Annual rupture risk of abdominal aortic aneurysm enlargement without detectable endoleak after endovascular abdominal aortic repair

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1 From the Society for Vascular Surgery Annual rupture risk of abdominal aortic aneurysm enlargement without detectable endoleak after endovascular abdominal aortic repair Dave Koole, MD, a,b Frans L. Moll, MD, PhD, a Jacob Buth, MD, PhD, c Roel Hobo, PhD, c Herman J. A. Zandvoort, MD, a Michiel L. Bots, MD, PhD, d Gerard Pasterkamp, MD, PhD, b and Joost A. van Herwaarden, MD, PhD, a for the European Collaborators on Stent-Graft Techniques for Aortic Aneurysm Repair (EUROSTAR), Utrecht and Eindhoven, The Netherlands Objectives: Whether abdominal aortic aneurysm (AAA) enlargement after endovascular aneurysm repair (EVAR), without an identifiable endoleak, is a risk factor for AAA rupture remains controversial. To our knowledge, studies including large patient numbers investigating this topic have not been done. Therefore, a considerable number of conversions to open AAA repair have been performed in this patient group. This study evaluated AAA rupture risk in patients without detectable endoleaks but with AAA enlargement after EVAR treatment. Methods: Baseline characteristics and follow-up data were collected prospectively by case record forms. Follow-up visits were scheduled at 1, 3, 6, 12, 18, and 24 months, and annually thereafter. The follow-up assessment included clinical examination and imaging studies. Patients were divided into three groups according to the degree of shrinkage or enlargement of the aneurysm. Group A included patients with >8 mm aneurysm shrinkage, group B consisted of patients with <8 mm shrinkage to <8 mm enlargement, and group C patients had an aneurysm enlargement of >8 mm. Results: The basis for this analysis was 6337 patients who were enrolled prospectively in the European Collaborators on Stent-Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) database between 1996 and Group A included 691 patients; group B, 5307 patients; and group C, 339 patients. Ruptures occurred in 3 patients in group A, in 14 patients in group B, and in 9 patients in group C. The annual rate of rupture in group C was <1% in the first 4 years but accelerated to 7.5% up to 13.6% in the years thereafter. The mortality rate of elective conversion to open AAA repair was 6.0%. Conclusions: The risk of rupture in patients with an AAA enlargement of 8 mm after EVAR, without detectable endoleaks, is <1% in the first 4 years. No ruptures were seen in patients with AAA enlargement without detectable endoleaks who were not treated with Vanguard stent grafts (Boston Scientific Corp, Natick, Mass) and had AAA diameters <70 mm. For this group, conversion to open repair might not be mandatory, and regular follow-up can be advised instead. After 4 years of follow-up, this study observed an increased annual rupture risk, which might indicate the need for conversion; however, groups are small, and follow-up bias could play a role. (J Vasc Surg 2011;54: ) From the Departments of Vascular Surgery a and Experimental Cardiology b and the Julius Center for the Health Sciences and Primary Care, d University Medical Center Utrecht, Utrecht; and the Department of Vascular Surgery, Catharina Hospital, Eindhoven. c Competition of interest: Frans L. Moll is a consultant with Medtronic and Nelix. Joost A. van Herwaarden is a consultant with Medtronic. Presented at the 2011 Vascular Annual Meeting of the Society of Vascular Surgery, Chicago, Ill, June 16-19, Reprint requests: D. Koole, Department of Vascular Surgery, Room G04.129, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands ( d.koole@umcutrecht.nl). The editors and reviewers of this article have no relevant financial relationships to disclose per the JVS policy that requires reviewers to decline review of any manuscript for which they may have a competition of interest /$36.00 Copyright 2011 by the Society for Vascular Surgery. doi: /j.jvs Treatment of abdominal aortic aneurysms (AAAs) aims at aneurysm exclusion, depressurization of the aneurysm sac, and thereby, prevention of aneurysm rupture. In the last decade, AAA treatment underwent a shift from open AAA repair to endovascular aneurysm repair (EVAR). 1 Endovascular repair of AAA disease is associated with a significantly lower operative mortality rate than open repair. 2,3 However, exclusion of the AAA is not always definitive, and a certain risk of AAA rupture after EVAR remains. 4-8 Rupture rates from different cohorts have varied between 0.5% and 1.2% per year after EVAR. 3,9-15 The reported mortality rate of a ruptured AAA after EVAR is 20% to 38%. 4 Confirmed risk factors for post-evar AAA rupture include advanced age, large initial AAA diameter, graft migration, or the presence of type I or III endoleaks. 4,7,8,16 Although one tends to think of AAA enlargement after EVAR, without an identifiable endoleak, as a risk factor for AAA rupture, this relation has not been unequivocally demonstrated. 4,7,17 A recent guideline of the Society for Vascular Surgery (SVS) states, On occasion, explantation and conversion may be required when no clear cause can be detected and endoleak, as a cause of sac expansion, cannot be excluded. 18 Also the guideline of the European Society of Vascular Surgery (ESVS) states, an enlarging abdominal aortic aneurysm after endovascular abdominal aortic repair without evidence of an endoleak and with an increase in diameter 10 mm should usually be repaired surgically or with a new stent graft. 19 Moreover, a previous consen-

2 JOURNAL OF VASCULAR SURGERY Volume 54, Number 6 Koole et al 1615 Fig 1. Flow chart shows the study cohort inclusion. CT, Computed tomography; EUROSTAR, European Collaborators on Stent-Graft Techniques for Aortic Aneurysm Repair; MRI, magnetic resonance imaging; US, ultrasound. sus conference suggested, An enlarging aneurysm after EVAR mandates surgical or interventional treatment. 20 As a consequence of these recommendations, a considerable number of conversions to open AAA repair have been performed. The purpose of this study was to assess the risk of rupture after EVAR in patients with AAA enlargement but without detectable endoleaks. This condition is also known as endotension, a term that was introduced in Perioperative mortality of conversion to open AAA repair in this patient category was also assessed. Finally, we addressed whether open conversion or a conservative approach with increased surveillance should be the preferred management policy. METHODS Study population and organization of the registry. An account of the organization of the European Collaborators on Stent-Graft Techniques for Aortic Aneurysm Repair (EUROSTAR) Registry has been published. 10,16,22,23 Briefly, preoperative patient characteristics, operative details, and follow-up data were initially collected prospectively by means of case record forms on paper, and after 2002 by using an on-line format (KIKA- Medical, Nancy, France). Follow-up visits, according to the protocol, were scheduled at 1, 3, 6, 12, 18, and 24 months, and annually thereafter. Findings of the clinical examination and imaging studies at the follow-up assessments were recorded and data returned at standard times to the Data Registry Center (Eindhoven, The Netherlands) for analysis. Inclusion criteria were elective treatment for AAA disease and suitable vascular anatomy for implantation of a stent graft. 23 Data of 6337 patients who were enrolled prospectively in the EUROSTAR database between 1996 and 2006 constituted the basis for this analysis. The study excluded patients without follow-up and those without AAA diameter measurements after EVAR. Additional exclusion criteria were imaging modalities other than computed tomography (CT), ultrasound (US) scans, or magnetic resonance imaging (MRI). Patients with reported endoleaks were also excluded (Fig 1). Aneurysm growth was determined by an increase in aneurysm diameter measured at its largest section, from outer wall to outer wall across the minor diameter, on the axial CT, US image, or MRI section. Aneurysm enlargement was defined as a diameter increase of 8 mm relative to the preoperative diameter measurements on the included image. 7,24-26 The maximum recorded aneurysm diameter during follow-up was used for this analysis. Three groups categorized by aneurysm enlargement, without detectable endoleaks, were created and stratified as follows: group A represented patients with 8 mm aneurysm shrinkage, group B consisted of patients with 8 mm shrinkage to 8 mm enlargement, and group C had an aneurysm enlargement of 8 mm. Statistical analysis. Results are reported as mean and standard deviation for continuous data and as percentage for discrete data. We tested by univariate analysis whether significant differences in baseline characteristics, operative complications, or brand of used device were present among the defined study groups. Differences among the study groups were analyzed with 2 tests for discrete variables and analysis of variance tests for continuous variables. Cumulative rates of freedom from aneurysm rupture, conversion to open repair, and aneurysm-related deaths after EVAR were

3 1616 Koole et al JOURNAL OF VASCULAR SURGERY December 2011 Table I. Demographic data of patients undergoing endovascular aneurysm repair, stratified by postoperative expansion Group A a Group B b Group C c Post hoc Bonferroni P e No. % Mean (SD) No. % Mean (SD) No. % Mean (SD) P d Group AvsB Group BvsC Group AvsC Age, years (8.0) (7.7) (8.0) Male sex ASA class Diabetes Cardiac history Renal insufficiency Pulmonary symptoms Hypertension Hypercholesterolemia Current smoker Aneurysm diameter, mm (13.4) (10.7) (14.9) Infrarenal aortic neck Diameter, mm (3.3) (3.2) (3.1) Length, mm (12.8) (11.9) (17.2) Aneurysmatic CIAs AAA, Abdominal aortic aneurysm; ASA, American Society of Anesthesiologists; CIA, common iliac arteries; SD, standard deviation. a Aneurysm shrinkage 8 mm. b Aneurysm shrinkage 8 mm to enlargement 8 mm. c Aneurysm enlargement 8 mm. d Overall P value was given to prevent multiple testing. e For continuous variables, Bonferroni post hoc analyses were performed to identify differences between the groups. For discrete variables, post hoc analyses between group A vs B, B vs C, and A vs C were performed with 2 tests concerning these groups. To correct for the 3 simultaneous comparisons, we applied Bonferroni s correction method. Missing data on comorbidity ranged from 75 to 267 per variable. assessed with survival table analysis, and rates with 10% standard error were excluded from the analysis. Significant differences among the defined study groups were analyzed with log-rank testing. s with a significant correlation with an adverse outcome event in the univariate analysis were entered in a multivariable Cox analysis to investigate independent associations. All tests were two-sided, with P.05 considered statistically significant. Statistical analyses were performed with SPSS 15.0 software (SPSS, Chicago, Ill). RESULTS The study included 6337 patients, comprising 5948 men (93.9%) and 389 women (6.1%), who were a mean age of 71.2 years (range, years). Mean aneurysm diameter was 57.2 mm (range, mm). Group A included 691 patients, group B included 5307 patients, and group C included 339 patients. Details of patient variables are summarized in Table I. Group A had significantly more women (2.3%) than group B; however, this was not the case when group A was compared with group C. The preoperative aneurysm diameter was significantly smaller in the group with AAA enlargement compared with groups A and B. Furthermore, group C had the smallest mean aortic neck diameter, but the difference among the groups was not significant (P.063). The mean infrarenal aortic neck length was 27.7 mm for group A, 27.5 mm for group B, and 29.8 mm in patients with an AAA enlargement (P.005). Mean duration of follow-up was 24.6 months (range, months) for the entire study cohort. The mean duration of follow-up was 26.4 months for group A, 25.8 months for group B, and 36.6 months for group C. Follow-up was significantly longer for patients with an AAA enlargement after EVAR compared with groups A and B (P.001). A total of 26 ruptures occurred in the entire study cohort. The median time to rupture was 48 months. Freedom from rupture in the entire study cohort was 95.9% at 7 years. Ruptures occurred in 3 patients (0.4%) in group A, in 14 (0.32%) in group B, and in 9 (2.6%) in group C. Freedom from rupture at 7 years was 96.3% in group A, 98.9% in group B, and 79.5% in group C (P.001, Fig 2). Univariate analysis for increased rupture risk was performed for baseline characteristics with significant differences between study groups, type of stent graft, and intraoperative or postoperative complications (Table II). Multivariable analysis indicated enlargement of the aneurysm, initial diameter of the aneurysm, length of the infrarenal aortic neck, and the Vanguard stent graft (Boston Scientific Corp, Natick, Mass) were independent factors for an increased rupture risk (Table III). Although group C had significantly higher rupture rates at 7 years, the mean annual rupture risk was 1.1%. The annual rate of rupture in group C was 1% in the first 4 years, but accelerated to 7.5% up to 13.6% in the years thereafter (Table IV). The mean AAA diameter at the last follow-up in group C between the nonruptured and ruptured AAAs was 60.1 vs 74.2 mm (P.021). Many of the ruptured AAAs had a diameter of 70 mm (Table V). Group C had 116 patients with an AAA diameter of 70 mm, and a rupture occurred in 6 of these patients (5.2%).

4 JOURNAL OF VASCULAR SURGERY Volume 54, Number 6 Koole et al 1617 Fig 2. Rupture rate stratified by aneurysm enlargement. Table II. Significant different variables between the groups in demographic characteristics, aneurysm anatomy, and type of stent were tested by univariate analysis for risk of rupture HR (95% CI) Age ( ) Male sex ( ) Hypercholesterolemia ( ) Pre-op aneurysm diameter per mm ( ) Infrarenal aortic neck length per mm ( ) Aneurysmatic common iliac arteries ( ) AAA expansion 8 mm ( ) 8 and 8 mm Reference 8 mm ( ) AneuRx a ( ) Excluder b ( ) Talent a ( ) Vanguard c ( ) Zenith d ( ) Procedure device-related complications ( ) Stent migration ( ) Kinking of the graft ( ) AAA, Abdominal aortic aneurysm; CI, confidence interval; HR, hazard ratio. a Medtronic, Minneapolis, Minn. b W. L. Gore and Associates, Flagstaff, Ariz. c Boston Scientific Corp, Natick, Mass. d Cook Inc, Bloomington, Ind. Table III. Independent risk factors for rupture of aneurysm, outcome of multivariable Cox analysis HR (95% CI) Pre-op aneurysm diameter per mm ( ) Length of infrarenal aortic neck per mm ( ) AAA expansion 8 mm ( ) Between 8 and 8 mm Reference 8 mm ( ) Vanguard stent graft a ( ) AAA, Abdominal aortic aneurysm; CI, confidence interval; HR, hazard ratio. a Boston Scientific Corp, Natick, Mass. Table IV. An overview of the different annual rupture risks in group C Year of FU Combined FU a (years) Ruptures (n) Annual rupture rate (%) FU, Follow-up. a Combined FU years were calculated for each interval. When the diameter of a ruptured aneurysm was 70 mm, patients had a Vanguard stent graft. Vanguard stent grafts had been used in 11 of the 26 patients (42.3%) in the cohort with a ruptured AAA, and in 4 of the 9 patients (44.4%) in the expansion group with ruptured AAAs. However, not all Vanguards (n 35) in group C led to rupture (n 4; 11.4%). The mortality rate from post-evar rupture in the 26 patients was 62%. There were 83 conversions to open AAA repair. Overall, the freedom from conversion at 7 years was 88.6%.

5 1618 Koole et al JOURNAL OF VASCULAR SURGERY December 2011 Table V. Characteristics of patients with a ruptured abdominal aortic aneurysm (AAA) in group C Patient AAA diameter at last FU, mm Vanguard 1 50 Yes 2 54 Yes 3 49 Yes 4 83 No 5 91 Yes No 7 88 No 8 70 No 9 77 No FU, Follow-up. When we compared group C with groups A and B, the freedom from conversion at 7 years in group C was 62% compared with 97.5% in group A and 92.1% in group B (P.001, Fig 3). Univariate analysis (Table VI) allowed selection of variables with significant differences, which were subsequently entered in a multivariable Cox model. This model indicated AAA enlargement without detectable endoleaks was an independent factor for conversion (Table VII). The mortality rate of conversion to open AAA repair in patients without AAA rupture was 6.0%. We also analyzed the risk of aneurysm-related death stratified by aneurysm growth. In total, 162 patients died of aneurysm-related causes. The freedom from aneurysmrelated death in the study cohort was 97.4%. In group C, 14.5% of aneurysm-related deaths occurred at 7 years, compared with 1.2% in group A and 10.5% in group B (P.001). Multivariable analysis did not identify aneurysm enlargement of 8 mm (group C) as an independent factor for aneurysm-related deaths in this study cohort (P.173). Excluder stent grafts (W. L. Gore and Associates, Flagstaff, Ariz) were more often used in group C than in the other groups (P.001, Table VIII). This was the only stent graft that was independently predictive for aneurysm enlargement without detectable endoleaks in a multivariable analysis (95% confidence interval, ; P.001). The EUROSTAR database registered 36 highpermeability Excluder stent grafts in group C patients. There was one low-permeability Excluder stent graft in the EUROSTAR database. For 18 patients, it was not clear whether they had a low- or high-permeability Excluder stent graft, because these stents were implanted during the transition era (2003 to 2005). Of the 55 patients with Excluder stent grafts, 52 had no transfemoral intervention, which means they did not receive a relining of their Excluder. Of the three patients who underwent a transfemoral intervention, one had a thrombectomy, and two had a relining. DISCUSSION In 2000 an international conference consisting of 27 experts was organized about the nature and significance of endoleaks and endotension, 20 and introduced a modified classification scheme to permit a more detailed categorization of endoleaks and endotension. This classification scheme specified that a detected type I or type III endoleak had to be treated. Type II endoleaks are usually benign and resolve spontaneously; however, not all type II endoleaks are benign, and some require treatment. 20 The classification scheme also describes the possible different forms of endotension, including endotension without any endoleak, sealed endoleak, or endoleaks that only become apparent when the aneurysm sac is opened at operation. An aggressive treatment policy is currently recommended for aneurysms without imaging-detected evidence of an endoleak that enlarge after EVAR. 18,20 We analyzed the EUROSTAR database to investigate the risk of rupture in patients without detectable endoleaks on imaging studies. Aneurysm enlargement was defined as a diameter increase of 8 mm because of a presumably larger interobserver variability in the large number of institutions participating in the registry compared with a singleinstitution assessment. 7,24-26 To our knowledge, this is the largest multicenter study to date evaluating the risk of rupture for this group. Our analysis demonstrated aneurysm enlargement without detectable endoleaks was an independent risk factor for AAA rupture after EVAR. Furthermore, a large preoperative AAA diameter, shorter infrarenal neck, and the Vanguard stent graft were independent risk factors for AAA rupture. However, group C had more patients with smaller preoperative diameters and shorter infrarenal necks. A reason for smaller AAAs in group C might be the 8 mm threshold. Shrinkage of 8 mm occurs predominantly in AAAs with large preoperative diameters. If a large preoperative AAA shrinks 15% in diameter, there is an increased chance of reaching the 8 mm threshold compared with a small preoperative AAA. Moreover, the multivariable analysis showed that preoperative AAA diameter and infrarenal neck length are not the only risk factors or the strongest risk factors; for example, group C had an increased percentage of Vanguard stent grafts, which were strongly associated with rupture. The Excluder stent graft was more often used in group C. This is an important factor for AAA expansion, and thereby could possibly increase rupture risk in this group, regardless of the preoperative AAA diameter size. A large number of high-permeability Excluder stent grafts were implanted in group C, and 53 were not relined. The calculated mean annual rupture risk in group C over 7 years was 1.1%. This rupture risk is comparable with rupture rates in general after EVAR in other cohorts, as reported in literature. 3,9-13,15,27 Furthermore, we observed an annual rate of rupture in group C of 1% in the first 4 years, which accelerated to 7.5% up to 13.6% in the years thereafter. According to the SVS and ESVS guidelines, an elective operation is indicated for patients with an AAA of at least 5.5 cm. The rupture risk of these patients varies between 3% and 15%. 18,19,28 The Vanguard stent graft is a strong independent risk factor for rupture in this cohort.

6 JOURNAL OF VASCULAR SURGERY Volume 54, Number 6 Koole et al 1619 Fig 3. Conversion rate stratified by aneurysm enlargement. Table VI. Significant different variables between the groups in demographic characteristics, aneurysm anatomy, and type of stent were tested by univariate analysis HR (95% CI) Age ( ) Male gender ( ) Hypercholesterolemia ( ) Pre-op AAA diameter per mm ( ) Length of infrarenal aortic neck per mm ( ) Aneurysmatic common iliac arteries ( ) AAA expansion 8 mm ( ) Between 8 and 8 mm Reference 8 mm ( ) AneuRx a ( ) Excluder b ( ) Talent a ( ) Vanguard c ( ) Zenith d ( ) Procedure device-related ( ) complications Stent migration ( ) Kinking of the graft ( ) Aortic stenosis or thrombosis ( ) AAA, Abdominal aortic aneurysm; CI, confidence interval; HR, hazard ratio a Medtronic, Minneapolis, Minn. b W. L. Gore and Assoc, Flagstaff, Ariz. c Boston Scientific Corp, Natick, Mass. d Cook Inc, Bloomington, Ind. From the literature we know that the material of these stent grafts is associated with fabric tears, stent fractures, and disintegration of the stent graft, which can result in rupture. 11,29,30 Table VII. Dependent and independent factors for conversion and outcome of multivariable Cox analysis HR (95% CI) Age ( ) AAA expansion 8 mm ( ) Between 8 and 8 mm Reference 8 mm ( ) Vanguard a ( ) Zenith b ( ) Procedure device-related complications ( ) Stent migration ( ) Kinking of the graft ( ) AAA, Abdominal aortic aneurysm; CI, confidence interval; HR, hazard ratio. a Boston Scientific Corporation, Natick, Mass. b Cook Inc, Bloomington, Ind. A Vanguard stent graft was used to treat 35 patients in group C, and the AAA ruptured in 4 patients (11.4%) during follow-up. Patients in group C treated with a Vanguard stent graft ruptured at relatively small AAA diameters of 70 mm. This is in contrast with the size of aneurysm sacs that were implanted with other stent grafts, which only ruptured at an AAA diameter of 70 mm. In group C, the annual rupture risk was 1% in the first 4 years and is probably minimal in patients without a Vanguard stent graft and an AAA diameter 70 mm. It might be even lower these days due to a better detection of endoleaks by improved imaging techniques. 31,32 The mortality rate for elective conversions in our cohort was 6.0%, which is considerable. Hence, the need for conversion in patients presenting with aneurysm enlargement without detectable

7 1620 Koole et al JOURNAL OF VASCULAR SURGERY December 2011 Table VIII. Stent graft type distribution in groups A, B, and C Group A a No. (%) Group B b No. (%) Group C c No. (%) Total No. (%) AneuRx d 83 (12.0) 558 (10.5) 31 (9.1) 672 (10.6) Excluder e 52 (7.5) 622 (11.7) 55 (16.2) f 729 (11.5) Talent d 163 (23.6) 1325 (25.0) 70 (20.6) 1558 (24.6) Vanguard g 50 (7.2) 447 (8.4) 35 (10.3) 532 (8.4) Zenith h 267 (38.6) i 1912 (36.0) 108 (31.9) 2287 (36.1) Other 76 (11.0) 443 (8.3) 40 (11.8) 559 (8.8) Total 691 (100) 5307 (100) 339 (100) 6337 (100) Vanguard tendency of P.091 more frequent use in group C than A. Talent tendency of P.074 more frequent in group B than C. a Aneurysm shrinkage 8 mm. b Aneurysm shrinkage 8 mm to enlargement 8 mm. c Aneurysm enlargement 8 mm. d Medtronic, Minneapolis, Minn. e W. L. Gore and Assoc, Flagstaff, Ariz. f P.001 resp P.013 more frequent use in group C than A resp group B. g Boston Scientific Corp, Natick, Mass. h Cook Inc, Bloomington, Ind. i P.034 more frequent use in group A than C. endoleaks, who are at a low risk for rupture, needs to be reconsidered and set alongside a conservative policy. This study observed an accelerated annual rupture risk after the first 4 years. After 4 years, the cohorts were small due to the long duration of follow-up, and therefore, the issue of loss to follow-up bias merits careful consideration. Patients with large aneurysms or fast-growing aneurysms may tend to be more compliant with the scheduled followup. This could explain the reduced rate of loss to follow-up in group C. In addition, this study analyzed the risk of rupture for patients with endoleaks combined with 8mm shrinkage, 8 mm shrinkage to 8 mm expansion, and 8 mm expansion. Rupture occurred significantly more in patients with endoleaks compared with patients without endoleaks (group A: 1.5% vs 0.3%, P.001; group B: 5.1% vs 0.4%, P.001; and group C: 7.5% vs 2.6%, P.012). We observed a significantly higher conversion rate in group C compared with groups A and B. Multivariable analysis confirmed aneurysm enlargement without detectable endoleak as an independent factor for conversion. Although excellent results were reported in some small series of patients, most studies report conversion to open AAA repair after EVAR with a comparable or higher mortality rate than primary open AAA repair. 14,27,33,34 This is in agreement with a mortality rate of 6.0% in our study when conversions in patients without rupture were considered. A higher preemptive conversion in group C may have affected the annual rupture risk. To get an impression of the possible influence of elective conversions on annual rupture risk in group C, we assumed that the 26 conversions in group C were ruptured on the day of conversion. We took these ruptures into account and recalculated the annual rupture rate. Nevertheless, even with this assumption, the annual rupture risks are 2% in the first 3 years, and still 5% in the fourth year. Management strategies for AAA enlargement without detectable endoleaks are still evolving. Before treatment, accurate imaging seems essential to rule out endoleaks. Because some endoleaks are not detectable with conventional CT angiography, visualizing low-flow endoleaks with a blood-pool contrast agent, dynamic electrocardiographically gated CT angiography, or MR angiography could possibly improve sensitivity for detecting endoleaks. 31,32 This might possibly result in better endoleak and endotension stratification and decrease the mortality risk from rupture in group C. Unfortunately, no specific registration concerning endoleaks detected at the time of rupture in the EUROSTAR database was available. Therefore, it remains unclear whether there were endoleaks that were not being detected by imaging in ruptured patients of group C. A variety of treatment options are presently available for patients with AAA enlargement without an endoleak. Strategies include conversion to open AAA repair, percutaneous translumbar puncture of the aneurysm sac with aspiration of the content, or conservative treatment. 35,36 For most patients, however, the mortality risk of a conversion seems higher than the risk of rupture, and a percutaneous translumbar puncture of the aneurysm sac also carries a small risk for complications. 37 Considering the results and reports above, we advise a conservative policy up to the first 4 years for patients at low-risk of rupture instead of conversion to open AAA repair for those with aneurysm enlargement without imaging-detected endoleaks. An exception is the first-generation Excluder stent graft. This stent graft has been associated with graft porosity. 32 Endograft relining for the first-generation Excluder and reinforcements of the proximal and distal seal zones with cuffs and additional limbs seems a safe and reliable alternative treatment option. 17,38 A limitation of the study includes different imaging modalities during the follow-up of some patients. However, most of the patients had the same types of imaging tests during follow-up, at the specific times in the study. CT

8 JOURNAL OF VASCULAR SURGERY Volume 54, Number 6 Koole et al 1621 imaging was used in 85.3% at the times evaluated. Moreover, an increased threshold of 8 mm was set in the EUROSTAR database to limit the influence of interobserver variability. 7,24-26 Therefore, it seems reasonable that a possible influence of variation between different imaging modalities in this study cohort is relatively limited. Furthermore, there were no requirements concerning the central lumen-line technique. This is also one of the reasons why the threshold for expansion is as high as 8 mm. With AAA diameter measurements only, it is possible to miss AAA sac growth. AAA volume measurements are more sensitive for AAA growth than AAA diameter measurements. 39 Therefore, it would be desirable to perform volume measurements in addition to (orthogonal) diameter measurements in future studies. Also, a large number of patients were lost to follow-up. After the 2-year interval, data for 50% of the patients in group A and B were not available and 30% of the patients in group C were lost to follow-up. Loss to follow-up in group C, which raised our interest, was significantly smaller but still large. This aspect is inherent to a registry such as EUROSTAR. Despite these limitations, a standard error 10% after 7 years in the survival table analysis is statistically adequate for a valid assessment. CONCLUSIONS The risk of rupture in patients with an AAA enlargement of 8 mm after EVAR without detectable endoleaks is 1% in the first 4 years. No ruptures were seen in patients with AAA enlargement without detectable endoleaks, who were not treated with Vanguard stent grafts and had AAA diameters of 70 mm. For this group, conversion to open repair might not be mandatory, and regular follow-up can be advised instead. After 4 years of follow-up, this study observed an increased annual rupture risk, which might indicate the need for conversion; however, groups are small, and follow-up bias could play a role. AUTHOR CONTRIBUTIONS Conception and design: DK, JH Analysis and interpretation: DK, JH Data collection: FM, JB, RH Writing the article: DK, JH Critical revision of the article: FM, JB, HZ, GP, JH Final approval of the article: DK, FM, JB, RH, HZ, MB, GP, JH Statistical analysis: DK, MB, JH Obtained funding: Not applicable Overall responsibility: DK REFERENCES 1. Albuquerque FC Jr, Tonnessen BH, Noll RE Jr, Cires G, Kim JK, Sternbergh WC 3rd. Paradigm shifts in the treatment of abdominal aortic aneurysm: trends in 721 patients between 1996 and J Vasc Surg 2010;51: ; discussion De Bruin JL, Baas AF, Buth J, Prinssen M, Verhoeven EL, Cuypers PW, et al. Long-term outcome of open or endovascular repair of abdominal aortic aneurysm. 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