JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 67, NO.

8, 2016

ª 2016 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER http://dx.doi.org/10.1016/j.jacc.2015.12.024

COUNCIL PERSPECTIVES

Acute Pulmonary Embolism

With an Emphasis on an Interventional Approach

Wissam A. Jaber, MD,a Pete P. Fong, MD,b Giora Weisz, MD,c Omar Lattouf, MD,d James Jenkins, MD,e
Kenneth Rosenfield, MD, MHCDS,f Tanveer Rab, MD,a Stephen Ramee, MDg

ABSTRACT

Compared with recent advances in treatment of serious cardiovascular diseases, such as myocardial infarction and
stroke, the treatment and outcome of acute pulmonary embolism (PE) have remained relatively unchanged over the
last few decades. This has prompted several experts to call for the formation of multidisciplinary PE response teams
with a more proactive approach to the treatment of PE. In the current document, we discuss the formation of such
teams and describe the available treatment options beyond anticoagulation, with a focus on the interventional
approach. Acknowledging the paucity of data to support widespread adoption of such techniques, we call for the
collection of outcomes data in multicenter registries and support for randomized trials to evaluate interventional
treatments in patients with high-risk PE. (J Am Coll Cardiol 2016;67:991–1002) © 2016 by the American College of
Cardiology Foundation.

T he American Heart Association classifies

pulmonary embolism (PE) into low-risk,
intermediate-risk (submassive), and high-
risk (massive) categories (1). Whereas massive PE is
defined by the presence of persistent hypotension,
submassive PE is defined as occurring in normoten-
sive patients with evidence of right ventricular (RV)
strain by echocardiogram, computed tomography
(CT) scan, or cardiac biomarkers. The most recent
European Society of Cardiology guidelines further
divide the intermediate-risk group into intermediate-
low– and intermediate-high–risk subgroups, with
the latter defined by the presence of both RV dysfunc-
tion and increased cardiac biomarkers (2). Despite a
high case fatality rate, most patients with massive
and submassive PE continue to be treated conserva-
tively with anticoagulation alone. This has prompted
alternate, intensive treatment options, including
systemic fibrinolysis, catheter-based therapy, and
surgical embolectomy. Because adequate studies
evaluating these therapies are scarce, and given the
difficulty in managing PE patients, multiple centers
have formed multidisciplinary pulmonary embolism
response teams (PERT, a trademark of the National
PERT Consortium) to engage specialists from different
backgrounds to discuss treatment options and pro-
vide immediate advice and therapy for patients in
the massive and submassive categories (3,4).

Listen to this manuscript’s
audio summary by
JACC Editor-in-Chief
Dr. Valentin Fuster.
The views expressed in this manuscript by the American College of Cardiology (ACC’s) Interventional Council do not necessarily
reflect the views of the Journal of the American College of Cardiology or the ACC.
From the aDivision of Cardiology, Emory University School of Medicine, Atlanta, Georgia; bVanderbilt Heart and Vascular Institute,
Nashville, Tennessee; cDivision of Cardiology, Shari Zadek Medical Center, Jerusalem, Israel; dDivision of Cardiothoracic Surgery,
Emory University School of Medicine, Atlanta, Georgia; eOchsner Medical Center, New Orleans, Louisiana; fSection of Vascular
Medicine, & Intervention, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; and the gStructural and
Valvular Heart Disease Program, Ochsner Medical Center, New Orleans, Louisiana. Dr. Rosenfield has served as a consultant to
Abbott, Cardinal Health, Inari Medical, Surmodics, Volcano, Capture Vascular, and Shockwave; has served as a board member for
VIVA Physicians, a 501c3 organization; has received research support from the National Institutes of Health, Atrium, Lutonix-Bard,
Abbott Vascular, and Gore; and has personal equity in CardioMems, Embolitech, MD Insider, Primacea, and Vortex. All other
authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Manuscript received September 28, 2015; revised manuscript received November 17, 2015, accepted December 14, 2015.
992 Jaber et al.
Pulmonary Embolism
ABBREVIATIONS This document summarizes current inva-
AND ACRONYMS sive treatment options beyond anti-
coagulation available to intermediate- and
CDF = catheter-directed
fibrinolysis
high-risk PE patients, with the understand-
ing that data supporting any of them is
CDT = catheter-directed
therapy either inconclusive or lacking, and therefore
CT = computed tomography not covered by American and European
IV = intravenous
guidelines. Most PE patients only require
simple anticoagulation; patients with high-
PA = pulmonary artery
risk features deserve consideration for an
PE = pulmonary embolism
invasive treatment approach.
PERT = pulmonary embolism
response team BUILDING AN ACUTE PE TEAM AND
RV = right ventricle/ventricular MANAGEMENT PATHWAY
t-PA = tissue-type
plasminogen activator
Intensive management of acute PE begins
with formation of a PERT. Assembling a team of
specialists and coordinating care through a system
similar to the management of ST-segment elevation
myocardial infarction (STEMI) has been described at
several institutions (3,5,6). A PERT may consist of
specialists from vascular medicine, pulmonary critical
care, emergency medicine, interventional cardiology/
radiology, hematology, vascular surgery, and car-
diothoracic surgery. Not every hospital system will
engage all of these subspecialists, but we recommend,
at a minimum, representatives from medicine, inter-
ventional cardiology/radiology, and surgery, as the
decisions to be made require an understanding of
the risks and benefits of all treatment modalities.
The PERT’s responsibility is to assess each case in a
timely manner, examine the patient, review the
available data, perform any additional testing, and
then (in conjunction with the patient, family mem-
bers, and care team) develop a consensus regarding
the optimal treatment plan. In certain patients with
massive PE and rapid deterioration, the decision to
give fibrinolytic agents, go to the interventional lab-
oratory, or proceed to the operating room will need to
be made urgently by a limited number of PERT
members. In such cases, prior experience assessing
multiple patients with PERT colleagues will lend
advantage to the on-call team members and inform
their decision making. As a foundation, we recom-
mend that the local PERT review current published
reports and society guidelines (1,2,7) and establish an
institutional acute PE protocol, as in the Central
Illustration (6). The key to team management is acti-
vation of the PERT with a single phone call. Team
members should have an easily accessible online
system allowing all members to review the available
medical information, including computed tomogra-
phy (CT) scans, echocardiograms, electrocardiograms,
and laboratory data. PE teams should leverage
JACC VOL. 67, NO. 8, 2016
MARCH 1, 2016:991–1002
existing systems, such as hospital electronic medical
records, imaging systems, virtual meeting rooms,
and STEMI or acute stroke activation protocols.
Furthermore, teams should identify the admission
location best able to manage sick patients with sub-
massive and massive PE. A defined area enables
consistency and further development of expertise in
management of complex PE patients. A cardiovascu-
lar intensive care unit where the surgeon, cardiovas-
cular specialist, and critical care specialist round
together is a reasonable choice. This type of team
approach is a well-established Class I recommenda-
tion for management of ischemic heart disease (8).
In May 2015, the National PERT Consortium
launch meeting, sponsored by the Massachusetts
General Hospital PERT, was held in Boston, Massa-
chusetts, and was attended by approximately 40
hospital-based PE teams. There was an important
call to action to gather and share data on patients
with PE. We encourage PERTs to establish institu-
tional review board–approved databases that can be
shared among like-minded institutions for further
advancement of PE management, such as Research
Electronic Data Capture (RedCap). Participation in a
multicenter registry, such as that under development
by the National PERT Consortium, will enable sys-
tematic, broad-based assessment of outcomes and
further our knowledge regarding optimal care and
best practices.
PRE-INTERVENTION
Unless contraindicated, anticoagulation should be
initiated when PE is suspected, prior to additional
work-up. Intravenous heparin is a good initial choice
while alternative options (such as invasive therapies)
are being evaluated. After confirmation, the first
question is whether the PE is low risk versus sub-
massive to massive. Massive PE is currently defined
by hypotension with a systolic blood pressure
(SBP) <90 mm Hg for >15 min or the requirement of
inotropic support to maintain SBP >90 mm Hg. Sub-
massive PE is defined by SBP >90 mm Hg with evi-
dence of right heart dysfunction, as noted by a
dilated RV with an RV to left ventricle ratio >0.9 in
the 4-chamber view by CT or echocardiogram, or
elevated biomarkers, such as troponin or B-type
natriuretic peptide. The echocardiogram has the
advantage of demonstrating depressed RV function
and providing an estimate of pulmonary arterial
systolic pressure. Other high-risk markers of sub-
massive PE include tachycardia, tachypnea, and
hypoxia, which may be less specific, and thus less
helpful in management selection. Special attention
JACC VOL. 67, NO. 8, 2016 Jaber et al. 993
MARCH 1, 2016:991–1002 Pulmonary Embolism

should be given to patients who had syncope, which

C EN T RA L IL LUSTR AT I ON PERT Protocol
may represent transient hemodynamic instability
and the potential for higher risk (9). Hemodynami-
cally stable patients without evidence of RV strain
Patient with suspected pulmonary embolism (PE)
are considered to be at low risk, may not require
PERT activation, and can be treated with anti-
coagulation alone. That said, the PERT might help the
Anticoagulation initiated, unless contraindicated
clinical team define the level of risk and optimal
therapy for each individual patient.
Once the PERT has been activated, members typi-
cally meet, either at the patient’s bedside or virtually, Acute PE confirmed by Computed Tomography (CT) scan
and review all patient-related data. The most impor-
tant data include the presenting history, with a focus
Multidisciplinary PE response team (PERT) alerted:
on symptoms and signs of hemodynamic instability,
Interventionalist, cardiac surgeon,
vital signs, CT, echocardiogram, and laboratory data. radiology, pulmonary/critical care medicine
Team members should discuss indications and con-
traindications to fibrinolytic therapy, catheter-based
intervention, and surgical embolectomy, followed PERT members review the available medical information
and develop optimal treatment plan
by discussion with the patient and family members,
including the risks and benefits of each therapy pro-
posed. A sample algorithm to help in triaging patients
presenting to the emergency room of a hospital with a
PERT is provided (Figure 1). The PERT should
consider the degree of hemodynamic compromise
and the existence of variable contraindications. The Catheter Surgical
Medical therapy
simplified PE severity index may be a useful aid when directed therapy embolectomy
further considering the risks and benefits of inter-
ventional therapies (10).
Jaber, W.A. et al. J Am Coll Cardiol. 2016; 67(8):991–1002.

SYSTEMIC FIBRINOLYSIS
Traditionally, intravenous (IV) fibrinolysis has been
considered the primary intensive therapy option in
patients with high-risk PE, although the data sup-
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. Adapted with
permission from Bloomer et al. (6). CT ¼ computed tomography; PE ¼ pulmonary
embolism; PERT ¼ pulmonary embolism response team.

porting its use in massive PE is poor. Most trials that

randomized patients with PE to fibrinolytics versus
standard anticoagulation included submassive PE
only. A meta-analysis of trials including patients with
massive PE showed a reduction in the composite of
recurrent PE and death with use of IV fibrinolytic
agents, but not in death alone (11). Univariate analysis
of a large inpatient sample found that among unsta-
ble patients with PE, use of IV fibrinolytic therapy was
associated with a lower mortality rate (12), but only
30% of unstable patients received such therapy.
Patients with submassive PE were better repre-
sented in randomized trials. The MAPPET (Manage-
ment, Strategies and Prognosis of Pulmonary
Embolism)-3 trial (13) randomized 256 patients with
PE and pulmonary hypertension or RV dysfunction to
100 mg of IV alteplase or placebo infused over 2 h plus
anticoagulation. IV alteplase was associated with a
lower risk of further need to escalate the treatment and
with a similar risk of death. Mortality was lower than
expected in both groups (3.4% in the alteplase and
2.2% in the placebo group; p ¼ 0.71). More recently,
the PEITHO (Pulmonary Embolism Thrombolysis) trial
(14) randomized 1,006 patients with submassive
PE (normal blood pressure, RV enlargement, and
increased troponin level) to tenecteplase or placebo.
The PEITHO trial showed a reduction in the primary
endpoint of hemodynamic collapse at 7 days with
tenecteplase, but a significant increase in hemorrhagic
stroke (most in patients older than 75 years of age),
with similar mortality in both groups. The smaller
MOPETT (Moderate Pulmonary Embolism Treated
With Thrombolysis) trial (15) randomized 121 patients
with moderate-risk PE to half-dose alteplase
(maximum 50 mg over 2 h) with anticoagulation versus
anticoagulation alone. Low-dose alteplase was asso-
ciated with lower pulmonary pressure at 28 months
and no major bleeding. A 1,700 patient meta-analysis
994 Jaber et al. JACC VOL. 67, NO. 8, 2016

Pulmonary Embolism MARCH 1, 2016:991–1002

F I G U R E 1 ER PE Protocol Utilizing PERT Consultation and sPESI Score

PE confirmed:
Anticoagulate

Unstable patient
Stable patient Massive PE
(SBP < 90)

PERT consult

Low risk PE pt Submassive PE

sPESI* 0 suspected 1. Discuss IV lytics/
sPESI ≥ 1 catheter/surgery
with PERT leader
2. If lytics,
consider
initiation in ER

Echo
+
Troponin

Echo and troponin

Echo or troponin (+)
(-) for RV
for RV dysfunction
dysfunction

PERT consult

Anticoagulate,
admit to medicine Admit to critical
floor care unit

*Simplified pulmonary embolism severity index (sPESI) score ¼ 1 point for age >80 years, cancer, chronic heart failure or chronic pulmonary
disease, heart rate >110 beats/min, SBP <100 mm Hg, or O2 saturation <90%. Adapted with permission from Bloomer et al. (6). Echo ¼
echocardiography; ER ¼ emergency room; IV ¼ intravenous; PE ¼ pulmonary embolism; PERT ¼ pulmonary embolism response team;
RV ¼ right ventricular; SBP = systolic blood pressure.

of all fibrinolysis trials, including patients with
catheter-directed fibrinolysis (CDF), demonstrated a
statistically significant mortality benefit from fibrino-
lysis in patients with intermediate-risk PE (16). There
was a significantly increased risk of hemorrhage, but
the benefit appeared to outweigh the risk when the
analysis excluded patients older than 65 years of age.
Importantly, subanalyses of patients younger than 65
years of age were performed post hoc in the trials
included in the meta-analysis.
Taken together, these studies show that the use of
IV fibrinolytic therapy in patients with massive or
submassive PE leads to improved hemodynamic sta-
bilization and, possibly, a lower risk of recurrent PE
and PE-attributed death. However, this benefit comes
with an increased risk of severe bleeding and intra-
cranial hemorrhage (14).
CATHETER-BASED THERAPIES
Catheter-based therapies aim to relieve obstruction
quickly and restore pulmonary blood flow, thus
improving cardiac output and converting a hemody-
namically unstable situation into a stable one. This
is accomplished with reduced or no doses of fibrino-
lytic agents. Catheter-directed therapies (CDT) might
include clot fragmentation, aspiration, and low-dose
fibrinolytic injection. The American Heart Associa-
tion and American College of Chest Physicians
guidelines address catheter-based management of
JACC VOL. 67, NO. 8, 2016
MARCH 1, 2016:991–1002
acute PE, giving advanced therapies a limited
recommendation because of a lack of randomized
control data (1,7).
Multiple percutaneous techniques have been
described for treatment of unstable patients with PE
(Table 1). They aim at relieving the obstruction in the
pulmonary circulation, thus immediately improving
the patient’s hemodynamics and potentially reducing
the long-term risk of pulmonary hypertension (17).
These techniques have been poorly studied, and they
face the challenge of trying to remove large, some-
times organized thrombi from a large space with
numerous 3-dimensional branches and multiple
angles. The simplest and most commonly performed
catheter-based therapy is a local, slow infusion of a
fibrinolytic agent through low-profile catheters
placed in the obstructed pulmonary artery (PA). CDF
is best suited for more stable patients or those who
have been hemodynamically stabilized, as thrombus
resolution may take several hours.
For unstable patients who require immediate
intervention and/or those with contraindication to
fibrinolysis, mechanical thrombus fragmentation,
debulking, or aspiration of occlusive thrombi may be
attempted.
Potential complications of any catheter-based
therapy may include pulmonary arterial injury, peri-
cardial tamponade, major bleeding, hemodynamic
deterioration, distal embolization and “no-reflow”
phenomenon, and access site bleeding. A meta-
analysis of CDT using #10-F low-profile devices
reported minor and major procedural complications
of 7.9% and 2.4%, respectively (18). Minor complica-
tions included: groin hematomas not requiring trans-
fusion, transient bradyarrhythmia, heart block,
hemoglobinuria, mild hemoptysis, temporary renal
insufficiency, embolus dislocation (n ¼ 1), and PA
dissection (n ¼ 1). Major complications included: groin
hematomas requiring transfusion, massive hemopty-
sis requiring transfusion, renal failure requiring
hemodialysis, cardiac tamponade (n ¼ 1), and death
(n ¼ 5; 1 each from bradyarrhythmia and apnea,
distal embolization, and cerebral vascular hemor-
rhage, plus 2 procedure-related deaths not otherwise
specified) (18).
FRAGMENTATION AND ASPIRATION. Fragmentation
and aspiration of PE may be helpful in stabilizing
patients with massive PE, especially when systemic
fibrinolysis is contraindicated or has failed. Multiple
techniques have been tried with some success (19). By
rotating a pigtail catheter in the PA, the PE can be
fragmented (20). The aim is to reduce the load on the
RV by partially relieving the obstruction in the main
Jaber et al. 995
Pulmonary Embolism
T A B L E 1 Catheter-Based Therapies
Device Size Mechanism of Action
Pigtail catheter 6- to 8-F Fragmentation
Peripheral balloon 5 to 10 mm Fragmentation
Catheter-directed 4- to 6-F Direct infusion of fibrinolytic agent
fibrinolysis
Ultrasound-accelerated 6-F Direct infusion of fibrinolytic agent
thrombolysis plus ultrasound for clot separation.
Currently the only catheter-based
therapy FDA-approved for PE treatment.
Guide catheter 6- to 10-F Manual aspiration
Pronto Xl catheter 6- to 14-F Manual aspiration
Penumbra Indigo system 6- to 8-F Suction pump aspiration
Inari FlowTriever 22-F sheath Disruption, retraction, and aspiration of clot
AngioVac 26-F sheath Large-volume aspiration with return of
and 18-F cannula filtered blood utilizing a centrifugal pump
FDA ¼ Food and Drug Administration; PE ¼ pulmonary embolism.
PA branches. Fragmentation alone may cause distal
embolization and potentially worsen distal branch
obstruction (21). Fragmentation is frequently com-
bined with local infusion of small-dose fibrinolytic
agents (e.g., 4 to 10 mg of tissue-type plasminogen
activator [t-PA]), delivered either at the time of the
procedure or subsequently via an infusion catheter
left in place. Concomitant aspiration can reduce the
risk of worsening obstruction (21). Fragmentation can
also be performed by inflation of an angioplasty
balloon, with care to keep inflation in larger vessels
and to choose a balloon smaller than the artery
diameter. Injection through a diagnostic catheter
(e.g., a multipurpose catheter) placed distal to the
intended inflation site can help determine the size of
the distal artery before selecting a balloon catheter.
Aspiration can be attempted using regular 8-F
guide catheters or specialized catheters. One of the
first aspiration catheters was the Greenfield embo-
lectomy catheter (22), which consisted of a suction
cup at the tip of a straight catheter. Its complexity
and the requirement for a surgical cutdown for access
prevented it from being widely adopted. Other
specialized devices used to treat peripheral thrombi
have also been used off-label to treat PE. These
include the 10-F Aspirex thrombectomy catheter
(Straub Medical, Wangs, Switzerland), currently un-
available in the United States, which combines rota-
tional thrombus fragmentation with aspiration (23);
the 7-F Helix Clot Buster (ev3, Plymouth, Minnesota),
approved for dialysis graft thrombosis treatment (24);
and 8- to 14-F Pronto XL manual extraction catheters
(Vascular Solutions, Minneapolis, Minnesota).
The Angiojet Rheolytic Thrombectomy System
(Possis, Minneapolis, Minnesota) deserves special
mention. This 8-F peripheral catheter utilizes the
996 Jaber et al. JACC VOL. 67, NO. 8, 2016

Pulmonary Embolism MARCH 1, 2016:991–1002

Venturi-Bernoulli effect, using multiple high-
velocity saline jets introduced through the distal
tip, creating a low-pressure vacuum through small
slits in the catheter that can entrain and fragment
thrombi. A meta-analysis reported higher mortality
and morbidity, including massive hemoptysis, renal
failure, and death from bradycardia and apnea or
from widespread distal embolization (18), which
resulted in a black-box warning from the Food and
Drug Administration (FDA) for use of Angiojet in
acute PE.
Additional embolectomy devices are discussed in
the following sections.
A n g i o V a c t h r o m b e c t o m y d e v i c e . The AngioVac
Cannula (Angiodynamics, Latham, New York), a 22-F
venous catheter that can remove soft thrombi utiliz-
ing the centrifugal pump and venous reinfusion
cannula used in cardiopulmonary bypass (Figure 2), is
FDA approved for the removal of undesirable
F I G U R E 2 AngioVac Device
C a learning curve for its use. AngioVac has been uti-
A lized in PE, although it is more commonly used to
B AngioVac Cannula
Saline Bag
Filter
Centrifugal Pump Console
Reinfusion
Cannula
AngioVac
Circuit
(A) AngioVac cannula. (B) 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. (C) Example of thrombus captured in the filter canister. Images from Angiodynamics.
intravascular material, including fresh, soft thrombi
or emboli. The AngioVac catheter consists of a
balloon-expandable, funnel-shaped distal tip, which
improves removal of large clots en masse. Patients are
prepped in 2 body locations that will allow for large
venous sheath placements (common femoral or in-
ternal jugular veins). A 26-F sheath is placed in 1 vein
and an 18-F reinfusion cannula is placed in another
vein. The AngioVac cannula is then attached to the
inflow tubing of the centrifuge pump and the outflow
tubing connected to the 18-F reinfusion cannula,
creating a “veno-veno” bypass circuit. The cannula is
inserted into the 26-F sheath and is advanced to the
thrombus, which is suctioned out and captured by a
filtration canister inserted proximal to the centrifuge
pump; filtered blood is returned continuously via the
reinfusion cannula. Limitations of this device include
the large dual sheaths required for access, leading to a
higher likelihood of bleeding complications, and the
relatively stiff suction catheter, which is difficult to
maneuver into the RV and PA. Furthermore, the
active participation of an experienced perfusionist is
required for AngioVac setup and operation, as there is
retrieve thrombi from the vena cava and right atrium
(25). The rapidity of initiation may limit its use in
massive PE situations; future iterations may render it
more useful for PE.
FlowTriever d e v i c e . The FlowTriever catheter
(Inari Medical, Irvine, California) is a recently
released device that has FDA 510(k) approval for
removal of emboli and thrombi from blood vessels
(Figure 3). The FlowTriever Infusion Aspiration Sys-
tem 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. Set-up is rapid, and
there is a modest learning curve for device utilization.
Limitations include the large size requirement of the
access sheath, and manipulation of the large-bore
catheter into the PA.
Penumbra Indigo thrombectomy s y s t e m . The
Indigo mechanical thrombectomy system (Penumbra,
Inc., Alameda, California) consists of a pump, 6- to
8-F straight or angled catheters, and a Separator de-
vice (Figure 4). It is approved for thrombus removal
in both peripheral arterial and venous systems.
An advantage is that it only requires an 8-F venous
JACC VOL. 67, NO. 8, 2016 Jaber et al. 997
MARCH 1, 2016:991–1002 Pulmonary Embolism

sheath and can be placed into the PA system quickly,

F I G U R E 3 FlowTriever Device
in an over-the-wire technique. Once placed proximal
to the clot, the thrombectomy catheter is advanced
while suction is supplied with the ACER pump. The
A
provided Separator wire is used to clear the system of
thrombus as the catheter is manipulated inside the
artery.
A distinct limitation of these last 3 devices is the
absence of published data on their overall success and
safety.

CATHETER-DIRECTED FIBRINOLYSIS. G e n e r a l
c o n s i d e r a t i o n s . Given that full-dose systemic fibri-
nolysis is helpful in stabilizing high-risk PE patients AGC
and reducing pulmonary pressure, but at the cost of FRC
increased systemic bleeding, interest has risen in local
delivery of low-dose fibrinolytics close to or into
the PA thrombus. Unfortunately, data supporting
B
such therapy is limited and mostly from small
case series (18,26–28). One small trial randomized RAD
34 patients with angiographically large PE to IV- or
catheter-based infusion of t-PA at a dose of 50 mg over
2 h (29), and showed similar safety and angiographic
and hemodynamic results by both techniques. How-
ever, the local fibrinolytic dose used in this older trial
was much higher than what is currently used. In a
more recent prospective registry of 101 massive and
submassive PE patients treated with catheter-based
therapy (mostly local fibrinolysis), there was a sig-
nificant decrease in PA pressure and improvement in
RV function, with no reported major complications,
(A) The flow restoration catheter (FRC) is used to enmesh clots and is pulled through the
major bleeding, or strokes (26). Given the low risk for aspiration guide catheter (AGC) utilizing (B) the retraction aspirator device (RAD). Images
major complications, it is reasonable to consider CDF from Inari Medical.
in patients with already stabilized massive PE who
have contraindications to systemic fibrinolysis and in
patients with intermediate-high–risk PE (those with
RV dysfunction and increased biomarkers), particu- selectively into each PA can be performed to identify
larly those deemed at increased bleeding risk with the location of the thrombi; these are typically in the
full-dose systemic fibrinolysis. In a series of 52 PE main and/or lower main PA branch (Figure 5). If
patients treated with CDF, a more prominent hemo- the location of the thrombi is not clear by manual
dynamic benefit was obtained in patients with symp- injection, or the anatomy has not been previously
tom duration <14 days, as compared with those with a established by CT, and if the pulmonary pressure is
longer symptom duration (28). not severely elevated, a power injection may be
T e c h n i q u e . CT images, if available, are the basis for necessary (e.g., at 15 to 20 m/s for a total of 30 ml
planning the CDT procedure. Most high-risk patients selectively in each main PA, with a 15  to 20 left
have bilateral PE, although some have a major anterior oblique projection for the left PA and 0 to
thrombus in 1 PA and only require unilateral treat- 20 right anterior oblique projection for right PA). The
ment. Internal jugular or femoral venous access with volume of contrast injected can be adjusted on the
ultrasound guidance is obtained. For femoral access, basis of the CT findings. An exchange-length soft- or
ultrasound is used to rule out iliofemoral thrombus. j-tipped wire is placed in the lower PA branch, and the
A catheter (e.g., balloon-tipped, pigtail, or multipur- diagnostic catheter is exchanged for an infusion
pose) is carefully advanced to the main PA, where catheter, which has a treatment zone of 6 to 12 cm
pressure and blood oxygen saturation sampling are through which t-PA may be infused into the clot.
obtained. Contrast injection into the main PA or A second infusion catheter may be placed in the
998 Jaber et al.
Pulmonary Embolism
F I G U R E 4 Penumbra Indigo Aspiration System
(A) The 6- to 8-F straight or angled aspiration catheter (CAT6 or CAT8, respectively)
is advanced to the thrombus and aspiration performed with the (B) ACER pump. Separator
wires may be inserted into the catheter and utilized in a gentle back-and-forth motion to
clear the catheter of thrombus. Images from Penumbra, Inc.
contralateral PA through a second venous sheath, if
needed, using the same technique. Alternatively, a
10- to 12-F sheath may be placed at the beginning of
the procedure and both catheters placed through the
larger sheath. 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. Low-
dose, weight-adjusted heparin infusion is usually
continued during t-PA infusion, with a target partial
thromboplastin time on the low end of the thera-
peutic range (e.g., 40 to 60 s).
Commonly available infusion catheters used off-
label for PE include the Cragg-McNamera catheter
(ev3 Endovascular Inc.), the Fountain catheter (Merit
Medical, South Jordan, Utah), and the Unifuse cath-
eter (Angiodynamics). The EkoSonic catheter, (EKOS
Corp., Brothell, Washington), discussed later, is
currently the only catheter specifically approved by
FDA for the treatment of high-risk PE.
The risk of serious complications, including major
hemorrhage, using CDT has been low in published
studies. The risk of intracranial hemorrhage is <0.2%
(18,26–28).
U l t r a s o u n d a c c e l e r a t e d fi b r i n o l y s i s . The
Sonic catheter (Figure 6) consists of a 5.2-F con-
ventional infusion catheter with an inner cable
that transmits high-frequency, low-power ultra-
sound signals, designed to loosen the fibrin strands
and enhance thrombus penetration of
JACC VOL. 67, NO. 8, 2016
MARCH 1, 2016:991–1002
fibrinolytic agent, hence theoretically achieving a
faster thrombus breakdown (30). The technique
used for in vivo insertion is similar to other infu-
sion catheters, as described earlier. Once the
catheter is in position over the 0.035-inch guide-
wire, the guidewire is replaced with the microsonic
cable, which is then locked into place. The cath-
eter has 2 infusion ports: 1 for the fibrinolytic
infusion, and the other for a coolant solution
(normal saline at $35 ml/h).
Limited evidence supports the use of ultrasound-
accelerated thrombolysis (discussed in detail by
Konstantinides et al. [31]). It is uncertain whether
this treatment is suitable for patients who are
hemodynamically unstable and need faster resolu-
tion of the PE or if there is long-term benefit of the
prolonged treatment in prevention of future pulmo-
nary hypertension, underscoring the need for more
evidence.
EXTRACORPOREAL MECHANICAL
OXYGENATION AND RV ASSIST DEVICES
Extracorporeal membrane oxygenator (ECMO) place-
ment has been described in case reports of patients
with massive PE, as it has the potential to unload
the RV and, importantly, provides oxygenation dur-
ing massive PE to allow for RV recovery (32,33). 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.
Technologies such as the percutaneous RV assist
device (Impella RP, Abiomed, Danvers, Massachu-
setts) may one day be considered for use in massive
PE, either as a bridge to definitive therapy, or to
support RV recovery after thrombus removal.
SURGICAL EMBOLECTOMY
Currently, surgical therapy is considered a last resort
for acute PE and is offered only to patients in
extremis. This concept is on the basis of data from
the 1960s, when the surgical pulmonary embolec-
tomy mortality rate was in excess of 50% (34). This
may have been due, in part, to selection bias, as only
patients with very poor prognosis were brought to
the operating room. Significant advances in cardiac
surgical techniques have led to an impressive
Eko- reduction in operative mortality, which is as low as
6% in the current era (35,36). Furthermore, there is
evidence to support reduced long-term mortality in
patients undergoing pulmonary embolectomy
(37,38). In a 2013 report on 27 consecutive surgical
the pulmonary embolectomy patients, there was no
JACC VOL. 67, NO. 8, 2016 Jaber et al. 999
MARCH 1, 2016:991–1002 Pulmonary Embolism

F I G U R E 5 Example of a PE Treated With CDF

(A and B) CT angiogram of a patient with acute submassive PE, with thrombi seen in bilateral main PAs extending into the lower branches
(yellow arrows). (C) Pulmonary angiography of the same patient, demonstrating hand injection of contrast into the lower left PA branches,
with thrombus noted by the orange arrow. (D) Infusion catheters noted in both PAs. Manual injection of contrast agent performed through the
left catheter (orange arrows), documenting that the catheter is imbedded in the clot. Note EkoSonic catheter markers in the right PA (red
arrow). CDF ¼ catheter-directed fibrinolysis; CT ¼ computed tomography; PA ¼ pulmonary artery; PE ¼ pulmonary embolism.

in-hospital mortality and a 10-year actuarial survival
rate of 93%; both late mortalities were unrelated to
PE or related therapy (39).
SURGICAL TECHNIQUE. After median sternotomy,
patients are anticoagulated with heparin and placed
on cardiopulmonary bypass. Dual venous cannula-
tion allows excellent venous drainage and full access
to the right heart. The PA is typically opened longi-
tudinally, distal to the pulmonic valve, to a length of
approximately 5 cm. Sponge forceps are used to grasp
and remove visible clots. Small clot fragments may be
extracted using targeted gentle suction. The aorta
may be circumferentially freed and gently retracted
to allow “deeper” visualization of the right PA.
Occasionally, a secondary distal incision of the right
PA is made to allow even more distal access. Clots are
typically not adhered to the artery wall, and thus are
easily removable in acute PE cases.
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 anti-
coagulation (1,2). 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 (40). Both
the American and the European guidelines do not
recommend routine use of IVC filters in patients
with PE (1,2). These recommendations are supported
1000 Jaber et al.
Pulmonary Embolism
F I G U R E 6 EkoSonic Endovascular Device
The 5.2-F infusion catheter (A), which contains 3 lumens: 1 each for the inner ultrasound
cable, drug infusion, and normal saline as a coolant. The inner cable (B) is shown with
ultrasound crystals (arrows). Ultrasound energy separates fibrin strands, allowing for
enhanced thrombus penetration of fibrinolytic agent. Images from EKOS Corporation.
by the PREPIC2 (Prevention of Recurrent Pulmonary
Embolism by Vena Cava Interruption 2) study,
recently conducted in intermediate- and low-risk
patients (41). However, 3 large analyses, including a
U.S. nationwide hospital sample (42) and a study from
Japan (43), suggest that IVC filters may result in better
outcomes in patients with massive or intermediate-
high–risk PE. In the International Cooperative Pul-
monary Embolism registry, IVC filter use in patients
with massive PE was associated with reduced rates of
recurrent PE and mortality at 90 days (44).
POST-INTERVENTION
Maintenance of anticoagulation post-intervention is
critical to prevent recurrent clot formation. However,
patients who have had a recent catheter-based inter-
vention are at risk of access site bleeding. One strategy
to potentially reduce bleeding risk is to hold the hep-
arin 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, as per
American College of Chest Physicians guidelines (7).
Low molecular weight heparin can be utilized in
lieu of IV heparin. Alternatively, novel
JACC VOL. 67, NO. 8, 2016
MARCH 1, 2016:991–1002
anticoagulants, including rivaroxaban, dabigatran,
apixaban, and edoxaban, can be used (45–48). How-
ever, no guidelines indicate when or how these
agents should be initiated post-CDT, especially if
fibrinolytic agents have been administered. If an
alternative anticoagulant agent is utilized, we suggest
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.
Appropriate transition of the patient from the
inpatient to the outpatient setting is important. This
includes assessment of adequacy of anticoagulation
or affordability of novel anticoagulant agents, if pre-
scribed. Outpatient follow-up with a medical provider
familiar with PE care is imperative; several in-
stitutions incorporate a PE follow-up clinic as part of
the PERT program. To be addressed at follow-up are:
monitoring of anticoagulation; assessment of length
of anticoagulation and bleeding risk; retrieval of IVC
filter, if appropriate; screening for the development
of chronic pulmonary hypertension in patients at risk;
and completion of a hypercoagulable profile, when
indicated.
CONCLUSIONS
At this time, there is not enough evidence to strongly
support routine utilization of any of the previously
discussed techniques in the management of sub-
massive or massive PE, beyond anticoagulation. Most
PE patients should continue to be treated conserva-
tively, with aggressive treatment options reserved for
those at high- or intermediate-high–risk without
contraindications. Several studies have shown benefit
from systemic fibrinolysis in this patient population,
at the expense of an increased bleeding risk.
Currently, CDF with use of the EKOS catheter is the
only FDA-approved catheter-based therapy for use in
treatment of acute PE, although adequate compara-
tive studies are lacking. Other catheter-based thera-
pies 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. Although some centers have
reported favorable outcomes with surgical embolec-
tomy as a first-line management of intermediate-
high– and high-risk PE, it is 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 intracar-
oral diac thrombus or paradoxical embolus.
JACC VOL. 67, NO. 8, 2016 Jaber et al. 1001
MARCH 1, 2016:991–1002 Pulmonary Embolism

Until appropriate studies fill knowledge gaps, we
recommend utilization of multidisciplinary PERTs
and collection and sharing of data in registries or
formal studies. We have provided sample algorithms
and pathways to coordinate response to PE and
encourage multidisciplinary decision making. Similar
to a “Code Stroke” or “Code STEMI,” PE should
be considered as a “lung attack,” and appropriate
resources utilized. Formation
PERT programs and collaboration across multiple in-
stitutions through the National PERT Consortium can
provide the foundation for global prospective regis-
tries and much-needed randomized trials.
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
Tanveer Rab, Division of Cardiology, Emory Univer-
sity Hospital, 1364 Clifton Road Northeast, F-606,
of hospital-based Atlanta, Georgia 30322. E-mail: srab@emory.edu.

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KEY WORDS embolectomy, fibrinolysis,
interventional management, pulmonary
artery