1. بسم الله الرحمن الرحيم

2. Identifying The Patient For Thrombolysis Or Thrombectomy By Ahmed Shafea Ammar MD, FACC

3. Epidemiology >600,00 patients/ year in the US 50,000-200,000 deaths/ year in the US 3-month MR is 15-20% 10% of symptomatic PE are fatal at 1 hour 70% of symptomatic PE have DVT 50% of asymptomatic DVT have PE. Semin Vasc Med 2001;1(2): 139-46

4. Risk Factors for DVT & PE

5. ۰ Antiphospholipid Antibodies Anticardiolipin & Lupus Anticoagulant

8. Diagnosis of PE

9. Most Common S&S of APE Among 2454 Patients in ICOPER Registry Symptom or sign % Dyspnea 82 RR> 20/min 60 HR>100 b/min 40 Chest pain 49 Cough 20 Syncope 14 Hemoptysis 7 Lancet 353:1386, 1999

10. Wells Clinical Bedside Scoring System for APE Parameter Points Clinical S&S of DVT 3 An alterative diagnosis is less likely 3 HR > 100 1.5 Immobilization or surgery within 4 weeks 1.5 Previous DVT/PE 1.5 Hemoptysis 1 Malignancy 1 Score < 4 APE is less likely Score> 6 is a high risk Thromb Haemost 83:416, 2000

11. Syndrome Presentation RVD Therapy Massive sob, syncope, cyanosis, ↓BP +ve heparin + thrombolysis > 50% obst. of PV (v/q scan) or thrombectomy Submassive Normal BP, > 30% obst of PV +ve heparin ± thrombolysis or thrombectomy Small to mod. Normal BP -ve heparin Pulmonary inf. Pleurisy (pain, rub), hemoptysis consolidation, s. periph. emboli rare heparin& NSAID Paradox. emb. Systemic embolization eg CVS rare heparin, defect closure Non-thrombotic Air, Fat, Tumor, Amniotic fluid rare supportive embolism Syndromes of Acute Pulmonary Embolism

12. Risk Stratified Performance of Tests in PE High risk Intermed. risk Low risk Test Sensitivity Specificity ppv npv ppv npv ppv npv (%) (%) Helical CT 77 89 96 52 73 91 20 99 MRI 77 87 96 51 70 91 17 99 TTE 68 89 96 43 70 88 18 99 TEE 70 81 93 43 59 88 12 99 D-dimer 89 59 89 60 46 93 7 99 V/Q 98 10 80 58 30 93 3 99 Am Fam Physcian 2004, 162: 1245-8

13. Advantages & Disadvantages of Different Tests Test Wells questionnaire Advantages Rapid assessment of likelihood of APE Disadvantages Influenced by one subjective Q about alternative diagnosis ABG & Hypoxaemia Rapid, widely available Does not discriminate well between Pts with & without PE

14. Advantages & Disadvantages of Different Tests Test D-dimer Advantages Rapid, widely available, high npv Disadvantages Not specific, low ppv ECG Chest X- ray Available, may indicate RV strain Identify mimics of PE eg. pneumonia, pneumothorax or CHF May be normal despite PE May be normal despite PE, Pts may have PE ± pneumonia ± CHF

15. Note Humpton’s Humps & Wedge opacity

16. Venous ultrasound May detect DVTMay be normal despite PE CT venography Echocardiography May detect DVT & obviat the need for US Identify high risk patients if RVD is present, may show the embolus Low sensitivity for calf DVT Radiation exposure Usually normal despite PE Test Advantages Disadvantages Advantages & Disadvantages of Different Tests

17. TestAdvantagesDisadvantages Lung Scanning Avoids high contrst injection Useful if normal or high probability Often non diagnostic PUL. ANGIO Spiral CT Standard test Displays pul. Vascular morphology Widely available Direct visualization of the thrombus and of alternative diagnosis Cost effective Now, gold standard Invasive & Costly Use of contrast Radiation exposure

18. Risk Stratification The 3 main pillars for risk stratification are : 1- Assessment of Clinical & haemodynamic status of the patient 2- Evidence of RV strain & infarction 3- Evidence of RV dilatation & dysfunction

19. Risk Stratification 1- Clinical Signs Geneva Score Index Clinical evidence of RVD : JV distension TR ↑ P2 2- ECG Signs RV strain (T ↓ in v1 – v4) New RBBB S1Q3T3

20. The Geneva Score for PE Prognosis Variable Point Score No of Points % of Pts with adverse outcome Cancer +2 0 0 CHF +1 1 2.5 Prior DVT +1 2 4.1 Hypotension +2 3 17.8 Hypoxemia +1 4 27.3 DVT on US +1 5 57.1 6 100 Throm Haemost 84:548, 2000

22. Risk Stratification 3- Echocardiographic Signs * Direct visualization of a large thrombus In the main PA (TEE) * RV dilatation * TR * RV hypokinesis sparing the apex (Mac Connell sign) * IVS flattening * PH ± PA dilatation * Lack of inspiratory collapse of IVC Outcomes with RV Dysfunction 2-fold ↑ 14-day MR 3-fold ↑1-year MR ↑ risk of PE recurrence ?Increased risk of in situ thrombosis in RV and Circulation 2002;121:877

23. SAX view Note marked RV dilatation & IVS flattening during systole & diastole

25. Risk stratification 4- Spiral CT A- RV dilatation relative to LV size. RV dilatation and pulmonary vascular obstruction (≥ 40%) on chest CT is a predictor of eary death after APE (Circulation 2005; 235(3): 798-803) B- Saddle or large proximal thrombus

26. Massive PE Note the large thrombus burden in the main pul. branches

28. Risk stratification 5- Biomarkers : Troponins, Pro-BNP BNP

29. Kucher, N. et al. Circulation 2003;108:2191-2194 Mechanism of cardiac biomarker level elevation in APE

30. Copyright ©2004 BMJ Publishing Group Ltd. La Vecchia, L et al. Heart 2004;90:633-637 Relation between cTnI concentrations ( 0.6 ng/ml) on admission and mortality (%).

31. Copyright ©2004 BMJ Publishing Group Ltd. La Vecchia, L et al. Heart 2004;90:633-637 Time course of cardiac troponin I (cTnI) concentrations in patients with a positive assay on admission.

32. Circulation 2003;107:2545

33. Management Strategies

34. What is the optimal management for such embolus?? Thrombolysis, Catheter or Surgical Thrombectomy

36. Copyright ©2003 American Heart Association Kucher, N. et al. Circulation 2003;108:2191-2194 Pulmonary embolism management strategy

37. Thrombolysis in APE (State of The Art) A meta-analysis of all randomized trials (11 trials including 748 pts) comparing thrombolytic therapy with heparin in patients with APE, provides no evidence for a benefit of thrombolytic therapy compared with heparin for the initial treatment of unselected patients with APE. However a benefit is clear in those at highest risk of recurrence or death. Whether patients with RVD and stable hemodynamics should receive fibrinolytic therapy is still unknown. (Evid. Based Med., April 1, 2005; 10(2): 41 – 41)

38. Possible mechanisms by which thrombolysis decreases mortality in patients with RVD 1- May prevent progressive RVD by lysis of massive PA thrombi 2- May prevent the ongoing release of vasoactive factors, such as serotonin, that may cause worsening pulmonary vasoconstriction and RVF 3- May dissolve a significant amount of thrombi in the source (e.g., pelvic and leg) veins to prevent recurrent emboli NB. Patients with APE are eligible for thrombolysis, if they have new S&S within 2 weeks of 1st presentation (Goldhaber S in Braunwald” Heart Disease 2005)

39. 1,500,000 U/1 Hour streptokinase with heparin is more effective than heparin alone in PE with heart failure Randomized trial intending to enroll 40 patients Massive PE, hypotension, and heart failure Stopped after 8 patients Results GroupOutcome SK+Heparin0 of 4 died Heparin4 of 4 died Autopsy in 3 of 4 revealed evidence of RV infarct and no significant CAD Jerjes-Sanchez et al. J Thromb Thrombolysis 1995;2:227-9

40. Konstantinides et al. NEJM 347 (15): 1143,October 10, 2002 Heparin + Altepase (118 pts) Heparin + Placebo (137 pts)

41. Before thrombolysis After thrombolysis Note the change in RV size

42. NB. The risk of cerebral Hge is 1-2%

43. Contraindications for Thrombolytic Therapy Absolute contraindications Active internal bleeding Recent spontaneous intracranial bleeding Relative contraindications Major surgery, delivery, organ biopsy or puncture of non- compressible vessels within 10 days Ischaemic stroke within 2 months Gastrointestinal bleeding within 10 days Serious trauma within 15 days Neurosurgery or ophthalmologic surgery within 1 month Uncontrolled severe hypertension (systolic pressure >180 mmHg; diastolic pressure >110 mmHg Recent cardiorespiratory resuscitation Platelet count <100 000/mm3, prothrombin time less than 50% Pregnancy Bacterial endocarditis Diabetic haemorrhage retinopathy

44. What is the optimal therapy for massive PE &RVF ? Surgery or Thrombolysis Registry of Massive PE with RV failure (n=37) Surgical embolectomy Thrombolysis (n=13) (n=24) 77% survival 67% survival Recurrent PE in 1 Recurrent PE in 5 28% bleed rate Gulba et al. Lancet 1994;343:576-7

45. Role of Surgery 47 patients, underwent emergency surgical embolectomy for massive central PE The indications for surgery were (1) C/I to thrombolysis (45%), (2) failed medical treatment (10%), and (3) RVD (32%). Preoperatively, (26%) patients were in cardiogenic shock, and (11%) were in cardiac arrest. There were (6%) operative & (12%) late deaths, 5 of which were from metastatic cancer. Actuarial survival at 1 and 3 years’ follow-up was 86% and 83%, respectively. We now perform surgical pulmonary embolectomy not only in patients with large central clot burden and hemodynamic compromise but also in hemodynamically stable patients with RVD documented by means of echocardiography. J Thorac Cardiovasc Surg 2005;129:1018-1023

46. Surgically-Removed Thrombus in Acute PE

47. What is the optimal embolectomy route for massive PE & RVF? Catheter embolectomy vs Surgical embolectomy AdvantagesDisadvantagesAdvantages Disadvantages More accessibleDistal embolizationMore controlLess experience Various toolsLarge clot burdenRevascularizeNeed for if neededsternotomy Limited Experience No randomized trials

48. Catheter Embolectomy Inteventional catheterization techniques includes : Mechanical fragmentation of thrombus with PA cath. Clot puverization with a rotating basket catheter. Rheolytic thrombectomy. Combination of mechanical fragmentation and thrombolysis. Catheter embolectomy is hindered by devices that are designed normally to remove small arterial clots rather than decompressing massive PE.

50. Suction catheter embolectomy + full dose thrombolysis

52. Duration of Anticoagulant Therapy (INR 1.5-2)

53. Summary (1) Risk Stratification based on Geneva score index (>4), ↑ S biomarkers, Echo signs of RVD and evidence of large thrombus burden on helical CT identification of patients for thrombolysis or thrombectomy Thrombolytic therapy is indicated in patients with massive PE, as shown by shock /or hypotension + RVD The use of thrombolytic therapy in patients with sub- massive PE (RVD without hypotension) is controversial. Thrombolytic therapy is not indicated in patients without right ventricular overload.

54. Surgical embolectomy is reserved for patients with massive PE (large thrombus burden) with C/I to thrombolysis and those having PTO or RV or RA thrmbus Catheter embolectomy can be used for patients with massive PE (moderate thrombus burden & C/I to thrombolysis Summary (2)

55. Fibrinolytic therapy Clinical questions - a) Pathophysiology ManagementEpidemiology & costs - c)Fibrinolytic trials- d)- e)- b) Please, do not rush Always, weigh: SafetyEfficacy Clinical questions - a)- e)

56. Ahmed Shafea MD, FACC