What is New in Acute Pulmonary Embolism?

Interventional Treatment

Prof. Nils Kucher

University Hospital Bern

Switzerland

nils.kucher@insel.ch

Disclosure of Interest

• Dr. Kucher received research grants from Sanofi-Aventis, GSK, BMS,

Pfizer and Bayer

• Dr. Kucher is consultant to EKOS Corporation and Bayer

• Dr. Kucher received speaker honoraria from Sanofi-Aventis, Bayer, GSK,

BMS, Boehringer Ingelheim, and Pfizer

- PE 2011 Guidelines -

Confirmed or intermediate/high clinical probability of acute PE

Initial treatment

Unfractionated heparin, low molecular weight heparin, or fondaparinux for at least 5 days (Grade I A; for intermediate/high clinical probability of acute PE Grade I C)

No routine IVC filter placement (Grade III C) except contraindication to anticoagulation (Grade I C)

or recurrent PE with therapeutic anticoagulation (Grade IIa C)

Low-risk PE (BP > 90 mm Hg, biomarkers – , ECHO – )

High-risk or massive PE (BP < 90 mm Hg, shock, CPR)

Risk stratification

Intermediate-risk or submassive PE (BP > 90 mm Hg, biomarker +, ECHO +)

No thrombolysis, catheter intervention,

or surgical embolectomy (Grade III B)

Systemic thrombolysis (Grade IIa B) Catheter intervention or

surgical embolectomy, if fibrinolysis contraindicated or if remains unstable

after fibrinolysis (Grade IIb C)

Systemic thrombolysis if bleeding risk is low (Grade IIb C)

Catheter intervention or surgical embolectomy (Grade IIb C)

Long-term treatment

Vitamin K antagonist for ≥ 3 months (Grade I A)

Engelberger R, Kucher N. Circulation 2011; 124:2139-44

The problems with Systemic PE Thrombolysis

• There is a 13% risk of major bleeding and a 1.8% risk of intracranial hemorrhage in randomized trials1

• There is a 20% risk of major bleeding and a 3% risk of intracranial hemorrhage in clinical practice2

• The rates of clinically relevant non-major bleeding have not been studied for patients undergoing systemic PE thrombolysis

• In clinical practice, systemic thrombolysis is withheld in up to two thirds of patients with high-risk (massive) PE3.

1ESC Guidelines. Eur Heart J 2008: 29:2276-2315 2Am J Cardiol. 2006;97:127-9

3ICOPER. Circulation 2006;113:577-82

Goals of Catheter Embolectomy

for Massive Pulmonary Embolism

• Decrease in pulmonary vascular resistance and pulmonary artery pressure

• Recovery of right ventricular dysfunction

• Increase in systemic arterial pressure

• Improvement of symptoms and survival

Kucher N, Goldhaber SZ. Circulation 2006;112:e28-32

Old & New Interventional Devices

for Acute Pulmonary Embolism

Greenfield Pigtail Clot buster AngioJet Aspirex

The Greenfield Suction Embolectomy Device

Courtesy of Lazar Greenfield, MD

Courtesy of Lazar Greenfield, MD

Combined Mechanical Techniques:

Fragmentation and Thrombectomy

Eidt-Lid et al. Chest 2008; 134:54

Hemodynamics Before Procedure After Procedure p Value

sSBP, mm Hg 94.8 ± 11.3 119.6 ± 14.9 0.001

mSBP, mm Hg 74.0 ± 7.9 88.8 ± 11.9 0.001

sPAP, mm Hg 64.1 ± 17.3 48.8 ± 20.1 0.001

mPAP, mm Hg 37.1 ± 8.8 31.1 ± 11.2 0.001

Miller index 20.8 ± 4.6 13.7 ± 6. 1 0.0001

Shock index 1.2 ± 0.2 0.7 ± 0.2 0.001

Eidt-Lid et al. Chest 2008; 134:54

Patients without additional thrombolysis (N=16)

Combined Mechanical Techniques:

Fragmentation and Thrombectomy

Pharmacomechanical Interventions

AngioJet Power Pulse thombolysis + thrombectomy

(Venturi effect)

EKOS Ultrasound-assisted thrombolysis

Aspiration technique

No lytics

89

60

81

33

21

72 (81)

6 (17)

22 (25)

Systemic lytics

9

50

87

31

20

9 (100)

0 (0)

1 (10)

Local lytics

9

-

-

31

24

9 (100)

0 (0)

0 (0)

Systemic + local

1

-

-

20

19

1 (100)

0 (0)

0 (0)

Fragmentation technique

No lytics 3

28

63

38

29

2 (67)

0 (0)

0 (0)

Systemic lytics 21

70

93

25

21

15 (71)

0 (0)

1 (5)

Local lytics 121

67

81

33

22

115 (95)

2 (2)

5 (4)

Systemic + local 30

65

69

32

30

24 (80)

3 (10)

6 (20)

Amplatz catheter

No lytics

8

86

108

49

53

7 (88)

1 (13)

1 (12)

Local lytics

6

85

93

64

60

6 (100)

0 (0)

0 (0)

AngioJet

No lytics 8

-

-

42

30

6 (75)

0 (0)

0 (0)

Local lytics 23

-

-

-

-

20 (87)

0 (0)

3 (13)

Hydrolyzer

Local lytics

12

47

97

46

30

11 (92)

0 (0)

1 (8)

Systemic + local 8

-

-

43

36

8 (100)

0 (0)

1 (12)

Catheter technique n

Mean BP,

mmHg

Before After

Mean PAP,

mmHg

Before After

Clinical

Success

Major

Bleeding Mortality

Clinical Outcome after PE Catheter Intervention

Skaf E et al. Am J Cardiol 2007;99:415-420.

Meta-analysis (35 studies)

PE catheter interventions

Clinical success*

Clinical success in

studies with >80%

patients receiving

thrombolysis

Clinical success in

studies with <80%

patients receiving

thrombolysis

Major complications

Minor complications

N = 594

86%

91%

83%

2%

8%

*defined as stabilization of hemodynamic parameters,

resolution of hypoxia, and survival of massive PE

Kuo WT, et al. J Vasc Interv Radiol. 2009;20:1431-1440

Complications of Catheter Embolectomy

• Pulmonary hemorrhage/ hemoptysis

• Right ventricular failure from distal embolization or contrast injections

• Bleeding from anticoagulation or thrombolysis

• Hemolysis, hemoglobinuria

• Arrhythmia

• Contrast-induced anaphylaxis and contrast-induced nephropathy

• Vascular access complications

Kucher N, Goldhaber SZ. Circulation 2006;112:e28-32

Ultrasound-Assisted Thrombolysis Effect of Ultrasound

Ultrasound +

Thrombolysis

Ultrasound pressure waves force drug

into thrombus, resulting in rapid removal

of thrombus even at low drug dose

Destabilization of fibrin strands,

enabling penetration of drug into thrombus

With Ultrasound

Without Ultrasound

Fibrin strands prevent drug from penetrating

thrombus and binding to plasminogen

receptor sites

The Ekosonic Endovascular System

5 fr Intelligent side-hole drug delivery catheter

Ekosonic Control Unit Ekosonic Mach4

Endovascular Device

Ultrasound MicroSonic™ Core

Pre to Post RV/LV Ratio

RV

/LV

Ratio

Pre RV/LV Post RV/LV0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

N= 24

mean rt-PA dose 33 ± 15 mg over 20 hours

1.33 ± 0.24 1.00 ± 0.13

P < 0.001

Ultrasound-Assisted Thrombolysis

Improvement in Right Ventricular Enlargement

Follow-up CT

at 38 ± 14 hours Engelhardt TC, et al. Thromb Res 2011;128:149-54

Baseline CT

RV/LV ratio

Normal : <0.7

Prognosis : >1.0

Main pulmonary artery

Upper pulmonary artery

Pulmonary arterytrunk

EKOS catheterdevices

Lower lobesegmentalbranches

Embolus

Proximal lowerlobe pulmonaryartery

Distal lowerlobe pulmonaryartery

The Bern PE Experience with EKOS

2010-2012 EKOS for acute PE: r-tPA 10 mg per device over 15 hours

Submassive PE: Systolic arterial pressure

≥ 90 mmHg and RV dysfunction or troponin

test positive

Massive PE: Systolic arterial pressure <

90 mmHg, cardiogenic shock, or CPR

N=14 N=11

Improvement of symptoms after procedure

12 (86%) 10 (91%)

Improvement of right heart dysfunction after procedure (hemodynamic parameters or echocardiography)

11 (79%) 10 (91%)

Death during hospitalization - 1 (9%) Death from worsening RV failure

Major bleeding 30 days 1 (7%) Intrapulmonal bleeding requiring

lobectomy

1 (9%) Drop of hemoglobin without overt

bleeding requiring transfusion

Minor bleeding 30 days 1 (7%) Access site bleeding

2 (18%) Access site bleeding

Recurrent VTE or death at 3 mts - -

50 of 62 patients

randomized

as of August 2012

Take Home Points

Systemic thrombolysis is recommended treatment for massive PE patients, however it is withheld in up to two thirds of patients

Catheter interventions are promising minimal-invasive alternatives for massive PE patients who are not ideal candidates for systemic thrombolysis

There is little evidence for mechanical catheter interventions without adjunctive thrombolytics

There is a need for clinical trials to establish the role for pharmacomechanical interventions in submassive PE patients