Background The Woven EndoBridge (WEB) device is a novel intrasaccular flow disruptor tailored for bifurcation aneurysms. We aim to describe the degree of aneurysm occlusion at the latest follow-up, and the rate of complications of aneurysms treated with the WEB device stratified according to rupture status.
Methods Our data were taken from the WorldWideWeb Consortium, an international multicenter cohort including patients treated with the WEB device. Aneurysms were classified into two groups: ruptured and unruptured. We compared clinical and radiologic outcomes of both groups. Propensity score matching (PSM) was done to match according to age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up.
Results The study included 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device. The PSM analysis had 55 pairs. In both the unmatched (85.8% vs 84.3%, p=0.692) and matched (94.4% vs 83.3%, p=0.066) cohorts there was no significant difference in the adequate occlusion rate at the last follow-up. Likewise, there were no significant differences in both ischemic and hemorrhagic complications between the two groups. There was no documented aneurysm rebleeding after WEB device implantation.
Conclusion There was no significant difference in both the radiologic outcomes and complications between unruptured and ruptured aneurysms. Our findings support the feasibility of treatment of ruptured aneurysms with the WEB device.
Data availability statement
Data are available upon reasonable request.
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WHAT IS ALREADY KNOWN ON THIS TOPIC
Numerous case series have shown the comparable efficacy of the Woven EndoBridge (WEB) device on unruptured aneurysms. Limited data are available for ruptured aneurysms.
WHAT THIS STUDY ADDS
No significant difference was found in both radiologic and clinical outcomes between ruptured and unruptured aneurysms. With no documented post procedure re-ruptures, the study adds to a growing body of literature demonstrating the feasibility intrasaccular flow disruption for ruptured aneurysms.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE AND/OR POLICY
Ruptured wide-necked bifurcation aneurysms present a difficult endovascular challenge because most effective endovascular treatment strategies require adjunct devices that may not be appropriate in a ruptured aneurysm scenario. This study impacts neuroendovascular practice as it shows that the WEB device may be used effectively in ruptured aneurysms.
The endovascular treatment of wide-necked bifurcation aneurysms is a technical challenge. The wide neck predisposes to coil displacement, while the bifurcation anatomy prevents optimal neck coverage by a flow diverting stent. The Woven EndoBridge (WEB) device, an intrasaccular flow diverter, was explicitly designed for this type of aneurysm.1 Its broad base provides for a stable construct and allows it to sit above the neck of the aneurysm. Landmark studies2 3 on the use of the device have shown adequate degrees of aneurysm occlusion comparable to other endovascular modalities such as stent-assisted coiling and flow diversion.4
However, unlike those devices, the WEB device does not require the use of antiplatelets because the thrombogenic mesh part of the device is placed inside the aneurysm dome. This has significant implications in treating ruptured aneurysms compared with unruptured aneurysms. Ruptured aneurysms have a significant rate of re-rupture, and there is a significant need for urgent open neurosurgical interventions such as insertion of external ventricular drains and clot evacuation. In these situations, antiplatelets and anticoagulants are generally avoided. The initial observational studies on the use of the WEB device5 included only a minimal number of ruptured aneurysms. A previously published cohort with the longest follow-up data found that the adequate occlusion rate for the device was 83.6% (51/61). However, only 2/61 (3.3%) of the included aneurysms were ruptured.6 There is an ongoing pragmatic randomized controlled trial on using the WEB device for both ruptured and unruptured aneurysms.7 While awaiting the results from this trial, we aim to study the radiologic and clinical outcomes of patients with ruptured aneurysms compared with unruptured aneurysms treated with the WEB device, using data from an international multicenter consortium.8
Data were obtained from the WorldWideWEB Consortium, which comprises retrospective multicenter data related to adult patients (age ≥18 years) with ruptured and unruptured intracranial aneurysms treated with the WEB device at academic institutions in North and South America, Europe, and Australia. The following information was collected: patient demographics, aneurysm characteristics, procedural details, complications, and angiographic and functional outcomes. Then, these aneurysms were stratified based on their ruptured status into ruptured and unruptured. Institutional review board approval was obtained at all contributing centers.
Outcomes and complications
The study’s primary outcomes were the degree of aneurysm occlusion at the latest follow-up and rate of complications (hemorrhagic and thromboembolic). The radiologic outcome was assessed using digital subtraction angiography (DSA), magnetic resonance angiography (MRA), or computed tomography angiography (CTA) using the WEB occlusion scale (complete occlusion, neck remnant, and aneurysm remnant).9
Secondary outcomes included: post-treatment rupture, technical complications, retreatment rate, and functional outcomes at the latest follow-up. Technical complications included access complications, vascular dissection, deployment issues, and air embolism. The functional outcome will be assessed using the modified Rankin scale.10 Thromboembolic complications occurring from the date of the procedure up to the last follow-up will be recorded. Intra-procedural thromboembolic complications were identified on DSA as either thrombus formation, delayed filling of a previously normal filling vessel, or complete vascular occlusion. Post-procedural thromboembolic complications were identified using a combination of clinical and radiographic findings. Post-procedural imaging was performed at the discretion of the individual institutions. Routine screening for clinically silent infarcts was not consistently performed. Post-procedural imaging obtained to detect symptomatic ischemic stroke could include any combination of non-contrast CT, CTA, or MRI. Only ischemic strokes in the territory of the treated vessel were included. An ischemic complication was considered symptomatic if there were patient-reported symptoms or clinical signs attributable to thromboembolism; this included transient or resolving signs and symptoms. Complications were considered permanent if still present at a 3 month follow-up. Hemorrhagic complications were identified intraoperatively as contrast extravasation on DSA or post-procedure imaging. Hemorrhagic complications occurring from the time of the procedure up until the last follow-up were included. Hemorrhages were considered symptomatic if the patient-reported symptoms or demonstrated signs attributable to hemorrhage. In contrast to ischemic complications, all vascular territories were included.
Statistical analysis was performed using R 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria) software. Categorical variables were presented as frequencies and percentages and compared using the χ2 test or Fisher’s exact test. In contrast, continuous variables were presented as median with IQR and compared using the Mann-Whitney test. The final follow-up modified Rankin Scale (mRS) scores were compared using the ordinal mixed-effects regression models. First, variables associated with clinical and angiographic outcomes and were significant to 0.1 or less in the univariable regression models were selected for propensity score matching (PSM) analysis. Then, a 1:1 PSM with the nearest neighbor method, without replacement, and with a caliper=0.20 was used to match by the following covariates: age, gender, bifurcation, location, prior treatment, neck, height, dome width, daughter sac, incorporated branch, pretreatment antiplatelets, and last imaging follow-up. Results were deemed statistically significant if they had a p value ≤0.05.
Patient and aneurysm characteristics
A total of 676 patients with 691 intracranial aneurysms (529 unruptured and 162 ruptured) treated with the WEB device were included in this study. In both groups, women comprised most patients (73.9% vs 63.0%). Unruptured aneurysms had more difficult aneurysm characteristics: larger neck (4.00 mm vs 3.50 mm, p<0.001), larger maximal diameter (6.90 mm vs 6.30 mm, p=0.003), larger dome width (5.60 mm vs 4.60 mm) and larger height (6.9 mm vs 6.3 mm, p=0.009). The aspect ratio was slightly lower for the unruptured group (1.1 vs 1.3, p=0.006). Unruptured aneurysms had more prior treatments (8.2% vs 0%, p<0.001) and presence of a daughter sac (42.3% vs 26.4%, p<0.001). There was no significant difference between the two groups regarding smoking, location, presence of multiple aneurysms, dome to neck ratio, imaging modality (CTA, MRA or DSA) on last radiologic follow-up, and presence of an incorporated branch (table 1). The ruptured aneurysms had the following Hunt and Hess (HH) grades: HH1 23.5%, HH2 24.1%, HH3 29.0%, HH4 9.9%, HH5 10.5%, missing data (3.1%).
Treatment and outcomes
More patients in the unruptured arm were pretreated with antiplatelets (79.2% vs 13.8%, p<0.001). Ruptured aneurysms had longer procedure times than unruptured ones (91 min vs 78 min, p=0.003). The imaging follow-up time was longer for unruptured aneurysms (12 months vs 6.2 months, p<0.001). Immediate adequate occlusion (complete occlusion and remnant neck) rate was lower for unruptured aneurysms (42.5% vs 62.8%, p<0.001). There was no significant difference between the adequate occlusion rate at the last follow-up between unruptured and ruptured aneurysms (85.8% vs 84.3%, p=0.692). Follow-up imaging was done using different modalities: 50 CTA, 252 DSA, 192 MRA, 3 CTA and MRA, and 50 MRA and DSA. There were two aneurysms in the ruptured group that ruptured again just before final WEB deployment, but bleeding for both was arrested after WEB deployment. No permanent clinical sequelae resulted from these events and both patients had a good functional outcome on latest follow-up. There was no significant difference between unruptured and ruptured aneurysms concerning hemorrhagic complications (2.3% vs 5.0%, p=0.228) and thromboembolic complications (6.6% vs 11.1%, p=0.060). Although this did not reach statistical significance it is noticeable that the ruptured arm overall had almost twice the complications. At the last follow-up, the unruptured group had better clinical outcomes (p<0.001). No significant differences were seen concerning adjunctive coiling, retreatment, and mortality (table 2). After WEB implantation, no cases of aneurysms ruptures were seen in either the ruptured or unruptured groups. Table 3 describes the radiologic outcomes of the ruptured aneurysms according to site.
Propensity score matching
PSM resulted in 55 matched pairs. There was no significant difference of adequate occlusion at the latest follow-up (94.4% vs 83.3%, p=0.066) and immediate adequate occlusion was similar (50.9% vs 53.7%, p=0.771). Ruptured aneurysms had longer procedure times (93.5 mins vs 63.5 mins, p<0.001). No significant difference was found in terms of procedure length, adjunctive coiling, immediate blood flow stagnation, retreatment rate, mortality, and complications (online supplemental tables 1 and 2).
In both the unmatched (85.8% vs 84.3%, p=0.692) and matched cohorts (94.4% vs 83.3%, p=0.066), there was no significant difference in the adequate occlusion rate at the last follow-up between unruptured and ruptured aneurysms. Most importantly, there were no documented aneurysm ruptures in either group after the WEB device was placed. We initially anticipated that operators might under-size WEBs in ruptured aneurysms for fear of iatrogenic aneurysm rupture or having the thrombogenic device protrude out of the aneurysm and necessitate the use of antiplatelets in the setting of a ruptured aneurysm. This idea does not seem to hold in our series, even after doing PSM. The PSM corroborates that the equivalent radiologic outcomes are not just because of the more favorable aneurysm characteristics in the ruptured group. Intuitively, mRS at the lastest follow-up was worse in the ruptured group. This reflects the expected more dynamic clinical course of ruptured aneurysms.
Like the CLARYS (CLinical Assessment of WEB device in Ruptured aneurYSms) study, a 1 year prospective multicenter study for ruptured aneurysms treated with the WEB device, no re-rupture was documented in our series over a 6 month follow-up.11 Despite 37.2% of the aneurysms in our series still having a residual immediately after the procedure, the immediate flow diverting effect of the device seems to be effective. While the exact mechanism remains to be elucidated, the aneurysm dome and likely rupture point is likely protected from another rupture by the WEB despite residual flow into the aneurysm base. Our finding that WEB deployment resulted in the arrest of two intraoperative ruptures supports this possibility. The radiologic outcome was also comparable to other ruptured aneurysm cohorts. A systematic review of nine observational studies tackling ruptured aneurysms treated with the WEB device had 84.9% and 54.6% adequate occlusion and complete occlusion rates, respectively.12 These figures are similar to the findings of our series (84.3% and 53.0%). In comparison with the same review, our retreatment rates are higher (4.5% vs 9.1%), with 71.4% (endovascular) and 28.6% (open surgical) needing further interventions.12 However, the lower rate in the review may have been driven by the two largest studies included there, which only had 3 months of follow-up. Our cohort had a median of 6 months. None of the retreatments in our series occurred in the acute phase of aneurysm rupture. The earliest retreatment (with a flow diverting stent) occurred 20 days after the initial WEB retreatment. The next earliest retreatment happened 3 months after the initial treatment. Despite the less-than-optimal immediate occlusion rate, the retreatments were done based on radiologic outcomes seen on routine imaging rather a clinical trigger.
Immediate occlusion was better in the ruptured aneurysm group. This is likely because of the more favorable anatomy (smaller domes, smaller necks) in the ruptured aneurysms treated with the WEB. In addition, antiplatelet use was understandably much less (79.2% vs 13.8%, p<0.001) in the ruptured aneurysm group. The difference in immediate occlusion rate disappeared after PSM. This suggests that the factors mentioned above (aneurysm characteristics) may have contributed. Another possible factor is that ruptured aneurysms were treated when the operators had more experience with sizing the device after treating unruptured aneurysms earlier on in their WEB experience.
Two of the hemorrhagic complications in the ruptured aneurysm group were from intraoperative ruptures before WEB deployment. Similar to the two intraoperative ruptures that we had, the aforementioned systematic review documented seven intraoperative ruptures that all halted after a successful deployment of the WEB device.12 The increased procedure time may be due to a multitude of factors that may include: (1) initial under sizing of the WEB resulting in more trials to obtain the optimal size, (2) an initial attempt to coil the aneurysm ending with a WEB bailout, and (3) complications related to aneurysm rupture such as vasospasm that may need to be addressed before aneurysm treatment.
This study has several limitations. First, the study’s retrospective nature has led to missing data and predisposes to recall bias. In addition, we lacked data on failed WEB deployments as the consortium only gathered data for deployed WEB devices. Complications arising from these procedures are not documented in our study. Third, we did not have a core lab to ascertain the degrees of occlusion objectively. Because the same operators performing the procedure are usually determining the degree of occlusion, there may be a tendency to report better outcomes. Given that the number of matched cases was trimmed after PSM, the results of the matched groups do not necessarily reflect the overall sample results. Lastly, the inclusion of different institutions introduces variability in the experience of operators and standards in adjudicating outcomes and complications.
There is no significant difference in the radiologic outcomes of ruptured and unruptured aneurysms treated with the WEB device in our sample. With no documented rebleeding after WEB device deployment, our findings support the feasibility of treating ruptured aneurysms with the WEB device.
Data availability statement
Data are available upon reasonable request.
Patient consent for publication
This study involves human participants and was approved by Louisiana State University Health Sciences Center institutional review board (IRB). ID: STUDY00001538. The study was a retrospective review of cases. No consent was required by the IRB given the lack of identifying information
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Contributors JBD, MD, NA and AAD were the lead investigators. AAD is the main guarantor of the study. They were involved in the design of the study, acquisition and analysis of data, drafting and revising the manuscript for intellectual content and final approval of the version to be published. RWR, JEV, AG, SVL, LR, AAB, ES, KP, KEN, GS, MAM, IL, PMF, JAV, VŽ, MUH, CR, HR, VMT, SM, SG, PH, NMA, JDR, YR, CMS, OG, MP, ALK, CM, SE, RMS, AH, AS, AN, JJ, MP, JS, CPF, MBB, MM, MMS, JKB, BTJ, RAD, TH, RT, CU, BL, PP, ASP, GP, CJG, HA, AS, AFD, FCA, RD, PK, VK, PL, SB, CJS, JK, PJ, ST, FC, ML, MAA, HHC, CC, ABP were coinvestigators. There were involved in the acquisition and analysis of data, drafting and revising the manuscript for intellectual content and final approval of the version to be published. All authors have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
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 JDBD: Honoraria from Medtronic. Travel grant from Microvention. MD: No relevant relationships NA: No relevant relationships RWR: Grants from National Institutes of Health, Heitman foundation, Society of vascular and interventional neurology; Advisory board participation for Rapid medical; Site PI for Microvention and Penumbra JEV: No relevant relationships AG : No relevant relationships SVL: No relevant relationships LR: No relevant relationships AAB: No relevant relationships ES: No relevant relationships KP: No relevant relationships KEL: No relevant relationships GS : No relevant relationships MAM: No relevant relationships IL: No relevant relationships PMR: No relevant relationships JAV: Fees from MicroVention for proctoring cases for new physician users of the Woven EndoBridge device; Medtronic travel expense VŽ: Participation on the data safety monitoring board or advisory board for KBC Sestre Milosrdnice, Zagreb / OB Nova Gradiška MUH: No relevant relationships CR: No relevant relationships HR: No relevant relationships VMT: No relevant relationships SM: No relevant relationships SG: No relevant relationships PH: No relevant relationships NA: No relevant relationships JDR: No relevant relationships YR: No relevant relationships CMS: No relevant relationships OG: No relevant relationships MP: No relevant relationships ALK: No relevant relationships CM: No relevant relationships SE: No relevant relationships RMS: Supported by the NREF, Joe Niekro Foundation, Brain Aneurysm Foundation, Bee Foundation, and the National Institutes of Health (R01NS111119-01A1, UL1TR002736, and KL2TR002737) through the Miami Clinical and Translational Science Institute, from the National Center for Advancing Translational Sciences and the National Institute on Minority Health and Health Disparities. AH: Consulting or speaker fees from Medtronic, MicroVention, Stryker, Penumbra, Cerenovus, Genentech, GE Healthcare, Scientia, Balt, Viz.ai, Insera Therapeutics, Proximie, NeuroVasc, NovaSignal, Vesalio, and Galaxy Therapeutics. AS: No relevant relationships AN: No relevant relationships JJ: Consulting and speaker fees from Cerenovus MP: No relevant relationships JS: No relevant relationships CPF: No relevant relationships MBB: No relevant relationships MM: Grants from Balt, Medtronic, MicroVention, and Stryker. MMS: No relevant relationships JB: No relevant relationships BTJ: No relevant relationships RAD: No relevant relationships TH: No relevant relationships RT: Medtronic Stocks CU: No relevant relationships BL : No relevant relationships PP: No relevant relationships ASP: Grants from NIH, Microvention, Cerenovus, Medtronic and Stryker; Consulting fees from Neurovascular, Stryker NeurovascularBalt, Q’Apel Medical, Cerenovus, Microvention, Imperative Care, Agile, Merit, CereVasc and Arsenal Medical; stock options from InNeuroCo, Agile, Perfuze, Galaxy and NTI GP: No relevant relationships CJG: Grants to institution from Medtronic and Penumbra; consulting fees from Stryker and MicroVention. HA: Proctoring fees from MicroVention. Grants to institution from the National Institutes of Health; consulting fees from Amnis Therapeutics, Apellis Pharmaceuticals, Boston Scientific, Canon Medical Systems, Cardinal Health 200, Cerebrotech Medical Systems, Cerenovus, Cerevatech Medical, Cordis, Corindus, EndoStream Medical, Imperative Care, Integra, IRRAS, Medtronic, MicroVention, Minnetronix Neuro, Penumbra, Q’Apel Medical, Rapid Medical, Serenity Medical, Silk Road Medical, StimMed, Stryker Neurovascular, Three Rivers Medical, VasSol, Viz.ai, and W.L. Gore & Associates; payment for participation on the steering committees for the Cerenovus EXCELLENT and ARISE II Trial; Medtronic SWIFT PRIME, VANTAGE, EMBOLISE, and SWIFT DIRECT Trials; MicroVention FRED Trial and CONFIDENCE Study; MUSC POSITIVE Trial; Penumbra 3D Separator Trial, COMPASS Trial, INVEST Trial, MIVI Neuroscience EVAQ Trial; Rapid Medical SUCCESS Trial; InspireMD C-GUARDIANS IDE Pivotal Trial; stock or stock options in Adona Medical, Amnis Therapeutics, Bend IT Technologies, BlinkTBI, Buffalo Technology Partners, Cardinal Consultants, Cerebrotech Medical Systems, Cerevatech Medical, Cognition Medical, CVAID, E8, EndoStream Medical, Imperative Care, Instylla, International Medical Distribution Partners, Launch NY, NeuroRadial Technologies, Neurotechnology Investors, Neurovascular Diagnostics, Perflow Medical, Q’Apel Medical, QAS.ai, Radical Catheter Technologies, Rebound Therapeutics (purchased in 2019 by Integra Lifesciences), Rist Neurovascular (purchased in 2020 by Medtronic), Sense Diagnostics, Serenity Medical, Silk Road Medical, Songbird Therapy, Spinnaker Medical, StimMed, Synchron, Three Rivers Medical, Truvic Medical, Tulavi Therapeutics, Vastrax, VICIS, and Viseon AFD: Consulting fees from Cerenovus, Penumbra, Medtronic, Stryker, Oculus, and Koswire. No relevant relationships RD: No relevant relationships PK: No relevant relationships. VK: No relevant relationships. PL: No relevant relationships SB: No relevant relationships CJS: Participation on the data safety monitoring board or advisory board for Zoll Circulation JK: No relevant relationships PJ: No relevant relationships ST: No relevant relationships FC: No relevant relationships NL: Honoraria for lectures from Cerenovus, Stryker, and CrossMed. MAA: Funding to institution from MicroVention for WEBIT trial; proctoring fees from MicroVention. HHC: No relevant relationships CC: Consulting fees from MicroVention, Stryker, Medtronic, MIVI, and Cerenovus. ABP: Grant to institution from Medtronic; consulting fees from MicroVention, Medtronic, and Q’Apel; workstation for research from Siemens AAD: No relevant relationships
Provenance and peer review Not commissioned; externally peer reviewed.
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