Sac behavior after aneurysm treatment with the Gore Excluder low-permeability aortic endoprosthesis: 12-month comparison to the original Excluder device

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 approved 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.

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)	P value
	Age (y)				.59
	Mean ± SD	74.2±8.1	73.2±8.3	73.0±5.9
	Median	74.0	75.0	74.0
	Range	59-88	55-88	63-89
	Sex (%)				.27
	Female	26.7	16.7	16.3
	Male	73.3	83.3	83.7
	Aneurysm size (mm)				.46
	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

OGE, Original Gore Excluder endoprosthesis; ELPD, Excluder Low-Permeability Device.

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 measuring 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 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, demographic, and anatomic variables were analyzed for each device type. Wilcoxon signed rank tests (pairwise) or Kruskal-Wallis tests (three groups) were used for intergroup comparison of continuous variables, whereas χ2 statistics or Fisher exact tests were used to compare categorical variables. Continuous variables are summarized 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 (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 severely 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 embolization 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 embolization 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 unchanged 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.

The percentage of patients with significant sac expansion 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 (≥5 mm) sac expansion at 1 year. Significant sac size reduction (≥5 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 compared with baseline, was 3.0 ± 6.3 mm (5.1%) with the OGE, 7.6 ± 6.2 mm (14.8%) with the ELPD, and 8.5 ± 6.3 mm (16.8%) with ZEN (Fig 3).

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Fig 2. Percentage of patients undergoing sac size change at 1 year. OGE, Original Gore Excluder endoprosthesis; ELPD, Excluder Low-Permeability Device; ZEN, Cook Zenith device.

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)				.46	.72	.36
	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
	Follow-up aneurysm size (mm)				<.001	.27	<.001
	Mean ± SD	52.2±11.2	44.8±9.6	43.6±11.0
	Median	50.5	45.0	43.0
	Range	32.0-87.0	24.3-65.0	28.0-99.0
	Change in size (mm)				<.001	.37	<.001
	Mean ± SD	−3.0±6.3	−7.6±6.2	−8.5±6.3
	Median	−1.0	−7.0	−9.0
	Range	−22.0-5.0	−25.0-2.0	−22.0-6.0
	% change in size				<.001	.39	<.001
	Mean ± SD	−5.1±10.8	−14.8±11.9	−16.8±12.3
	Median	−1.9	−13.1	−18.0
	Range	−36.7-9.6	−48.3-4.4	−44.0-6.0
	% patients with a decrease in sac size at 1 y	25.0	63.9	65.3	<.001	.87	<.001
	Endoleak ≥1 month (%)	36.7	23.6	20.4	.11	.68	.10

OGE, Original Gore Excluder endoprosthesis; ELPD, Excluder Low-Permeability Device.

⁎ Overall P value. † Zenith vs ELPD. ‡ OGE vs ELPD.

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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 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 permeable 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, however, 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 is a significant problem with the original device. Sac enlargement (≥5 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. Significant sac regression was noted in only 23%, 24%, and 21% of subjects at those same time points in the Pivotal Trial (Table III).

Table III. Aneurysm size change with OGE: site-reported Excluder trial data6

	Change in aneurysm size	1-6 mo (N = 196), n (%)	1-12 mo (N = 191), n (%)	1-24 mo (N = 165), n (%)	1-36 mo (N = 130), n (%)	1-48 mo (N = 113), n (%)	1-60 mo (N = 94), n (%)
	Decrease	24(12)	44(23)	41(25)	31(24)	23(20)	20(21)
	No change	168(86)	142(74)	108(65)	72(55)	53(47)	40(43)
	Increase	4(2)	5(3)	16(10)	27(21)	37(33)	34(36)

OGE, Original Gore Excluder endoprosthesis. One-month baseline, ≥5 mm, minor diameter.

The original Excluder device was associated, throughout 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. Furthermore, 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 endotension 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 ≥5 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. Benchtop permeability comparisons performed by Gore by using pressurized bovine serum demonstrated significant differences between the devices (OGE, 0.233 g·min−1 · cm−2; ELPD, 0.000 g · min−1 · cm−2). On the basis of our preliminary data, the modification of the Excluder endograft may be 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 compared with the older OGE device. This represents a 39% increase in the number of patients who experience sac regression when treated with the ELPD. These rates compare well to the ZEN, for which early favorable sac changes have previously 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 significant 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 marketing 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 endotension 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 desirable end point of EVAR. However, excessive AAA sac regression may have deleterious consequences. These problems 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 component disjunction in the face of accelerated sac regression. So far, in our experience, no graft migration or limb disconnection 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 sponsored 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 minimal sac expansion were noted after EVAR with ELPD. Since release of the ELPD for EVAR, no patient has experienced significant sac growth after implantation in our experience. Furthermore, up to 64% of patients were noted to have significant (≥5-mm) aneurysm sac diameter regression at 1 year. These rates are an improvement over those seen with the original Excluder, and they compare favorably 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.

Author contributions