Pulmonary embolism

Physician should have a high suspicion to diagnose patient with pulmonary Embolism, this slides will give you precise Diagnosis, Investigation and guideline directed Treatment.

1. Pulmonary Embolism Dr. Rohan Sonawane MBBS, MD, DNB ( Interventional Cardiology reg)

2. Introduction Definition & Sources Risk factors & aetiology Pathogenesis Clinical presentation Differential Diagnosis Investigations Management Complications Prevention

3. It is the third most common cardiovascular disease after MI and stroke. Annual incidence of 100-200 per 1 lac population. It is the only preventable lethal disease.

4. Pulmonary Embolism Thrombus dislodges (DVT) and travels to pulmonary arteries causing occlusion of a pulmonary artery( ies ) . Provoked PE : PE in patients with recent occurrence of major clinical risk factor for VTE. Like recent Sx , trauma, OCP. Proximal DVT : DVT in popliteal vein or above (40%) Unprovoked PE : PE in patients with no recently occurring major clinical risk factors for VTE or patients with active cancer, thrombophilia or family history of DVT (these are risks, but they are constant)

5. Source DVT Intracardiac Clot Air embolism Fat embolism Amniotic fluid embolism Septic embolism Tumor embolism

6. Risk Factors Virchow’s Triad

7. Risk Factors Prior DVT or PE Congestive Heart Failure Malignancy Obesity smoking Estrogen, OCP, HRT Pregnancy Lower limbs injury Orthopedic Surgery Prolonged immobilization, travel Surgery requiring > 30 minutes general anesthesia

8. Risk Factors Age > 40 Venous Stasis Factor V Leiden mutation Protein C deficiency Protein S deficiency Antithrombin deficiency Anticardiolipin antibodies SLE, APS Hyperhomocystinemia

9. Risk Factors ICU-related factors: Immobility Neuromuscular paralysis (drug-induced) Central venous catheters Severe sepsis

10. Pathogenesis

11. Clinical Presentation Small PE : Asymptomatic, SOB, chest discomfort. Medium PE : SOB, Haemoptysis, Pleuritic chest pain, Tachycardia, Tachypnea, Pleural rub. Massive PE : Death, Shock, Severe central chest pain, Syncope, Pallor, Sweating, Central cyanosis, Elevated JVP, Loud P2, S2 split, gallop rhythm. 1

12. Clinical Prediction Score Clinical decision points Wells rule Original version 1 Simplified version 2 Previous PE or DVT 1.5 1 Heart Rate ≥ 100 bpm 1.5 1 Sx or immobilisation within past 4 weeks 1.5 1 Hemoptysis 1 1 Active Cancer 1 1 Clinical Sign of DVT 3 1 Alternative Δ less likely 3 1 Clinical probability PE unlikely 0-4 0-1 PE likely > 5 ≥2 Wells PS et al. Thromb Haemost 2000;83(3):416–420. Gibson NS, Wells PS et al. Thromb Haemost 2008;99(1):229–234.

13. Clinical Prediction Score Clinical decision points Revised Geneva Score Original version 1 Simplified version 2 Previous PE or DVT 3 1 Heart rate 75-94 bpm ≥95 bpm 3 5 1 2 Surgery or Fracture within past month 2 1 Hemoptysis 2 1 Active Cancer 2 1 Unilateral lower limb pain 3 1 Pain on deep veinous palpation/ unilateral edema 4 1 Age ≥ 65 years 1 1 Clinical probability PE unlikely 0-5 0-2 PE likely ≥6 ≥3 1. Le Gal G et al. Ann Intern Med 2006;144(3):165–171. 2. Klok FA et al. Arch Intern Med 2008;168(19):2131–2136 .

14. Differential Diagnosis Myocardial Infraction Pleurisy Pneumonia Bronchitis Pneumothorax Costochondritis Rib #

15. Investigations D-dimer ECG Chest X-ray Echocardiography Ventillation Perfusion Scan CT Pulmonary Angiography Invasive Pulmonary Angiography

16. D-dimer Levels elevate in acute thrombosis High negative predictive value and low positive predictive value False positive in many conditions like in cancer & pregnancy Specificity decreases with age (almost 10% in patients > 80years) Age adjusted cut offs used after 50 years i.e. (age x 10 ug /L) For < 50 years, cut off is 500 ug /L

17. ECG In severe cases RV strain, like inversion of T waves in leads V1–V4, a QR pattern in V1 S1Q3T3 pattern 2) Incomplete or complete RBBB In milder cases Only anomaly may be sinus tachycardia - 40% Atrial arrhythmias, most frequently atrial fibrillation may be seen

18. E C G

19. Westermark’s sign Focal olegemia

20. Dilated RDPA Palla’s Sign

21. 2D Echo Echo doesnot provide conclusive evidence of PE. Sensitivity is only 65% But is available bedside and cheap. Rules out other causes like MI, Tamponade

22. IVC is dilated without any inspiratory collapse

23. Ventilation/Perfusion Ratio Increases specificity In acute PE, ventilation is expected to be normal in hypoperfused segments Radiation exposure lower than CT angiography Radiation and contrast medium-sparing procedure So can be done in : Outpatients with low clinical probability In young (particularly female) patients, In pregnancy History of contrast medium-induced anaphylaxis In severe renal failure Results are interpreted as low, intermediate or high probability of PE

24. Ventilation/Perfusion Ratio

25. CT Pulmonary Angiography Method of choice for imaging patients with suspected PE Highly sensitive and specific Cannot interpret subsegmental thrombus Radiation and Iodine contrast are major drawbacks Can’t be used in renal failure patients.

26. CT Pulmonary Angiography

27. The PIOPED II trial observed a sensitivity of 83% and a specificity of 96% for MDCT Negative Predictive Value low clinical probability of PE - 96% intermediate clinical probability - 89% high pre-test probability - 60% Positive Predictive Value Low clinical probability of PE – 58% Intermediate clinical probability – 92% High clinical probability- 96% PIOPED ll trail (Prospective Investigation on Pulmonary Embolism Diagnosis)

28. Pulmonary Angiography Was Gold Standard for decades Replaced now by CT pulmonary angiography Often used to guide percutaneous catheter-directed treatment of acute PE Procedure-related mortality 0.5%, major non-fatal complications 1%

29. Pulmonary Angiography

30. Management of PE

31. Risk Stratification

32. Diagnostic algorithm for Non high-risk PE [2014 ESC Guidelines. European Heart Journal (2014) 35, 3033–3080 ]

33. Diagnostic algorithm for High-risk PE [2014 ESC Guidelines. European Heart Journal (2014) 35, 3033–3080 ]

34. Pulmonary Embolism Severity Index

35. Original PESI Simplified PESI

36. Intermediate risk PE Hemodynamically stable with evidence of myocardial injury and RV dysfunction with high PESI They have high 30 day mortality Early reperfusion is required in them

37. Thrombolytic Therapy Primary reperfusion PE with hemodynamic instability use in stable pt is contaversial . Initiated within 48 hrs of symptoms can be extend upto 6-14 days of symptoms. Aim to : Relieve pulmonary vasculature obstruction, Improve right ventricular efficacy, Correct the hemodynamic instability. Risk: Bleeding

38. Thrombolytic Agents

39. Anticoagulation Therapy Pt with PE should receive at least 3 months of Anticoagulation treatment. Pt with cancer are candidate for indefinite treatment due to high recurrence rate (20% after 12 months of index event) Parentral anticoagulation should be started immediately with thrombolysis in high/ intermediate high risk pt. In Low risk/ intermediate low risk PE pt oral anti-coagulation (VKA/NOAC) to be started immediately VKA should be started under cover of UFH/LMWH till INR 2-3 for two consecutive day. Maintain INR 2-3 Risk of bleeding: old age, GI bleed, Renal and hepatic disease etc.

40. Parenteral Anticoagulant Therapy Unfractionated Heparin Used for primary reperfusion Bolus dose about 100 U / kg body weight Maintenance Dose 12U / kg iv infusion Follow up by a PTT (1.5-2. ) Preferred in creatinine clearance < 30ml/kg/min 20 / 01 / 2016

41. LMWH Preferred over UFH Low risk of bleeding No need for monitoring

42. LMWH

43. Oral Anticoagulant Therapy Warfarin 3-5 mg/day o rally with LMWH (5 days to start acting) Duration: 3-6 months Monitor INR (2-3)

44. New Oral Anticoagulants Drug Dose Rivaroxaban (EINSTEIN-DVT 2010 /PE 2012 ) 15mg BD x 3weeks then 20mg OD Dabigatran (RE-COVER 2009 / RE- COVER ll 2014 ) 150mg twice a day (110 bd for elderly) Apixaban (AMPLIFY 2013 ) 10mg BD x 7 days then 5mg BD

45. Vena cava filter 1 3

46. IVC filter use is restricted to Contraindication to anti-coagulation Recurrent PE despite adequate anticoagulation Retrievable IVC filters should be implanted and removed within 3 months if possible. Routinely placing filters maybe harmful

47. Embolectomy Surgical Embolectomy Catheter Embolectomy Massive life-threatening PE

48. Prevention Prophylaxis is the single most important measure for ensuring patient safety in hospitalized patients

49. RISK FACTOR SCORING Cancer 3 Previous VTE 3 Immobility 3 Thrombophilia 3 Trauma/surgery 2 Age ≥ 70 years 1 Heart/respiratory failure 1 Acute MI or stroke 1 Infection/rheumatologic disorder 1 Obesity 1 Hormonal treatment 1 Padua Prediction Score for Identification of Hospitalized Patients at Risk for Venous Thromboembolism High risk for developing PE is defined as 4 score points or greater.

50. Condition Prophylaxis Hospitalization with medical illness -Unfractionated heparin 5000 units SC bid or tid or -- Enoxaparin 40 mg SC qd or - Dalteparin 2500 units or 5000 units SC qd or - Fondaparinux 2.5 mg SC qd with normal renal function (in patients with a heparin allergy such as heparin-induced thrombocytopenia) or - Graduated compression stockings or intermittent pneumatic compression for patients with contraindications to anticoagulation -Consider combination pharmacologic and mechanical prophylaxis for high-risk patients General surgery -Unfractionated heparin 5000 units SC bid or tid or - Enoxaparin 40 mg SC qd or - Dalteparin 2500 or 5000 units SC qd Major orthopedic surgery -Warfarin (target INR 2 to 3) or Enoxaparin 30 mg SC bid or - Enoxaparin 40 mg SC qd or - Dalteparin 2500 or 5000 units SC qd or - Fondaparinux 2.5 mg SC qd or Rivaroxaban 10 mg qd or - Aspirin 81 mg qd or - Dabigatran 220 mg qd (not in the U.S.) or - Apixaban 2.5 mg twice daily (not in the U.S.) or -i ntermittent pneumatic compression (with or without pharmacologic prophylaxis)

51. Take home message PE is common but overlooked High suspicion to make diagnosis D- dimer, Echo, CTPA diagnostic tools Immediate reperfusion for high risk cases Give anticoagulants to all for 6 months Prophylaxis is important for hospitalized patients.