1. Pulmonary embolism - diagnosis and treatment
Radka Adlová

2. Definition
Penetration of material into branches of the pulmonary artery
a situation mostly when venous emboli becomes dislodged from their site of origin and they embolize to the pulmonary arterial circulation

3. Epidemiology
- Third most common acute cardiovascular disease after coronary ischemia and stroke
- 90% of pulmonary emboli originate in the deep venous system of the lower extremities
- Other locations include:
uterine and prostatic veins
upper extremities
renal veins
right side of the heart

4. Introduction
PE is the most common preventable cause of death in hospitalized patients
Pts. are Male>Female, old > young
80% of pulmonary emboli occur without prior warning signs or symptoms
75% 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

5. Risk factors inherited acquired Virchow’s Triad:
- Rudolf Virchow postulated more than a century ago that a triad of factors predisposed to venous thrombosis:
Local trauma of the vessel wall
Hypercoagulability
Stasis of blood flow
inherited
acquired

6. Risk factors Previous or current DVT
Venous Stasis - Immobilization - Stroke/paralysis,…
Surgery requiring > 30 minutes within last 3 months
Age > 70
Obesity
Malignancy, autoimmune diseases
Air travel
Coagulopathy - Factor V Leiden mutation , Protein C deficiency ,
Protein S deficiency , Antithrombin deficiency ,Prothrombin gene mutation A20210 ,
Anticardiolipin antibodies , Lupus anticoagulant
In Women - pregnancy, smoking

7. Clinical presentation
Most common symptoms:
dyspnoea
tachypnoea
chest pain (RV ischemia)
pleuritic pain (pleural irritation)
syncope (indicates severely reduced
hemodynamic reserve)

8. Clinical presentation

9. How do we make a diagnosis?
History
Physical examination
ECG
Serum studies - D - dimer, troponins, natriuretic peptide, arterial blood gases (Hypoxemie, hypocapnia, respiratory alkalosis)
Chest X-Ray
Echocardiography
V/Q scan - Ventilation-Perfusion Scans
CT angiography
Pulmonary Angiography
MRI angiography

10. Chest X-Ray
Usually abnormal, only a small portion of patients with PE have a normal Chest X-Ray
Not a sensitive or specific test for the diagnosis of PE
Findings:
Cardiac enlargement (27%)
Normal (24%)
Pleural effusion (23%)
Elevated hemidiaphragm (20%)
Pulmonary artery enlargement (19%)
Atelectasis (18%)
Parenchymal pulmonary infiltrates (17%)

11. Radiographic Signs - Westermark Sign
disappearance of vascularity (oligemia) on the affected side

12. Radiographic Signs - Hamptons Hump
pleuraly based opacification

13. Atelectasis
collapse of segment of a lung lobe

14. Prominent PA

15. ECG
most commonly sinus tachycardia, with possible nonspecific ST/T wave changes
RV strain patterns suggest severe PE:
Inverted T waves V1-V4
QR in V1
Incomplete RBBB
S1Q3T3 - only 10% of patients
Other ECG abnormalities including atrial arrhythmias, right bundle branch block, inferior Q-waves, and precordial T-wave inversion and ST-segment changes

16. S1Q3T3 and T wave changes

17. D-dimer Fibrin degradation product
ELISA tests are highly sensitive (>95%)
Non specific (~40%): cancer, sepsis, inflammation increase D-dimer levels
Negative result excludes PE safely
For D-dimer <500ng/mL - negative predictive value (NPV) %
For D-dimer >500ng/mL, sens = 93%,
spec = 25%, and positive predictive value
(PPV) = 30%

18. D-dimer False Positive: False Negative: Pregnancy Trauma
Postoperative Recovery
Inflammation
Cancer
Rheumatoid Factor
Older Age
False Negative:
Heparin

19. Echocardiography
Useful for rapid triage of pts, sensitive indicator of massive or unstable PE
should be done on any patient with suspected massive or unstable PE
also useful for selecting patients for thrombolysis or other aggressive therapy
may be used for chronic monitoring durint treatment
to exclude other diagnosis (dif. Dg.)

20. Echocardiography Findings: Right ventricle - dilated hypokinetic
Abnormal septal motion - distortion of the interventricular septum in diastole
Thrombus - right-heart, main pulmonary arteries
Tricuspid regurgitation associated with increase in systolic pressure in pulmonary artery

21. Echocardiography Dilated RV and RA, distortion of
the interventricular septum

22. Echocardiography
Dilated RV

23. Echocardiography Tricuspid regurgitation
Increase in systolic pressure in pulmonary artery

24. Echocardiography - clot in RA and RV

25. Ventilation - Perfusion Scans
Historically, the principal imaging test for the
diagnosis of PE
A perfusion defect indicates absent or decreased blood flow
Ventilation scan obtained with radiolabeled gases
A high probability scan is defined as two or more segmental perfusion defects in presence of normal ventilation scan

26. Ventilation - Perfusion Scans
Useful if normal (negative predictive value of 97%)
Also useful if high probability (positive predictive value of 85 to 90%)
Unfortunately, only diagnostic in 30 to 50% of patients (normal V/Q scan and high probability V/Q scans are helpful in ruling out, but intermediate category required additional testing)

27. High Probability V/Q Scan

28. CT Angiography Direct visualization of emboli
Advantage: both parenchymal and mediastinal structures can be evaluated - an ability to detect alternative pulmonary abnormalities that may explain the patient's symptoms and signs
Studies have shown sensitivity to 95% with an experienced observer
Disadvantage: radiation dose

29. CT Angiography

30. CT - infarction

31. CT - pre and postlytic therapy
thrombus in the pulmonary artery branch

32. CT

33. RV/LV

34. Pulmonary Angiography
This had been the “gold standard” for diagnosis but it is highly invasive
Positive result is a filling defect in a pulmonary artery branch - can detect emboli as small as 1-2 mm
A negative pulmonary angiogram excludes clinically relevant PE - the risk of embolization in patients with a negative angiogram is extremely low 
The pulmonary catheter may also be used therapeutically

35. Pulmonary Angiography

36. Magnetic Resonance Angiography
Estimated sensitivity ~80% (~100% for larger emboli), specificity 95%
Dynamic gadolinium enhancement is used, allowing high quality images
Advantages: no radiation
non-invasive without iodinated contrast media
Disadvantages: low availability high time demand often not suitable for evaluation examination artifacts

37. Magnetic Resonance Angiography
Emboli in segmental an subsegmental arteries

38. Magnetic Resonance Angiography vs. CT angiography

39. Diagnostic Algorithm

40. Case report
A 63-year-old woman with stage IV lymphoma has acute shortness of breath
History - she is also taking hormone replacement therapy
On the day of admission - she develops a sudden shortenss of breath and pleuritic chest pain
Physical examination - her pulse is 115 bpm, respiratory rate = 36/min, O2 sat = 88% , her lungs are clear, and her extremities are normal
A chest x-ray shows mild right-sided atelectasis,
An ABG shows hypoxemie, hypocapnia, respiratory alkalosis
What is this patient’s pretest probability for having a pulmonary embolism?
What diagnostic method would you use to confirm this?

41. Treatment Pain Relief Oxygen
Dobutamine - pts with right heart failure and cardiogenic shock
Anticoagulant therapy :
- unfractioned heparin
- LMWH
- Thrombolysis
Embolectomy

42. Therapy RISK STRATIFICATION
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?
RISK STRATIFICATION

43. Risk stratification Poor Prognostic Signs:
Hypotension (SBP <90 mm Hg )
Syncope
Shock
Troponin levels - correlate with in-hospital mortality and clinical course in PE (Significantly increased mortality in patients with troponin level >0.1 ng/ml)
Brain natriuretic peptide (elevated levels related to worse outcomes)
RV dilation ( RV/LV short axis >1.5)

45. Treatment - unstable patient
Thrombolysis
rtPA (recombinant tissue plasminogen activator - alteplase)
100 mg over 2 h or 0.6 mg/kg over 15 min (maximum dose 50 mg)
1. Hemodynamically compromised by PE
2. Pulmonary hypertension or right ventricular
dysfunction detected by echocardiography,
pulmonary arterial catheterization
Embolectomy
Reserved for pts at high risk for death and those at
risk for recurrent PE despite adequate
anticoagulation, contraindication for thrombolytics

46. Trombolytic therapy Indications : Absolute Contraindications:
Hemodynamic instability
RV dysfunction (by echocardiogram) - RV dilatation,
abnormal septal motion
Anatomically large PE - multiple segments on V/Q Scan or angiogram
Extensive DVT - controversial use (probably decreases post-thrombotic syndrome)
Absolute Contraindications:
Active or recent internal bleeding
History of hemorrhagic stroke
Intracranial neoplasm
Recent cranial surgery or head trauma

47. Catheter Embolectomy & Fragmentation
An alternative in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed

48. Treatment Surgical Embolectomy
Surgical embolectomy (thrombectomy) only in very selective cases
Perioperative morality is 25-50%
Massive pulmonary embolism where thrombolysis contraindicated
Chronic thromboembolic pulmonary hypertension

49. Therapy
Intermediate Risk PE - Hemodynamic stability yet with evidence of RV dysfunction/injury:
Controversial
No clinical trial or meta-analysis has been large enough to demonstrate a mortality benefit of thrombolysis compared to anticoagulation alone.
The decision to use thrombolytic therapy in the intermediate risk PE group should be made on a case-by-case basis after carefully thinking the strength of the indication, the potential benefits, the contraindications, and potential adverse effects.

50. Therapy 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 is the recommended for of initial
treatment for most patients with non-high-risk PE
In patients at high risk of bleeding and in those with
severe renal dysfunction, unfractionated heparin with
an aPTT target range of times normal is a
recommended form of initial treatment

51. Therapy Non-High Risk PE:
Initial treatment with unfractionated heparin,
or LMWH 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
Duration of Anticoagulation
Dependent upon the clinical situation
Cancer, and Obesity most likely will need indefinite treatment
For other pts with isolated calf vein thrombosis (3 months), proximal leg DVT (6 months) and PE (1 year)

52. Prevention
Heparin       
LMW heparin appears to be more effective for prophylaxis
than standard heparin
Variety of low dose heparins and heparinoids have been
used
Enoxaparin or Dalteparin (sc qd)
Low dose (INR ~1.5X control) warfarin may also be effective       
Compression stockings should be used in ALL patients unless contraindicated

53. Prevention IVC Filters implantation:
- usually "Bird's Nest Filter" is placed in IVC
- May provide lifelong protection against PE
Use:
pts. with absolute contraindications to anticoagulation and a high risk of VTE recurrence
pts. for patients with recurrent PE on anti-coagulation
in pregnant women with extensive thrombosis

54. Prevention Optimal duration of retrievable filters is unclear
IVC Filters:
Optimal duration of retrievable filters is unclear
Generally an accepted therapy and safe to implant

55. Conclusion
The clinical presentation of acute pulmonary embolism is variable and nonspecific
PE is often a misdiagnosed clinical disorder
The major diagnostic tests employed in the evaluation of a patient with suspected PE include
D-dimer testing, CTPA, V/Q scanning, venous ultrasonography and clinical assessment
Rapid identification and appropriate treatment may often prevent unnecessary morbidity and mortality

56. Thank you for your attention