1. Case Presentation 45f acute CP, dyspnea, near-syncope Pale, diaphoretic, looks unwell Afebrile, HR 110, RR 32, BP 118/68 Sats 75% RA, 92% on NRB JVP elevated HS Normal Chest clear 45f acute CP, dyspnea, near-syncope Pale, diaphoretic, looks unwell Afebrile, HR 110, RR 32, BP 118/68 Sats 75% RA, 92% on NRB JVP elevated HS Normal Chest clear

2. Portable CXR

3. ECG

4. Next?

5. ECHO Significant RV dilation Increased R sided pressures RV hypokinesis Clot visible in RV Significant RV dilation Increased R sided pressures RV hypokinesis Clot visible in RV

6. CT-pulmonary angiogram

7. Management Heparin PE protocol initiated Colleague asks why you haven’t thrombolysed yet “But she’s not in shock!” “Yeah, but she’s a submassive PE” “…what’s a submassive PE?” Heparin PE protocol initiated Colleague asks why you haven’t thrombolysed yet “But she’s not in shock!” “Yeah, but she’s a submassive PE” “…what’s a submassive PE?”

8. Thrombolysis of the Submassive PE Michael Kenney MD CCFP(EM) Dept of Emergency Medicine University of Calgary Michael Kenney MD CCFP(EM) Dept of Emergency Medicine University of Calgary

9. Objectives 1.Define submassive PE 2.Discuss clinical significance of a submassive PE 3.Determine an evidence-based approach to identifying the SMPE 4.Review the literature regarding efficacy of thrombolytics in SMPE 5.Review contraindications to thrombolytics in PE 6.Local expert opinion on alternate therapy 1.Define submassive PE 2.Discuss clinical significance of a submassive PE 3.Determine an evidence-based approach to identifying the SMPE 4.Review the literature regarding efficacy of thrombolytics in SMPE 5.Review contraindications to thrombolytics in PE 6.Local expert opinion on alternate therapy

10. Massive PE Pulmonary embolism in the setting of hemodynamic instability (SBP<90) PE + Shock = Massive PE Literature supports thrombolytics (Kearon et al, Chest 2008) Pulmonary embolism in the setting of hemodynamic instability (SBP<90) PE + Shock = Massive PE Literature supports thrombolytics (Kearon et al, Chest 2008)

11. Submassive PE (SMPE) Pulmonary embolism in the setting of a hemodynamically stable patient with ECHO-proven evidence of right ventricular dysfunction PE + NBP + RV dysfunction = SMPE Pulmonary embolism in the setting of a hemodynamically stable patient with ECHO-proven evidence of right ventricular dysfunction PE + NBP + RV dysfunction = SMPE

12. ECHO in Submassive PE RV hypokinesis RV dilation Pulmonary hypertension >30mmHg Septal shift > RV hypokinesis > RV dilation (Wolde et al, Arch Int Med 2004; Kline et al, Am Heart Journal, 2008) RV hypokinesis RV dilation Pulmonary hypertension >30mmHg Septal shift > RV hypokinesis > RV dilation (Wolde et al, Arch Int Med 2004; Kline et al, Am Heart Journal, 2008)

13. ECG Strain  RV Dysfunction

14. Clinical Significance When compared to patients with PE and normal RV function –Higher mortality (8-13%) –Higher in-hospital complications –Higher long-term cardiopulmonary morbidity Pulm hypertension R CHF ( Kreit et al, Chest 2005) When compared to patients with PE and normal RV function –Higher mortality (8-13%) –Higher in-hospital complications –Higher long-term cardiopulmonary morbidity Pulm hypertension R CHF ( Kreit et al, Chest 2005)

15. Pathophysiology

16. Identifying the SMPE 1.Clinical 2.ECG 3.Cardiac biomarkers Troponins BNP 4.CT Scan 1.Clinical 2.ECG 3.Cardiac biomarkers Troponins BNP 4.CT Scan

17. Clinical Clues Syncope Significant tachycardia Significant hypoxia P/E –JVD –Parasternal heave –Split P2 –TR murmur Syncope Significant tachycardia Significant hypoxia P/E –JVD –Parasternal heave –Split P2 –TR murmur

18. ECG in SMPE Strain pattern (T inversion V1-V4)* S1-Q3-T3 RAD RBBB Insensitive and mostly non-specific Strain pattern specific for RV strain  RV dysfunction Strain pattern (T inversion V1-V4)* S1-Q3-T3 RAD RBBB Insensitive and mostly non-specific Strain pattern specific for RV strain  RV dysfunction

19. Cardiac Markers Troponins BNP Troponins BNP

20. Cardiac Markers Troponins –Correlates with presence of RV dysfunction –Predictive of complicated in-hospital course –Associated with increased mortality in setting of PE –NPV 93-97% for 30 day mortality (Konstantinides, Circulation 2002; La Vecchia et al Heart, 2005; Askey et al, Am J or Emer Med 2007) Troponins –Correlates with presence of RV dysfunction –Predictive of complicated in-hospital course –Associated with increased mortality in setting of PE –NPV 93-97% for 30 day mortality (Konstantinides, Circulation 2002; La Vecchia et al Heart, 2005; Askey et al, Am J or Emer Med 2007)

21. Cardiac Markers BNP –Correlates with RV dysfunction –95-99% NPV for complicated in-hospital course –Predictive of elevated 30 day mortality –Significantly predicted greater dyspnea at rest, decreased exercise tolerance at 6 months (Wolde et al, Circulation, 2003; Binder, Circulation 2005; Kline et al, Am Heart Journal, 2008) BNP –Correlates with RV dysfunction –95-99% NPV for complicated in-hospital course –Predictive of elevated 30 day mortality –Significantly predicted greater dyspnea at rest, decreased exercise tolerance at 6 months (Wolde et al, Circulation, 2003; Binder, Circulation 2005; Kline et al, Am Heart Journal, 2008)

22. Cardiac Markers Negative markers = lower risk, more favorable course Positive markers = ECHO Use clinical judgement Serial testing Negative markers = lower risk, more favorable course Positive markers = ECHO Use clinical judgement Serial testing

23. CT Scan RV enlargement on the CT angiogram defined as RV diameter >90% LV diameter, appears to be an independent risk factor for death and nonfatal clinical complications (Kucher et al, Circulation, 2006; Schoepf et al Circulation, 2005) RV enlargement on the CT angiogram defined as RV diameter >90% LV diameter, appears to be an independent risk factor for death and nonfatal clinical complications (Kucher et al, Circulation, 2006; Schoepf et al Circulation, 2005)

24. ED assessment of the Hemodynamically Stable PE

25. Therapy 1.Anticoagulation (heparin) 2.Thrombolytic therapy 1.Efficacy 2.Choice of agent 3.Absolute Contraindications 4.Risk factors for Major Bleeding 3.Catheter embolectomy 4.Surgical embolectomy 1.Anticoagulation (heparin) 2.Thrombolytic therapy 1.Efficacy 2.Choice of agent 3.Absolute Contraindications 4.Risk factors for Major Bleeding 3.Catheter embolectomy 4.Surgical embolectomy

26. Efficacy of Thrombolytics in SMPE The Literature –<800 patients overall –Not all randomized controlled –Some studies lysed all PE’s –SMPE not consistently defined –UK, SK, tPA The Literature –<800 patients overall –Not all randomized controlled –Some studies lysed all PE’s –SMPE not consistently defined –UK, SK, tPA

27. Efficacy of Thrombolytics in SMPE Cardiopulmonary Physiology –Markedly improves PAP, RV function and pulmonary perfusion –Only one study long-term benefit persists @ 7years Cardiopulmonary Physiology –Markedly improves PAP, RV function and pulmonary perfusion –Only one study long-term benefit persists @ 7years

28. Efficacy of Thrombolyitics in SMPE Clinical Outcome Measures –Lower inhospital complication Fewer recurrent PE Less use of vasopressors, intubation, rescue embolectomy –Trends toward improved mortality –No study or meta-analysis large enough to clearly show mortality benefit Clinical Outcome Measures –Lower inhospital complication Fewer recurrent PE Less use of vasopressors, intubation, rescue embolectomy –Trends toward improved mortality –No study or meta-analysis large enough to clearly show mortality benefit

29. Major Bleed 1.Intracranial Hemorrhage 2.Any bleed leading to shock –GI and retroperitoneal most common 3.Any bleed leading to transfusion > 2U PRBCs or surgery 1.Intracranial Hemorrhage 2.Any bleed leading to shock –GI and retroperitoneal most common 3.Any bleed leading to transfusion > 2U PRBCs or surgery

30. Contraindications Absolute Hx of hemorrhagic CVA Active intracranial neoplasm Recent (<2 months) intracranial surgery or trauma Recent (<2 weeks) major GI bleed or major surgery Tapson et al, Chest, Oct 2008 Absolute Hx of hemorrhagic CVA Active intracranial neoplasm Recent (<2 months) intracranial surgery or trauma Recent (<2 weeks) major GI bleed or major surgery Tapson et al, Chest, Oct 2008

31. Risk Factors for ICH Age > 70 Female Weight < 70kg SBP >170 or DBP >95 PHx ischemic CVA DM Elevated INR PLT < 100 RF 0-1 = 0.5-1% 2-4 = 2.5% >5 = 4% Age > 70 Female Weight < 70kg SBP >170 or DBP >95 PHx ischemic CVA DM Elevated INR PLT < 100 RF 0-1 = 0.5-1% 2-4 = 2.5% >5 = 4%

32. Thrombolytics cause Intracranial Hemorrhage 1%

33. Choice of Thrombolytic tPA only lytic approved tPA 100mg –10mg bolus, remaining 90mg over 2 hours –most widely studied and accepted in PE TNK has not been studied adequately in PE –0.5mg/kg (50mg max) –One study 22 patients, equivalent to tPA tPA only lytic approved tPA 100mg –10mg bolus, remaining 90mg over 2 hours –most widely studied and accepted in PE TNK has not been studied adequately in PE –0.5mg/kg (50mg max) –One study 22 patients, equivalent to tPA

34. Bottom Line of Thrombolytics in SMPE tPA Trends but no definitive mortality benefit in SMPE Case-by-case, not routine Benefit vs bleeding risk assessment Involve intensivist early Involve patient and family tPA Trends but no definitive mortality benefit in SMPE Case-by-case, not routine Benefit vs bleeding risk assessment Involve intensivist early Involve patient and family

35. Embolectomy Percutaneous Catheter Extraction –Pigtail rotational catheter –Usually tPA in addition –May take hours –Angiojet coming Surgical Embolectomy –Rare benefit over percutaneous –If absolute contraindications and IR unable Percutaneous Catheter Extraction –Pigtail rotational catheter –Usually tPA in addition –May take hours –Angiojet coming Surgical Embolectomy –Rare benefit over percutaneous –If absolute contraindications and IR unable

36. IVC Filter Placement Reduces short term risk of recurrent PE Consider in PE –Little cardiac reserve –Significant extremity clot burden –Contraindications to lytics, or high risk for bleeding Reduces short term risk of recurrent PE Consider in PE –Little cardiac reserve –Significant extremity clot burden –Contraindications to lytics, or high risk for bleeding

37. Summary Submassive PE = normal BP + RVD Significant morbidity and mortality associated Reviewed clinical clues, ECG findings, and cardiac markers helpful in identifying the patient with SMPE ECHO if RV dysunction suspected Submassive PE = normal BP + RVD Significant morbidity and mortality associated Reviewed clinical clues, ECG findings, and cardiac markers helpful in identifying the patient with SMPE ECHO if RV dysunction suspected

38. Summary Thrombolytics improve cardiopulmonary hemodynamics lower in-hospital complications Trends, but no clear mortality benefit Reviewed absolute contraindications and risk factors for major bleed Discussed non-medical therapeutic options Thrombolytics improve cardiopulmonary hemodynamics lower in-hospital complications Trends, but no clear mortality benefit Reviewed absolute contraindications and risk factors for major bleed Discussed non-medical therapeutic options

39. Questions ?