Vascular Medicine
Predictors of Abdominal Aortic Aneurysm Sac Enlargement
After Endovascular Repair
Andres Schanzer, MD; Roy K. Greenberg, MD; Nathanael Hevelone, MPH; William P. Robinson, MD;
Mohammad H. Eslami, MD; Robert J. Goldberg, PhD; Louis Messina, MD
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
Background—The majority of infrarenal abdominal aortic aneurysm (AAA) repairs in the United States are performed
with endovascular methods. Baseline aortoiliac arterial anatomic characteristics are fundamental criteria for appropriate
patient selection for endovascular aortic repair (EVAR) and key determinants of long-term success. We evaluated
compliance with anatomic guidelines for EVAR and the relationship between baseline aortoiliac arterial anatomy and
post-EVAR AAA sac enlargement.
Methods and Results—Patients with pre-EVAR and at least 1 post-EVAR computed tomography scan were identified from
the M2S, Inc. imaging database (1999 to 2008). Preoperative baseline aortoiliac anatomic characteristics were reviewed
for each patient. Data relating to the specific AAA endovascular device implanted were not available. Therefore,
morphological measurements were compared with the most liberal and the most conservative published anatomic
guidelines as stated in each manufacturer’s instructions for use. The primary study outcome was post-EVAR AAA sac
enlargement (⬎5-mm diameter increase). In 10 228 patients undergoing EVAR, 59% had a maximum AAA diameter
below the 55-mm threshold at which intervention is recommended over surveillance. Only 42% of patients had anatomy
that met the most conservative definition of device instructions for use; 69% met the most liberal definition of device
instructions for use. The 5-year post-EVAR rate of AAA sac enlargement was 41%. Independent predictors of AAA sac
enlargement included endoleak, age ⱖ80 years, aortic neck diameter ⱖ28 mm, aortic neck angle ⬎60°, and common
iliac artery diameter ⬎20 mm.
Conclusion—In this multicenter observational study, compliance with EVAR device guidelines was low and post-EVAR aneurysm
sac enlargement was high, raising concern for long-term risk of aneurysm rupture. (Circulation. 2011;123:2848-2855.)
Key Words: abdominal aortic aneurysm 䡲 endovascular procedures 䡲 graft
T
he elective management of abdominal aortic aneurysms
(AAAs) has traditionally depended on open surgical aneurysm repair.1,2 However, recent developments in catheter-based
endovascular techniques have led to a substantial increase in the
proportion of AAAs managed electively with endovascular
aortic aneurysm repair (EVAR). In 2006, 21 725 EVAR procedures were performed in the United States, exceeding for the
first time the number of open surgical AAA repairs.3
phology) are recommended to guide patient selection for
EVAR. These instructions for use (IFU) are published and
packaged with each device used in the United States.
Clinical trials for regulatory approval and postmarketing
analyses, as well as randomized, controlled trials that compared EVAR with open AAA repair, have evaluated various
clinical outcomes in patients meeting the specific anatomic
requirements defined in the IFU.4 – 8 Several studies using
national databases have also reported on clinical outcomes
after EVAR; however, these studies lacked access to aortic
and iliac artery anatomic data and therefore were unable to
assess whether devices were used in accordance with published IFU or whether adherence to IFU affected clinical
outcomes.3,9 Thus, the proportion of patients and the outcomes of patients who undergo EVAR with anatomy outside
the device IFU are largely undocumented with respect to both
short- and long-term complications, with the exception of a
small number of single-center reports.10 –12
Editorial see p 2782
Clinical Perspective on p 2855
The regulatory approval of EVAR devices in the United
States requires manufacturers to measure technical factors
such as fixation strength, sealing ability, and delivery accuracy in the laboratory. On the basis of these preclinical
engineering assessments and clinical study results, specific
anatomic characteristics (including aortic neck diameter,
aortic neck length, aortic neck angle, and iliac artery mor-
Received December 16, 2010; accepted March 17, 2011.
From the University of Massachusetts Medical School, Worcester (A.S., W.P.R., M.H.E., R.J.G., L.M.); Cleveland Clinic Foundation, Cleveland, OH
(R.K.G.); and Harvard School of Public Health, Boston, MA (N.H.).
Guest editor for this article was Gilbert Upchurch, Jr.
Correspondence to Andres Schanzer, MD, Division of Vascular and Endovascular Surgery, Department of Quantitative Health Sciences, U Mass
Memorial Medical Center, 55 Lake Ave North, Worcester, MA 01655. E-mail [email protected]
© 2011 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
DOI: 10.1161/CIRCULATIONAHA.110.014902
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Schanzer et al
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These issues are of paramount importance when considering the long-term results of 2 randomized trials comparing
EVAR and open AAA repair.13,14 These studies have demonstrated substantially lower morbidity and mortality after
EVAR than after open repair. However, late follow-up of
these cohorts has demonstrated that the early survival advantage of patients undergoing EVAR disappears with time, and
a significant proportion of late deaths after EVAR are due to
aneurysm rupture.13,14 The cause of aortic rupture after
EVAR relates to repressurization of the aneurysm sac as a
result of device failure or progression of native disease in the
regions used to fixate and seal the device. Although the exact
mechanism was not determined for each case of aortic rupture
after endovascular repair in the EVAR study, these events
were found to be closely linked with aortic aneurysm sac
enlargement.15 Because aortic rupture has been shown to be
an important cause of late death in highly selected patient
populations within clinical trials, it is reasonable to hypothesize that commercial use of EVAR devices in patients who
did not meet device IFU could result in a greater risk of aortic
rupture.
The purpose of the present study was to use data from a
large, multicenter cohort to determine the degree of compliance with IFU anatomic guidelines for EVAR, to examine
changes in compliance with the IFU over the last decade, and
to determine the relationship between baseline aortic and iliac
artery anatomic characteristics and incidence of aortic aneurysm sac enlargement after EVAR.
Methods
Study Population
Patients undergoing EVAR between January 1, 1999, and December
31, 2008, were assembled from a medical imaging repository at
M2S, Inc. (West Lebanon, NH). Using standardized algorithms,
M2S creates 3-dimensional computer models from computed tomography (CT) images of aortic aneurysms. In addition to serving as the
core imaging laboratory for several large aneurysm management
trials,16 –18 M2S also provides these services to both private and
academic hospitals throughout the world. For the purposes of this
study, M2S provided deidentified data on all patients in its prospectively acquired database who underwent a CT scan before EVAR and
had at least 1 CT scan after EVAR between 1999 and 2008 in the
United States. M2S did not play any role in the study design,
analysis, or interpretation of the data provided.
From the M2S database, patients were selected for inclusion in the
present analysis according to the following criteria: clinical diagnosis
of AAA with an aortic diameter ⬎30 mm, preoperative CT scan
demonstrating the absence of an infrarenal endovascular stent graft
within the AAA (confirming the EVAR had not yet occurred), and at
least 1 postoperative CT scan demonstrating the presence of a stent
graft within the AAA (confirming that EVAR had occurred).
In an effort to further restrict our analyses to patients treated for an
AAA (and to exclude patients treated primarily for an isolated iliac
artery aneurysm), the required minimum aortic diameter was increased to 40 mm if either iliac artery diameter exceeded 20 mm.
Patients were also excluded if they underwent EVAR in the context
of premarketing or postmarketing studies in which M2S served as the
core imaging laboratory.
Data Elements and Image Analysis
All patient, physician, and hospital identifiers were removed by M2S
before the investigators received the data set. Available demographic
variables included patient age, sex, and the US state in which the
imaging studies were obtained. The exact date on which the CT scan
Predictors of AAA Enlargement
2849
Figure 1. The aortic and iliac arterial anatomy boundary conditions defined by the instructions for use that are packaged with
each Food and Drug Administration–approved commercial
endovascular aortic device. CIA, common iliac artery; EIA, external iliac artery.
was obtained was available for every patient for every CT scan. All
other data elements were anatomic in nature and were obtained after
CT scans underwent 3-dimensional processing and standardized
measurements by M2S personnel. Measurements were performed by
trained individuals blinded to patient, center, and operator through
the use of validated techniques; all measurements obtained were
consistent with the Society for Vascular Surgery Reporting Standards.19 All diameter measurements were calculated orthogonal to
the vessel of interest (ie, in a plane at a right angle to the centerline
of the lumen). All length and angle measurements were made along
the lumen centerline.
Key anatomic measurements included maximum AAA sac diameter, aortic diameter at the lowest renal artery, aortic diameter at
15 mm below the lowest renal artery, aortic neck length (distance
between the lowest renal artery and the origin of the aneurysm,
indicated by a 10% increase in diameter), aortic neck angulation
(angle calculated between the lowest renal artery, the origin of the
aneurysm, and the aortic bifurcation), conical neck (aortic diameter
15 mm below the lowest renal artery ⱖ10% larger than the aortic
diameter at the lowest renal artery), AAA volume, maximum
common iliac artery diameter, minimum external iliac artery diameter, and length from the lowest renal artery to the aortic bifurcation.
It is important to note that M2S does not collect data relating to
which specific AAA endovascular device was used and that this level
of detail could not be discerned from the CT images. In addition,
there were no data available detailing whether patients underwent
any secondary reinterventions.
Compliance With Instructions for Use
The IFU for each approved endovascular device was reviewed with
respect to year of device approval (Figure 1 and Table 1). For the
purposes of this study, these criteria were incorporated into 3
descriptive variables called conservative IFU (most restrictive),
liberal IFU (least restrictive), and time-dependent IFU (reflecting the
most liberal IFU at each time point during the study period) (Table
2). As mentioned, the specific AAA endovascular device used was
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June 21, 2011
Table 1. Anatomic Criteria as Presented in the Instructions for Use for Abdominal Aortic Aneurysm Endovascular Devices Approved
by the US Food and Drug Administration
Guidant
Ancure
Medtronic
AneuRX
Gore
Excluder
Cook
Zenith
Gore Excluder
Low Permeability
Endologix
Powerlink
Cook Zenith
Enlarged Neck
Medtronic
Talent
Endologix
Enlarged Neck
Gore Excluder
Enlarged Neck
2002
2003
2004
2004
2006
2008
2009
2009
Year of release
1999
1999
Neck
diameter, mm
18–26
18–25
19–26
18–28
19–26
18–26
18–32
18–32
18–32
19–29
Neck
length mm
ⱖ15
ⱖ10*
ⱖ15
ⱖ15
ⱖ15
ⱖ15
ⱖ15
ⱖ10
ⱖ15
ⱖ15
NS
ⱕ45
ⱕ60
ⱕ60
ⱕ60
ⱕ60
ⱕ60
ⱕ60
ⱕ60
ⱕ60
Iliac fixation
length, mm
ⱖ20
NS
ⱖ10
ⱖ15
ⱖ10
ⱖ15
ⱖ15
ⱖ15
ⱖ15
ⱖ10
Iliac
diameter, mm
⬍13.5
NS
10–18.5
10–20
10–18.5
8–18
10–20
8–22
10–23
10–18.5
Neck angle, °
NS indicates not specified.
*Changed to ⱖ15 mm in 2003 instruction for use revision.
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not contained in the data set, so graft-specific deviations from IFU
for each specific patient could not be assessed.
End-Point Definitions
End points were assessed at the time of each post-EVAR CT scan.
The primary study end point, AAA sac enlargement, was defined as
a growth of ⱖ5 mm in the AAA maximal diameter from pre-EVAR
to any post-EVAR CT scan (based on Society for Vascular Surgery
Reporting Standards19). The secondary study end point, endoleak,
was assessed via a single-phase arterial contrast CT scan, and was
defined as the presence of contrast-opacified blood within the
aneurysm sac and outside the endovascular stent graft.
Statistical Analysis
All anatomic measurements were analyzed in SAS (version 9.2, SAS
Institute, Inc., Cary, NC). Variations over time in baseline demographic and anatomic characteristics were calculated with the CochranArmitage test for trend. For time-trend analyses, patients undergoing
Table 2. Conservative, Liberal, and Time-Dependent
Instructions For Use Definitions Used to Characterize Baseline
Preoperative Anatomy
Conservative IFU
Aortic neck angle ⬍45°
Aortic neck length ⱖ15 mm
Aortic diameter at lowest renal artery ⬍28 mm
Liberal IFU
Aortic neck angle ⬍60°
Aortic neck length ⱖ10 mm
Aortic diameter at lowest renal artery ⬍32 mm
Time-dependent IFU
EVAR before 2006
Aortic neck angle ⬍60°
Aortic neck length ⱖ15 mm
Aortic diameter at lowest renal artery ⬍28 mm
EVAR in 2006 and 2007
Aortic neck angle ⬍60°
Aortic neck length ⱖ15 mm
Aortic diameter at lowest renal artery ⬍32 mm
EVAR in 2008
Aortic neck angle ⬍60°
Aortic neck length ⱖ10 mm
Aortic diameter at lowest renal artery ⬍32 mm
IFU indicates instructions for use; EVAR, endovascular aortic repair.
EVAR between 1999 and 2003 were grouped together to represent the
early experience with EVAR (first 5 years of commercial device
availability). Analysis of time-to-event occurrence of AAA sac enlargement was performed with the Kaplan-Meier method, and group differences (stratified by compliance with IFU) were compared by use of the
log-rank test. For these survival analyses, all observations were censored
at the time of the patient’s last CT scan. To identify independent
predictors of aortic aneurysm sac enlargement, all demographic and
anatomic variables that were statistically significant on univariate
analysis (P⬍0.05) were then introduced into a multivariable Cox
proportional hazards model with backward selection. In addition to
baseline characteristics, we evaluated the presence of an endoleak
during follow-up as a potential predictor of AAA sac enlargement. This
study was approved by the Institutional Review Board at the University
of Massachusetts Medical School.
Results
The study population consisted of 10 228 patients in the
United States who underwent EVAR for AAA repair between
1999 and 2008. This cohort did not include the 216 patients
(2.1%) who were identified as having isolated iliac artery
aneurysms without a concurrent AAA, and were therefore
excluded. The patients were primarily men (84.1%), had an
average age of 73.9 years, and represented all regions of the
United States (Table 3).
Baseline Anatomic Characteristics
All patients had a baseline CT scan before EVAR and at least
1 follow-up CT scan after EVAR; in total, 31 013 CT scans
were reviewed. The average preoperative AAA maximum
diameter was 54.8 mm; 6075 patients (59%) had an AAA
maximum diameter ⬍55 mm (Table 3). The average AAA
neck diameter was 23.1 mm, with a mean length of 20.7 mm
and a mean angle of 36.9°. In addition to the presence of an
AAA, 1215 patients (11.9%) were found to have at least 1
common iliac artery aneurysm (⬎20-mm diameter). When all
EVAR-treated patients were classified according to IFU
criteria, 5983 patients (58.5%) were outside compliance with
the conservative IFU, 3178 patients (31.1%) patients were
outside the liberal IFU, and 4507 patients (44.1%) were
outside the time-dependent IFU.
Demographic and Anatomic Trends Over Time
An increasing proportion of patients undergoing EVAR were
ⱖ80 years of age over the decade-long period under study
Schanzer et al
Table 3. Baseline Characteristics for All Patients Who
Underwent Endovascular Aortic Repair for the Treatment of an
Infrarenal Abdominal Aortic Aneurysm (1999 to 2008)
Patients, n
10 228
Demographics
Age (mean), y
Female gender, n (%)
73.9⫾8.2
1619 (15.9)
Geographic region, n (%)
Northeast
3113 (28.4)
Southeast
3457 (31.6)
Midwest
2659 (24.3)
West
1724 (15.7)
Anatomic factors
AAA diameter
Maximum, mm
54.8⫾10.1
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Maximum ⱖ55 mm, n (%)
4153 (40.6)
Maximum ⬍55 mm, n (%)
6075 (59.4)
Volume
Renal to aortic bifurcation, cm3
152.1⫾79.1
Renal to hypogastric, cm3
170.9⫾82.0
Aortic neck
Length, mm
⬎15, n (%)
20.7⫾12.7
5910 (57.8)
10–15, n (%)
1824 (17.8)
⬍10 mm, n (%)
2494 (24.4)
Diameter at lowest renal artery, mm
⬍28 mm, n (%)
23.1⫾3.9
9351 (91.4)
28–32 mm, n (%)
655 (6.4)
⬎32 mm, n (%)
222 (2.2)
Diameter 15 mm from lowest renal artery, mm
Conical neck, n (%)
Aortic neck angle, °
24.7⫾5.1
3300 (32.4)
36.9⫾15.4
⬍45°, n (%)
7440 (72.7)
45–60°, n (%)
2004 (19.6)
⬎60°, n (%)
784 (7.7)
Iliac artery diameter
Right common iliac artery diameter, mm
14.8⫾5.1
Left common iliac artery diameter, mm
14.2⫾4.5
Only 1 common iliac artery ⬎20 mm, n (%)
897 (8.8)
Both common iliac arteries ⬎20 mm, n (%)
318 (3.1)
Right external iliac artery diameter, mm
Left external iliac artery diameter, mm
6.9⫾1.6
7.0⫾1.6
Only 1 external iliac artery ⬍6 mm, n (%)
1352 (13.2)
Both external iliac arteries ⬍6 mm, n (%)
1756 (17.2)
Length
Lowest renal to aortic bifurcation, mm
125.3⫾16.8
Outside conservative IFU, n (%)
5983 (58.5)
Outside liberal IFU, n (%)
3178 (31.1)
Outside time-dependent IFU, n (%)
4507 (44.1)
AAA indicates abdominal aortic aneurysm; IFU, instructions for use. Values
are mean⫾SD when appropriate.
Predictors of AAA Enlargement
2851
(Table 4). The maximum AAA diameter before EVAR did
not change significantly over time, yet the average diameter
of the AAA neck increased significantly over time. A greater
proportion of patients undergoing EVAR had conical aortic
necks as time progressed (30.0% in 1999 to 2003 versus
35.7% in 2008; P⬍0.001). Similarly, in more recent years, a
larger proportion of patients undergoing EVAR had highly
angulated aortic necks (7.0% in 1999 to 2003 versus 9.5% in
2008; P⫽0.004). The external iliac artery diameter decreased
over the study period; 14.8% of patients in 1999 to 2003 had
both external iliac arteries ⬍6 mm compared with 17.5% in
2008 (P⫽0.05). Notably, no significant differences were
observed in the proportion of patients treated outside either
the conservative or liberal IFU throughout the study period.
Aortic Aneurysm Sac Enlargement
The mean duration of follow-up was 31⫾18 months, with an
average of 3.03⫾0.93 postoperative CT scans available per
patient. In the entire cohort, the proportions of patients who
developed AAA sac enlargement at 1, 3, and 5 years after
EVAR were 3%, 17%, and 41%, respectively. Importantly,
30% of patients who eventually manifested AAA sac enlargement did not demonstrate this enlargement until ⬎3 years
after EVAR. The rate of AAA sac enlargement was significantly higher in patients who underwent EVAR outside the
IFU, regardless of whether lack of compliance was to
conservative IFU, liberal IFU, or time-dependent IFU (Figure
2). In addition, when the cohort was stratified by year of
endograft implantation (before 2004 versus after), the rate of
AAA sac enlargement was significantly greater in the group
undergoing EVAR more recently (2004 to 2008) than in those
who underwent EVAR between 1999 and 2003 (Figure 2).
The presence of any endoleak during follow-up was
documented in 3279 patients, for an overall incidence of
32%. The majority of endoleaks (76%) became evident
during the first year of post-EVAR imaging. Of the 3279
patients who developed an endoleak, 692 (21.1%) were
found, at some point on post-EVAR imaging, to develop
aortic aneurysm sac enlargement.
Determinants of Aortic Aneurysm
Sac Enlargement
On univariate analysis, the following patient characteristics
were associated with an increased risk for AAA sac enlargement: age ⱖ80 years; conical aortic neck; aortic neck diameter
ⱖ28 mm; aortic neck angle ⬎60°; common iliac artery diameter
⬎20 mm; anatomy outside conservative, liberal, or timedependent IFU specifications; and presence of an endoleak
during follow-up. On multivariable analysis (Table 5), the
primary determinant of AAA sac enlargement was the presence
of an endoleak on any postoperative CT scan (hazard ratio, 2.70;
95% confidence interval, 2.40 to 3.04). Additional significant
predictors of AAA sac enlargement on multivariable analysis
were patient age ⱖ80 years, aortic neck diameter ⱖ28 mm, neck
angle ⬎60°, and common iliac artery diameter ⬎20 mm.
Discussion
This study demonstrates that, in a large population of patients
who underwent EVAR with commercial devices in the
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June 21, 2011
Table 4.
Baseline Characteristics for All Patients Who Underwent Endovascular Aortic Repair for the Treatment of an Infrarenal
Abdominal Aortic Aneurysm Stratified by Year of Treatment
Year
1999 –2003
Sample size, n
1632
2004
1640
2005
1883
2006
1830
2007
1650
2008
P
1593
Age, %
⬍60 y
13.1
8.1
6.2
5.8
5.0
5.2
60–69 y
23.3
25.0
26.2
26.2
26.1
26.9
⬍0.001
70–79 y
43.6
44.0
45.9
45.5
44.2
41.6
ⱖ80 y
20.0
23.0
24.8
22.5
24.7
26.3
Female, %
15.7
15.9
15.5
17.2
15.1
15.6
0.93
40.6
41.5
40.6
38.4
41.2
41.6
0.93
0.009
AAA diameter, %
Maximum AAA diameter ⱖ55 mm
Aortic neck (lowest renal artery to aneurysm) , %
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Length ⬎15 mm
54.7
59.1
58.0
58.0
58.5
58.3
Length 10–15 mm
16.5
17.4
19.0
18.1
18.4
17.5
Length ⬍10 mm
28.8
23.5
23.1
23.8
23.2
24.2
Diameter at lowest renal artery, %
⬍28 mm
⬍0.001
93.9
93.6
91.7
89.6
89.5
90.5
28–32 mm
4.7
5.1
6.4
7.1
7.8
7.3
⬎32 mm
1.4
1.3
1.9
3.3
2.8
2.3
Conical neck, %
30.0
30.7
31.6
32.9
33.7
35.7
⬍0.001
⬍45°
74.4
72.7
72.0
72.4
74.9
70.1
0.004
45–60°
18.6
21.0
20.7
19.6
17.2
20.4
7.0
6.2
7.3
8.0
8.0
9.5
Aortic neck angle, %
⬎60°
Iliac artery diameter, %
1 Common iliac artery ⬎20 mm
9.3
7.8
9.2
7.9
9.0
9.5
0.57
Both common iliac arteries ⬎20 mm
2.6
2.9
3.6
3.4
3.5
2.6
0.55
1 External iliac artery ⬍6 mm
13.6
14.2
13.2
13.1
13.4
11.9
0.12
Both external iliac arteries ⬍6 mm
14.8
17.1
18.1
17.5
17.9
17.5
0.052
Outside conservative IFU
60.3
56.3
57.9
59.4
56.4
60.8
0.70
Outside liberal IFU
34.6
28.8
29.6
30.9
30.3
32.6
0.68
Outside time–dependent IFU
49.4
44.8
47.0
45.0
44.7
32.6
⬍0.001
IFU, %
AAA indicates abdominal aortic aneurysm; IFU, instructions for use.
United States over a recent 10-year period, the incidence of
AAA sac enlargement after EVAR was 41% at 5 years, a rate
that increased over the study period. Liberalization of the
anatomic characteristics deemed suitable for EVAR has
occurred, and several of these factors, including aortic neck
diameter, aortic neck angle, and common iliac artery diameter, were independently associated with aortic aneurysm sac
enlargement. These observations raise the question of
whether such liberalization is justified with current device
designs. It is also interesting to note that 60% of the AAAs in
this study were smaller than the 55-mm recommended threshold for elective repair established by data from randomized
controlled trials.1,2
Endovascular stent-graft implantation requires proximal aortic neck anatomy and distal iliac artery anatomy that interact
with the device in such a way that all blood flow is excluded
from entering the aneurysm in an effort to eliminate pressuriza-
tion of the aneurysm wall. These anatomic factors include vessel
diameter, length, and angulation, among other factors. However,
there is no agreement as to the specific minimal aortoiliac
anatomic characteristics required to achieve durable endovascular repair. As a result, the IFU-specified anatomic characteristics
changed over the study period. Because of these changes, we
analyzed the preoperative anatomy in the context of the most
conservative IFU, most liberal IFU, and time-dependent IFU.
In the absence of any information about the incidence of
clinical complications or repeat interventions, we examined
as our primary end point, AAA sac enlargement, because it
provides the most direct evidence of EVAR failure to reduce
the risk of rupture. This study end point has been used in
other published reports,20,21 and has been associated with an
increased risk of adverse outcomes, including the need for
subsequent open repair and aneurysm rupture.22,23 The natural
history of untreated aneurysms is to enlarge over time until
Schanzer et al
Predictors of AAA Enlargement
2853
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Figure 2. Aortic aneurysm sac freedom from enlargement after endovascular aortic repair stratified according to (A) conservative
instructions for use (IFU), (B) liberal instructions for use, (C) time-dependent instructions for use, and (D) year of procedure performed
before or after January 1, 2004.
eventual rupture. Endovascular repair aims to prevent aortic
rupture; thus, AAA sac enlargement represents treatment
failure, because it leaves the patient at risk of death resulting
from rupture.
One possible exception to this rule relates to a subset of
patients treated with the first-generation Gore Excluder device, which was marketed commercially from 2002 to 2003.
This device was made of a higher-porosity graft material, and
the post-EVAR AAA sac enlargement associated with this
device has been suggested to carry a more benign prognosis,
at least through intermediate-term follow-up.24 To assess
whether this specific high-porosity device was an important
factor contributing to the high rate of AAA sac enlargement
seen in this study, we evaluated the patient groups before and
after the first generation of this device was altered (2004).
Surprisingly, the rate of AAA sac enlargement increased from
2004 to 2008 (Figure 2), suggesting that the use of this
specific device did not explain our observed trends during the
years under study. More likely, the liberalization of the anatomic
characteristics deemed suitable for EVAR observed over the
study period (ie, increased aortic neck diameter, increased
proportion of patients with conical aortic necks, increased
proportion of patients with highly angulated aortic necks) explains this trend. An alternative explanation for this trend may be
that patients treated before 2004 were at higher medical risk, and
that these procedures therefore carried a higher associated
mortality. If so, more patients treated before 2004 may have died
before manifesting AAA sac enlargement.
When analyzing the dates of the CT scans included in this
study, we identified 1221 patients (11.9%) in this cohort who
did not have any post-EVAR CT scans beyond 90 days from
the date of the pre-EVAR CT scan. In these patients, it is
possible that an insufficient amount of time elapsed for them
to manifest AAA sac enlargement. As a result, the rate of
AAA sac enlargement reported in this study may represent an
underestimate.
The present study is the largest investigation to date using
detailed pre-EVAR and post-EVAR anatomic CT imaging
data to assess determinants of AAA sac enlargement after
EVAR. However, several limitations are inherent in the
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Circulation
June 21, 2011
Table 5.
Determinants of Aortic Aneurysm Sac Enlargement
Identified on Multivariable Cox Proportional Hazards Analysis
Covariates
Hazard Ratio (95%
Confidence Interval)
P
Age, y
⬍60
Reference
60–69
0.80 (0.60–1.05)
0.11
70–79
0.87 (0.67–1.14)
0.31
ⱖ80
1.32 (1.03–1.75)
0.05
Female
0.96 (0.82–1.13)
0.64
0.97 (0.86–1.10)
0.62
AAA diameter
Maximum AAA diameter
ⱖ55 mm
Aortic neck length, mm
⬎15
Reference
Downloaded from http://circ.ahajournals.org/ by guest on June 17, 2017
10–15
0.87 (0.71–1.07)
0.19
⬍10
0.94 (0.77–1.15)
0.53
Aortic neck diameter
Diameter at lowest renal artery
⬍28 mm
Reference
Diameter at lowest renal artery
28–32 mm
1.80 (1.44–2.23)
⬍0.0001
Diameter at lowest renal artery
⬎32 mm
2.07 (1.46–2.92)
⬍0.0001
1.17 (0.97–1.42)
0.10
Conical neck
Aortic neck angle, °
⬍45
Reference
45–60
1.04 (0.90–1.21)
0.58
⬎60
1.96 (1.63–2.37)
⬍0.0001
Iliac diameter
Both common iliac arteries
ⱕ20 mm
Reference
Only 1 common iliac arteries
⬎20 mm
1.46 (1.21–1.76)
⬍0.0001
Both common iliac arteries
⬎20 mm
1.31 (0.99–1.74)
0.06
2.70 (2.40–3.04)
⬍0.0001
Endoleak during follow–up
AAA indicates abdominal aortic aneurysm.
analysis of this data set. All CT-, patient-, and hospital-related
data were de-identified, so that there was no knowledge by
the investigators about the enrolling clinicians, centers, or
implanted devices. As a result, additional clinical data,
including occurrences of secondary interventions, cannot be
ascertained for patients included in this study. If a large
number of the enlarging aneurysms were easily treated with a
repeat intervention, the clinical implications of this end point
would, to some extent, be mitigated. In addition, nonconsecutive submission of patient data by hospitals may have
introduced an important selection bias. It is possible that
hospitals may have submitted only their most complicated
cases to M2S, such as those requiring secondary interventions
or those with more challenging anatomy, but we are unable to
assess this potential concern with the available data. However, one would hypothesize that if the impetus to obtain
more detailed imaging information were driven by anatomic
complexity, the aneurysms would be larger. This is clearly
not the case, given that the majority of aneurysms in this
study were actually smaller than the current treatment recommendations for treatment of AAA. To better understand
the potential impact of these biases, we compared the characteristics of the 8596 patients in the M2S data set during the
second half of our study period (2004 to 2008) with those of
the 103 237 Medicare patients undergoing EVAR from 2004
to 2008 (approximating an 8% sample). The average age (74
years versus 76 years) and proportion of men (84% versus
83%) in the M2S and Medicare data sets were similar.9 These
findings suggest that results from the M2S database are
generalizable to a significant proportion of patients undergoing EVAR in the United States.
An additional potential limitation of this study relates to
the fact that the exact date on which the EVAR procedure was
performed is not known. As a result, it is impossible to know
how much time elapsed between the pre-EVAR baseline CT
scan and the date of the EVAR procedure. If enough time did
elapse between the pre-EVAR baseline CT scan and the
EVAR procedure, it is conceivable that the AAA sac enlargement observed may have occurred before the AAA repair.
However, given that the average rate of AAA growth has
been demonstrated to be only 3.2 mm/y,1 and that most
surgeons proceed with repair well before 1 or 2 years has
elapsed since obtaining the relevant imaging study, we do not
believe that this mechanism plays a significant role in the
findings observed.
In this study, we used the standard definition of maximum
diameter growth ⱖ5 mm for AAA sac enlargement. We
acknowledge that recent reports have suggested that changes
in AAA sac volume may provide a more sensitive way in
which to detect AAA sac growth.24 –26 Future studies may
help shed more light on which metric for detecting AAA sac
growth is the most clinically useful.
In this multicenter patient population, compliance with
published EVAR device IFU guidelines was low, and postEVAR aneurysm sac enlargement was high, raising concern
for long-term risk of aneurysm rupture. The anatomic determinants of AAA sac enlargement identified in this study
clearly demonstrate the importance of patient selection when
deciding to proceed with EVAR. The liberalization in anatomic criteria deemed appropriate for EVAR, observed
throughout the study period, was associated with worse
outcomes. A prospective EVAR registry that incorporates an
independent imaging registry is necessary to define more
precisely the specific aortic and iliac artery anatomic characteristics suitable for EVAR with currently available commercial devices. An improved understanding of these anatomic
characteristics will ultimately improve the effectiveness and
durability of EVAR to protect patients against AAA rupture.
Sources of Funding
This work was supported by the William Rogers Family Foundation.
The funding agency had no role in the design and conduct of the
study; in the collection, analysis, and interpretation of the data; or in
the preparation, review, or approval of the manuscript.
Schanzer et al
Disclosures
Dr Greenberg receives research support from an intellectual property
license and grant support from Cook Medical. The remaining authors
have no conflicts to disclose.
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CLINICAL PERSPECTIVE
Two recently published randomized trials comparing the effectiveness of open surgical and endovascular repair (EVAR)
for the treatment of abdominal aortic aneurysms have demonstrated a significantly lower mortality rate for patients
undergoing EVAR. However, the initial short-term survival advantage for patients undergoing EVAR was lost after
long-term follow-up. A significant proportion of the late deaths of patients undergoing EVAR were due to aneurysm
rupture. These concerning findings raise questions about the effectiveness and durability of EVAR to prevent death caused
by abdominal aortic aneurysm rupture. This study uses a large multicenter cohort of patients who underwent endovascular
abdominal aortic aneurysm repair in the United States. This data set is the largest EVAR cohort assembled to date that
contains standardized, validated computed tomography anatomic measurements performed on all patients before and after
EVAR. We demonstrate that compliance with published EVAR device guidelines is low, and that the incidence of
aneurysm sac enlargement after EVAR is high. These unexpected findings raise significant concerns about the long-term
risk of aneurysm rupture in patients undergoing EVAR in the United States. Furthermore, over the decade of study,
liberalization of the anatomic characteristics deemed suitable for EVAR by device manufacturers has occurred, and several
of these liberalized anatomic characteristics independently predict aortic aneurysm sac enlargement.
Predictors of Abdominal Aortic Aneurysm Sac Enlargement After Endovascular Repair
Andres Schanzer, Roy K. Greenberg, Nathanael Hevelone, William P. Robinson, Mohammad
H. Eslami, Robert J. Goldberg and Louis Messina
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Circulation. 2011;123:2848-2855; originally published online April 10, 2011;
doi: 10.1161/CIRCULATIONAHA.110.014902
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2011 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
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Correction
In the article by Schanzer et al, “Predictors of Abdominal Aortic Aneurysm Sac Enlargement
After Endovascular Repair,” which was published in the June 21, 2011 issue of the journal
(Circulation. 2011;123:2848 –2855), the authors neglected to disclose a potential conflict of
interest: Dr Greenberg receives research support from an intellectual property license and grant
support from Cook Medical. The remaining authors have no conflicts to disclose.
The text has been corrected in the current online version of the manuscript. The authors regret
the error.
DOI: 10.1161/CIR.0b013e31824686be
(Circulation. 2012;125:e266.)
© 2012 American Heart Association, Inc.
Circulation is available at http://circ.ahajournals.org
e266