Pulmonary embolism - diagnosis and treatment

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 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 • Physicalexamination • ECG • Serumstudies - D - dimer, troponins, natriuretic peptide, arterial blood gases (Hypoxemie, hypocapnia, respiratoryalkalosis) • Chest X-Ray • Echocardiography • V/Q scan - Ventilation-PerfusionScans • 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) 91-99% • For D-dimer >500ng/mL, sens=93%, spec=25%, and positive predictive value (PPV) = 30%

18. D-dimer False Positive: • 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 intermediatecategory 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-invasivewithout iodinated contrast media Disadvantages:low availabilityhigh time demandoften not suitable for evaluation examination artifacts

37. Magnetic Resonance Angiography Emboli in segmental ansubsegmental 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 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 : • 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: • Activeorrecentinternalbleeding • Historyofhemorrhagicstroke • 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 SurgicalEmbolectomy • 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 1.5 - 2.5 times normal is a recommended form of initial treatment