Abstract
Objective:
Type 3 Endoleaks (T3EL) following complex EVAR (c-EVAR) for abdominal aortic aneurysm have been historically difficult to study due to their relative rarity. Previous studies within standard infrarenal EVAR have found an association between T3EL and decreased survival. This study aims to evaluate the occurrence of T3EL in a national multicenter cohort, identify potential procedural characteristics associated with T3EL development, and determine their impact on clinical outcomes in c-EVAR.
Methods:
A retrospective cohort review was conducted of elective c-EVAR for non-ruptured aneurysms within the Vascular Quality Initiative (VQI) between January 2010 and March 2020. The VQI standards define c-EVAR as suprarenal or pararenal AAA repaired with any thoracoabdominal repairs, fenestrated/branched repairs, parallel stent repairs, custom manufactured devices, and physician modified endografts. End-points assessed were rates of T3EL within c-EVAR, and impact of T3EL on reintervention and survival. Index endoleaks were defined as endoleaks discovered during index hospitalization. Incident endoleaks were defined as new endoleaks, that were not present at index hospitalization, discovered at follow-up.
Results:
4,070 c-EVAR cases were identified between January 2010 and March 2020, of which, 2,656 (65.2%) had appropriate follow-up data. Half the cohort had a modified or custom graft (n=2,055/4,070, 50.5%). Branches were employed in 3,687 patients (90.5%), while fenestrations and chimney techniques were documented in 13% (n=533) and 15.1% (n=613) respectively. The rate of index T3EL was 4.1% (n=167), and the rate of incident T3EL at follow-up was 0.04% (n=1). Devices categorized as either custom or physician modified were utilized more frequently in patients with index T3EL (78.4%, n=131/167) compared to patients without index T3EL (49.2%, n=1,924/3,903) (p<0.001). Compared to those without T3EL, the presence of index T3EL was not statistically associated with increased aortic reinterventions or increased mortality.
Conclusions:
T3EL in c-EVAR remain relatively uncommon and are identified predominately at index hospitalization. Development of T3EL was associated with higher device modularity and modification, which suggests that as device technologies continue to advance and become more intricate the occurrence of T3EL may persist and continue to require evaluation. In this study, the presence of T3EL did not appear to have a statistically significant relationship with aortic reinterventions or survival, however these findings are not definitive due to low event rate numbers and high potential for Type 2 errors. Amid the theoretical risk of device fatigue and degeneration, continued evaluations of large cohorts at extended follow-up intervals and diligent reporting remain paramount.
Table of Contents:
T3EL in c-EVAR were not associated with increased reinterventions or mortality at 1 year follow-up. Extending reporting intervals would improve ability to fully understand the clinical impact of T3EL. As devices continue to evolve and become more complex, the occurrence of T3EL will continue to require mindful management.
Introduction:
Dramatic evolution of endovascular technology now allows complex endovascular aortic aneurysm repair to address the 20–40%1,2,3,4 of abdominal aneurysms with anatomy prohibitive to standard EVAR, either due to inadequate length of neck or extensive involvement of the visceral vessels that inhibit ability to achieve appropriate seal zone and aneurysm exclusion3–5.Utilization of complex EVAR (c-EVAR), encompassing fenestrated/branched EVAR, physician modified endografts, and parallel stenting techniques (e.g. “chimney,” “snorkel,” and “sandwich” stents), has become increasingly common6–8. Despite engineering advances associated with c-EVAR, technical challenges and complications remain.
Endoleaks, defined as persistent pressurization of the aneurysm sac, continue to pose a threat to the integrity and longevity of complex endovascular aortic repairs. Type 3 Endoleaks (T3EL) occur due to modular device disconnection (3a Endoleak) or graft fabric disruptions (3b Endoleak)9,10. Prior to the VQI and large database development, T3EL were historically difficult to study due to their relative rarity and potential specificity to device or technique. The full clinical impact of T3EL is not yet fully understood.
The majority of knowledge regarding occurrence and clinical impact of T3EL is derived from data for standard EVAR and extrapolated to c-EVAR. In prior database investigations of standard EVAR, the majority of T3EL are incident – not detected at the initial procedure but seen in follow-up, with incident T3EL associated with significantly increased mortality11. Evaluations of T3EL within complex EVAR have been limited to date. This study aims to evaluate the occurrence of T3EL in a national multicenter cohort, to identify potential procedural characteristics associated with T3EL development, and to determine the impact of T3EL on clinical outcomes in complex EVAR.
Methods:
Vascular Quality Initiative Database
The Society of Vascular Surgery Vascular Quality Initiative (SVS VQI) is a Patient Safety Organization comprised of 18 regions, representing more than 700 hospital systems, and over 800,000 vascular procedures within 9 major vascular categories12. Data collection and entry is maintained by individual physicians and ensured through scheduled audits against hospital billing claims data13. In-depth aspects of procedural care and follow-up data is required for 1 year post-procedure (defined as a reporting interval of 9–21 months), but physicians are encouraged to continue follow-up data entry indefinitely14. In contrast to other clinical follow-up outcomes, VQI continuously updates patient mortality data as the information is available from contributing centers, and as supplemented by use of the Social Security Death Index; therefore we are able to further characterize survival beyond the 9–21 month reporting of other clinical outcomes. This project has been reviewed and approved by the VQI Research Advisory Council and was considered by the Institutional Review Board at the University of Alabama at Birmingham as non-Human Subjects Research due to the de-identified nature of the database analysis
Cohort Selection
A retrospective cohort review was conducted of elective c-EVAR for non-ruptured aneurysms within the Vascular Quality Initiative (VQI) between January 2010 and March 2020. Per VQI standards, c-EVAR includes suprarenal or pararenal abdominal aortic aneurysms repaired with any thoracoabdominal repairs, fenestrated/branched repairs, parallel stent repairs, custom manufactured devices, and physician modified endografts15. In order to facilitate comparison of our results to those within the existing literature, we choose to isolate and examine only patients with visceral segment disease. This was accomplished by limiting inclusion to patients with proximal graft deployment distal to and including Zone 5. Zone definitions used in this study correspond with those of the 2021 SVS reporting guidelines for aneurysms involving the renal-mesenteric arteries16.
Standard definitions of endoleaks were used; Type 3 endoleaks are defined as persistent flow into the aneurysm sac through graft components (3a module disconnections or 3b graft fabric disruptions)18,19. Per VQI standards, all imaging modalities for T3EL identification was were allowed. Endoleaks were evaluated and defined with respect to two key timeframes: index and incident endoleaks. Index endoleaks were defined as endoleaks discovered during index hospitalization. Incident endoleaks were defined as new endoleaks, that were not present at index hospitalization, discovered at follow-up. Categorization in this manner prevents duplicate counting of persistent endoleaks. Long-term follow-up, per VQI definitions, is the mandatory reporting period between 9 to 21 months following initial procedure; mortality assessment is continuously supplemented by use of the Social Security Death Index.
Outcomes Examined
Primary and secondary outcomes were examined during index hospitalization and at long-term follow-up. The primary end-point assessed was rate of T3EL within c-EVAR, with secondary endpoints evaluating the impact of T3EL on reintervention and survival. Reinterventions were defined per VQI standards as any repeat surgical procedure to address a complication of the primary procedure. Aortic reinterventions were defined per VQI standards as involving any of the following: aneurysm sac growth, aneurysm rupture, device migration or misalignment, device occlusion or stenosis, device infection, or endoleak development (with sub-categories of endoleak represented). All-cause and aortic mortality were evaluated. Aortic mortality per VQI standards is defined as any death related to disease or treatment interventions.
Statistical Analysis:
Collected data was analyzed in SPSS statistical software, version 23.0 (SPSS Inc, Chicago, IL). Continuous variables were presented as mean ± SD and were compared using an independent Student t test. Categorical variables were presented as number and percentage, and were compared using a Chi-square test. Kaplan-Meier curves and Log-Rank analysis were used to plot outcomes related to survival and freedom from intervention. A p value <0.05 defined statistical significance.
Results:
Demographics and Procedural Details
A total of 4,070 c-EVAR cases were identified within the VQI database between January 2010 and March 2020. Out of the included cohort, 65.2% (n=2,656) had appropriate follow-up data available for analysis. Baseline cohort demographics are shown in Table 1. A history of prior vascular surgery was seen in 30% (n=1,221) of the patients, with endovascular peripheral intervention being the most predominant (6.7%). Figure 1 demonstrates cohort paths based on occurrence of T3EL, follow-up interventions, and mortality.
Table 1:
Summary of patient medical and prior surgical baseline characteristics for all patients with c-EVAR within the SVS VQI between 2010–2020
| Variable | All (N=4,070) |
|---|---|
| Age (years) | 73.3 ± 8.3 |
| Male Gender | 3014 (74.1%) |
| Race | |
| Non-Caucasian | 285(7%) |
| Caucasian | 3457 (84.9%) |
| Unknown | 328 (8%) |
| Hypertension | 3537 (86.9%) |
| Diabetes Mellitus | 735 (18%) |
| COPD | 1544 (37.9%) |
| Congestive Heart Failure | 616 (15.1%) |
| Coronary Artery Disease | 1198 (29.4%) |
| Hemodialysis | 72 (1.7%) |
| Smoking Status | |
| Never | 489 (12%) |
| Former | 1253 (33.2%) |
| Current | 1253 (33.2%) |
| Prior Aortic Surgery | 525 (12.8%) |
| Open | 320 (7.9%) |
| Thoracic | 194 (4.7%) |
| Abdominal | 126 (3.1%) |
| Endovascular | 205 (5%) |
| Thoracic | 193 (4.7%) |
| Abdominal | 12 (0.3%) |
| Aneurysm Size (mm) | 59 (5, 65) |
COPD=Chronic Obstructive Pulmonary Disease. Categorical variables are presented as number (%). Continuous variables are presented as mean ± standard deviation or median (interquartile range)
Figure 1:
Distribution and clinical outcomes of Type 3 Endoleaks in Complex EVAR
Device details for the whole cohort are shown in Table 2. Half the cohort had a modified or custom graft (n=2,055/4,070, 50.5%), with custom devices more common compared to physician modified devices. Treatment of visceral vessels was highly variable; patients can have multiple combinations of modifications and customizations, with designations not being mutually exclusive. The right renal artery was the most frequently treated vessel, receiving interventions in 74.1% of cases. The left renal artery was treated in 73.7% of cases while the superior mesenteric artery (SMA) and celiac arteries were treated in 54.6% and 19.3% of cases respectively. All four visceral vessels were involved in 617 cases (15.1%). Across all four visceral vessels the most common treatment type was fenestration, with branched fenestrations predominating. In all vessels, stents, when utilized, were more commonly bare metal compared to covered stents. Side arm branches were the least frequently observed treatment, and were seen in less than 2% of cases. The number of main body device components ranged from 1 (20.8%) to 6 (0.4%), with the majority having 2 main aortic body components implanted (n=2,493, 61.2%). The most common zone for device proximal deployment was Zone 7 (n=1,328, 32.6%).
Table 2:
Description of procedural details, device characteristics, and visceral segment treatment methods within complex EVAR cohort
| Entire Cohort (n=4,070) | Index T3EL (n=167) | No Index T3EL (n=3,903) | p | |
|---|---|---|---|---|
|
| ||||
| Proximal Zone of Deployment | 0.059 | |||
| Zone 5 | 1,008 (24.7%) | 41 (24.5%) | 967 (24.7%) | |
| Zone 6 | 490 (12%) | 26 (15.5%) | 464 (11.8%) | |
| Zone 7 | 1328 (32.6%) | 62 (37.1%) | 464 (11.8%) | |
| Zone 8 | 864 (21.2%) | 33 (19.7%) | 1266 (32.4%) | |
| Zone 9 | 190 (4.6%) | 2 (1.1%) | 188 (4.8%) | |
|
| ||||
| Number Aortic Graft Components | <0.001 | |||
| 1 Component | 845 (20.7%) | 18 (10.7%) | 827 (21.1%) | |
| >1 Component | 3,095 (76%) | 149 (89.2%) | 2,946 (75.4%) | |
|
| ||||
| Modified/Custom Device | 2055 (50.5%) | 131 (78.4%) | 1,924 (49.2%) | <0.001 |
| Custom* | 1381 (33.9%) | 6 (3.5%) | 1,289 (33%) | <0.001 |
| Physician Modified* | 432 (10.6%) | 30 (17.9%) | 402 (10%) | |
|
| ||||
| Celiac Treatment | 786 (19.3%) | 41 (24.5%) | 745 (19.1%) | 0.08 |
| Stent | 126 (3.1%) | 11 (6.5%) | 115 (2.9%) | 0.056 |
| Bare Metal* | 71 (56.3%) | 3 (27.2%) | 68 (59.1%) | |
| Covered* | 55 (43.6%) | 8 (72.7%) | 47 (40.9%) | |
| Scallop | 116 (2.8%) | 5 (2.9%) | 111 (2.8%) | 0.056 |
| Non-stented Scallop* | 108 (93.1%) | 5 (100%) | 103 (92.7%) | |
| Stented Scallop* | 8 (6.8%) | 0 | 8 (7.2%) | |
| Fenestration | 405 (9.9%) | 22 (13.1%) | 383 (9.8%) | 0.056 |
| Non-stented Fenestration* | 57 (14.1%) | 5 (22.7%) | 52 (13.5%) | |
| Stented Fenestration* | 66 (16.2%) | 6 (27.2%) | 60 (15.6%) | |
| Branched Fenestration* | 282 (69.6%) | 11 (50%) | 271 (70.7%) | |
| Chimney | 72 (1.7%) | 2 (1.1%) | 70 (1.7%) | 0.056 |
| Side Arm Branch | 67 (1.6%) | 1 (0.5%) | 66 (1.7%) | 0.056 |
|
| ||||
| Superior Mesenteric Treatment | 2,183 (54.6%) | 116 (69.4%) | 2,067 (52.9%) | <0.001 |
| Stent | 328 (8.0%) | 22 (13.1%) | 306 (7.8%) | <0.001 |
| Bare Metal* | 192 (58.5%) | 9 (40.9%) | 183 (59.8%) | |
| Covered* | 136 (41.4%) | 13 (59.1%) | 123 (40.2%) | |
| Scallop | 531 (13.0%) | 43 (25.7%) | 488 (12.5%) | <0.001 |
| Non-stented Scallop* | 498 (93.7%) | 43 (100%) | 455 (93.2%) | |
| Stented Scallop* | 33 (6.2%) | 0 | 33 (6.7%) | |
| Fenestration | 1,048 (25.7%) | 44 (26.3%) | 1,004 (25.7%) | 0.067 |
| Non-stented Fenestration* | 369 (35.2%) | 10 (22.7%) | 359 (35.7%) | |
| Stented Fenestration* | 206 (19.6%) | 16 (37.3%) | 190 (18.9%) | |
| Branched Fenestration* | 473 (45.1%) | 18 (40.9%) | 455 (45.3%) | |
| Chimney | 198 (4.8%) | 6 (3.5%) | 192 (4.9%) | <0.001 |
| Side Arm Branch | 78 (1.9%) | 1 (0.5%) | 77 (1.9%) | <0.001 |
|
| ||||
| Right Renal Treatment | 3,019 (74.1%) | 143 (85.6%) | 2,875 (73.5%) | <0.001 |
| Stent | 839 (20.6%) | 47 (28.1%) | 792 (20.9%) | 0.002 |
| Bare Metal* | 459 (54.7%) | 23 (48.9%) | 436 (55%) | |
| Covered* | 380 (45.2%) | 24 (51.1%) | 356 (45%) | |
| Scallop | 47 (1.1%) | 3 (1.7%) | 44 (1.1%) | 0.002 |
| Non-stented Scallop* | 26 (55.3%) | 3 (100%) | 23 (52.2%) | |
| Stented Scallop* | 21 (46.6%) | 0 | 21 (47.7%) | |
| Fenestration | 1,815 (44.5%) | 86 (51.4%) | 1,729 (44.2%) | 0.002 |
| Non-stented Fenestration* | 76 (4.1%) | 1 (1.1%) | 75 (4.3%) | |
| Stented Fenestration* | 698 (38.4%) | 48 (55.8%) | 650 (37.5%) | |
| Branched Fenestration* | 1,041 (57.3%) | 37 (43.0%) | 1,004 (58%) | |
| Chimney | 259 (6.3%) | 7 (4.1%) | 252 (6.4%) | 0.002 |
| Side Arm Branch | 59 (1.4%) | 1 (0.5%) | 58 (1.4%) | 0.002 |
|
| ||||
| Left Renal Treatment | 3,003 (73.7%) | 155 (92.8%) | 2,868 (73.4%) | <0.001 |
| Stent | 867 (21.3%) | 57 (34.1%) | 821 (21.0%) | 0.001 |
| Bare Metal* | 482 (55.5%) | 24 (42.1%) | 458 | |
| Covered* | 385 (44.5%) | 33 (57.8%) | 363 | |
| Scallop | 23 (0.5%) | 0 | 23 (0.5%) | 0.001 |
| Non-stented Scallop* | 11 (47.8%) | 0 | 11 | |
| Stented Scallop* | 12 (52.1%) | 0 | 12 | |
| Fenestration | 1,789 (43.9%) | 90 (53.8%) | 1708 (43.7%) | 0.001 |
| Non-stented Fenestration* | 74 (4.1%) | 3 (3.3%) | 71 | |
| Stented Fenestration* | 702 (39.2%) | 50 (55.5%) | 652 | |
| Branched Fenestration* | 1,022 (57.1%) | 37 (41.1%) | 985 | |
| Chimney | 268 (6.5%) | 7 (41.9%) | 261 (6.6%) | 0.001 |
| Side Arm Branch | 56 (1.3%) | 1 (0.5%) | 55 (1.4%) | 0.001 |
percents are shown as relative to subgroup.
Categorical variables are presented as number (%).
Type 3 Endoleaks at Index Hospitalization
The overall index hospitalization T3EL rate was 4.1% (n=167) (Figure 1). Endoleak rates and distributions at index hospitalization are shown in Table 3. The overall rate of any endoleak was 29.5% (n=1,203); T3EL make up 13.8% (n=167/1,203) of all endoleaks discovered at index hospitalization. A total of 33 T3EL (19.8%) occurred in conjunction with another endoleak; the most common endoleak to co-occur with a T3EL was a Type 2 Endoleak (n=17). The majority of index T3EL occurred due to modular component separation (n=133, 85%) rather than fabric tears (n=24, 15%).
Table 3:
Rates of Type 3 Endoleaks at Index Hospitalization and at Follow-up in Complex EVAR Patients
| Index Hospitalization | |
| Endoleak Type | N=4,070 |
| Any Endoleak | 1,203 (29.5%) |
| Type 1 | 257 (6.3%) |
| Type 1a* | 167 (65%) |
| Type 1b* | 51 (20%) |
| Type 1c* | 39 (15%) |
| Type 2 | 550 (13.5%) |
| Type 3 | 167 (4.1%) |
| Type 4 | 63 (1.5%) |
| Indeterminate | 166 (4.1%) |
| Follow-Up | |
| Endoleak Type | N=2,656 |
| Any Endoleak | 82 (3.1%) |
| Type 1 | 76 (2.8%) |
| Type 1a* | 73 (96%) |
| Type 1b* | 2 (3%) |
| Type 1c* | 1 (1%) |
| Type 2 | 5 (0.18%) |
| Type 3 | |
| Incident | 1 (0.04%) |
| Index^ | 116 (4.3%) |
| Type 4 | 0 |
| Indeterminate | 0 |
Categorical variables are presented as number (%).
percents are shown as relative to subgroup.
Index T3EL persistent from initial hospitalization
Device details for patients with Index T3EL are shown in Table 2. Involvement of all four visceral vessels was seen 44.9% of patients (n=75/167) that experienced an index T3EL. Within patients with index T3EL, the renal arteries were the most commonly treated (92.8% Left Renal, 85.6% Right Renal). Compared to patients without index T3EL, patients with index T3EL had significantly higher treatment rates, across all treatment types, for the SMA (69.4% [n=116/167] vs. 52.9% [n=2,067/3,903], p<0.001), right renal artery (85.6% [n=143/167] vs. 73.5% [n=2,875/3,903], p<0.001), and left renal artery (92.8% [n=155/167] vs. 73.4% [n=2,868/3,903], p<0.001). Compared to patients without index T3EL, there was no significant difference in the rate of interventions on the celiac artery. Devices categorized as either custom or physician modified were utilized more frequently in patients with index T3EL (78.4%, n=131/167) compared to patients without index T3EL (49.2%, n=1,924/3,903) (p<0.001). Patients with index T3EL were more frequently treated with multicomponent main body aortic devices compared to patients without index T3EL (89.2% [n=149/167] vs. 75.4% [n=2,946/3,903], p<0.001). Within patients with an index T3EL, 37.1% had a Zone 7 proximal deployment, however differences in zone of proximal deployment did not reach statistical significance.
Reinterventions for T3EL during index hospitalization were 0.36% (n=15/4,070), accounting for 60% (n=15/25) of all endoleak reinterventions and 7.8% (n=15/190) of all aortic reinterventions (Table 4). All T3EL that received reintervention at index hospitalization resolved and did not recur. Of the 15 patients that had reinterventions for T3EL during index hospitalization, 2 patients (13.3%) died following reintervention during that hospitalization (Figure 1). The presence of an index T3EL did not significantly affect the overall rate of reinterventions at index hospitalization (7.4% vs. 6%, p=0.52), but among aortic reinterventions, presence of an index T3EL was associated with reduced mean time to index hospitalization reintervention (1.4 ± 0.4 vs. 2.1 ± 0.6 days, p= 0.006).
Table 4:
Reinterventions Rates at Index Hospitalization and at Follow-Up after Complex EVAR
| Variable | Index Hospitalization (N=4070) | Follow-Up (N=2,656) |
|---|---|---|
| Any Reintervention | 245 (6%) | 208 (7.8%) |
| Aortic Reintervention | 190 (4.8%) | - |
| Time To First Reintervention (days) | 1.86 ± 2 | 324 ± 339 |
| Reinterventions for Endoleaks | ||
| Any Endoleak | 25 (0.6%) | 97 (3.6%) |
| Type 1 Endoleak* | 6 (24%) | 43 (44.3%) |
| Type 2 Endoleak* | 4 (16%) | 35 (36.1%) |
| Type 3 Endoleak* | 15 (60%) | 19 (19.5%) |
percents are shown as relative to subgroup.
Categorical variables are presented as number (%).
Continuous variables are presented as mean ± standard deviation.
The all-cause mortality of T3EL at index hospitalization was 4.7% (n=8/167), which was not significantly elevated compared to patients without T3EL (3.9%, n=154/3,903, p=0.59). Of the 8 patients with T3EL who died during index hospitalization, 6 received surgical reintervention prior to their death; 2 (25%) received reintervention for T3EL and 4 (50%) had reintervention for other indications (1 access bleeding, 1 bowel ischemia, 1 type 1 endoleak, and 1 unspecified).
Type 3 Endoleaks at Follow-Up
A total of 2,656 patients (68.0% of the original cohort, accounting for in-hospital mortalities) had any long-term follow-up data past index admission recorded at any point in their care. Median total length of follow-up for the entire cohort was 383 days (IQR 194 days), with no significant difference in total follow-up length between patients with and without index T3EL (384 days (IQR 219 days) vs. 380 days (IQR 190 days), p=0.367). Follow-up beyond the mandated 21-month follow-up interval was rare (6.5% of all follow-up) in absence of reintervention.
Incident T3EL were rare (n=1, 0.04%, Table 3), accounting for 1.2% of all incident endoleaks (n=1/82). The single incident T3EL had a total length of follow-up of 473 days. A total of 116 patients with index T3EL (n=116/167, 69.4%) were included in the follow-up database, and accounted for 4.3% of the entire cohort at follow-up (Figure 1).
Reinterventions performed after discharge for the treatment of any (index or incident) T3EL occurred at a rate of 0.7% (n=19), accounting for 19.5% (n=19/97) of endoleak reinterventions and 9.7% (n=19/195) of all aorta-related reinterventions performed after index hospitalization discharge (Table 4). All T3EL that underwent reintervention during the follow-up period (n=19) were persistent index T3EL unaddressed during index admission rather than new T3EL discovered during follow-up. A single index T3EL presented as a rupture requiring reintervention. Ultimately, the presence of an index T3EL was not significantly associated with increased reinterventions through 21 months of follow-up. Similarly there was no significant effect on time to reintervention based on the presence of T3EL.
Within the entire cohort, the cumulative all-cause mortality rate of 12.8%, with a median survival of 638 days (IQR370–1373.5 days). The long-term unadjusted all-cause mortality rate was not significantly higher in patients with T3EL (11.7%) compared to patients without T3EL (12.8%) within univariate analysis (p=0.735). Kaplan-Meier curves of survival through 2 years are shown between those with and without index T3EL in Figure 2, in which aortic mortality rates do not appear to have a significant relationship with index T3EL (log rank=0.821). These results were supported by Cox Regression Survival Analysis controlling for age, gender, race, and aneurysm size in which T3EL did not appear to have a significant association with survival (HR=0.02, p=0.963).
Figure 2:
Kaplan-Meier Analysis of Impact of Index Type 3 Endoleaks on Overall Survival
Discussion:
Recent substantial endovascular advancements, such as, fenestration devices, parallel stenting (e.g. “chimney,” “snorkel,” and “sandwich” stents), and physician modified grafts allow endovascular therapy to address aneurysms with inadequate infrarenal neck and visceral vessel involvement18,19,20. C-EVAR repair is now accepted as safe, and the number of c-EVAR repairs performed is rising yearly according to studies of Vascular Quality Initiative (VQI) and Medicare databases7,8,21. Despite relatively rapid advances in technology, endoleaks remain a complex problem within c-EVAR.
This study represents one of the largest and most modern reviews of the occurrence of T3EL in complex EVAR. One of the earliest series to evaluate T3EL in fenestrated repair was published out of the United Kingdom in 2010, and found a 1.7% rate of T3EL at index hospitalization22. In 2015, Mastracci et al. reported a 4.5% rate of T3EL within 610 fenestrated repairs23. That same year, Starnes et al. reported a 3.3% rate of T3EL within 59 cases of physician modified grafts at a single center6. Reports of T3EL within parallel stenting remain rare, likely due to small volume of cases, with several reports of no occurrences in series with less than 15 patients24,25. Our study (inclusive of fenestrate, physician modified, and parallel stenting) found a 4.1% rate of T3EL at index hospitalization within 4,070 patients. This rate is supported by the previous literature and reaffirms that while T3EL remain less common than Type 1 or Type 2 endoleaks their occurrence should remain at the forefront of consideration when performing post-procedure surveillance.
Interestingly, this study found that the majority of T3EL occur during index hospitalization and persist until follow-up. This data reflects real-world clinical practice patterns seen at our institution and described in the literature. Within our cohort, 91.1% of T3EL identified during index hospitalization were unrepaired prior to discharge. This value, while high, is in line with observations in patients infrarenal EVAR T3EL, where 95.5% of index T3EL were not repaired during index hospitalization11, and clinical practice of many physicians. Our institutional practice is general a preference for treating T3EL during the index procedure if it is identified on intraoperative imaging. However, if they are identified on post-operative CTA and patient’s medical status makes early reintervention prohibitively high- risk, we have adopted a delayed reintervention approach with continued stringent follow-up.
In this study, incident T3EL identified during follow-up was an exceedingly rare event (n=1, 0.04%). These results are in line with previous studies which have failure to identify any T3EL at follow-up, however it is unclear if the data represents a true lack of T3EL or failure to adequately capture the rare events 3,26. In our study, the median duration of follow-up for the whole cohort was 383 days (IQR 194 days), while the single incident T3EL had follow-up of 473 days. It is possible that incident T3EL occur later in follow-up and are therefore not being adequately captured, which does introduce potential for Type 2 error, in which a significant relationship is missed due to data inadequacy. Results highlight the benefit of aggregate databases in identified low incidence events, and reinforces the importance of long-term imaging surveillance in capturing late complications.
This study did not identify a statistically significant relationship between index T3EL and either rate of reintervention nor 2-year mortality rate. Within complex EVAR, there is very little previous data exploring the relationship between T3EL and mortality, however work within standard infrarenal EVAR does demonstrate a possible relationship between T3EL and decreased survival. Specifically, the relationship between T3EL in standard EVAR and aneurysm sac growth and rupture was first demonstrated in the early 2000’s with the EUROSTAR registry27 and later supported by findings in the EVAR1 trial28 and OVER trial29. In 2019, a review of VQI standard EVAR demonstrated decreased long-term survival in patients with incident T3EL (74% vs. 80%, p=0.041)11. Given the impact of T3EL within infrarenal EVAR, we hypothesized that a relationship between T3EL and mortality would exist within c-EVAR cohorts, however this was not conclusively demonstrated within the data. In our study, no statistical difference was noted in long-term mortality by index T3EL presence; however, due to the possibility of Type II error, we do not conclude that there is no relationship between survival outcomes and index T3EL. We present our Kaplan-Meier analysis for descriptive purposes with the understanding that, despite the large national capture in our cohort, we remain likely underpowered for commentary on impact of index T3EL on survival in cEVAR.
Factors that were significantly associated with the development of T3EL include higher device modularity and modified devices. Patients with T3EL were treated with physician modified devices in 17.9% of cases, and had more than 1 component in 89.2% of cases. The VQI does not identify location of T3EL relative to which branches were involved, but authors hypothesize that they are likely to occur at interfaces between the main-body and branch segments. These results suggest that as devices continue to evolve, and undergo more complex modifications that the occurrence of T3EL may persist and require mindful management. Extending reporting intervals of endoleaks beyond the first year in registries would improve the ability to fully understand the clinical impact of T3EL.
Limitations
The largest limitations of this study, incomplete data and reporting bias, are inherent to retrospective reviews. The VQI is the largest database of vascular procedures,30 despite the large national presence, the VQI is not comprehensive in its representation and capture of complex EVAR data in the United States. However, the VQI procedural volumes remains significantly more robust compared to alternative US based national surgical quality databases31. The VQI actively works to mitigate reporting bias, discrepancies, and errors through comparison against hospital insurances claims, but complete accuracy cannot be completely guaranteed.
The VQI is further limited by relatively short timeframe of mandatory follow-up documentation. It is impossible to differentiate attrition due to poor provider documentation from true lack of patient follow-up after procedural intervention. Further, the limited timeframe of follow-up introduces difficulty with drawing conclusions regarding long-term outcomes. While survival outcomes past 21 months are reliable due to VQI linkage with the Social Security Disability Index (SSDI), outcomes such as incident T3EL and reinterventions are less reliable past this timeframe. Limited completeness past 21 months introduces potential for bias and Type 2 error, which is why we have reported on 2 year survival outcomes. Despite the limitations of working with self-reported data, the VQI remains the largest and most complete vascular surgical quality database and the aforementioned limitations do not nullify the conclusions drawn from this analysis.
Conclusion:
Reported Type 3 Endoleaks in complex EVAR remain relatively uncommon and are identified predominately at index placement rather than incident through 21-month follow-up. Development of T3EL was associated with higher device modularity and modification, which suggests that as device technologies continue to advance and become more intricate the occurrence of T3EL may persist and continue to require evaluation. In this study, the presence of index T3EL did not appear to have a statistically significant relationship with aortic reinterventions or survival, however these findings are not definitive due to low event rate numbers and high potential for Type 2 errors. Amid the theoretical risk of device fatigue and degeneration, continued evaluations of large cohorts at extended follow-up intervals and diligent reporting remain paramount.
Article Highlights.
Type of Research:
Retrospective review of prospectively collected Vascular Quality Initiative (VQI) data from March 2010 to January 2020.
Key Findings:
The rate of T3EL was 4.1% (n=167) at index hospitalization and 0.04% (n=1) at follow-up. In univariate and Kaplan-Meier analysis, the presence of T3EL was not associated with decreased long-term survival, however results are limited by potential for Type 2 error.
Take Home Message:
In this large study designed to evaluate T3EL, it was found that the majority of T3EL occurred during index hospitalization with an exceedingly low rate of new incidence T3EL during follow-up. No statistically significant relationship between T3EL and survival was identified; results are limited by potential for Type 2 error.
Disclosures:
Blakeslee-Carter, J: Supported by the National Institute of Health Agency for Healthcare Research and Quality grant 5T32HS013852
Spangler, E L: Supported by National Institute of Health grant KL2 TR 003097
Footnotes
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