Catheter-based therapy for acute pulmonary embolism involves the use of devices in the pulmonary artery with or without low-dose thrombolysis. Recent literature does not prove that ultrasound-accelerated thrombolysis is superior to other catheter-directed methods. Guidelines recommend catheter-directed thrombolysis for massive pulmonary embolism or intermediate-high risk patients who cannot receive systemic thrombolysis due to bleeding risk. The procedure involves placing infusion catheters in the pulmonary arteries to deliver low-dose thrombolytics over several hours.
3. TERMINOLOGY
• “CATHETER-BASED THERAPY” (CBT)- refers to the
use of any of several devices and techniques in the
pulmonary artery (PA) with or without low-dose
thrombolytic therapy.
• “CATHETER-DIRECTED THROMBOLYSIS”
(CDT) - refers to the infusion of thrombolytics into the PA
via an infusion catheter with multiple exit ports, placed
into the PA, preferably into the embolus.
3
4. STATISTICS
300k-600k per year.
1-2 per 1000 people, or as high as 1 in 100 .
Overall 30 day mortality = 9-11%
At 3 months = 8.6- 17%
Sudden death is presenting symptom in ~ 34%
2012: 166,665 primary admissions for PE.
In-hospital mortality ~ 3%
Most commonly from lower extremity DVT.
Evidence of DVT in > 50%
CDC.GOV; Agency for Healthcare Research and Quality
5. High
risk
Moderate/intermediate
risk
Low
risk
• Sustained hypotension
(systolicBP <90 mmHg for ≥15 min)
• Inotropic support
• Pulseless
• Persistent profound
bradycardia (HR <40 bpm with
signs or symptoms of shock)
• Systemically normotensive
(systolic BP ≥90
mmHg)
• RV dysfunction
• Myocardial necrosis
• Systemically normotensive
(systolic BP ≥90
mmHg)
• No RV dysfunction
• No myocardial
necrosis
RV dysfunction
•RV/LV ratio > 0.9 or RV systolic dysfunction on
echo
•RV/LV ratio > 0.9 on CT
•Elevation of BNP (>90 pg/mL)
•Elevation of NTpro-BNP (>500 pg/mL)
•ECG changes:
• new complete or incomplete RBBB
• anteroseptal ST elevation or depression
• anteroseptal T-wave inversion
Jaff et al. Circulation 2011;123(16):1788-
1830.
Jaff et al. Circulation 2011;123(16):1788-1830.
BACKGROUND AND DEFINITIONS
Patient risk stratification (per AHA Scientific Statement 20111)
Massive PE Submassive PE Minor/Nonmassive PE
High risk Moderate/intermediate risk Low risk
– Sustained hypotension (systolic BP
<90 mmHg for ≥15 min)
– Inotropic support
– Pulselessness
– Persistent profound bradycardia (HR
<40 bpm with signs or symptoms of
shock)
– Systemically
normotensive (systolic BP
≥90 mmHg)
– RV dysfunction
– Myocardial necrosis
– Systemically normotensive
(systolic BP ≥90 mmHg)
– No RV dysfunction
– No myocardial necrosis
6. massive PE
submassive PE
minor PE
Massive PE
< 5% of the PE population
58% mortality at 3 months
Submassive PE
40% of the PE population
21% mortality at 3 months
Minor PE
55% of the PE population
Good prognosis
No mortality
ACUTE PE: PATIENT PROFILE
ICOPER . Lancet1999;353:1386
7. − Registry of 1,416 patients
− Mortality rate:
1.9% if RV/LV ratio < 0.9
6.6% if RV/LV ratio ≥ 0.9
Fremont et al. CHEST 2008;133:358-362
HOW TO DETERMINE RISK
8. − Retrospective analysis of 120
patients with hemodynamically
stable PE based on chest CT
− PE-related mortality at 3
months:
17% if RV/LV ≥ 1.5
8% if 1.0 ≤ RV/LV < 1.5
0% if RV/LV < 1.0
Van der meer et al. Radiology 2005; 235:798-803.
HOW TO DETERMINE RISK
11. 11
The primary efficacy outcome was mortality. Outcomes were pooled across studies with the
random-effects model. Twenty-four studies enrolled 700 patients in total; 653 received
mechanical thromboembolectomy treatments for PE (mortality rate, 9% [95% confidence
interval (CI), 6%-13%], P ¼ .12; rate of minor complications, 6% [95% CI, 2%-13%]). In the
ultrasound-accelerated thrombolysis (USAT) studies, the mortality rate was 4% (95% CI,
1%-11%) and in the non-USAT studies, it was 9% (95% CI, 6%-13%). Secondary safety
outcomes were all bleeding events, which occurred in 12% (95% CI, 7%-20%) of the USAT
studies and in 10% (95% CI, 5%-20%) of the non-USAT studies. CURRENT CLINICAL
EVIDENCE DOES NOT PROVE USAT IS SUPERIOR OVER CDT METHODS.
12. Various studies report presence of right ventricular
dysfunction (RVD) as a predictor of poor clinical outcomes:
1.Mortality
2.Adverse events
3.VTE recurrence
WHY TREAT SUBMASSIVE PE PATIENTS
AGGRESSIVELY?
13. PULMONARY EMBOLISM RESPONSE TEAM
(PERT)
• Multiple centers have formed multidisciplinary pulmonary
embolism response teams (PERT) to engage specialists
from different backgrounds to discuss treatment options
and provide immediate advice and therapy for patients in
the massive and submassive categories.
13
15. PERT PROTOCOL
15
•Example of an
intensive PE
management pathway
utilizing a single phone
call to the PE team
leader.
•Further review with
PERT members can
occur while the patient
is transferred to the
critical care unit,
interventional
laboratory, or operating
room.
Jaber, W.A. et al. J Am Coll
Cardiol. 2016; 67(8):991–1002.
23. BENEFIT OF IV THROMBOLYSIS IN SUBMASSIVE OR
INTERMEDIATE RISK PE
• PEITHO Trial
• Primary Objective:
• To investigate the clinical benefits
(efficacy) of thrombolysis with
tenecteplase over placebo in
normotensive patients with acute
intermediate risk PE‐ (both
treatment arms receive standard
heparin anticoagulation)
• Secondary Objective:
• To assess the safety of tenecteplase
in patients with intermediate risk‐
PE
APRIL,2014
24. IV THROMBOLYSIS REDUCES THE RISK OF
HEMODYNAMIC COLLAPSE
Tenecteplase
(n=506)
Placebo
(n=499)
P value
All cause mortality
within 7 days
6 (1.2%) 9 (1.8%) 0.43
Hemodynamic collapse
within 7 days
8 (1.6%) 25 (5.0%) 0.002
• Need for CPR 1 5
• Hypotension / BP drop 8 18
• Catecholamines 3 14
• Resulted in death 1 6
Meyer et al. N Engl J Med. 2014 Apr
10;370(15):1402-11
25. BUT THE BENEFIT OF LYSIS CAME AT THE
COST OF MAJOR BLEEDS (INCLUDING ICH)
Meyer et al. N Engl J Med. 2014 Apr 10;370(15):1402-11
Tenecteplase
(n=506)
Placebo
(n=499)
P value
All strokes by day 7 12 (2.4%) 1 (0.2%) 0.003
• Hemorrhagic
• Ischemic
10
2
1
0
Serious adverse
events (SAE)
29 (5.7%) 39 (7.8%) 0.19
26. CRITERIA FOR THROMBOLYSIS IN PULMONARY
EMBOLISM : PRINCIPAL INCLUSION CRITERIA
1. Massive pulmonary embolism
2. Anatomically small or moderate PE with
hemodynamic instability
3. Hemodynamically stable, but RV dysfunction
detected on baseline echocardiogram
28. RESULTS OF SYSTEMIC THROMBOLYTIC
THERAPY OF PULMONARY EMBOLISM
1. Thrombolytic treatment results in faster thrombus resolution
than treatment with heparin alone.
2. Thrombolytic treatment results in a significant reduction of PE
induced pulmonary hypertension within 24 hrs. of treatment.
3. Thrombolytic treatment results in a significant improvement
of pulmonary perfusion scans at 24 hrs.
4. Thrombolytic treatment appears to reduce mortality in pts with
shock due to massive PE
Sanchez et. Al J Thrombolysis 1995;2: 227-229.
Goldhaber et. Al. Lancet 1999; 341:507-511
29. RESULTS OF THROMBOLYTIC THERAPY OF
PULMONARY EMBOLISM
5. Thrombolytic treatment does not reduce mortality or
incidence of recurrent PE in hemodynamically
stable pts.
6. Thrombolytic treatment possibly improves
hemodynamic response to exercise.
(Arcasoy,Chest 1999; 115:1695-1707)
31. CATHETER BASED THERAPIES
• Alternative or additive treatment for massive PE
• Wide variety of devices and techniques, with goal of
rapidly reducing clot burden:
1. Intra thrombus lytic administration
2. Thrombus fragmentation
3. Thrombus aspiration
36. CATHETER-DIRECTED THROMBOLYSIS
VIA INFUSION CATHETERS
• Catheter-directed thrombolysis via multi-sidehole infusion
catheters is the least technically challenging.
• Relatively superior.
36
37. • In recent prospective registry of 101 massive and
submassive PE patients treated with catheter-based therapy
(mostly local fibrinolysis), there was a significant decrease
in PA pressure and improvement in RV function, with no
reported major complications, major bleeding, or strokes.
PERFECT registry Chest 2015;148:667–73.
• In a series of 52 PE patients treated with CDF, a more
prominent hemodynamic benefit was obtained in patients
with symptom duration <14 days, as compared with those
with a longer symptom duration.
Engelberger RP et al.Eur Heart J 2015;36:597–604.
37
38. INDICATIONS
• Stabilized massive PE who have contraindications to
systemic fibrinolysis .
• In patients with intermediate-high–risk PE (those with RV
dysfunction and increased biomarkers), particularly those
deemed at increased bleeding risk with full-dose systemic
fibrinolysis.
38
39. PROCEDURE
• Internal jugular or femoral venous access with ultrasound
guidance is obtained.
• For femoral access, ultrasound is used to rule out
iliofemoral thrombus.
• A catheter (e.g., balloon-tipped, pigtail, or multipurpose) is
carefully advanced to the main PA, where pressure and
blood oxygen saturation sampling are obtained.
• Contrast injection into the main PA or selectively into each
PA can be performed to identify the location of the
thrombi; these are typically in the main and/or lower main
PA branch.
39
40. • Power injection may be necessary (e.g., at 15 to 20 m/s
for a total of 30 ml selectively in each main PA) if
location of the thrombi is not clear and pulmonary
pressure is not severely elevated.
• An exchange-length soft- or j-tipped wire is placed in the
lower PA branch, and the diagnostic catheter is exchanged
for an infusion catheter, which has a treatment zone of 6 to
12 cm through which t-PA may be infused into the clot.
• A second infusion catheter may be placed in the
contralateral PA through a second venous sheath, if
needed, using the same technique.
40
41. • A commonly used t-PA dose is 0.5 to 1.0 mg/h per
catheter.
• The total t-PA dose is typically between 12 and 24 mg,
delivered over 6 to 24 h.
• Lowdose, weight-adjusted heparin infusion is usually
continued during t-PA infusion, with a target partial
thromboplastin time on the low end of the therapeutic
range (e.g., 40 to 60 s).
• Commonly available infusion catheters –
Cragg-McNamera catheter,
Fountain catheter
Unifuse catheter
41
42. • The risk of intracranial hemorrhage is <0.2%.
SEATTLE II Study. J Am Coll Cardiol Intv2015;8:1382–92
PERFECT: Registry.Chest 2015;148:667–
73..
Engelberger RP, et al Eur Heart J 2015;36:597–
604.
42
43. CATHETER FRAGMENTATION FOLLOWED
BY LOCAL INTRAPULMONARY
THROMBOLYSIS
• GOAL OF THERAPY - Breakdown the large central
fresh clot into multiple small fragments to achieve partial
reperfusion for thrombolysis to act and not complete
removal of thrombus.
• The proposed mechanisms of improved thrombolytic
action are increased exposure of fresh clot surfaces caused
by fragmentation accelerating the thrombolytic action.
43
44. • In addition when there is total occlusion of pulmonary
artery occlusion by an embolus, any fluid infused will
theoretically make only evanescent contact with thrombus
and be washed into the nonoccluded ipsilateral and
contralateral pulmonary artery.
• After fragmentation, infused thrombolytics will have
greater contact with the distal thrombus throughout the
pulmonary arterial tree.
Tajima H et al AJR Am J Roentgenol. 2004;183:589e595.
Mohan et al. Indian Heart Journal 66(20 14)294 e301
44
45. 45Tajima H, Murata S, Kumazaki T, et al. AJR Am J Roentgenol. 2004;183:589e595.
CONCLUSION. Hybrid treatment with mechanical fragmentation using a
rotating pigtail catheter combined with local fibrinolysis and manual clot
aspiration resulted in a rapid and safe improvement in the hemodynamic
condition of patients with acute massive pulmonary thromboembolism.
This hybrid treatment appears to be especially useful in patients at high
risk for right ventricular failure and is a minimally invasive alternative to
surgical embolectomy
46. 46Indian Heart Journal 66 (2014)294e301
Conclusions: Rapid reperfusion of pulmonary arteries with
mechanical fragmentation by pigtail catheter followed by
intrapulmonary thrombolysis results in excellent immediate
and intermediate term outcomes in patients presenting with
high risk pulmonary embolism.
48. ULTRASOUND - ASSISTED LYSIS
• Ultrasound-assisted thrombolytic infusion catheters
achieve accelerated thrombolysis using ultrasound waves.
• The EndoWave System (EKOS System) consists of a 5-Fr
106-cm long catheter containing microinfusion pores
within the 6–50 cm treatment segment of the catheter that
optimize the interface of thrombus with an ultrasound core
wire that contains small transducers allowing for delivery
of ultrasound waves to the thromboembolus .
48
50. • Following access to the PA and angiographic examination,
exchange is made over a 0.035-inch guidewire for
EndoWave catheters containing the ultrasound core wire.
• The catheter also contains a port for tPA infusion (e.g., 0.5
mg/hour per catheter if bilateral, or 1 mg/hour per
unilateral catheter), a port for saline to cool heat generated
by the ultrasound waves, and an interface cable connected
to a control unit in order to deliver ultrasound waves.
• Typically, tPA administration is performed over 18–24
hours.
50
51. Jaber, W.A. et al. J Am Coll Cardiol. 2016; 67(8):991–1002.
52.
53.
54. 54
Conclusions—In PE patients at intermediate risk, a standardized USAT regimen was
superior to anticoagulation with heparin alone in reversing RV dilatation at 24 hours,
without an increase in bleeding complications.
ULTIMA TRIAL NOVEMBER 13, 2013
55. 55
Conclusions: Ultrasound-facilitated, catheter-directed, low-dose
fibrinolysis decreased RV dilation, reduced pulmonary
hypertension, decreased anatomic thrombus burden, and
minimized intracranial hemorrhage in patients with acute massive
and submassive PE
JACC AUGUST
2015
57. CATHETER MEDIATED THROMBUS
FRAGMENTATION
• The most widely used method
is thromboembolus
fragmentation by manual
rotation of a pigtail catheter in
the main, right, or left PA.
• One group achieved an average
of 33% recanalization through
the thrombosed vessel, with
concomitant reduction in PA
pressure and shock index.
Schmitz-Rode T, Janssens U et al J Am Coll Cardiol 2000;36:375-80.
58. TECHNIQUE – RHEOLYTIC
THROMBECTOMY
• Rheolytic thrombectomy involves thromboembolus
fragmentation using a saline jet directed from the tip of the
catheter with simultaneous emulsified thrombus removal
via a separate channel .
1. Amplatz thrombectomy device
2. the Cordis hydrolyser hydrodynamics thrombectomy
catheter
3. the Oasis Thrombectomy System
4. the AngioJet Rapid Thrombectomy System.
58
59. TECHNIQUE – RHEOLYTIC ASPIRATION
• The AngioJet system employs
BERNOULLI
HYDRODYNAMICS: high
velocity moving fluid has low
central pressure, creating a
vacuum, with preferential
movement of surrounding
molecules into the center of the
fluid.
• The AngioJet device rapidly
infuses heparinized saline, up to
360 mph, via the catheter endhole,
reducing local pressure to a −600
mmHg, extracting soft thrombus
into the catheter via a distal
sideport .
62. CATHETER-MEDIATED
THROMBOEMBOLUS ASPIRATION
• The Greenfield embolectomy device : first catheter
designed for percutaneous embolectomy .
• No longer commercially available due to its large profile
necessitating venous cut down or direct surgical PA
access, and challenging steerability, which limited its use.
62
63. ANGIOVAC DEVICE
• Newer device
• Hampered by bulky size requiring 24-Fr introducer sheath
access, difficulty accessing the PA, and requirement of
veno-venous bypass .
• For treatment IVC thrombosis in the setting of PE and
can result in resolution of significant thrombus burden
captured in an extracorporeal filter using veno-venous
bypass and cardiac pump.
63
64. 64
Diagram of AngioVac insertion and reinfusion circuit. The cannula
has been inserted into the right internal jugular vein. Blood and thrombus is aspirated
through the filter canister, allowing clot capture utilizing a centrifugal pump canister,
prior to return of blood to the patient via the reinfusion cannula placed into the femoral
vein.
65. 65
(A) AngioVac cannula. (B) Example of thrombus captured in the
filter canister. Images from Angiodynamics.
67. PRONTO XL EXTRACTION CATHETER
• Its pigtail shape can be used for thromboembolus
extraction from the main PA, and the straight tip version
from segmental PAs.
• The pigtail version can also be used like a rotational
catheter to manually fragment thrombus, simultaneously
suctioning clot via distal sideholes using a 60-mL syringe.
• This device is FDA-approved for peripheral application.
67
68. FLOW TRIEVER DEVICE
• The FlowTriever catheter is a recently released device that
has FDA approval for removal of emboli and thrombi from
blood vessels
• It requires a 22-F venous sheath and consists of 3 parts:
the Flow Restoration Catheter, which is made up of 3 self-
expanding nitinol disks; the Aspiration Guide Catheter;
and the Retraction Aspirator Device.
• The FlowTriever device is advanced over the wire and into
the thrombus, where the expandable disks are deployed
using a pin and pull method.
• The disks and disrupted thrombus are then retracted and
removed through the aspiration catheter.
68
69. 69
(A) The flow restoration
catheter (FRC) is used to
enmesh clots and is
pulled through the
aspiration guide catheter
(AGC) utilizing (B) the
retraction aspirator
device (RAD).
71. PENUMBRA INDIGO THROMBECTOMY
SYSTEM
• The Indigo mechanical thrombectomy system consists of a
pump, 6- to 8-F straight or angled catheters, and a
Separator device.
• It is approved for thrombus removal in both peripheral
arterial and venous systems.
• An advantage is that it only requires an 8-F venous sheath
and can be placed into the PA system quickly, in an over-
the-wire technique.
71
73. EXTRACORPOREAL MECHANICAL
OXYGENATION
• Extracorporeal membrane oxygenator (ECMO) placement
has been described in case reports of patients with massive
PE, as it has the potential to unload the RV and,
importantly, provides oxygenation during massive PE to
allow for RV recovery .
• The ability of the interventional team to place the ECMO
underscores the importance of a multidisciplinary
approach.
• In many institutions, PERT members are also ECMO
service members.
73
Carroll BJ et al Am J Cardiol 2015;116:1624–30.
74. SURGICAL EMBOLECTOMY
• Surgical therapy is considered a last resort for acute PE
and is offered only to patients in extremis.
• Significant advances in cardiac surgical techniques have
led to an impressive reduction in operative mortality,
which is as low as 6% in the current era.
Yalamanchili K et al . Ann Thorac Surg 2004;77:819–23.
• 27 consecutive surgical pulmonary embolectomy patients,
there was no in-hospital mortality and a 10-year actuarial
survival rate of 93%; both late mortalities were unrelated
to PE or related therapy.
Lattouf O et al.World J Cardiovasc Surg 2013;3:190–7.
74
75. VENA CAVA FILTER
• Placement of an inferior vena cava (IVC) filter is indicated
in patients with acute PE who have absolute
contraindications to anticoagulation or in patients who
have recurrent PE, despite adequate anticoagulation.
• The position of the filter below or above the renal veins
depends on the absence or presence of renal vein
thrombus, respectively.
• Retrievable filters are preferable because they are
associated with lower complication rates.
Weinberg I et al. J Am Coll Cardiol Intv 2013;6:539–47.
75
76. 76
CONCLUSIONS AND RELEVANCE Among hospitalized patients with
severe acute pulmonary embolism, the use of a retrievable inferior vena
cava filter plus anticoagulation compared with anticoagulation alone did
not reduce the risk of symptomatic recurrent pulmonary embolism at 3
months. These findings do not support the use of this type of filter in
patients who can be treated with anticoagulation.
PREEPIC 2 TRIAL JAMA
APRIL 2015
77. • Both the American and the European guidelines do not
recommend routine use of IVC filters in patients with PE.
• However, 3 large analyses, including a U.S. nationwide
hospital sample and a study from Japan , suggest that IVC
filters may result in better outcomes in patients with
massive or intermediate high– risk PE.
Stein PD et al Am J Med 2012;125:478–84.
Isogai T et alAm J Med 2015;128:312.e23–31.
77
78. POST-INTERVENTION
• Maintenance of anticoagulation post-intervention is critical
to prevent recurrent clot formation.
• Also they are at risk of access site bleeding.
• Bleeding risk can be reduced by holding the heparin drip
for 1 to 2 h after sheath removal, then restart without a
bolus.
• Warfarin is administered on the night of the procedure, and
parenteral anticoagulation and warfarin are overlapped
until the international normalized ratio is 2 to 3 for at least
24 h.
American College of Chest Physicians evidence based clinical practice guidelines. Chest
2012;141: e419S–94S.
78
79. • Novel oral anticoagulants, including rivaroxaban,
dabigatran, apixaban, and edoxaban, can be used.
• If an alternative anticoagulant agent is utilized, heparin
alone for the first 24 to 48 h post-intervention and then
discontinuation of the heparin at the time of the first
alternative anticoagulant agent dosing.
• This strategy does not include dabigatran or edoxaban
usage, which require at least 5 days of parenteral therapy
before initiation.
79
80. KEY STUDIES REGARDING TREATMENT
OF PE WITH SYSTEMIC THROMBOLYSIS,
CATHETER-DIRECTED THERAPY AND IVC
FILTER PLACEMENT - SUMMARY
80
84. 84
Distribution of systolic right ventricular (RV)
dysfunction in 64 patients pre- and post-CDT.
Following CDT, 89.1% (95% CI, 76.8%-
94.4%) had alleviation of RV strain, and this
improvement occurred significantly more
often than worsening of heart strain ( P , .
0001).
The initial results from the present prospective multicenter registry
demonstrate clinical CDT success rates of 85.7% for massive PE
and 97.3% for submassive PE.
86. 86
Chest 2015;148(3):667 - 673
CONCLUSIONS: CDT improves clinical outcomes in
patients with acute PE while minimizing the risk of
major bleeding. At experienced centers, CDT is a safe
and effective treatment of both acute massive and
submassive PE.
87. CONCLUSIONS
• CDF with use of the EKOS catheter is the only FDA-
approved catheter-based therapy for use in treatment of
acute PE.
• Other catheter-based therapies focus on direct thrombus
removal without use of fibrinolytic agents and may be an
option for patients who either cannot receive fibrinolysis
or cannot wait for CDF to take effect.
87
88. • Surgical embolectomy reasonable to reserve it for patients
with massive PE and shock, who have contraindications to
fibrinolysis, who have failed other treatments, or who have
concomitant intracardiac thrombus or paradoxical
embolus.
• Similar to a “Code Stroke” or “Code STEMI,” PE should
be considered as a “lung attack,” and appropriate
resources utilized.
88