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Optimizing Management of Pulmonary Embolism: From Threat to Therapy

DVT-WRAP SlideCAST. Optimizing Management of Pulmonary Embolism: From Threat to Therapy. Samuel Z. Goldhaber, MD Cardiovascular Division Brigham and Women’s Hospital Professor of Medicine Harvard Medical School. Learning Objectives. Epidemiology Diagnosis Risk Stratification

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Optimizing Management of Pulmonary Embolism: From Threat to Therapy

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  1. DVT-WRAP SlideCAST Optimizing Management of PulmonaryEmbolism: From Threat to Therapy Samuel Z. Goldhaber, MD Cardiovascular Division Brigham and Women’s Hospital Professor of Medicine Harvard Medical School

  2. Learning Objectives • Epidemiology • Diagnosis • Risk Stratification • Treatment: anticoagulation thrombolysis embolectomy • Prevention

  3. Epidemiology

  4. Incidence • 900,000 PEs/ DVTs in USA in 2002. • Estimated 296,000 PE deaths: 7% treated, 34% sudden and fatal, and 59% undetected. Heit J. ASH Abstract 2005 ----------------------------------------- 762,000 PEs/ DVTs in EU in 2004. Thromb Haemostas 2007; 98: 756

  5. The high death rate from PE (exceeding acute MI!) and the high frequency of undiagnosed PE causing “sudden cardiac death” emphasize the need for improved preventive efforts. Failure to institute prophylaxis is a much bigger problem with Medical Service patients than Surgical Service patients.

  6. Annual At-Risk for VTE:U.S. Hospitals • 7.7 million Medical Service inpatients • 3.4 million Surgical Service inpatients • Based upon ACCP guidelines for VTE prophylaxis Anderson FA Jr, et al. Am J Hematol; 2007; 82: 777-782

  7. Outpatient and Inpatient VTE are Linked • 74% of VTEs present in outpatients. • 42% of outpatient VTE patients have had recent surgery or hospitalization. • Only 40% had received VTE prophylaxis. Spencer FA, et al. Arch Intern Med 2007; 167: 1471-1475

  8. 25 20 15 10 5 0 ICOPER Cumulative Mortality 17.5% Mortality (%) 7 14 30 60 90 Days From Diagnosis Lancet 1999; 353: 1386-1389

  9. Progression of Chronic Venous Insufficiency From UpToDate 2006

  10. Cardiovascular Risk Factors and VTE (N=63,552 meta-analysis) RFRR Obesity 2.3 Hypertension 1.5 Diabetes 1.4 Cigarettes 1.2 High Cholesterol 1.2 Ageno W. Circulation 2008; 117: 93-102

  11. Eat Veggies and Lower VTE Risk; Careful with Red Meat Steffen LM. Circulation2007;115:188-195

  12. Dabish 20-Year Cohort: VTE, Subsequent CV Events • Assessed risk of MI, Stroke • 25,199 with DVT • 16,925 with PE • 163,566 population controls Sorensen HT. Lancet 2007; 370: 1773-1779

  13. RR CV Event in PE Patients Sorensen HT. Lancet 2007; 370: 1773-1779

  14. Reversible Risk Factors • Nutrition: eat fruits, veggies, fish; less red meat • Quit cigarettes • Lose weight/ exercise • Prevent DM/ metabolic syndrome • Control hypertension • Lower cholesterol

  15. DIAGNOSIS

  16. PE SXS/ Signs (PIOPED II) • Dyspnea (79%) • Tachypnea (57%) • Pleuritic pain (47%) • Leg edema, erythema, tenderness, palpable cord (47%) • Cough/ hemoptysis (43%) Stein PD. Am J Med 2007; 120: 871-879

  17. Clinical Decision Rule JAMA 2006; 295: 172-179

  18. CT Leg Venography & U/S:Necessary or “Overkill”? • Incremental value of CTV (N=829): 0.7% in low-risk patients and 2.6% in high risk patients (prior VTE, cancer). CTV more than doubles radiation dose (Hunsaker. AJR 2008; 190: 322-328) • Chest CT alone (N=1,819) was noninferior to chest CT plus leg U/S. (Lancet 2008; 371: 1343-1352)

  19. Saddle Embolus

  20. PE Diagnosis

  21. Risk Stratification

  22. Risk Stratification: PE is essential to decide: Anticoagulation aloneversus anticoagulation plusthrombolysis/ embolectomy Triage to Intensive Care Unit Consider RFs for fatal PE: massive PE, immobilization, age > 75 years, cancer. Circulation 2008; 117: 1711-1716

  23. TROPONIN META-ANALYSIS: Indicates RV Micro Infarct (Even “Leaks” Are Important) • 1,985 patients from 20 PE studies • 20% of 618 with elevated levels died • 3.7% of 1,367 with WNL levels died • In hemodynamically stable PE patients, elevated troponin levels increased mortality 6-fold. Circulation 2007; 116: 427-433

  24. Risk Stratify PE:Assess RV Size, Function • ECHO: RV/LV EDD > 0.9 predicts increased hospital mortality (OR=2.6) (Fremont B. CHEST 2008;133: 358) and recurrent (often fatal) PE (Arch Intern Med 2006; 166: 2151) • Chest CT: an alternative to ECHO to compare RV/LV size

  25. RV ENLARGEMENT: CHEST CT Circulation 2004; 110: 3276

  26. Treatment

  27. VTE: Immediate Anticoagulation • Unfractionated heparin: target PTT between 60 to 80 seconds • Low molecular weight heparins: enoxaparin, dalteparin, tinzaparin • Fondaparinux • Direct thrombin inhibitors (HIT): argatroban, lepirudin, bivalirudin

  28. Cancer and VTE • 3-fold higher recurrence and bleeding, when treating cancer patients (Prandoni. Blood 2002; 100: 3484) • LMWH Monotherapy halves recurrence, compared with warfarin. (Lee AYY. NEJM 2003; 349:146) (FDA approved May 2007)

  29. Aggressive VTE Therapy • Surgical embolectomy (Stein PD. Am J Cardiol 2007; 99: 421) • Catheter embolectomy (Kucher N. CHEST 2007; 132: 657-663) • PE Thrombolysis (Wan S. Circulation 2004; 110: 744) • Catheter-based DVT therapies (Chang R. Radiology 2008; 246: 619) (VascIntervRadiol 2008; 19: 372-376)

  30. 47 EMERGENCY EMBOLECTOMIES Survival = 94 % N=47 J Thorac Cardiovasc Surg 2005;129:1018

  31. Surgical Embolectomy at BWH:Surgeon’s Cell Phone

  32. PE Thrombectomy Device Dimension: 11 French SuctionPorts Spiral Coil

  33. Heparin “Catches Up” with Lysis: Lung Perfusion Arch Intern Med 1997; 157: 2550

  34. Thrombolysis in submassive PE remains controversial. A multinational European clinical trial (85 centers/ 12 countries) will enroll about 1,100 submassive PE patients with normal BP, elevated Troponin, and RV enlargement on ECHO. Reduce death/ CV collapse from 12.9% to 7.6% in 1 week? (1st patient enrolled 11/10/2007; 65th on 8/25/2008)

  35. LYSIS VS. Filter: Massive PE(N=108) Lysis Filter Lysis Filter

  36. 8 YEAR F/U IVC FILTERS: RCT PREPIC. Circulation 2005; 112: 416-422

  37. BARDRECOVERY FILTER

  38. Risks for Recurrence • “Unprovoked” • Strong FH; PMH of VTE • Antiphospholipid antibody syndrome • Cancer • Male (Kyrle PA. NEJM 2004; 350: 2558) (McRae S. Lancet 2006; 368: 371-8) • Presentation with PE Symptoms Eichinger. Arch Intern Med 2004;164: 92)

  39. Trials of Unprovoked VTE : Favor Indefinite Duration Anticoagulation (NEJM 2003) TRIAL TAKE-HOME POINT . PREVENT Low intensity A/C (INR 1.5-2.0) reduces recurrence rate by 2/3. ELATE Standard A/C (INR 2.0-3.0) is more effective but as safe as low intensity A/C. THRIVE-3Ximelagatran effective, safe.

  40. Does Thrombophilia Predict Recurrent VTE? • 474 VTE patients followed for an average of 7 years. • Most patients were anticoagulated for < 12 months. • 90 (20%) suffered recurrence. • Thrombophilia did not increase likelihood of recurrence. Christiansen SC. JAMA 2005; 293: 2352

  41. How Often and For How Long Does CT Remain Abnormal After PE? Nijkeuter M. CHEST 2006; 129: 192-197

  42. WarfarinPharmacogenomics • Cytochrome P450 2C9 genotyping can identify mutations associated with impaired warfarin metabolism. • Vitamin K receptor polymorphism testing can identify whether patients require low, intermediate, or high doses of warfarin. Schwartz UI. NEJM 2008; 358: 999

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