From the Society for Clinical Vascular Surgery
`
`Sac behavior after aneurysm treatment with
`the Gore Excluder low-permeability aortic
`endoprosthesis: 12-month comparison
`to the original Excluder device
`
`Shan-e-ali Haider, MD,a Samer F. Najjar, MD,b Jae-Sung Cho, MD,a Robert Y. Rhee, MD,a
`Mark K. Eskandari, MD,b Jon S. Matsumura, MD,b Michel S. Makaroun, MD,a
`and Mark D. Morasch, MDb Pittsburgh, Pa; and Chicago, Ill
`
`Background: The original Gore Excluder endoprosthesis (OGE) used both during and briefly after clinical trials was
`associated with less sac regression and more sac growth than some other devices, even without apparent endoleaks,
`presumably because of transmural movement of serous fluid across the expanded polytetrafluoroethylene material. In July
`2004, the device was modified to decrease graft permeability. This study evaluated the efficacy of the new Excluder
`Low-Permeability Device (ELPD) at 1 year and compared it with the OGE and the Cook Zenith device (ZEN).
`Methods: From Food and Drug Administration approval of the Excluder in November 2002 until June 2005, 283 patients
`underwent endovascular repair of abdominal aortic aneurysms with the Gore Excluder or the ZEN. Postoperative
`surveillance included computed tomographic scans at 1 and 12 months; 181 (64%) patients completed both scans. The
`1-month computed tomographic scan served as a baseline, and the minor axis diameter, measured at the largest axial cut
`of the abdominal aortic aneurysm, was compared with the same measurement at 1 year. A sac size change of 5 mm or more
`was considered significant. Sixty patients treated with the OGE were compared with 72 patients treated with the ELPD.
`Forty-nine patients treated during the same time period with the ZEN, known for early sac shrinkage, were used as a
`reference. All measurements were performed by one observer from a digital workstation. Wilcoxon signed rank tests
`(pairwise) or Kruskal-Wallis tests (three groups) were used for intergroup comparison of continuous variables, whereas
`␹2 statistics or Fisher exact tests were used to compare categorical variables.
`Results: Patient age and sex and mean maximum aneurysm diameter at baseline were similar among groups (P ⴝ .59, .27,
`and .46, respectively). Graft migration, stent fractures, acute surgical conversion, late abdominal aortic aneurysm
`rupture, or aneurysm-related deaths were not observed. Type II endoleak rates were similar between ELPD and ZEN
`(23.6% and 20.4%; P ⴝ .68). Although a higher rate of endoleaks was seen with OGE (36.7%), this was not significant
`when compared with the other two devices (P ⴝ .11). At 1 year, patients treated with ELPD had a sac regression rate that
`was significantly higher than that for patients treated with OGE (63.9% vs 25%; P < 0.001) and was similar to that for
`patients treated with ZEN (65.3%). Significant sac expansion was not observed with ELPD.
`Conclusions: At 1 year, similar to ZEN, significant aneurysm sac regression and minimal sac expansion were noted after
`endovascular repair of abdominal aortic aneurysms with ELPD. Low-porosity fabric used in the construction of
`endoprostheses seems to be an important factor in early aneurysm sac shrinkage. Long-term efficacy regarding the
`prevention of sac enlargement remains unclear, and further follow-up is suggested. ( J Vasc Surg 2006;44:694-700.)
`
`No fewer than 10 commercial devices for endovascular
`repair of abdominal aortic aneurysms (EVAR) have been
`developed and deployed in US clinical trials.1 Five have
`received Food and Drug Administration (FDA) approval,
`
`From the University of Pittsburgh School of Medicinea and the Division of
`Vascular Surgery, Northwestern University Feinberg School of Medicine,
`Chicago.b
`Competition of interest: Drs Eskandari, Matsumura, and Morasch serve as
`consultants to W. L. Gore & Associates, Inc, and are on their speakers’
`bureau. Dr Morasch receives research support from W. L. Gore &
`Associates. Dr Makaroun has a consulting agreement with W. L. Gore &
`Associates and receives research support from them.
`An earlier version of this manuscript was presented in the poster session at
`the Society for Clinical Vascular Surgery Thirty-fourth Annual Sympo-
`sium, Las Vegas, NV, March 8-11, 2006.
`Reprint requests: Mark D. Morasch, MD, Division of Vascular Surgery, 201
`E Huron, #10-105, Chicago, IL 60611 (e-mail: mmorasch@nmh.org).
`0741-5214/$32.00
`Copyright © 2006 by The Society for Vascular Surgery.
`doi:10.1016/j.jvs.2006.06.018
`694
`
`and four remain commercially available. Previous reports
`have suggested that endograft type is strongly correlated
`with the likelihood of sac regression.2-5 The Excluder en-
`dograft (W. L. Gore & Associates, Inc, Flagstaff, Ariz) used
`in clinical trials was associated with less sac regression and
`more sac growth than some other commercial devices.
`Significant sac regression (ⱖ5 mm) was noted in 23% and
`21% of patients, respectively, at 1 and 5 years, and signifi-
`cant sac expansion occurred in 3% and 36% at the same time
`points after treatment in the Excluder 98-03 Pivotal Trial.6
`Of greatest concern, sac growth was occurring even with-
`out apparent endoleaks.4-6
`Although shrinkage of the aneurysm sac after EVAR
`may be desirable, a stable aneurysm has not been linked to
`any untoward effects. Sac enlargement, however, implies
`increased pressure within the aneurysm sac, and this has
`been associated with endoleaks and with sac rupture. 7
`When no endoleak can be identified after aggressive
`
`TMT 2123
`Medtronic v. TMT
`IPR2021-01532
`
`

`

`JOURNAL OF VASCULAR SURGERY
`Volume 44, Number 4
`
`Haider et al 695
`
`Table I. Patient demographics (mean age, sex, and
`aneurysm size) compared for the three endografts:
`Zenith, OGE, and ELPD
`
`Variable
`
`OGE
`(n ⫽ 60)
`
`ELPD
`(n ⫽ 72)
`
`Zenith
`(n ⫽ 49)
`
`73.2 ⫾ 8.3 73.0 ⫾ 5.9
`75.0
`74.0
`55-88
`63-89
`
`Age (y)
`Mean ⫾ SD 74.2 ⫾ 8.1
`Median
`74.0
`Range
`59-88
`Sex (%)
`Female
`Male
`Aneurysm size
`(mm)
`Mean ⫾ SD 55.2 ⫾ 11.6 52.5 ⫾ 7.7 52.1 ⫾ 7.7
`Median
`52.0
`51.5
`51.0
`Range
`41-106
`40-71
`43-93
`
`26.7
`73.3
`
`16.7
`83.3
`
`16.3
`83.7
`
`P
`value
`
`.59
`
`.27
`
`.46
`
`OGE, Original Gore Excluder endoprosthesis; ELPD, Excluder Low-
`Permeability Device.
`
`sac change at 12 months after EVAR using the modified
`device; second, to compare sac changes before and after
`device modification; and third, to compare sac changes
`after EVAR with the Excluder device to sac changes with a
`device known for early sac shrinkage (Zenith; Cook Medi-
`cal, Bloomington, Ind). The main goal was to determine
`whether the new alterations incorporated into the con-
`struct of the Excluder Low-Permeability Device (ELPD)
`would significantly influence the frequency or degree of sac
`regression at an early stage after EVAR.
`
`METHODS
`From November 2002, after FDA approval, through
`the release of the ELPD, until June 2005, 209 consecutive
`patients underwent elective endoluminal AAA repair at
`these institutions with the Gore Excluder (106 OGE and
`103 ELPD). Over a similar time period, 74 patients were
`treated with the Cook Zenith device (ZEN). Patients who
`were predominantly treated for iliac artery aneurysms or
`aortic pseudoaneurysms were excluded from this study.
`The institutional review boards at Northwestern University
`School of Medicine and the University of Pittsburgh ap-
`proved the study protocol. Patient demographics were
`compared among the three groups (Table I). Institutional
`protocols included, among other measures, patient follow-up
`computed tomographic (CT) scans at 1 month and 1 year
`after EVAR. Only patients who completed both scans within a
`4-month window of their scheduled test were included in this
`analysis.
`Aneurysm anatomy and the presence, or absence, of an
`endoleak were determined by CT scans, performed first
`without contrast and followed by early- and late-phase
`contrast-enhanced imaging. The method used for measur-
`ing changes in the dimension of the aneurysm sac was in
`accordance with the Society for Vascular Surgery reporting
`standards for endovascular aortic aneurysm repair.12 Sac
`measurements were completed at a digital workstation
`by a single observer from each institution. Aneurysm sac
`
`Fig 1. Hygroma formation on an original-design Excluder stent
`graft.
`
`evaluation, continued sac growth has been attributed to
`endotension.8,9 In permeable stent grafts, endotension is
`thought to be the result of transmural movement of serous
`fluid across the expanded polytetrafluoroethylene material,
`thus resulting in hygroma formation (Fig 1). Aneurysm sac
`hygroma has been documented at the time of open re-
`pair,10 and in vitro studies demonstrate that the particular
`device construct correlates with the degree of plasma per-
`meability.11 Apparent endotension has resulted in rupture
`of aneurysms treated with other devices in their clinical
`trials,12 and sac rupture in the absence of an associated
`endoleak has now been observed in three patients treated
`with the original Gore Excluder endoprosthesis (OGE).
`Clearly, sac growth as a result of this permeability phenom-
`enon has been a source of consternation and frustration for
`patients, practitioners, and manufacturers alike.
`In July 2004, Gore released an updated version of the
`Excluder device. The new device incorporates an additional
`low-permeability layer to reduce fluid flow across the graft
`material. This modification should, in theory, prevent hy-
`groma formation and, we hypothesized, would also result
`in favorable sac behavior. Implantation of the modified
`device began at Northwestern Memorial Hospital and at
`the University of Pittsburgh Medical Center shortly after its
`release in July 2004. This study had three objectives: first,
`to evaluate the rates of abdominal aortic aneurysm (AAA)
`
`

`

`696 Haider et al
`
`JOURNAL OF VASCULAR SURGERY
`October 2006
`
`size, for measurement purposes, was defined as the minor
`axis on the largest axial cut of the aneurysm on the
`two-dimensional CT scan measured from adventitia to
`adventitia. The minor axis measurements were chosen
`for primary comparison to avoid overestimation of AAA
`size as a result of tortuosity of the aorta. 13 We, therefore,
`compared the minor axis at the largest area of the AAA
`on a baseline postoperative CT scan at 1 month (range,
`3-8 weeks) with a second CT scan performed 12 months
`later (range, 10-14 months). A sac diameter size change
`of 5 mm or more at 12 months compared with the
`baseline CT scan was considered significant. Finally, sac
`changes after implantation of the ELPD were compared
`with sac changes after treatment with the OGE and with
`changes after treatment with the ZEN. Clinical, demo-
`graphic, and anatomic variables were analyzed for each
`device type. Wilcoxon signed rank tests (pairwise) or
`Kruskal-Wallis tests (three groups) were used for inter-
`group comparison of continuous variables, whereas ␹2
`statistics or Fisher exact tests were used to compare
`categorical variables. Continuous variables are summa-
`rized as mean ⫾ SD, whereas categorical variables are
`summarized as counts or percentages.
`
`RESULTS
`There were no perioperative aneurysm-related deaths.
`No patient experienced AAA rupture or late aneurysm-
`related death during follow-up. Twenty-four patients (8%)
`died from non–aneurysm-related causes before reaching
`1 year, including myocardial infarction (three OGE, six
`ELPD, and one ZEN), cancer (three OGE, two ELPD, and
`no ZEN), and other miscellaneous non–aneurysm-related
`causes (two OGE, four ELPD, and three ZEN). Three
`patients with a baseline aneurysm minor axis diameter less
`than 40 mm who were treated for symptoms (tenderness or
`embolization) were excluded from analysis. Seventy-five
`(26%) additional patients (26 OGE, 28 ELPD, and 21 ZEN)
`were lost to follow-up, did not have a 1- or 12-month CT
`scan within the window, or had CT follow-up elsewhere and
`films were unavailable for review. When adequate follow-up
`data could not be obtained, the patients were excluded
`from further analysis. These excluded patients were equally
`distributed among the three study groups.
`There were 181 patients (60 OGE, 72 ELPD, and 49
`ZEN) who completed both the 1- and 12-month CT scans,
`and these are the basis for all further review. Patient age was
`similar among the groups (OGE, 74.2 ⫾ 8.1 years; ELPD,
`73.2 ⫾ 8.3 years; and ZEN, 73.0 ⫾ 5.9 years; P ⫽ .59). In
`terms of sex, there was also no significant disparity noted
`among the three groups (Table I). The mean minimum
`baseline aneurysm diameter was also similar among groups
`(OGE, 55.2 ⫾ 11.6 mm; ELPD, 52.5 ⫾ 7.7 mm; and
`ZEN, 52.1 ⫾ 7.7 mm; P ⫽ .46). The mean interval
`between the 1- and 12-month scans was 11.3 months (SD,
`1.5 months) for OGE, 10.7 months (SD, 2.2 months) for
`ELPD, and 11.3 months (SD, 2.1 months) for ZEN. No
`statistical difference was seen between OGE and ELPD
`(P ⫽ .3), OGE and ZEN (P ⫽ .98), and ZEN and ELPD
`
`Fig 2. Percentage of patients undergoing sac size change at 1
`year. OGE, Original Gore Excluder endoprosthesis; ELPD, Ex-
`cluder Low-Permeability Device; ZEN, Cook Zenith device.
`
`(P ⫽ .3) when the time interval between the two CT
`scans was compared.
`Three (2%) type Ia endoleaks were noted at 1 month.
`One occurred in a ZEN patient who, despite multiple
`coilings and placement of a proximal Palmaz stent, required
`eventual graft explantation for continued sac expansion at
`12 months. Sac size increased from 93 mm at baseline to
`99 mm at 1-year follow-up. A second type Ia leak also
`occurred in a ZEN patient. Despite sac regression from
`58 to 54 mm, this patient underwent placement of a
`proximal Palmaz stent, with a subsequent decrease in the
`size of the endoleak. The third type Ia leak occurred in an
`ELPD patient. This patient had an increase in sac size
`from 45 to 47 mm at 1-year follow-up and is currently
`being managed conservatively. All three patients had se-
`verely angulated and short infrarenal necks. One (0.5%)
`type III endoleak was seen in a ZEN patient. The leak
`emanated from a modular disconnect between the main
`body and the left iliac limb. This was picked up on the
`1-month scan and bridged by using an extension cuff. At
`1-year follow-up, there was no endoleak, and the aneurysm
`diameter had decreased from 52 to 36 mm.
`Forty-three patients (24%; 21 OGE, 15 ELPD, and 7
`ZEN) had a type II endoleak on their 1-month CT scan.
`Type II endoleaks resolved spontaneously by 12 months in
`four OGE, two ELPD, and four ZEN patients. One OGE
`patient had a type II endoleak treated with coil emboliza-
`tion at 2 months for a 6-mm sac expansion and then
`experienced 10 mm of sac shrinkage by 12 months. One
`patient treated with ELPD also underwent coil emboliza-
`tion of a type II endoleak at 3 months for a 4-mm sac
`expansion and experienced 5 mm of sac reduction by 12
`months. Sixteen OGE patients, 10 ELPD patients, and 3
`ZEN patients had stable type II leaks that remained un-
`changed and untreated between the 1- and 12-month
`scans. One OGE patient and one ELPD patient developed
`new type II leaks at 12 months that were not present on the
`1-month scan.
`
`

`

`JOURNAL OF VASCULAR SURGERY
`Volume 44, Number 4
`
`Haider et al 697
`
`Table II. Sac behavior before and after device placement
`
`Variable
`
`OGE (n ⫽ 60)
`
`ELPD (n ⫽ 72)
`
`Zenith (n ⫽ 49)
`
`P value*
`
`P value†
`
`P value‡
`
`Starting aneurysm size (mm)
`Mean ⫾ SD
`Median
`Range
`Follow-up aneurysm size (mm)
`Mean ⫾ SD
`Median
`Range
`Change in size (mm)
`Mean ⫾ SD
`Median
`Range
`% change in size
`Mean ⫾ SD
`Median
`Range
`% patients with a decrease in sac size at 1 y
`Endoleak ⱖ1 month (%)
`
`55.2 ⫾ 11.6
`52.0
`41-106
`
`52.2 ⫾ 11.2
`50.5
`32.0-87.0
`
`⫺3.0 ⫾ 6.3
`⫺1.0
`⫺22.0-5.0
`
`⫺5.1 ⫾ 10.8
`⫺1.9
`⫺36.7-9.6
`25.0
`36.7
`
`52.5 ⫾ 7.7
`51.5
`40-71
`
`44.8 ⫾ 9.6
`45.0
`24.3-65.0
`
`⫺7.6 ⫾ 6.2
`⫺7.0
`⫺25.0-2.0
`
`⫺14.8 ⫾ 11.9
`⫺13.1
`⫺48.3-4.4
`63.9
`23.6
`
`52.1 ⫾ 7.7
`51.0
`43-93
`
`43.6 ⫾ 11.0
`43.0
`28.0-99.0
`
`⫺8.5 ⫾ 6.3
`⫺9.0
`⫺22.0-6.0
`
`⫺16.8 ⫾ 12.3
`⫺18.0
`⫺44.0-6.0
`65.3
`20.4
`
`.46
`
`.72
`
`.36
`
`⬍.001
`
`.27
`
`⬍.001
`
`⬍.001
`
`.37
`
`⬍.001
`
`⬍.001
`
`.39
`
`⬍.001
`
`⬍.001
`.11
`
`.87
`.68
`
`⬍.001
`.10
`
`OGE, Original Gore Excluder endoprosthesis; ELPD, Excluder Low-Permeability Device.
`*Overall P value.
`†Zenith vs ELPD.
`‡OGE vs ELPD.
`
`OGE, 7.6 ⫾ 6.2 mm (14.8%) with the ELPD, and 8.5 ⫾
`6.3 mm (16.8%) with ZEN (Fig 3).
`The endoleak rate at any one point (all comers) was
`36.7% for OGE, 23.6% for ELPD, and 20.4% for ZEN.
`Although there was a trend toward a higher leak rate with
`the OGE, there was no statistically significant difference
`among the devices (Table II).
`
`DISCUSSION
`Several recent reports have shown that the change in
`aneurysm size after EVAR is device specific.4,5,11 Aneurysm
`shrinkage has been reported to be more pronounced with
`thicker endografts than those constructed with more perme-
`able materials. In trials, the Excluder and AneuRx (Medtronic
`Vascular, Santa Rosa, Calif) devices had a sharply lower
`incidence of shrinkage when compared with other devices
`such as the Talent (Medtronic Vascular) and the ZEN
`endografts. The clinical significance of these changes, how-
`ever, is not entirely clear. Most would agree that regression
`of AAA size implies complete exclusion of the aneurysm sac
`and is a useful marker for successful repair. This led the Ad
`Hoc Committee for Standardized Reporting Practices in
`Vascular Surgery to include size reduction as a criterion for
`clinical success.
`The OGE was used throughout phase I and phase II
`clinical trials. These trials concluded in November 2002,
`and FDA approval was granted during the same month. At
`5 years, the 98-03 Gore Excluder Pivotal Trial data, as
`reported by the clinical test sites, showed no ruptures, one
`postprocedure migration, one stent fracture, no graft tears,
`and a 10% total endoleak rate (all type II or indeterminate).
`The postprocedure conversion rate was 4.3%, and patency
`was 100%. The most recent analysis of the 60-month
`Pivotal Trial data confirms, however, that sac enlargement
`
`Fig 3. Mean change in aneurysm size at 1 year. OGE, Original
`Gore Excluder endoprosthesis; ELPD, Excluder Low-Permeability
`Device; ZEN, Cook Zenith device.
`
`The percentage of patients with significant sac expan-
`sion or regression and the percentage of patients with no
`significant sac changes are shown in Fig 2. One patient with
`ZEN (2%), 1 patient with OGE (2%), and no patient with
`ELPD (0%) experienced significant (ⱖ5 mm) sac expansion
`at 1 year. Significant sac size reduction (ⱖ5 mm) with
`OGE, ELPD, and ZEN was noted in 25.0%, 63.9%, and
`65.3%, respectively (P ⬍ .001). The mean minor axis AAA
`size at 1 and 12 months and the percentage decrease in size
`from baseline for all three devices are shown in Table II.
`The mean minor axis AAA sac size was 55.2 ⫾ 11.6 mm at
`baseline and 52.2 ⫾ 11.2 mm at 1 year in patients treated
`with OGE, 52.5 ⫾ 7.7 mm at baseline and 44.8 ⫾ 9.6 mm
`at 1 year in patients treated with ELPD, and 52.1 ⫾ 7.7 mm
`at baseline and 43.6 ⫾ 11.0 mm at 1 year in patients treated
`with ZEN. The average diameter reduction, when com-
`pared with baseline, was 3.0 ⫾ 6.3 mm (5.1%) with the
`
`

`

`698 Haider et al
`
`JOURNAL OF VASCULAR SURGERY
`October 2006
`
`Table III. Aneurysm size change with OGE: site-reported Excluder trial data6
`
`Change in
`aneurysm size
`
`Decrease
`No change
`Increase
`
`1-6 mo
`(N ⫽ 196),
`n (%)
`
`24 (12)
`168 (86)
`4 (2)
`
`1-12 mo
`(N ⫽ 191),
`n (%)
`
`44 (23)
`142 (74)
`5 (3)
`
`1-24 mo
`(N ⫽ 165),
`n (%)
`
`41 (25)
`108 (65)
`16 (10)
`
`1-36 mo
`(N ⫽ 130),
`n (%)
`
`31 (24)
`72 (55)
`27 (21)
`
`1-48 mo
`(N ⫽ 113),
`n (%)
`
`23 (20)
`53 (47)
`37 (33)
`
`1-60 mo
`(N ⫽ 94),
`n (%)
`
`20 (21)
`40 (43)
`34 (36)
`
`OGE, Original Gore Excluder endoprosthesis.
`One-month baseline, ⱖ5 mm, minor diameter.
`
`is a significant problem with the original device. Sac en-
`largement (ⱖ5 mm) at 1, 3, and 5 years after implantation
`was 3%, 21%, and 36%, respectively. Of 34 patients with
`significant (⬎5-mm) sac growth at 5 years, 18 (53%) of
`them had no identifiable endoleak, and device permeability
`and endotension were thought to be the culprits. Signifi-
`cant sac regression was noted in only 23%, 24%, and 21% of
`subjects at those same time points in the Pivotal Trial
`(Table III).
`The original Excluder device was associated, through-
`out all the clinical trials, with some early significant sac
`expansion.6 The problem with sac expansion became more
`evident at 3 to 4 years.6,7 In Cho and colleagues’ study,7 19
`clinical trial patients were followed up for 4 years after
`implantation using the original Excluder device. A sac
`growth rate of 40% was noted, and endotension was the
`apparent culprit in 9 (75%) of 12 of the cases; the other 3
`(25%) had type II endoleaks. This sac growth, however, is
`not universal, because Melissano et al14 followed up 19
`patients for 4 years, and, although sac growth occurred in
`association with type IA and type II endoleaks, there was no
`case of sac enlargement secondary to endotension. Further-
`more, they noted no adverse events when aneurysm sac size
`remained unchanged. Relatively poor rates of sac regression
`were also noted early on in clinical trials, and corroborating
`studies noted sac regression rates of only 14% to 35% at 1
`year and 19% to 44% at 2 years after treatment with the
`original Excluder device.4,5,7,15
`Although no rupture has been reported in the absence
`of an endoleak in the 98-03 Pivotal Trial cohort, one
`rupture due to endotension has now been reported to the
`device manufacturer in the 99-04 phase of the Gore clinical
`trial. A second rupture, also without an endoleak, was
`reported after FDA approval but before the launch of
`ELPD, and a third rupture was reported from outside the
`United States. Although no rupture was identified in our
`postmarketing OGE patients, some significant sac growth
`(2%) and only 25% sac shrinkage were observed. This clearly
`suggests that continued close follow-up of this subgroup of
`EVAR patients is warranted.
`In search of the best explanation for this observation,
`Fillinger16 and the Excluder Bifurcated Endoprosthesis
`Clinical Investigators recently evaluated the subgroup of
`patients from the 98-03 Pivotal Trial who experienced sac
`expansion. They used trial core laboratory data to identify
`cases in which the aneurysm sac had grown 5 mm or more
`
`and in which at least 4 years of patient follow-up had taken
`place. Three-dimensional morphologic analysis was used
`rather than simple diameter measurements. They concluded
`that, at a minimum, in 21% of cases, sac growth could be
`attributed to nothing else but material permeability and that,
`in upwards of 74% of cases, device permeability and endoten-
`sion were likely important factors contributing to sac growth.
`The ZEN AAA endograft was first introduced in 1993
`and was modified shortly thereafter. The device design that
`was available in 1997 was used through clinical trials. The
`ZEN is constructed by using thick, impermeable Dacron
`(DuPont, Wilmington, Del). This endoprosthesis has been
`associated with aneurysm sac size regression at an early
`stage after its use. Greenberg et al17 reported a significant
`sac shrinkage (defined as a change in the size of the major
`axis ⱖ5 mm) rate of 68% at the 1-year follow-up. A couple
`of caveats include, however, that (1) anatomic exclusion
`criteria were very stringent during clinical trials, and these
`guidelines are generally not as strictly adhered to outside of
`trials, and (2) sac size change was considered significant if
`the major axis of the sac changed 5 mm or more. We used
`the minor axis for comparison, because this is believed to be
`a more reliable measure. In a similar study evaluating the
`transcontinental Zenith trial data, a 58% sac shrinkage rate
`was seen. The devices used were mainly the bifurcated
`variety, but a small number of patients were treated with the
`aortomonoiliac device.18
`This OGE was distributed throughout the United
`States after FDA approval at the end of 2002. Delivery of
`this device continued through the postmarketing phase
`until July 2004. Because of concerns regarding aneurysm
`expansion after treatment with the original endoprosthesis,
`the device was altered to address the phenomenon of fluid
`accumulation within the sac. The ELPD was first delivered
`in the United States in July 2004 and then was delivered in
`Europe 3 months later. The new low-porosity expanded
`polytetrafluoroethylene film incorporated into the device
`construct makes the new Excluder less permeable to fluids
`when compared with the previous construct. The ELPD
`incorporates this less permeable interior layer but maintains
`the same luminal and abluminal stent graft surfaces. Bench-
`top permeability comparisons performed by Gore by using
`pressurized bovine serum demonstrated significant differ-
`ences between the devices (OGE, 0.233 g · min⫺1 · cm⫺2;
`ELPD, 0.000 g · min⫺1 · cm⫺2). On the basis of our prelim-
`inary data, the modification of the Excluder endograft may be
`
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`JOURNAL OF VASCULAR SURGERY
`Volume 44, Number 4
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`Haider et al 699
`
`effective in preventing aneurysm enlargement over time, and
`the new device clearly leads to more sac size reduction at 1 year
`than did the original device. Using the ELPD device, we have
`observed that the percentage of patients with significant sac
`regression increased from 25% to 64% at 1 year when com-
`pared with the older OGE device. This represents a 39%
`increase in the number of patients who experience sac regres-
`sion when treated with the ELPD. These rates compare well
`to the ZEN, for which early favorable sac changes have previ-
`ously been documented.
`It seems fairly clear that, at least at 1 year, device
`permeability does have some influence on sac behavior. It is
`unclear, however, what role the presence or absence of an
`endoleak plays in sac behavior. Type II endoleaks persisting
`out to 1 year were more common in patients treated with
`OGE vs patients treated with ELPD or ZEN. It could be
`argued that the lack of shrinkage seen in OGE was due not
`to material permeability but rather to the fact that this
`group had a higher percentage of leaks. As in Fillinger’s
`report,16 however, this leak rate cannot fully explain the
`nearly threefold improvement in sac size reduction seen
`with the ELPD. A counter argument, as has been alluded to
`by Fillinger, is that the more permeable material may
`actually play a role in perpetuating type II endoleak flow.
`Furthermore, sac reduction is not universal with any device.
`Some patients, regardless of device type, show no signifi-
`cant change despite adequate exclusion.
`We also compared our postmarketing results with core
`laboratory data from the 98-03 Pivotal Trial.6 The original
`Excluder, as expected, performed no differently after mar-
`keting than it did during trials, even though Instructions
`for Use were not strictly adhered to after FDA approval.
`Conversely, the percentage of patients treated with the
`ELPD who were found to have significant shrinkage was
`much greater than the percentage treated with the OGE in
`the Pivotal Trial. In our cohort, at 1 year, 64% of the
`patients (46/72) experienced a significant aneurysm sac
`diameter reduction when compared with the 1-month
`postdeployment CT scan. This compares favorably with the
`23% shrinkage rate at 12 months reported in the 98-03
`Pivotal Trial, because it represents a threefold increase in
`the rate of aneurysm regression over the same time period.
`The additional low-permeability layer seems to have
`affected the incidence of hygroma and reduced endoten-
`sion after AAA exclusion. Limitations included our nearly
`36% patient dropout rate. Given our referral patterns, a
`large proportion of our patients chose not to travel back to
`our centers and elected to continue follow-up at their local
`hospitals. Nonetheless, the dropout rate was similar among
`the three study groups, and this gives validity to our results.
`In addition, our review is preliminary given that the ELPD
`has been in use for just over 20 months. Of note, Cho et al7
`showed that sac enlargement can have a delayed (3-year)
`onset after implantation. Furthermore, sac expansion can
`develop even after initial shrinkage. Cho et al noted late sac
`growth in three patients in whom re-expansion was noted
`after initial shrinkage of more than 5 mm. In one patient,
`the sac had regressed by 10 mm at the 6-month follow-up,
`
`but it then slowly re-expanded back to baseline by the
`fourth year.7 Clearly, more follow-up is necessary in our
`patient cohort to ensure that late sac enlargement does not
`occur after these encouraging initial results.
`Intuitively, AAA regression would seem to be a desir-
`able end point of EVAR. However, excessive AAA sac
`regression may have deleterious consequences. These prob-
`lems were well documented in the experience with early
`modular endografts.12 It may be that, in fact, a stable sac is
`most desirable because this reduces new stresses on the
`modular junctions and on the seal zones as sac shrinkage
`changes anatomic geometry.19 Again, we recommend
`longer follow-up to look for graft migration and compo-
`nent disjunction in the face of accelerated sac regression. So
`far, in our experience, no graft migration or limb discon-
`nection has been noted. With the low migration rates
`(2%-3%) reported for the Excluder graft, this study was not
`sufficiently powered to address this concern, however. A
`prospective study that is currently under way and is spon-
`sored by the device manufacturer may provide data that can
`answer many of the questions that remain. Unfortunately,
`the results from this trial will not be available for a number
`of years.
`
`CONCLUSIONS
`At 1 year, significant aneurysm sac regression and min-
`imal sac expansion were noted after EVAR with ELPD.
`Since release of the ELPD for EVAR, no patient has expe-
`rienced significant sac growth after implantation in our
`experience. Furthermore, up to 64% of patients were noted
`to have significant (ⱖ5-mm) aneurysm sac diameter regres-
`sion at 1 year. These rates are an improvement over those
`seen with the original Excluder, and they compare favor-
`ably to other endoprostheses, such as the ZEN, that also
`have low-permeability constructs. Low-porosity fabric seems
`to be an important factor in early aneurysm sac shrinkage.
`Long-term efficacy regarding prevention of sac enlargement
`remains unclear, and further follow-up is suggested. Although
`our preliminary data are encouraging, further studies and
`more patients with longer follow-up are needed to determine
`the continued long-term benefits of the ELPD.
`We thank Faith Selzer, PhD, University of Pittsburgh
`School of Public Health, for her biostatistical help and
`Diana Eastridge, RN, CNP, for her assistance in data
`collection and analysis. This article was written without the
`knowledge or support of W.L. Gore & Associates.
`
`AUTHOR CONTRIBUTIONS
`Conception and design: SH, SFN, MSM, MDM
`Analysis and interpretation: SH, SFN, MSM, MDM
`Data collection: SH, SFN, J-SC, RYR, MKE, JSM, MSM,
`MDM
`Writing the article: SH, SFN, MSM, MDM
`Critical revision of the article: SH, SFN, J-SC, RYR, MKE,
`JSM, MSM, MDM
`Final approval of the article: SH, SFN, MSM, MDM
`Statistical analysis: SH, MSM, MDM
`
`

`

`700 Haider et al
`
`JOURNAL OF VASCULAR SURGERY
`October 2006
`
`Overall responsibility: MDM
`SH and SFN contributed equally to this work.
`
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