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Abstract
Background Woven EndoBridge (WEB) devices are becoming a reliable option for the treatment of wide-neck bifurcation aneurysms, but clear predictive factors are still missing to understand the one in five aneurysm remnant rate.
Objective To evaluate occlusion outcomes after WEB treatment to identify potential determinants of aneurysm occlusion.
Methods A single-center database with consecutive aneurysms treated with WEB between July 2012 and October 2021 was reviewed for potential determinants of aneurysm adequate occlusion (defined as a Bicêtre Occlusion Scale Score (BOSS) of 0, 0’, 1 or 2), through univariate and multivariable analysis. Patients without angiographic follow-up were excluded.
Results 215 of 247 individual aneurysms were included in the final analysis, of which 59 (27%) were ruptured. Mean age of patients was 56 years (range 23–90 years) and 65% were female. Mean angiographic follow-up was at 18 months (range 3–97 months). Adequate and complete occlusion were achieved in 171/215 (79.5%) and 135/215 (62.8%) of cases, respectively. Aneurysm irregular shape (aOR=0.42, 95% CI 0.20 to 0.88; p=0.02), aneurysm height (aOR=0.79, 95% CI 0.66 to 0.94; p<0.01), and WEB shape modification (aOR=0.98, 95% CI 0.97 to 1.00; p=0.02) were all independent predictors of aneurysm recurrence, whereas the WEB oversizing ratio (WEB width/aneurysm mean width) (aOR=16.4, 95% CI 1.4 to 266.7; p=0.04) was an independent predictor of adequate occlusion.
Conclusion In this study we demonstrated that a width oversizing strategy of the WEB device was an independent predictor of aneurysm angiographic occlusion. Conversely, aneurysm height, irregular aneurysm, and WEB shape modification were all independent determinants of angiographic aneurysm remnant. These results may help to select aneurysms suitable for the WEB device and WEB sizing.
- Aneurysm
- Intervention
- Technique
- Device
Data availability statement
Data are available upon reasonable request. Study data are available from the corresponding author upon reasonable request.
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Introduction
The Woven EndoBridge (WEB) device (Microvention, Californis, USA) was introduced for the treatment of wide-neck and bifurcation cerebral aneurysms over a decade ago.1 It is an intrasaccular flow-disruptor device, formed of a dense nitinol mesh, used to seal the aneurysm neck while the parent artery is unaffected. Since then indications for WEB have been widened—for example, to ruptured aneurysms, side-wall aneurysms. or in association with other devices.2–4
Efficacy and safety of the WEB device have been reported in several observational studies and in prospective trials5–7; yet the reliability of the device continues to be discussed.8 Two recent meta-analyses on the WEB device found that overall rates of adequate occlusion was between 80% and 83.3%, meaning that one in five aneurysms is inadequately cured with the WEB device.9 10 Furthermore, inconsistent follow-up, imaging modality, and occlusion grading can lead to flawed conclusions and fail to find reliable predictors of aneurysm occlusion.
Here, in a high-volume care center, with standardized angiographic follow-up and a large number of patients treated with the WEB device in a 10-year period, we evaluated occlusion outcomes after WEB treatment to identify potential determinants of aneurysm occlusion.
Methods
Patient analysis
We retrospectively analyzed the prospectively maintained database of a French tertiary care center for consecutive patients with ruptured or unruptured aneurysms treated with the WEB device between July 2012 and October 2021. The main analysis was the adequate occlusion on the last angiographic follow-up available, defined as a score on the Bicêtre Occlusion Scale Score (BOSS) of 0, 0’, 1, or 2. We also evaluated the stability of the angiographic outcome over time. Patient without a follow-up angiogram at least 3 months after the treatment were excluded.
Patient selection and web procedure
The main indication for using a WEB device was a wide-neck bifurcation aneurysm. The decision for WEB treatment of unruptured aneurysms was decided by multidisciplinary consensus; in our center, we prioritize endovascular procedures over surgery for the treatment of most aneurysms. For bifurcation aneurysms, we tend to avoid the use of stents. Instead, a WEB was selected if the aneurysm was suitable for this device (depending on the biometry of the aneurysm and the angulation with the parent artery). For acutely ruptured aneurysms, selection of the treatment strategy was left to the operator. Over time, five generations of WEB device were used,11 and three different designs: double layer (WEB-DL), single layer (WEB-SL) or SL sphere (WEB-SLS).12 Devices were mostly delivered through VIA catheters (Microvention, California, USA). The operator used measurements from 3D rotational angiograms to decide which size of WEB device to use. Balloon remodeling technique or associated stenting were also reported among the procedure characteristics.13
Antiplatelet regimen
In ruptured aneurysms, no antiplatelet therapy was used before the treatment. Patients with unruptured aneurysms received aspirin (75 mg a day) and ticagrelor (80 mg twice a day) or clopidogrel 75 mg per day (before 2015) the day prior to WEB implantation, and oral treatment was continued only in cases of WEB protrusion or if a stent was used. Patient were noted as receiving antiplatelet therapy if they received it for 7 days or more after the embolization. For either ruptured or unruptured aneurysms, treatment was performed under systemic heparinization that was stopped at the end of the procedure.
Imaging analysis
Angiographic outcomes were analyzed by two neurointerventional radiologists; one was not involved in the treatment. For this study we used the BOSS six-point grading scale,14 as follows: grade 0 indicates complete occlusion; grade 0’ is similar but with opacification of the proximal recess and is also considered as complete occlusion; grade 1 indicates limited opacification only inside the WEB; grade 2 indicates a neck remnant; grade 3 indicates an aneurysm remnant with contrast agent inside the sac between the wall and the WEB device. In grade 1+3, contrast agent is depicted inside and around the device. Discrepancies were resolved by a third neuroradiologist.
Besides the last angiographic follow-up available, each control angiography was divided into three periods: short term (3–12 months), mid-term (13–24 months), and long term (>24 months) to evaluate the stability of the outcome. In general, patient angiographic follow-up was planned at 3, 15, and 39 months for patients with ruptured aneurysms or at 6, 18, and 42 months for unruptured cases.
The following aneurysm characteristics were reported: neck, width, height (all average of two axis measurements), width/neck ratio, aspect ratio (height/neck), and shape (rated as regular (smooth aneurysm surface on 3D image) versus irregular (in cases of bleb or multilobar shape)). We defined a WEB ‘oversizing ratio’ to quantitatively evaluate the WEB constraint inside the aneurysm as it is often described as an important point for treatment.12
WEB shape modification refers to a loss of device height occurring during the follow-up.15 16 As previously described, WEB shape modification was quantitatively defined as a ratio (%) and was obtained by standardized measuring of the distance between proximal and distal WEB markers on cross-sectional images obtained with cone-beam computed tomography (VasoCT; Philips Healthcare, Best, the Netherlands) performed after WEB detachment and at last follow-up.17
Statistical analysis
Continuous variables are reported as mean±SD if normally distributed, or as median (IQR), while categorical variables are expressed as frequency (%). A Χ2 or Fisher’s exact test was used to evaluate qualitative factors as appropriate, and a Student’s t test or Wilcoxon U test was applied to assess quantitative variables as appropriate. Multivariable logistic regression analysis was performed to identify potential predictive factors of adequate occlusion, using a stepdown procedure with all candidate variables (p<0.2 in the univariate analysis) until all selected variables were p<0.05 in the final model. For selected variables, ORs with a 95% CI and p value of the likelihood-ratio test are given. P values of non-selected candidate variables are also given. A sensitivity analysis was performed to test the obtained model to see if it was also predictive of angiographic complete occlusion. No adjustment for multiple testing was performed, and analyses are regarded as explorative. P values <0.05 were considered statically significant. All statistical analyses were performed using R software (version 3.6.1).
Results
Patient and aneurysm characteristics
A total of 247 independent aneurysms were treated with WEB devices in 223 patients in our center, and follow-up angiogram(s) was (were) available for 215 (87.0%) of them (table 1 and patients’ flowchart online supplemental figure 1). The mean age of the resulting 191 patients was 56.1±11.3 years (range 23–90 years), 64.7% were female. Mean aneurysm size was 6.5±2.4 mm and a total of 59 (27.4%) aneurysms were acutely ruptured. Most aneurysm were located on a middle cerebral artery bifurcation (47%) and on the anterior communicating artery (27%). Basilar artery (BA) aneurysms represented 9% and terminal internal carotid artery (Tcarotid) aneurysms 6%. Finally, 11% were located in other bifurcations (others).
Supplemental material
Baseline patient and aneurysm characteristics and angiographic outcomes
Treatment characteristics
The mean fluoroscopy time and dose–area product for WEB procedures were 32±13.4 and 181±68 Gy.cm², respectively. The majority of cases were WEB-SL (77%), and fifth-generation devices (65%). An adjunctive stent was used in 11 aneurysms (5%), and a total of 104 patients (48%) received antiplatelet therapy for at least 1 week after the procedure. Of note, around a quarter of these patients (25 cases) was already receiving antiplatelet therapy before the procedure for other reasons.
Angiographic outcomes
Mean and median last angiographic follow-up were 18 and 16 months (range 3–97 months), respectively. Overall angiographic adequate occlusion and complete occlusion were achieved in 171/215 (79.5%) and 135/215 (62.8%) of cases, respectively. Figure 1 presents the evolution of the angiographic outcome in patients with available control at each time point. Among patients with both a short-term and a mid-term angiographic follow-up, a worsening to neck and aneurysm recurrence was noted in 8/127 (6.3%) and 6/127 (4.7%) of cases, respectively, while 5/127 (3.9%) cases improved to a better occlusion. Among patients with a mid-term and a long-term angiographic follow-up (49 cases), no evolution of the occlusion grading was noted except for one case (intra-WEB opacification toward complete occlusion). During follow-up 20 aneurysms (9.3%) were re-treated because of recurrence (BOSS 3 or 1+3). Finally, the median WEB shape modification was 37% (20-50) with an average of 38% for all cases.
Evolution of occlusion outcome at (A) short term (<12 months) versus mid-term (12–24 months) and at (B) short term versus mid-term versus long term (>24 months).
Predictive factors of angiographic outcome
Multivariable logistic regression was performed to identify significant predictors of angiographic adequate occlusion of aneurysm treated with WEB device (table 2). Aneurysm irregular shape (aOR=0.42, 95% CI 0.20 to 0.88; p=0.02), aneurysm height (aOR=0.79, 95% CI 0.66 to 0.94; p<0.01) and WEB shape modification (aOR=0.98, 95% CI 0.97 to 1.00; p=0.02) were all independent predictors of aneurysm recurrence, whereas the oversizing ratio (aOR=16.4, 95% CI 1.4 to 266.7, p=0.04) was an independent predictor of adequate occlusion. The rupture status of the aneurysm (p=0.27) or follow-up time (p=0.99) did not affect the outcome in our series.
Univariate analysis and multivariable logistic regression for angiographic adequate occlusion of intracranial aneurysms treated with WEB
A sensitivity analysis was conducted to test the robustness of the obtained model by testing angiographic complete occlusion instead of adequate occlusion. Results were very similar as aneurysm irregular shape (aOR=0.52, 95% CI 0.29 to 0.96; p=0.04), aneurysm height (aOR=0.80, 95% CI 0.68 to 0.92; p<0.01), WEB shape modification (aOR=0.99, 95% CI 0.97 to 1.00; p=0.04), and the oversizing ratio (aOR=10.3, 95% CI 1.5 to 85.6; p=0.02) were all independently associated with complete occlusion on the last angiographic control.
Discussion
Main results
Similar to previous studies on a WEB device, we obtained comparable results of complete (63%) and adequate (80%) occlusion.9 10 Eliminating the potential confounding factors by using a multivariable analysis, we were able to identify several independent predictors of angiographic outcome: irregular aneurysm shape, aneurysm height, WEB shape modification, and WEB oversizing.
Aneurysm size
Limbucci et al in a series of 24 aneurysms and Cagnazzo et al in a series with 86 aneurysms, found that larger aneurysm neck was an independent factor of incomplete occlusion.4 18 The latter authors hypothesized that it could be secondary to a higher impact of the arterial blood flow in aneurysms with wider neck, using a comparison with observations with coiling.4 However, a recent analysis of WEB in anterior communicating artery aneurysms observed that the WEB device was not affected by the direct arterial blood flow (as in a unique A1 segment configuration), conversely to coils.19
Here, aneurysm neck, width, and height size were all significantly greater in the aneurysm remnant group, but only aneurysm height was ‘selected’ by the stepdown procedure for the final model, meaning it had the highest impact on the outcome. In their three-center study, Kabbasch et al included 71 aneurysms treated with WEB only but they found no independent predictive factor of aneurysm remnant or recurrence.20 However, recurrent aneurysms had a significant larger aneurysm height and aspect ratio in the univariate analysis.
Irregular aneurysm
Also consistent with their study,4 aneurysm irregular shape was predictive of aneurysm incomplete occlusion (likelihood of aneurysm remnant was 2.4 times higher if the aneurysm was irregular in our cohort). The irregular shape of the aneurysm sac may lead to poor constraining of the WEB inside the aneurysm through two mechanisms: (1) incomplete apposition of the WEB on the aneurysm wall, (2) more difficult WEB size selection, with possible undersizing.
WEB shape modification
WEB shape modification was also part of the evaluation in the Cagnazzo et al study, but as a binary, subjective, variable.4 Although significantly more frequent in the aneurysm remnant group (p=0.01), WEB shape modification remained dependent in the multivariable analysis. Conversely, WEB shape modification defined as a continuous, objective, variable in our model was a strong independent factor of poor angiographic outcome in our analysis. Whether WEB shape modification reflects ‘retraction’ or ‘compaction’ of the WEB device is still disputed in the literature (presumably both)15 21; but our results suggest it should be avoided anyway. In their recent publication, Caroff et al proposed to use a WEB oversizing strategy to prevent the shape modification of the WEB, as both were significantly correlated.22
Oversizing strategy
The choice of the WEB size is a critical point of the procedure; undersizing can lead to poor occlusion, whereas a too important oversizing can cause protrusion of the device in the parent artery and thromboembolic complication. A slight oversizing of its width is recommended in order to obtain better outcome.12 Here, we were able to confirm this hypothesis, oversizing the WEB width compared with the aneurysm average width was highly predictive of a better occlusion. In our department, an oversizing strategy has been progressively set up over the year, which may partly explain the improvement of our results over the past decade (figure 2). This strategy is responsible for constraining the WEB against the aneurysm side wall with a better and more stable coverage of the neck. The sealing of the neck by the flow-disruptive dense nitinol mesh leads to thrombosis of the aneurysm sac. This mesh is also the support for a progressive endothelialization and neointimal formation21; by analogy with a flow diverter,23 24 we hypothesize that constrained sealing of the neck by the WEB improves the arterial healing over the device, therefore favors a better angiographic outcome.
Evolution of (A) WEB oversizing strategy and (B) adequate occlusion rate over the past decade (2012–2022). Graphs are obtained using the LOWESS (locally weighted scatterplot smoothing) regression technique. The gray area indicates the 95% CI.
Notable factors that did not influence the angiographic outcome
In accordance with recent publications,2 25 the use of the WEB in a ruptured aneurysm or in association with a stent was feasible and effective, without significantly influencing the rate of angiographic occlusion. Also, we noted that the use of antiplatelet therapy after embolization did not significantly influence the outcome. Finally, it is important to note that the newest generation of WEB device, including the lower profile WEB 17 system, was not associated with a different outcome than the previous generation.
Stability of the outcome
In our series the length of time between treatment and the last angiographic follow-up did not influence the occlusion results (p=0.99). However, a worsening of the angiographic outcome can be observed during the initial follow-up of an aneurysm treated with the WEB device. Arthur et al reported that it occurred between the 6- month and 12- month follow-up angiogram in 15/131 (11.5%) aneurysms treated with a WEB,5 very similar to our results between shot-term and mid-term follow-up (11.0%). However, the angiographic outcome seemed to be stable after the mid-term control (17.6 months on average in our series). This was also observed in a small series of eight aneurysms.26 Conversely, in the 3- year follow-up of the WEBCAST and the WEBCAST-2 study, they noted that 8/61 (13.1%) aneurysms worsened to neck (six) or aneurysm (two) recurrence between the 1- year and 3- year follow-up, while 6/61 (9.8%) improved.6 However, this discrepancy can be explained by the absence of standardized angiographic follow-up, with the use of different modalities of imaging at each time point (angiography, MRI, or CT angiography). Insufficient reproducibility between MRA and angiography have been shown.27
Limitations of the study
Several limitations hinder analysis, primarily the retrospective nature and patient selection bias at a single academic center. Although it is a relatively large cohort, with homogeneous aneurysms and treatment strategy, it is possible that it might be insufficiently powered to detect a modest effect of some variables. Also we used the BOSS classification to evaluate the occlusion and defined an aneurysm recurrence as a BOSS 3 or 3+1, therefore focusing on adequate occlusion as a success of the treatment. We acknowledge that ‘adequate occlusion’ is still a disputed terminology in our field, but it is more commonly used for WEB evaluation, thus legitimate to use for the evaluation of WEB occlusion determinants.
Nevertheless, by including quantitative ratio for WEB shape modification and oversizing, we were able to obtain valuable information concerning aneurysm occlusion after WEB embolization. Furthermore, because of our standardized follow-up strategy with angiography, we found a stability of the angiographic outcome after the mid-term follow-up.
Conclusions
In this single-center study analyzing 215 aneurysms treated with the WEB device, we showed that a larger aneurysm height, irregular aneurysm shape, and WEB shape modification were all independent determinants of aneurysm remnant. However, a width oversizing strategy of the WEB device was an independent predictor of aneurysm occlusion. Thus, these results may contribute to a better selection of aneurysms suitable for the WEB device, as well as a better selection of the WEB size.
Supplemental material
Data availability statement
Data are available upon reasonable request. Study data are available from the corresponding author upon reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
The French Ethical Committee for Research in Medical Imaging (CERIM) approved this study (institutional review board number CRM2101-127). Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
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Footnotes
Twitter @jildazz, @doc soph, @SeptimiuPopescu, @CRISTIANMIHALEA
Contributors JCo, JCa, and LS they contributed to the conception and design of the studies and interpretation of the data. All authors contributed to the acquisition and/or the analysis of the data and/or drafted the work or revised it for significant intellectual content; All authors approved the final version of the manuscript; agree to be accountable for all aspects of the work, including its accuracy and integrity. JCo, JCa, and LS are acting as guarantor.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests LS is a consultant for Microvention, Balt, Phenox, Stryker, Medtronic; data safety monitoring board or advisory board for CHOICE Study, INSPIRE Study, CLEVER study, COATING study; grant or contract from Philips with institution. JM is a consultant for Microvention and Balt.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.