A 42-year-old female presented with chest pain, shortness of breath, and hypotension due to massive bilateral pulmonary emboli. Initial treatment with thrombolytic infusion and pigtail rotation catheter failed to improve her condition. Angiojet mechanical thrombectomy was then performed across the clots, which improved her hypotension and oxygenation. Catheter-directed thrombectomy is an alternative treatment to systemic thrombolysis for massive pulmonary embolism when thrombolysis is contraindicated or has failed. It allows for direct delivery of thrombolytics or mechanical disruption of clots and can rapidly improve hemodynamics. However, the optimal technique and regimen remains uncertain given limited data currently.

1. Catheter-directed thrombectomy
Massive and submassive PE
Justin McWilliams, MD and Scott Genshaft, MD
UCLA Interventional Radiology

2. 42 y/o female
Chest pain
Shortness of breath

4.  CT shows large bilateral saddle emboli
 Blood pressure 84/58
 Heart rate 110
 O2 sat 90% on 4L NC
 Bleeding ulcer 2 mo ago

5. Pulmonary artery pressure: 55/13

6. 5 F pigtail rotation
No improvement

7. 5 cm infusion length
McNamara lysis
catheter
10 mg tPA given
across each main PA
Still no improvement

8. Repeat pigtail rotation

9. Remains hypotensive
Tachycardic to 130s

10. 6F Angiojet activated
across clot
Hypotension and
oxygenation improved

11. next morning

12. PE basics

13. pathophysiology of PE
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

14. definitions
 Massive PE: Acute PE with sustained hypotension
(SBP <90 mmHg) for at least 15 minutes without
other cause
 Or drop in SBP >40 mmHg
 Or pulselessness/cardiac arrest
 Or HR <40 with signs or symptoms of shock
 Massive PE inpatient mortality is 15-50%
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

15. definitions
 Submassive PE: Acute PE without systemic
hypotension but with either RV dysfunction or
myocardial necrosis
 RV dysfunction could include:
 RV dilation on echo or CT (RV diameter/LV diameter >0.9)
 Elevation of BNP (>90 pg/mL)
 EKG changes (new RBBB, anteroseptal ST changes,
anteroseptal TWI)
 Myocardial necrosis is defined as troponin I >0.4 ng/mL
 Inpatient mortality of submassive PE is 5-12%
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

16. definitions
 Low-risk PE: Everybody else
 Short-term mortality about 1%
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

17. anticoagulation versus thrombolysis
 Heparin allows passive reduction of thrombus size
 No substantial improvement in first 24 hours
 65-70% reduction in perfusion defect by 7 days
 Thrombolysis actively promotes hydrolysis of fibrin
 Convert native circulating plasminogen into plasmin
 Plasmin cleaves fibrin, lysing the thrombus
 30-35% reduction in perfusion defect in first 24 hours
 65-70% reduction in perfusion defect by 7 days
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

18. treatment of PE
 Systemic anticoagulation
 IV thrombolytics
 Standard FDA-approved therapy for PE with hemodynamic
instability
 100 mg tPA IV over 2 hours
 Catheter directed therapy – uncertain indications
 Thrombolytic infusion
 Mechanical thrombolysis
 Mechanical thrombectomy
 Surgical embolectomy

19. ACCP 2012 recommendations
 In patients with acute PE associated with
hypotension (eg, systolic BP <90 mmHg) who do not
have a high bleeding risk, we suggest systemically
administered thrombolytic therapy over no such
therapy (Grade 2C)
Guyatt GH, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians
evidence-based practice guidelines. Chest 2012;141: 2 suppl 7S-47S.

20. Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

21. contraindications to systemic lysis
Absolute Relative
 Any prior intracranial  Age >75
hemorrhage  Current anticoagulation
 Brain AVM or tumor  Pregnancy
 CVA in last 3 months  Noncompressible vascular
 Active bleeding or puncture
bleeding diathesis  Traumatic/prolonged CPR
 Recent surgery  Internal bleeding in last
encroaching on spinal month
canal or brain  Uncontrolled HTN (SBP
>180 or DBP >110)
 Recent significant head
 Remote stroke
trauma
 Major surgery in last 3
weeks

22. contraindications to systemic lysis
Half of all patients with acute PE have contraindications
to systemic lysis
Piazza G, Goldhaber SZ. Management of submassive pulmonary embolism. Circulation 2010; 122:1124-1129.

23. systemic lysis in massive PE
The good The bad
 Recurrent PE or death is  Overall major bleeding rate
reduced from 19.0% to 9.4% of ~20%
compared to heparin alone
 Intracranial hemorrhage rate
~3%
 30% reduction in PA
pressures
 Effects not immediate (2
hour infusion + time for drug
 15% increase in cardiac to work)
index
 Many patients are
 Noninvasive contraindicated
Marshall PS, Mathews KS, Siegel MD. Diagnosis and management of life-threatening pulmonary embolism. J Intensive Care Med
2011;26:275-294.

24. is there a better way?

25. catheter-directed therapy for
massive PE

26. catheter-directed therapy (CDT)
 Alternative or additive
treatment for massive PE
 Wide variety of devices
and techniques, with the
goal of rapidly reducing clot
burden
 Thrombus fragmentation
 Thrombus aspiration
 Intra-thrombus lytic
administration

27. techniques – pigtail rotation

28. techniques – balloon angioplasty

29. techniques – aspiration thrombectomy

30. techniques – rheolytic aspiration

31. techniques – ultrasound-aided thrombolysis

32. history of CDT for PE
 Verstraete et al 1988: 34 randomized patients, no
benefit seen for PA lysis over IV systemic lysis (50
mg tPA)
 Administered lytics into the main trunk of the PA
 Did not place lytic directly into thrombus
 No mechanical fragmentation or aspiration of the
thrombus
 Tapson et al 1994: Animal model showed that
intra-thrombus administration of lytic was faster
and more effective
 Improves exposure of drug to thrombus surface
 Fava et al 1997: 17 patients, intraclot
fragmentation + lysis produced clinical
improvement in 88%
 Dozens more studies over the next decade, all
observational, using a wide variety of devices, lytic
agents, regimens

34. ACCP 2008 recommendations
 “For most patients with PE, we recommend against
use of interventional catheterization techniques
except in selected highly compromised PE patients
who are unable to receive thrombolytic therapy
because of bleeding risk, or whose critical status
does not allow sufficient time for thrombolytic therapy
to be effective.”
Kearon C et al. Antithrombotic therapy for venous thrombembolic disease:American College Chest Physicians evidence-based clinical
practice guidelines (8th edition). Chest 2008;133:454S-545S.

35. CDT: meta-analysis
 Meta-analysis of CDT for massive PE
 6 prospective, 29 retrospective uncontrolled studies (level 2)
 Total 594 patients
 Variety of techniques, most commonly pigtail rotation (70%) combined
with intraclot lysis [on-table (67%) and/or via infusion catheter (60%)]
 Clinical success in 86.5%
 Stabilized hemodynamics, resolved hypoxia, and survival to discharge
 Compare to 77% survival rate in ICOPER
 Major hemorrhage in 2.4%, only one case of cerebral hemorrhage
(0.2%)
 Compare to 22% major hemorrhage rate and 3% cerebral hemorrhage
rate in ICOPER
 Catheter-directed therapy may be considered a first-line treatment
option in lieu of IV tPA
Kuo WT, et al. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern
techniques. J Vasc Interv Radiol 2009;20:1431-1440.

36. CDT: analysis of the meta-analysis
 Pooled clinical success rate of 86.5%
 96% received CDT as 1st adjunct to heparin (no prior systemic lysis)
 33% initiated with mechanical treatment alone – no on-table lytic drug
 Minor complication rate 8%
 Groin hematoma
 Bradycardia, renal insufficiency, hemoglobinuria, hemoptysis, heart block (all
Angiojet)
 Embolus dislocation
 PA dissection
 Major complication rate 2.4%
 Large groin hematoma (pRBC)
 Non-cerebral hemorrhage (pRBC)
 Severe hemoptysis
 Renal failure
 Central vascular perforation causing tamponade
 5 deaths (all Angiojet) – bradycardia, apnea, widespread distal embo, ICH
Kuo WT, et al. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern
techniques. J Vasc Interv Radiol 2009;20:1431-1440.

37. IV tPA vs. CDT for massive PE
IV tPA (ICOPER registry) CDT (Stanford meta-analysis)
 2454 patients, global  594 patients, global
 304 treated with IV lysis  All treated with mechanical
thrombectomy +/- catheter-directed
lysis
 1/3 were hemodynamically
unstable
 All hemodynamically unstable
 23% PE mortality
 13.5% PE mortality
 22% major complications
 2.4% major complications
 3% cerebral hemorrhage
 <0.2% cerebral hemorrhage
Kuo WT, et al. Catheter-directed therapy for the treatment of massive pulmonary embolism: systematic review and meta-analysis of modern
techniques. J Vasc Interv Radiol 2009;20:1431-1440.

38. CDT for massive PE: the good and bad
The good The bad
1. Less invasive than surgery 1. No universal protocol
2. Off-label use
2. Can quickly debulk central PE,
without needing 2 hour infusion
3. Limited availability/expertise
3. Useful when IV tPA fails or is 4. May delay treatment if angio
contraindicated suite not ready
5. Fear of complications (Angiojet)
4. Appears safer than systemic
lysis (~20 mg tPA vs. 100 mg
tPA)
Guyatt GH, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians
evidence-based practice guidelines. Chest 2012;141: 2 suppl 7S-47S.
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

39. CDT for massive PE: consensus statements
AHA 2011 ACCP 2012
1. Reasonable for patients with 1. Suggested for massive PE with
massive PE and contraindication to thrombolysis
contraindications to lysis (class (grade 2C)
IIa)
2. Suggested for massive PE with
failed thrombolysis (grade 2C)
2. Reasonable for patients with
massive PE who remain
unstable after systemic lysis 3. Suggested for massive PE with
(class IIa) shock likely to cause death
within hours (grade 2C)
Guyatt GH, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians
evidence-based practice guidelines. Chest 2012;141: 2 suppl 7S-47S.
Jaff MR et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic
thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation 2011; 123:1788-1830.

40. CDT for massive PE: controversies
 Should CDT replace IV tPA as first-line therapy at
institutions with expertise?
 Delay in treatment?
 Should CDT be an adjunctive treatment to IV tPA?
 Perform in all patients, stopping the IV infusion once the angio
suite is ready?
 Perform only in patients where IV tPA did not work?
 What regimen should be used?
 Which mechanical thrombectomy device is best?
 Should on-table lysis be performed?
 Should prolonged intra-thrombus lytic infusion be performed?
 What contraindications are truly contraindications for
CDT?

41. PERFECT registry
 Pulmonary Embolism Response to Fragmentation,
Embolectomy, & Catheter Thrombolysis
 Prospective observational trial
 Primary outcome measures
 Resolution of hypoxia (post-procedure and 3 months)
 Survival from acute PE (post-procedure and 3 months)
 Stabilization of hemodynamics (post-procedure and 3
months)
 Estimated completion in 2014

42. Catheter-directed thrombectomy
for submassive PE

43. submassive pulmonary embolism

44. submassive pulmonary embolism
 “No consensus on the exact definition of “submassive”
or “intermediate-risk” PE exists to date.”
 Normotensive patient with predictors of poor outcome
 Evidence that several factors predict poor outcome in
normotensive patients with PE
PEITHO Investigators, American Heart Journal, Volume 163, Issue 1, Jan 2012, Pg 33-38

45. prognosticating in submassive PE
 Imaging
 Echocardiogram
 Presence of RV dysfunction doubles all-cause mortality at 3 months
 Useful to differentiate low-risk from submassive PE
 CTA
 Signs of RV strain correlate well with echo
 Cardiac biomarkers
 Troponin I
 Released from RV in response to pressure overload and RV ischemia/infarction
 Meta-analysis: elevated troponin increases mortality risk of PE 6-fold
 Troponin I <0.07 ng/mL has 98% negative predictive value for in-hospital mortality
 BNP
 Neurohormone sythesized and released by the ventricles in response to strain
 May take several hours after onset of RV strain to see increased BNP
 BNP <50-85 has 99% negative predictive value for death in normotensive patients
 Because of high NPV, a low troponin or BNP level may mean echo not needed
 D-dimer
 93% sensitive for segmental PE or larger, 50% sensitive for subsegmental PE
 D-dimer <1500 mcg/mL has 99% NPV for 3-month all-cause mortality
Marshall PS, Mathews KS, Siegel MD. Diagnosis and management of life-threatening pulmonary embolism. J Intensive Care Med
2011;26:275-294.

46. right heart dysfunction
 RV:LV ratio > 0.9 has been shown to be a predictor of
in-hospital mortality
 1.9% if RV/LV < 0.9
 6.6% if RV/LV > 0.9
Fremont B, Pacouret G, Jacobi D. CHEST 2008;133:358-362

47. submassive pulmonary embolism

48. clinical outcomes of submassive PE
 3-12 % inpatient mortality
 1-5% develop Chronic Thromboembolic Disease with
PAH

49. ACCP 2012 guidelines for submassive PE
5.6.1.2. In most patients with acute PE not associated with
hypotension, we recommend against systemically administered
thrombolytic therapy (Grade 1C).
5.6.1.3. In selected patients with acute PE not associated with
hypotension and with a low risk of bleeding whose initial clinical
presentation or clinical course after starting anticoagulant therapy
suggests a high risk of developing hypotension, we suggest
administration of thrombolytic therapy (Grade 2C).
5.6.2.2. In patients with acute PE, when a thrombolytic agent is
used, we suggest administration through a peripheral vein over a
pulmonary artery catheter (Grade 2C).

50. AHA 2011 guidelines for submassive PE
 1. Fibrinolysis may be considered for patients with submassive acute PE
judged to have clinical evidence of adverse prognosis (new hemodynamic
i stability, worsening respiratory insufficiency, severe RV dysfunction, or
major myocardial necrosis) and low risk of bleeding complications (Class
IIb; Level of Evidence C).
 2. Fibrinolysis is not recommended for patients with low-risk 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).
 3. Either 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).

51. Piazza G, Goldhaber SZ. Management of submassive pulmonary embolism. Circulation 2010; 122:1124–1129

52. role of IR in submassive PE
 Role of catheter directed treatment of submassive PE was slotted
for “Hot Topic” debate at SIR 2012
 Rationale for CDT in submassive PE
 Rapid debulking of thrombus
 Prevention of adverse outcomes
 Early
 Worsening right ventricular afterload/cardiac ischemia, respiratory
compromise
 Late
 Chronic thromboembolic disease and pulmonary hypertension
 Limit dose of thrombolytic
 Reduction in hemorrhage rate

53. Role for catheter treatment of submassive
PE requires an answer to these questions
 How important is rapid clearance of thrombus?
 Role of thrombolysis
 How does the effectiveness of catheter directed
thrombolysis compare to systemically delivered lytic
agents?

54. Role for catheter treatment of submassive
PE requires an answer to these questions
 How important is rapid clearance of thrombus?
 Role of thrombolysis
 How does the effectiveness of catheter directed
thrombolysis compare to systemically delivered lytic
agents?

55. role of thrombolysis in submassive PE
 Registries have failed to show a survival benefit in
patients with submassive PE
Jaff 2011

56. role of thrombolysis in submassive PE
 Meta-analysis of 9 randomized control trials of
thrombolytics and heparin in treatment of acute PE
 461 patients included in analysis
 Mortality
 4.6% lytic
 7.7% heparin
 Bleeding
 12.9% lytic (2.1% fatal)
 8.6% heparin
 Recurrence of PE slightly decreased in lytic group
Agnelli. Arch Internal Medicine 2002

57. role of thrombolysis in submassive PE
 Management Strategies and Prognosis of Pulmonary
Embolism Trial 3
 256 patients randomized to
 100 mg tPA administered IV over 2 hours followed by infusion
of unfractionated heparin
 Placebo + heparin
 tPA group had lower rate of in-hospital death or escalation
of care
 Largely attributed to escalation of care
Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin
alone in patients with submassive pulmonary embolism. N Engl J Med 2002; 347:1143–1150.

58. 1/2
7
UFH 
2/
7
t-PA

2/11

59. role of thrombolysis in submassive PE
 Kline et al evaluated echocardiograms in patients with
submassive PE at the time of diagnosis and at 6 months
 Two groups
 Heparin
 tPA + heparin
 Pts treated with tPA had a greater median decrease in
pulmonary systolic pressure
 22 mmHg vs 2 mmHg
 6 months – PA pressure elevated in 27% of pts treated
with only heparin
 50% of patients had symptoms of PAH
Kline JA, Steuerwald MT, Marchick MR, Hernandez-Nino J, Rose GA. Prospective evaluation of right ventricular
function and functional status 6 months after acute submassive pulmonary embolism: frequency of persistent or
subsequent elevation in estimated pulmonary artery pres- sure. Chest 2009; 136:1202–1210.

61. 5/2011
2/2012

63. chronic thromboembolic disease

64. Role for catheter treatment of submassive
PE requires an answer to these questions
 How important is rapid clearance of thrombus?
 Role of thrombolysis
 How does the effectiveness of catheter directed
thrombolysis compare to systemically delivered lytic
agents?

65. comparative effectiveness of IV tPA vs. CDT
for submassive PE
 We don’t know
 Literature regarding catheter based approach is limited
to case series and meta-analyses

66. submassive PE: pigtail delivery of tPA

67. submassive PE: Angiojet

68. submassive PE: thrombectomy and
overnight thrombolysis

69. submassive PE: pulse-spray lysis

70. evidence needed
 Clinical benefits of escalation of therapy for acute PE
beyond anticoagulation?
 Reduction of mortality
 Prevention of chronic thromboembolic disease
 Improved outcomes with catheter directed thrombolyis
vs systemic thrombolysis?
 More effective?
 Reduced hemorrhage?

71. active clinical trials
 PERFECT
 PEITHO
 ULTIMA
 SEATTLE I and II

72. ongoing clinical trials
 PEITHO STUDY
 Pulmonary Embolism Thrombolysis trial
 Prospective, multicenter, randomized, double-blind
 IV Tenecteplase + UFH vs UFH
 Randomized within 2 hours of dx of PE with RV dysfunction
and myocardial injury
 Primary outcome
 Death or hemodynamic collapse within 7 days
 Safety outcomes
 Related to hemorrhage
 Long term follow-up
 Death
 Echo evaluation for PAH and RV dysfunction

73. PEITHO trial criteria

74. PEITHO trial design

75. ULTIMA trial
 ULTrasound Accelerated ThrombolysIs of PulMonAry
Embolism
 Comparison of ultrasound-accelerated thrombolysis
through the EKOS catheter system vs systemic
anticoagulation with heparin
 Two arm, prospective, randomized
 Experimental arm: low-dose (<20 mg) r-tPA + full dose
IV heparin
 Control arm: IV heparin alone

76. ULTIMA trial
 Primary endpoint
 Reduction of RV/LV ratio: RV/LV ratio will be
measured by echocardiography at baseline and at 24
hours
 Inclusion criteria
 Patients with acute PE symptoms < 14 days.
 CT evidence of PE in at least one main or proximal lower lobe
pulmonary artery
 RV/LV end diastolic diameter ratio is ≥ 1.0

77. SEATTLE II
 Submassive and massive pulmonary Embolism
treatment with AcceleraTed ThromboLysis thErapy
 Question: Will t-PA delivered via the EKOS catheter +
IV heparin decrease the ratio of RV to LV diameter
within 48 hours in patients with massive or submassive
PE?
 Single arm, prospective study
 All pts get catheter directed t-PA + IV UFH
 PE diagnosed on CT
 Submassive inclusion
 RV:LV ratio > 0.9 on CT angiography

78. SEATTLE II
 Primary outcomes
 RV:LV Diameter Ratio measured at 48 hours
 Major bleeding at 72 hours
 Inclusion criteria
 CT evidence of proximal PE Age ≥ 18 years AND
 PE symptom duration ≤14 days AND
 Massive PE or
 Submassive PE
 (RV:LV ≥ 0.9 on contrast-enhanced chest CT)

79. summary
 The role of early thrombolysis in treatment of massive
and submassive PE is not well defined and currently
under active investigation
 IRs have the tools and skills to perform catheter
directed treatment of acute PE
 Infusion of lytic agents
 Mechanical thrombolysis and thrombectomy
 Theoretical rationale for catheter directed treatment of
PE
 Rapid clot debulking
 Reduction of lytic agent (decreased hemorrhage)

81. Stanford PE protocol
 Massive PE
 Anesthesia involved when possible
 8F sheath into common femoral vein, select main PA
 Measure pulmonary pressures (if time)
 Bury pigtail into clot
 Administer bolus of tPA (start with 10 mg per lung)
 Pigtail fragmentation
 Conclude the procedure when hemodynamic improvement with resolution
of shock is achieved, regardless of angiographic results.
 Submassive PE
 Treated with CDT if there is RV strain or severe hypoxia
 No bolus dose, no fragmentation
 Place infusion catheter across clot and perform low-dose infusion
 PERFECT registry

82. Proposed CDT recommendations by JVIR
 SBP <90 mmHg or drop >40 mmHg
 Cardiogenic shock with hypoxia
 Circulatory collapse requiring CPR
 RV strain +/- pulm HTN
 Precapillary pulm HTN
 Widened A-a O2 gradient (>50 mmHg)
 Clinically severe PE with CI to anticoagulation or lytic
therapy
Uflacker R. Interventional therapy for pulmonary embolism. J Vasc Interv Radiol 2001;12:147-164

83. systemic thrombolysis
Potential benefits Potential harm
 More rapid symptom  Hemorrhage
resolution  ~20% major hemorrhage
 Stabilization of  ~3% cerebral
respiratory and heart hemorrhage
function
 Reduction of RV
damage
 Reduced risk of chronic
PE with pulmonary HTN
 Increased probability of
survival

84. systemic thrombolysis
 In hemodynamically unstable patients, systemic lysis
reduces recurrent PE and death (OR 0.45)
 No proven advantage of one lytic over another
 2-hour infusion provides faster results and less risk
compared to longer infusions
 Unfractionated heparin should be stopped when decision
to deliver lytics is made; then resumed after infusion
without a bolus [?]
 Greatest benefit when delivered within 48 hours of
symptom onset
Marshall PS, Mathews KS, Siegel MD. Diagnosis and management of life-threatening pulmonary embolism. J Intensive Care Med
2011;26:275-294.

85. Intraclot lytic injection is essential
 Proximal vortex
Schmitz-Rode T, Kilbinger M, Gunther RW. Simulated flow pattern in massive pulmonary embolism: significance for selective
intrapulmonary thrombolysis. Cardiovasc Intervent Radiol 1998;21:199-204.

86. catheter-directed lysis
 111 patients with massive PE had CDT
 200k-500k units of urokinase in situ
 Mechanical fragmentation in 85% (pigtail rotation +/- balloon angioplasty)
 Catheter placed most obstructed segment and infused 100k units/hr for mean 22 hours
 Heparin to achieve PTT 2-2.3x normal
 Technical success in 100%
 On table fragmentation + initial bolus did not reduce mean PAP
 Mean PA pressure reduced from 40 to 25 mmHg at conclusion of lysis
 Mean PA pressure was 20 mmHg at 30-90 day follow-up (only 6% had mean PA pressure >25
mmHg)
 4 major complications (4%), 1 death
 1 cerebral hemorrhage (death)
 1 gluteus hematoma
 1 GI hemorrhage
 1 jugular DVT
De Gregorio et al. Endovascular treatment of a haemodynamically unstable massive pulmonary embolism using fibrinolysis and
fragmentation. Experience in 111 patients in a single centre. Why don’t we follow ACCP recommendations?

87. ACCP 2012 recommendations
 “In patients with acute PE associated with
hypotension and who have (i) contraindications to
thrombolysis, (ii) failed thrombolysis, or (iii) shock
that is likely to cause death before systemic
thrombolysis can take effect (eg, within hours), if
appropriate expertise and resources are available,
we suggest catheter-assisted thrombus removal over
no such intervention (Grade 2C)”
Guyatt GH, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians
evidence-based practice guidelines. Chest 2012;141: 2 suppl 7S-47S.

88. devices and techniques
 Pigtail rotation
 Cheap, easy, accessible, can debulk proximal emboli
 Aspiration thrombectomy
 8F guide catheter
 Balloon maceration
 Sized smaller than target artery
 Angiojet
 Used in 11% of cases but accounts for 76% of major complications
 28% major complication rate
 Bradyarrhythmia, heart block, hemoglobinuria, hemoptysis,death
 Ekos
 Ultrasound-aided lysis infusion
 Others not available at UCLA: Amplatz thrombectomy device,
Straub Aspirex catheter, Helix ClotBuster, etc

89. Catheter-guided lysis
 25 patients with massive PE had 33 catheter interventions
 EKOS in 15
 Standard CDT in 18
 EKOS showed more effective thrombus removal
 EKOS group had complete thrombus removal in 100%
 CDT group had complete thrombus removal in 50%, partial
thrombus removal in 14%
 EKOS group had lower mean time of lysis (17 vs. 25 hours)
 Treatment-related hemorrhagic complication rate lower for
EKOS (0% vs. 21%)
 Mortality similar (9.1% for EKOS, 14.2% for CDT)
Lin PH, et al. Comparison of percutaneous ultrasound-accelerated thrombolysis versus catheter-directed thrombolysis in patients with acute
massive pulmonary embolism. Vascular 2009;17 Suppl 3:S137-47.

90. CDT devices/techniques
 Pigtail rotation (314)
 Pigtail rotation with adjunctive measures (94)
 Aspiration thrombectomy
 Infusion catheter
 Balloon
 Amplatzer thrombectomy device
 Oasis, Hydrolyser
 AngioJet
 Rotarex
 Wire disruption

91. Intrapulmonary administration of Lytics
 A study from 1992 found no signification difference between IV
and PA administration of tPA 1
 Patients received 100 mg tPA IV or in the PA
 No significant difference in outcomes
 Conclusion: IV and PA administration of tPA equally effective in PE
 BUT
 Administration of tPA was NOT directly into the clot
 Current preferred administration of lytics into thrombosed vessels
is through multisidehole infusion catheters placed directly into clot
 Increases the surface area of the clot exposed to lytics
 Avoids lost dose from preferential flow of lytic into
nonthrombosed vessels
Goldhaber

92. tPA Contraindications
 Active internal bleeding
 History of CVA in last 6 months?
 Recent neurosurgery or head trauma
 Intracranial AVM, aneurysm or tumor
 Known bleeding diathesis
 Severe uncontrolled HTN

93. Relative CI to tPA
 Recent major surgery
 CV disease
 Recent GI or GU bleeding
 Recent trauma
 SBP >175 or DBP >110
 Acute pericarditis
 Subacute bacterial endocarditis
 Severe hepatic or renal disease
 Pregnancy
 Hemorrhagic ophthalmic conditions
 Septic thrombophlebitis
 Advanced age >75
 Patients on oral anticoagulants

94. Major hemorrhage from tPA
 Independent predictors of major hemorrhage in PE
patients treated with systemic tPA
 Cancer
 Elevated INR
 DM
 Hemodynamic instability
Fiumara et al. Predictors of major hemorrhage following fibrinolysis for acute pulmonary embolism. Am J Cardiol 2006;97:127-129..

95. Major hemorrhage from tPA
 Acute MI: 5% major, 1% intra-cerebral
 Acute PE (Fiumura): 19% major, 5% intra-cerebral
 Acute PE (Goldhaber): 22% major, 3% intra-cerebral
Bovill EG et al. Ann Int Med 1991;115:256-265
Fiumara et al. Predictors of major hemorrhage following fibrinolysis for acute pulmonary embolism. Am J Cardiol 2006;97:127-129.
Goldhaber et al. Lancet 1999;353:1386-89.

96. Controversies
 Bradyarrhthymia and hemolysis from rheolytic
thrombectomy
 Fears of vascular perforation
 “A double-edged sword” chest 2007 vs. shining
saber chest 2008

97. Meta-analysis
 0 RCTs
 6 prospective trials
 29 retrospective reviews
 594 patients
 All level 2 and 3 evidence
 Reported indications were severe shock,
cardiopulmonary arrest, contraindication to IV tPA,
failure of IV tPA

98. CASE: Thrombectomy followed by overnight
peripheral thrombolysis
Initial 3 days later

99. Role for catheter treatment of submassive
PE requires an answer to these questions
 How important is rapid clearance of thrombus?
 Role of thrombolysis
 How does the effectiveness of catheter directed
thrombolysis compare to systemically delivered lytic
agents?
 Can catheter directed therapy achieve the same
results as systemic lytic therapy at a lower dose of the
lytic agent?
 Reduce hemorrhage?

100. thrombolysis and hemorrhage
 Half of patients have a contraindication to thrombolysis
 20% major hemorrhage rate when systemic lytics
administered
 3-5% hemorrhagic stroke
 Case series of ten patients with massive PE treated with
catheter directed ultrasound-accelerated thrombolysis
Reteplase (0.5 mg)
 Heparin not simultaneously delivered
 No major complications
 1 patient with nonfatal hemoptysis
 1 patient with small groin hematoma

101. OnGOING CLINICAL TRIALS
 PERFECT 1
 Pulmonary Embolism Response to Fragmentation,
Embolectomy, & Catheter Thrombolysis
 A prospective observational study to evaluate the safety and effectiveness
data of catheter-directed therapy (CDT) including percutaneous mechanical
thrombectomy (PMT) for treatment of acute pulmonary embolism (PE)
NCT01097928

102. ACCP 2012 recommendations
 In patients with acute PE associated with
hypotension (eg, systolic BP <90 mmHg) who do not
have a high bleeding risk, we suggest systemically
administered thrombolytic therapy over no such
therapy (Grade 2C)
 In most patients with acute PE not associated with
hypotension, we recommend against systemically
administered thrombolytic therapy (Grade 1C)
 In patients with acute PE when a thrombolytic agent
is used, we suggest administration through a
peripheral vein over a pulmonary artery catheter
(Grade 2C)
Guyatt GH, et al. Executive summary: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians
evidence-based practice guidelines. Chest 2012;141: 2 suppl 7S-47S.