Pulmonary Embolism 2016:

Transcription

1 Pulmonary Embolism 2016: Evidences & Controversies Boonsong Patjanasoontorn, MD, FRCPT FACP, FCCP, FCCM Immediate Past President, Thai Society of Critical Care Medicine(TSCCM) Chief, Division of Pulmonary and Critical Care Medicine Department of Medicine, Khon Kaen University Khon Kaen, 40002, THAILAND

2 อาย รแพทย อน สาขาโรคระบบการหายใจ และ อน สาขาเวชบาบ ด ว กฤต ห วหน าสาขาเวชบาบ ดว กฤต ภ.อาย รศาสตร คณะแพทยศาสตร มหาว ทยาล ยขอนแก น คณะกรรมการบร หารราชว ทยาล ยอาย รแพทย แห งประเทศไทย กรรมการแพทยสภาจากการเล อกต ง อด ตนายกสมาคมเวชบาบ ดว กฤตแห งประเทศไทยคนล าส ด Board of Directors, Asia Ventilation Forum (AVF) Executive Council, Asia Pacific Association of Critical Care Medicine (APACCM) ผ ทรงค ณว ฒ ประจาว ทยาล ยอาย รแพทย อเมร ก น (FACP) ผ ทรงค ณว ฒ ประจาว ทยาล ยแพทย โรคทรวงอกอเมร ก น (FCCP) ผ ทรงค ณว ฒ ประจาว ทยาล ยเวชบาบ ดว กฤตอเมร ก น (FCCM)

3 AGENDA Clinical spectrum of acute pulmonary embolism (APE) Risk Stratification & Classification of APE Sub-massive VS Massive Pulmonary Embolism Evidence-based Approach on management of APE Anticoagulant therapy Management of massive PE Thrombolytic Therapy Controversies in APE Management Management of Sub-massive PE LMWH VS UFH Is there roles of Thrombolysis in sub-massive PE? Management of massive PE What to do for Unsuccessful Initial Thrombolysis: Catheter-based therapy, Surgical embolectomy, or Repeat thrombolysis, IVC filter for APE & extensive proximal DVT Summary

4 Disclosure I have no conflict of interest about methods, machines, and products use in this lecture.

5 PE VTE DVT Venous thromboembolism

6 Origin of Pulmonary Embolism SVC RH + IVC ~ 4.5 % SVC: 1.6 % RH: 1.9 % IVC: 45 % Morpugo & Schmid. Chest 1995;107:18s-20s. 583 autopsy-case-series 53% Known primary IVC 45 % RH 1.9 % SVC 1.6 % Mixed 4.5 % Clot in Venous System 47% Unknown?!?!?!

7 05/04/2008 BOONSONG PATJANASOONTORN, MD, FCCP, FCCM Rudolf Virchow R Virchow was the first one who discovered that most of PE came from DVT of lower extremities. Virchow s Triad : predisposing conditions to develop DVT Venous stasis Vascular injuries Hypercoagulability states

8 Common Risk Factors* of Venous Thromboembolism (VTE) Clinically detectable risk factors (~60%) Surgery >30 min of GA Surgery or trauma of legs or pelvis, & spines CHF, acute MI Immobilization > 3 days Malignancy Pregnancy and postpartum within 6 weeks Systemic disease: aging >60, estrogen, obesity, hypertension Primary or idiopathic VTE (~40%) Age < 40, Recurrent DVT/PE Familial history of DVT/PE 9 % found malignancy during follow-up ~ 40% >> Factor V Leiden (activated protein C resistance) Giuntini,et al. Chest 1995;107(1):3s-9s., The PIOPED investigators. JAMA 1990; 263:2753. Caprini and Arcelus. Scope Phlebol Lymphol. 2001;8: American Public Health Association. Presented at: Public Health Leadership Conference on Deep-Vein Thrombosis: February 26, 2003: Washington, DC.

9 Incidence & Pathway of Pulmonary Embolism Patient in the United States * Total Incidence 630,000 11% 71% 89% Survival >1hr 563,000 29% Death within 1 hr 67,000 Dx not made Dx made, therapy 400,000 instituted 163,000 70% 30% 92% 8% Survival Death Survival Death 280, , , ,000 *Progress in Cardiovascular Diseases, Vol. XVII, No. 4 (Jan/Feb 1975)

10 Pathological Classification According to Clot Burden Small PE : Pulmonary vascular bed (PVB) occlusion ~30-50% PAP ~ normal or slightly elevate Moderate PE : PVB occlusion ~50-75 %, significantly elevate PAP & evidence of RV dilatation/akinesia Massive PE: PVB occlusion >75 %, Less correlate with clinical presentati on and mortality Miller GA, et al., Br Med J 1971; 2:681-4

11 Mortality 100% Clinical Presentations & Mortality of Acute Pulmonary Embolism Normotensive, normal RV function Normotensive, RV dysfunction Sudden death 70 % 50% Non-massive 48 % Sub-massive 32% Massive 20 % Cardiac arrest 30% Asymptom. Symptomatic Shock 10% 0 % Severity Spectrum» Embolism size» Cardiopulmonary reserve

12 Risk Stratification In APE: According to Clinical Features & Diagnostic Tests Mortality Clinical Status At Presentation 65% Cardiac Arrest 25% Shock 15% Hypotension without hypoperfusion 8.1% Normal BP with RV dysfunction Higher Risk Predictions Intermediate Risk History/Physical Diagnostic Studies EKG CXR ABG D-Dimer Troponin, BNP Echocardiography Confirmatory Studies 0-1% Normal BP and RV function Lower Risk V/Q CT Angiography Angiography MAPPET Kasper JACC 1997; 30:

13 Classification based on Severity Spectrum of Acute Pulmonary embolism Asymptomatic Mild Symptoms RV Dysfunction Non-massive Sub-massive Shock >> CPR Massive Normotensive Hypotensive Life-threatening APE

14 Sub-massive or Massive PE? Sub-massive PE APE without systemic hypotension but with either RV dysfunction or myocardial necrosis RV dysfunction : the presence of at least 1 of the following Imaging RV dilatation (RV/LV Ø > 0.9) by echo. or CT. Cardiac biomarkers BNP > 90 pg/ml. NT pro BNP >500 pg/ml. & Troponin I > 0.4 ng/ml. or Troponin T> 0.1 ng/ml Massive PE APE with sustained hypotension (BPs <90 mmhg.) for at least 15 min. or requiring vasopressor (not for other explanable cause(s) of shock APE present with cardiac arrest The International Cooperative Pulmonary Embolism Registry (ICOPER) Amer J Respir Crit Care Med 2005:172:

15 MEDICAL PRACTICE Life is short, art is long, experience is fallacious, So (the medical) decision (making) is difficult. Hippocrates 500 BCE Medicine is an art that based on sciences Ars Longa Veta Brevis

16 What are the evidences?

17 Current Evidence Based Guidelines for an Approach on Diagnosis and Management of Acute pulmonary Embolism (APE)

18 Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension by Michael R. Jaff, M. Sean McMurtry, Stephen L. Archer, Mary Cushman, Neil Goldenberg, Samuel Z. Goldhaber, J. Stephen Jenkins, Jeffrey A. Kline, Andrew D. Michaels, Patricia Thistlethwaite, Suresh Vedantham, R. James White, Brenda K. Zierler, and AHA 2011 Circulation Volume 123(16): April 26, 2011 Copyright American Heart Association, Inc. All rights reserved.

19 NICE 2012

20 CHEST 2012

21 ESC 2014

22 ACP 2015 Ann Intern Med. 2015;163: doi: /m

23 Management of Massive and Submassive Pulmonary Embolism, Iliofemoral Deep Vein Thrombosis, and Chronic Thromboembolic Pulmonary Hypertension by Michael R. Jaff, M. Sean McMurtry, Stephen L. Archer, Mary Cushman, Neil Goldenberg, Samuel Z. Goldhaber, J. Stephen Jenkins, Jeffrey A. Kline, Andrew D. Michaels, Patricia Thistlethwaite, Suresh Vedantham, R. James White, Brenda K. Zierler, and 2011 Circulation Volume 123(16): April 26, 2011 Copyright American Heart Association, Inc. All rights reserved.

24 2012

25 2012

26 2014

27 2015 Ann Intern Med. 2015;163: doi: /m

28 Options of APE Management Thrombolystics Catheterbased therapy Heparin (UFH VS LMWH) & anticoagulants (Warfarin, NOACs) Options Surgical embolectomy

29 Anticoagulant Therapy

30 Overview of Management Anticoagulants used in VTE management Unfractionated Heparin (UFH) Low Molecular Weight Heparins (LMWH) Warfarin New Oral Anticoagulants (NOACs) 30

31 Acute Pulmonary Embolism Diagnostic confirmatory studies can delay definitive treatment and contribute to additional mortality; 14%- 67% Mortality decreasing with early anticoagulant therapy, but variable (16% - 46%) Sub-therapeutic level of anticoagulant in the first 24 hours may contribute additional mortality

32 Recommendations for Initial Anticoagulation for Acute PE 1. Therapeutic anticoagulation during the diagnostic workup should be given to patients with intermediate or high clinical probability of PE and no contraindications to anticoagulation ESC 2014 (Class I; Level of Evidence C). ACCP 2012

33 ACCP Therapeutic Recommendations 2012 Highly suspicion PE- anticoagulate during evaluation period Non-massive APE LMWH > UFH esp. as Outpatient Ɍ Initial LMWH/UFH for at least 5 days Renal failure- IV UFH > LMWH Initiate VKA on day 1 and discontinue heparin when INR is stable and greater than 2.0 > 24 hours Submassive APE IV. UFH > LMWH Aim to achieve therapeutic aptt within 24 hours Measure anti-xa for LMWH Initiate VKA on day 1 and discontinue heparin when INR is stable and greater than 2.0 > 24 hours

34 Weight-Based a UFH Dosing for Continuous IV Infusion Indication Initial Loading Dose Initial Infusion Rate DVT/PE units/kg Max = 10,000 units units/kg/hr Max = 2,300 units/hr AntiXa(U/mL)/aPTT (sec) b Maintenance Infusion Rate Dose adjustment < 0.15/< units/kg bolus, then infusion by 4 units/kg/hr / units/kg bolus, then infusion by 2 units/kg/hr /48-71 No change /72-93 Infusion by 2 units/kg/hr > 1/> 93 Hold infusion for 1 hr, then by 3 units/kg/hr a Use actual body weight for all calculations. Adjusted body weight may be used for obese patients. b aptt may vary based on individual assays. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition: 34

35 Long-term therapy Anticoagulation Warfarin is recommended due to extensive prior clinical experience. Rivaroxaban and other new oral agents can be considered if warfarin is not an option. LMWH is preferred in those with active malignancy.

36 Timing of Initiation of VKA and Associated Duration of Parenteral Anticoagulant Therapy In patients with acute DVT of the leg, we recommend early initiation of VKA (eg, same day as parenteral therapy is started) over delayed initiation, and continuation of parenteral anticoagulation for a minimum of 5 days and until the international normalized ratio (INR) is 2.0 or above for at least 24 h (Grade 1B).

37 Duration of Treatment Guidelines 1st event, reversible risk factor 1st event, spontaneous 3-6 months >= 6 months 2nd event 2nd spontaneous event, or 1st spontaneous and life threatening 3rd event or Ongoing risk factors >=12 months or lifelong Lifelong Lifelong

38 Thrombolytics Therapy In Massive PE

39 Recommendations for Fibrinolysis for Acute PE-1 1. Fibrinolysis is reasonable for patients with massive acute PE and acceptable risk of bleeding complications (Class IIa; Level of Evidence B).

40 Classification based on Severity Spectrum of Acute Pulmonary embolism Asymptomatic Mild Symptoms RV Dysfunction Non-massive Sub-massive Shock >> CPR Massive Normotensive Hypotensive Life-threatening APE

41 Sub-massive or Massive PE? Sub-massive PE APE without systemic hypotension but with either RV dysfunction or myocardial necrosis RV dysfunction : the presence of at least 1 of the following Imaging RV dilatation (RV/LV Ø > 0.9) by echo. or CT. Cardiac biomarkers BNP > 90 pg/ml. NT pro BNP >500 pg/ml. & Troponin I > 0.4 ng/ml. or Troponin T> 0.1 ng/ml Massive PE APE with sustained hypotension (BPs <90 mmhg.) for at least 15 min. or requiring vasopressor (no explanable cause(s) of shock APE present with cardiac arrest The International Cooperative Pulmonary Embolism Registry (ICOPER) Amer J Respir Crit Care Med 2005:172:

42 Cardiac Arrest Shock > 15 min. NO Absolute contraindications Imaging Confirmed of PE Prolonged CPR is not C/I

43 Contraindications to Thrombolytic Therapy Absolute Contraindications Major trauma, surgery, head trauma (within 3 weeks) Relative Contraindications Cancer Prior hemorrhagic stroke Age > Ischemic stroke within prior 6 months Central nervous system neoplasm Gastrointestinal bleeding within one month Concurrent active bleeding Transient ischemic attack within 6 months Oral anticoagulant therapy Non-compressible punctures Traumatic resuscitation Refractory hypertension Advanced liver disease Infective endocarditis Active peptic ulcer Pregnancy or within one week postpartum * Torbicki A, Perrier A, Konstantinides S, et al. Eur Heart J. 2008;29(18): Kasper W, Konstantinides S, Geibel A, et al. J Am Coll Cardiol. 1997;30(5):

44 Massive Pulmonary Embolism (MPE) Prevalence and mortality The MAPPET (Germany based) APE with hypotension MR 25 %, APE required CPR MR 65% as compared to other Massive PE: 90 day Mortality rate 52.4 % Hemodynamic stable APE (non-massive & submassive) MR 8 % ICOPER 2005 Kasper W, et al. J Am Coll Cardiol 1997; 30:

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46 What are controversies about PE or VTE?

47 Is venous thromboembolism common in Asia and Thailand?

48 EPIDEMIOLOGY OF PULMONARY EMBOLISM IN WESTERN COUNTRIES An estimated in Western Countries; /100,000 populations/year suffering from pulmonary embolism, 2 % die within the first day Without treatment, mortality rate ~ 30 %, mostly as the result of recurrent embolism Venous thromboembolism in the third most common cadiovascular disease after CAD & stroke Anticoagulant therapy significantly reduced mortality rate to 2-8 %

49 PULMONARY EMBOLISM 2002 Incidence (case/100,000/yr) Is pulmonary embolism common in Asia and Thailand 40 20? 0 USA Italy Japan USA Italy Japan Goldhaber Giuntini Kumasaka* /04/2004 Boonsong Patjanasoontorn, MD, FCCP * Level 5, expert opinions

50 IS VENOUS THROMBOEMBOLISM A RARE CONDITION IN ASIA AND THAILAND? Cause of death from pulmonary embolism (fatal PE) in autopsy series. (Level 4) Prakit Vathesatokit, et al. J Med Assoc Thai 1989;72: in 4,896 autopsy-cases in 18 years ~ 0.24 % Chau KY, et al. Pathology 1997;29: Fatal PE 4.7 % 4.5 % in male, 5.2 % in famale Rubinstein, et al. Arch Intern Med 1988;148: Stein, et al. Chest 1995; 108: % 5% 4% 4% 3% 3% 2% 2% 1% 1% 0% 27/04/2004 Boonsong Patjanasoontorn, MD, FCCP 5% Incidence (%) 0.24 % 4.7 % USA Thailand HongKong

51 IS VENOUS THROMBOEMBOLISM A RARE CONDITION IN ASIA AND THAILAND? Cause of death from pulmonary embolism (fatal PE) in autopsy series: A comparative study. (Level 3) Dickens P, et al. Forensic Sci Int 1997; 90: Chau KY, et al. Pathology 1997; 29: autopsy reports compare between Chinese in Hong Kong vs. Caucasian No difference in Crude incidence rate Adjusted incidence rate 27/04/2004 Boonsong Patjanasoontorn, MD, FCCP

52 DVT FOLLOWING KNEE ARTHROPLASTY CHAIRAT PERMPIKUL, ET AL. SIRIRAJ HOSPITAL Boonsong Patjanasoontorn, MD, FCCP Prospective study 27 KAP in 25 patients without heparin prophylaxis Measurement: IPG at Day 7, 14 Contrast venography for IPG+ V/Q Scan in proximal DVT Results: Distal (calf) DVT 70.3 % Proximal DVT 14.8 % Pulmonary embolism 11.1 % 27/04/2004

53 IS PULMONARY EMBOLISM COMMON IN ASIA AND THAILAND? Prospective studies of peri-operative venous thromboembolism (Level 2b, 1b) Dhillon, et al. J Bone Joint Surg Br 1996; 78: Ruban, et al. Ann Acad Med Singapore 2000; 29: Wang, et al. J Formos Med Assoc 2000;99: Lee, et al. ANZ J Surg 2001; 71: Chairat Permpikul, et al (pub. pending) 80.00% 70.00% 60.00% 50.00% 40.00% 30.00% 20.00% 10.00% 0.00% Malaysia Dhillon 1996(88) CV VTE Singapore Ruban 2000(100) d-us Taiwan Wong 2000(102) CV HongKong Lee 2001(51) d-us Thailand Chairat 2002(27) IPG,CV 27/04/2004 Boonsong Patjanasoontorn, MD, FCCP

54 CLASSIFICATION ON LEVEL OF RISK OF VENOUS THROMBO-EMBOLISM* Low Moderate High Very High Calf vein thrombosis (%) Proximal DVT (%) Pulmonary embolism (%) Fatal PE (%) Appropriate Prophylaxis Boonsong Patjanasoontorn, MD, FCCP None Heparin SQ 5,000 q 12 h IPC Device Heparin SQ 5,000 Q 8 H IPC Device * The 9 th ACCP Consensus Conference on Antithrombotic Therapy. Chest 2014;119:1s-370s. LMWH or adjusted-dose UH or IPC+UH/LMWH 27/04/2004

55 IS VENOUS THROMBOEMBOLISM A RARE CONDITION IN ASIA AND THAILAND? Some Level 4, 5 evidences point out that pulmonary thromboembolism (PTE) is much less common than Western countries. Vathesatokit 89, Kumasaka 99 Two case-control studies (Level 3b) found that incidence of fatal PE were comparable between Chinese and Caucasian. Dickens 97, Chau 97. Four cohort studies (Level 2b, 2a, 1b ) showed that perioperative VTE in Asia and Thai were similar to the reported in Western populations. Dhillon 1996, Wang 2000, Lee 2001, Permpikul 2002.

56 IS VENOUS THROMBOEMBOLISM A COMMON CONDITION Yes IN ASIA AND THAILAND? The incidence of VTE and fatal PE in many countries in Asia (including Thailand) in high-risk operations are comparable to the Western / Caucasian populations. Evidence Level 1b, Strength A Extrapolation in other conditions Strength B

57 DO WE-THAILAND HAVE HIGHER RATIO OF CHRONIC PULMONARY EMBOLISM? WHY?

58 CHRONIC PULMONARY THROMBOEMBOLISM Sonakul 1992: 33 % 8 24 Palwatwichai 2000: ~ 12 % 6 49 USA: < 0.1 % Chronic PTE Acute Pulmonary Embolism Sonakul, et al. Southeast Asian J Trop Med Public Health 1992;23Suppl:25-8. Palwatwichai, et al. J Med Assoc Thai 2000; 83: Moser, et al. Eur Respir J 1992;5:

59 CHRONIC PULMONARY THROMBOEMBOLISM At least three possibilities those could be; 1. Significant cause(s) of chronic PTE, or 2. underdiagnosis of acute PE 3. Selection bias Palwatwichai2 000: ~ 12 % 6 49 USA: < 0.1 % Chronic PTE Acute Pulmonary Embolism Palwatwichai, et al. J Med Assoc Thai 2000; 83: Moser, et al. Eur Respir J 1992; 5:

60 CHRONIC PULMONARY THROMBOEMBOLISM Thailand: ~ 12 % 6 49? missed ~ 5951 acute PE cases USA: < 0.1 % Chronic PTE Acute Pulmonary Emboloism Palwatwichai, et al. J Med Assoc Thai 2000; 83: Moser, et al. Eur Respir J 1992; 5:

61 What are still the controversies? Thrombolysis in submassive APE? What s next if 1 st thrombolysis fail? Roles of IVCs filter?

62 Thrombolytics Therapy In Sub-massive PE

63 Central Debate for last 3 Centuries Thrombolytic in Sub-massive PE Pros o Feel better quicker o Resolve clots faster? o Improved RV function o Decrease PA pressure faster Cons o Increased ICH rate oincreased other life threatening hemorrhage o Increased cost o No survival benefit?

64 RV Necrosis

65 How many subgroups in Sub-massive Acute Pulmonary Embolism:

66 Indicators of RV dysfunction use in studies EKG Echocardiography S 1 Q 3 T 3 and T wave changes RV Dilation, RV: LV 1, leftward septal bowing RV hypokinesia Estimated RVSP> 40 mmhg Cardiac Biomarkers: BNP >100 pg/ml or pro-bnp >900 pg/ml)

67 Meta-analysis of Thrombolytic Therapy in Sub-massive Pulmonary Embolism S U B M A S S I V E P E NO CLEAR TREND IN BENEFIT Wan S, Circ 110:744, 2004

68 Meta-analysis of Thrombolytic Therapy in Sub-massive Pulmonary Embolism No SURVIVAL BENEFIT but with significant risk Wan S, Circ 110:744

69 30% of normotensive PE have RV dysfunction 10 % further developed hypotension 5 % mortality during admission

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73 The PEITHO Trial 2014

74 From: Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-analysis JAMA. 2014;311(23): doi: /jama Date of download: 8/29/2015 Copyright 2015 American Medical Association. All rights reserved.

75 From: Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-analysis JAMA. 2014;311(23): doi: /jama Odds of Mortality in Patients With Pulmonary Embolism Treated With Thrombolytic Therapy vs AnticoagulationEvaluated using the Peto method of meta-analysis. MOPETT indicates Moderate Pulmonary Embolism Treated with Thrombolysis trial; PEITHO, Pulmonary Embolism Thrombolysis trial; PIOPED, Prospective Investigation of Pulmonary Embolism Diagnosis; TIPES, Tenecteplase Italian Pulmonary Embolism Study; TOPCOAT, Tenecteplase or Placebo: Cardiopulmonary Outcomes At Three Months; ULTIMA, Ultrasound Accelerated Thrombolysis of Pulmonary Embolism trial; UPETSG, Urokinase Pulmonary Embolism Trial Stage 1. Date of download: 8/29/2015 Copyright 2015 American Medical Association. All rights reserved.

76 From: Thrombolysis for Pulmonary Embolism and Risk of All-Cause Mortality, Major Bleeding, and Intracranial Hemorrhage: A Meta-analysis JAMA. 2014;311(23): doi: /jama Odds of Mortality in Patients With Intermediate-Risk Pulmonary Embolism Treated With Thrombolytic Therapy vs Anticoagulation Evaluated using the Peto method of meta-analysis. The standard practice in meta-analysis of odds ratios (ORs) and risk ratios is to exclude studies from the meta-analysis where there are no events in either group. A 0-cell or continuity correction was not used based on recommendations regarding calculation of a Peto OR for studies with 0 events in only 1 group. MOPETT indicates Moderate Pulmonary Embolism Treated with Thrombolysis trial; PEITHO, Pulmonary Embolism Thrombolysis trial; TIPES, Tenecteplase Italian Pulmonary Embolism Study; TOPCOAT, Tenecteplase or Placebo: Cardiopulmonary Outcomes At Three Months; ULTIMA, Ultrasound Accelerated Thrombolysis of Pulmonary Embolism trial. Copyright 2015 American Medical Date of download: 8/29/2015 Association. All rights reserved.

77 Recommendations for Fibrinolysis for Acute PE-2 2. Fibrinolysis may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory insufficiency, severe RV dysfunction, or major myocardial necrosis) and low risk of bleeding complications (Class IIb; Level of Evidence C).

78 Recommendations for Fibrinolysis for Acute PE-2 3. Fibrinolysis is not recommended for patients with lowrisk PE (Class III; Level of Evidence B) or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (Class III; Level of Evidence B). 4. Fibrinolysis is not recommended for undifferentiated cardiac arrest (Class III; Level of Evidence B).

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80 Suspected acute life threatening PE Hypotensive Optimize fluid status Persisting Hypotension > 15 min. Massive PE Anatomical diagnosis of PE TTE/TEE or CTPA Thrombolysis Normotensive Evidences of RV function Normotensive Clinical signs of RV failure ECG: RV strain. IRBBB Biomarkers: Troponin, BNP Echocardiography: TTE, TEE CTPA Evidence of RV dysfunction Sub-massive PE UFH Hypotensive No evidence of RV dysfunction Non-massive PE Achieve Hemodynamic goals 2 nd Thrombolysis or Surgical embolectomy or Catheter-based thrombectomy LMWH or UFH Anticoagulant and/or IVC filter Suggested algorithm for acute life threatening pulmonary embolism. PE, pulmonary embolism; RV, right ventricle; ECG, electrocardiography; BNP, brain natriuretic peptide; TTE, transthoracic echocardiography, TEE, trans-esophageal echocardiography; CTPA, computerize tomography pulmonary angiography; UFH, unfractionated heparin; LMWH, low molecular weight heparin

81 In Massive PE, What s next if 1 st thrombolysis fail?

82 Contemporary Catheter Techniques 1. Conventional Catheter-Directed Thrombolysis 2. Thrombus Fragmentation 3. Rheolytic Thrombectomy 4. Suction Thrombectomy 5. Rotational Thrombectomy 6. Ultrasound Assisted Catheter-Direct Thrombolysis (USAT) 7. Pharmaco-mechanical Thrombolysis Rolf P. Engelberger, and Nils Kucher. Circulation Volume 124(19): November 8, 2011

83 Catheter Embolectomy & Fragmentation An alternative in high-risk PE patients when thrombolysis is absolutely contraindicated or has failed Kucher N Chest 2007;132:

84 Angio-Jet AngioJet-a catheter that breaks up the clot with a high speed jet of saline, heparin, or tpa that then sucks up clot using Bernoulli physics. Very little systemic drug is

85 Angio-Vac This device uses an ECMO-like system to suck up clot and then return the de-clotted blood to the venous circulation. It requires huge introducer sheaths. Oren alluded to its main benefit being intra-cavitary or vena cavae clots. Some are

86 Eko-sonic Endovascular Catheter

87 Embolism_Systematic_Review_and_Meta-analysis_of_Modem_Techniques?enrichId=rgreq-f e32- cebef0fa7bc2&enrichsource=y292zxjqywdlozm4mduzntqyo0ftojiwnzmzmzg0nzi0ndgwmuaxndi2ndqznjq5 OTgw&el=1_x_2

88 Catheter-directed Therapy for Massive Pulmonary Embolism From the overall 35 studies: 594 patients treated with catheterbased therapy, 86.5 % success rate, 2.5 % major bleeding WT Kuo 2009

89 Surgical Thrombo-embolectomy

90 Surgical Embolectomy in APE: Massive

91 Representative pulmonary endarterectomy specimens A, Type 1 disease (25% of cases of thromboembolic pulmonary hypertension): Fresh thrombus in the main or lobar pulmonary arteries. B, Type 2 disease (40% of cases): Intimal thickening and fibrosis with or without organized thrombus proximal to segmental arteries. In these cases, only thickened intima can be seen on initial dissection into the pulmonary arteries, occasionally with webs in the main or lobar arteries. C, Type 3 disease (30% of cases): Fibrosis, intimal webbing, and thickening with or without organized thrombus within distal segmental and subsegmental arteries only. No occlusion of vessels can be seen initially.

92 BOONSONG PATJANASOONTORN, MD, FCCP, FCCM

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94 Repeated thrombolytic Therapy 8% (40 of 488 massive PE need further Mx after 1st thrombolysis) Accumulative success rate 70-80%

95 Success rate (%) In Massive PE, What s next if 1st thrombolysis fail or contraindicate? 86.5 % 83.6 % 80.0 % Catheter-based therapy* Surgical Thrombo-embolectomy# Repeated thrombolysis** *Catheter directed Therapyfor the Treatment of Massive Pulmonary Embolism Systematic Review and Meta-analysis of Modem Techniques. WT Kuo, et al. JVIR 2009 # Modern surgical treatment of massive pulmonary embolism. M Leache, et al. JCVTS 2005 ** Repeated thrombolysis after unsuccessful initial thrombolysis RJM van den Beggerlar, et al. Thorax 2008

96 Recommendations for Catheter Embolectomy and Fragmentation & Surgical Embolectomy 1. Depending on local expertise, either catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE and contraindications to fibrinolysis (Class IIa; Level of Evidence C). 2. Repeat thrombolysis or catheter embolectomy and fragmentation or surgical embolectomy is reasonable for patients with massive PE who remain unstable after receiving fibrinolysis (Class IIa; Level of Evidence C).( with in 1 hour)

97 Recommendations for Catheter Embolectomy and Fragmentation & surgical embolectomy 3. Either thrombolysis, catheter embolectomy or surgical embolectomy may be considered for patients with submassive acute PE judged to have clinical evidence of adverse prognosis (new hemodynamic instability, worsening respiratory failure, severe RV dysfunction, or major myocardial necrosis) (Class IIb; Level of Evidence C). 4. Catheter embolectomy and surgical thrombectomy are not recommended for patients with low-risk PE or submassive acute PE with minor RV dysfunction, minor myocardial necrosis, and no clinical worsening (Class III; Level of Evidence C).

98 Roles of IVCs filter?

99 Inferior Vena Cava Filter Greenfield filter A filter placed in IVC to prevent emboli from moving into pulmonary circulation while maintaining caval patency Firstly placed in1967, but most of the IVC filter insertion (>70%) performed in the 1990s.

100 Inferior Vena Cava Filter Type of IVC Filters The Greenfield filter The Vena Tech filter The Bird s Nest filter The Nitinol filter Indications; Contraindication to anticoagulation Complication of anticoagulation Failure of anticoagulation Prophylaxis in patient with already significantly compromised pulmonary vascular bed & after embolectomy

101 Inferior Vena Cava Filter Theoretically benefits by prevent recurrent PE but Fatal complication 0.12 %, Other complications thrombosis, filter migration, filter erosion, and IVC obstr. (5-18 %) Boonsong Patjanasoontorn, MD, FCCP, FCCM

102 Recommendations on IVC Filters in Acute PE 1. Adult patients with any confirmed acute PE (or proximal DVT) with contraindications to anticoagulation or with active bleeding complication should receive an IVC filter (Class I; Level of Evidence C). 2. Anticoagulation should be resumed in patients with an IVC filter once contraindications to anticoagulation or active bleeding complications have resolved (Class I; Level of Evidence B). 3. Patients who receive retrievable IVC filters should be evaluated periodically for filter retrieval within the specific filter s retrieval window (Class I; Level of Evidence C).

103 Recommendations on IVC Filters in Acute PE 4. For patients with recurrent acute PE despite therapeutic anticoagulation, it is reasonable to place an IVC filter (Class IIa; Level of Evidence C). 5. For DVT or PE patients who will require permanent IVC filtration (eg, those with a long-term contraindication to anticoagulation), it is reasonable to select a permanent IVC filter device (Class IIa; Level of Evidence C).

104 Recommendations on IVC Filters in Acute PE 5. For DVT or PE patients with a time-limited indication for an IVC filter (eg, those with a short-term contraindication to anticoagulation therapy), it is reasonable to select a retrievable IVC filter device (Class IIa; Level of Evidence C). 6. Placement of an IVC filter may be considered for patients with acute PE and very poor cardiopulmonary reserve, including those with massive PE (Class IIb; Level of Evidence C). 7. An IVC filter should not be used routinely as an adjuvant to anticoagulation and systemic fibrinolysis in the treatment of acute PE & DVT (Class III; Level of Evidence C).

105 Classification on Level of Risk of Venous Thrombo-embolism* Low Moderate High Very High Calf vein thrombosis (%) Proximal DVT (%) Pulmonary embolism (%) Fatal PE (%) Appropriate Prophylaxis None Heparin SQ 5,000 q 12 h IPC Device Heparin SQ 5,000 Q 8 H IPC Device LMWH or adjusted-dose UH or IPC+UH/LMWH * The 7 th ACCP Consensus Conference on Antithrombotic Therapy. Chest 2008;119:1s-370s. 05/04/2008 BOONSONG PATJANASOONTORN, MD, FCCP, FCCM

106 Summary-I When clinical suspicion for PE is reasonable high, anticoagulant therapy should be start during further work up Patient with clinical suspicious PE and evidence of hypotension or hypoperfusion need urgent evaluation of other possibility cause of shock and imaging confirmation of MPE Anatomically confirmed Massive PE with persistent hypotension > 15 min. despite optimized fluid therapy, and no absolute contraindication for, should start thrombolysis promptly PE Boonsong Patjanasoontorn, MD, FACP, FCCP, FCCM

107 Summary-II UFH is the preferred anticoagulant of choice for submassive PE Evidence support is unclear regarding thrombolytic therapy in sub-massive PE (subgroup categorization) Need further large clinical trials or meta-analysis for demonstrate a survival benefit & safety profile of thrombolysis compared to anticoagulation alone in submassive PE PE-2012: Boonsong Patjanasoontorn, MD, FACP, FCCP, FCCM

108 Summary-III The options for unsuccessful initial thrombolysis with confirmed residual clot are Cather-based endovascular treatment Surgical embolectomy or 2 nd Thrombolysis Depend on availability & experience of institution Patients with absolute C/I for thrombolysis, catheterbased clot fragmentation or surgical embolectomy should be considered Consider IVC filter for patients with C/I for anticoagulant, serious hemorrhagic complications, or failure anticoagulation PE-2016: Boonsong Patjanasoontorn, MD, FACP, FCCP, FCCM

109 6 E= 2 m.c E=M.C 3

110 E = m.c 2 Albert Einstein in Physics E = m 6.c 3 E M C 1 C 2 C 3 Boonsong P soontorn in Clinical Medicine = Excellence in Clinical Medicine = Mastering of at least 6 Multiple Sciences = Commitment = Competence = Compassion

111 Competency without compassion may be (sometimes) useless. No one cares how much you know, until they know how much you care

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