embolectomy & Fragmentation

An alternative in high-risk PE patients when thrombolysis
is absolutely contraindicated or has failed

Kucher N Chest 2007;132:657-663
Optimal rx?
Intermediate Risk PE:
Hemodynamic stability yet with
evidence of RV dysfunction/injury
 Controversial! Evidence is limited
regarding optimal therapy
 No clinical trial or meta-analysis has been
large enough to demonstrate a mortality
benefit of thrombolysis compared to
anticoagulation alone.
Heparin plus Alteplase Compared with Heparin
Alone in Patients with Submassive Pulmonary
Stavros Konstantinides, M.D., Annette Geibel, M.D., Gerhard Heusel, Ph.D., Fritz
Heinrich, M.D., Wolfgang Kasper, M.D. and the Management Strategies and Prognosis
of Pulmonary Embolism-3 Trial Investigators

N Engl J Med
Volume 347;15:1143-1150
October 10, 2002
In-Hospital Clinical Events

Konstantinides, S. et al. N Engl J Med 2002;347:1143-1150
 A combination of alteplase (100 mg given
over a two-hour period) and heparin
prevented the need for escalation of
treatment (with open-label alteplase,
catecholamine infusion, or mechanical
ventilation) due to clinical deterioration
more often than a combination of placebo
and heparin. Clinical deterioration usually
meant worsening symptoms, especially
worsening respiratory failure.
The PEITHO (Pulmonary EmbolIsm THrOmbolysis) Trial
Est. completion
date November
Bottom line
 The decision to use thrombolytic therapy
in the intermediate risk PE group should
be made on a case-by-case basis after
carefully weighing the strength of the
indication, the potential benefits, the
contraindications, and potential adverse
ESC Guidelines: Non-High Risk PE
1. Anticoagulation should be initiated without delay
in patients with high or intermediate clinical
probability of PE while diagnostic workup is still
2. Use of LMWH or fondaparinux is the
recommended form of initial treatment for most
patients with non-high-risk PE
3. In patients at high risk of bleeding and in those
with severe renal dysfunction, unfractionated
heparin with an aPTT target range of 1.5–2.5
times normal is a recommended form of initial
Guidelines on the diagnosis and management of acute pulmonary embolism
European Heart Journal (2008) 29, 2276–2315
Non-High Risk PE
4. Initial treatment with unfractionated
heparin, LMWH or fondaparinux should be
continued for at least 5 days and may be
replaced by vitamin K antagonists only
after achieving target INR levels for at
least 2 consecutive days
5. Routine use of thrombolysis in non–high-
risk PE patients is not (yet) recommended,
but it may be considered in selected
patients with intermediate-risk PE (RV
dysfunction, elevated troponin, BNP) and
low bleeding risk
Guidelines on the diagnosis and management of acute pulmonary embolism
European Heart Journal (2008) 29, 2276–2315
Treatment of Acute Pulmonary Embolism

First unprovoked PE: Recurrent PE
or PE and uncured
rx for at least 3-6
months Consider long term
anticoagulation if

Agnelli G, Becattini C. N Engl J Med 2010;363:266-274
Case revisited
 A 69 year old man presents to the ER with acute dyspnea. BP is 120/80
(baseline) and pulse is 120 BPM. Wells score = 5 (intermediate), D-Dimer
is positive.
 Spiral CT shows bilateral pulmonary emboli in >50% of arterial tree.
 Troponin 0.3 ng/ml
 Echocardiogram showed RV enlargement with septal bowing into LV. RV
function nl.
 BP remained at baseline 130/80, persistent tachycardia 120 BPM.
 Risk of 30-day mortality estimated to be ~10%.
 Given the intermediate risk PE profile and lack of contraindications, after
discussion with the patient it was decided that the benefits of t-Pa
 Pt was admitted to the CCU and 100 mg t-Pa infused over 2 hours; dyspnea
resolved over the course of the afternoon.
 Pt discharged to complete 6 months of warfarin, target INR 2.5. Pt referred
to PMD for regular screening colonoscopy.
 On f/u pt had no evidence of pulmonary htn or post thrombotic syndrome.
IVC Filters
•May provide lifelong protection against PE
•Unclear effect on overall survival
• Complications:
•DVT (20%)
•Post thrombotic syndrome (40%)
•IVC thrombosis (30%)
•Risk/benefit ratio difficult to determine since no RCT
•Use when there are absolute contraindications to
anticoagulation and a high risk of VTE recurrence
•Consider in pregnant women with extensive
•Optimal duration of retrievable filters is unclear
Bard Recovery vena cava filter (Bard Peripheral Vascular, Tempe, Arizona) implanted in patient 2

Nicholson, W. et al. Arch Intern Med 2010;0:2010.316-5.

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The key is prevention
 DVT prophylaxis in at-risk patients is quite
 Just do it!