1. Acute Pulmonary Embolism: Diagnosis and Management
Robert Sidlow, MD
November 8, 2010

2. 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 symptoms
2/3 of deaths due to pulmonary emboli occur within 30 minutes of embolization
Death due to massive PE is often immediate
Diagnosis can be difficult
Early treatment is highly effective
YOU WILL TAKE CARE OF PATIENTS WITH PE!

3. Pathology
At least 90% of pulmonary emboli originate from major leg veins.

6. Natural History of VTE
40-50% of pts with DVT develop PE, often “silent”
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)

7. Diagnosis: Clinical Presentation
Dyspnea, tachypnea, or pleuritic chest pain most common
Pleuritic pain = 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

9. Non-Specific!!

10. 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 :3338; /chest

11. Diagnosis: ECG Usually non-specific ST/T waves changes and tachycardia
RV strain patterns suggest severe PE
Inverted T waves V1-V4
QR in V1
Incomplete RBBB
S1Q3T3

12. S1Q3T3 and T wave changes

13. Diagnosis:Other tests
Most patients with PE have a normal pulse oximetry
A-a gradient is insensitive and non-specific

14. 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

15. Diagnosis-Probability Assessment
Implicit clinical judgement is fairly accurate: “Do you think this patient has a PE?”
Validated prediction rules standardize clinical judgement
Wells
Geneva

16. Proportion with PE
65% 30 10%

18. Diagnosis D-Dimer SnNOut Fibrin degradation product
ELISA tests are highly sensitive (>95%)
Non specific (~40%): cancer, sepsis, inflammation increase d-dimer levels
SnNOut
Negative result excludes PE safely in PE-unlikely patients (using Clinical probability scores)

19. 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.
BUT…
Dye load and large radiation dose
Optimally used when incorporated into a validated diagnostic decision tree

22. 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

23. Diagnosis- Summary History and physical examination
Then 1,2,3 approach:
Clinical decision score
D-Dimer test
Chest CT
3’. (V/Q scan remains a valid option for patients with contraindication to CT)

24. 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.

25. Congratulations! You’ve made the diagnosis.
What’s next?

26. 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?

27. RISK STRATIFICATION

28. Poor Prognostic Signs
Hypotension (not caused by arrhythmia, sepsis, or hypovolemia)
SBP <90 mm Hg = 53% 90-day all cause mortality
SBP drop of 40 mm Hg for at least 15 minutes = 15% in–hospital mortality
Syncope= bad
Shock= really bad

29. 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 2007;116:

30. Poor Prognosis: myocardial dysfunction
Brain natriuretic peptide
Elevated levels related to worse outcomes.
Low levels can identify patients with a good prognosis (NPV %)
Prognostic role of brain natriuretic peptide in acute pulmonary embolism. Circulation 2003;107:

31. CT evidence of RV dysfunction
RV dilation
RV/LV short axis >1= pulmonary hypertension
RV/LV short axis >1.5= severe PE
Leftward septal bowing

32. Graph of mean values of the RV/LV ratio relative to clinical outcome.
Figure 2. Graph of mean values of the RV/LV ratio relative to clinical outcome. Bars represent means and lines represent 95% confidence intervals. The mean RV/LV ratio was significantly higher in patients who died of PE than in the other patients (analysis of variance, P = .018). Brackets show significant differences between groups.
van der Meer R W et al. Radiology 2005;235:
©2005 by Radiological Society of North America

33. Transverse contrast-enhanced CT scan shows maximum minor axis measurements of the right ventricle (A) and left ventricle (B).
Figure 1. Transverse contrast-enhanced CT scan shows maximum minor axis measurements of the right ventricle (A) and left ventricle (B). Note the flattening of the interventricular septum. RV/LV ratio = 1.81.
van der Meer R W et al. Radiology 2005;235:
©2005 by Radiological Society of North America

37. Echocardiograms before and after Thrombolysis
Echocardiography-RV Dilation
Echocardiograms before and after Thrombolysis. A 29-year-old woman presented with progressive shortness of breath. A computed tomographic scan of the chest showed a central "saddle" pulmonary embolism. An echocardiogram (Panel A) showed an enlarged right ventricle and hypokinetic motion of the right ventricular free wall. After treatment with alteplase, the right ventricular size and wall motion returned to normal (Panel B). Echocardiograms courtesy of Scott D. Solomon, M.D., and Jose M. Rivero. (Videos of these images are available with the full text of this article at

38. RV dysfunction-Echocardiogram
Arch Intern Med. 2005;165:

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

40. Summary-Elements of PE Risk Stratification

42. High Risk PE

43. Approved thrombolytic regimens for pulmonary embolism
Streptokinase IU as a loading dose over 30 min, followed by 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)

45. Catheter Embolectomy & Fragmentation
An alternative in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed
Kucher N Chest 2007;132:

46. Optimal rx?

47. 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.

48. Heparin plus Alteplase Compared with Heparin Alone in Patients with Submassive Pulmonary Embolism
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:
October 10, 2002

49. In-Hospital Clinical Events
Konstantinides, S. et al. N Engl J Med 2002;347:

50. Conclusions:
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.

51. The PEITHO (Pulmonary EmbolIsm THrOmbolysis) Trial
Est. completion date November 2012

52. 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 effects.

53. ESC Guidelines: Non-High Risk PE
Anticoagulation should be initiated without delay in patients with high or intermediate clinical probability of PE while diagnostic workup is still ongoing
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 treatment
Guidelines on the diagnosis and management of acute pulmonary embolism
European Heart Journal (2008) 29, 2276–2315

54. 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

55. Treatment of Acute Pulmonary Embolism
First unprovoked PE:
rx for at least 3-6 months
Recurrent PE or PE and uncured cancer:
Consider long term anticoagulation if benefits>risk
Agnelli G, Becattini C. N Engl J Med 2010;363:

56. 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 administration>risks.
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.

57. 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 thrombosis
Optimal duration of retrievable filters is unclear

59. Bard Recovery vena cava filter (Bard Peripheral Vascular, Tempe, Arizona) implanted in patient 2
Nicholson, W. et al. Arch Intern Med 2010;0:
Copyright restrictions may apply.

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

61. Q&A