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Abstract
Background Wide-necked bifurcation aneurysms (WNBAs) present unique challenges for endovascular treatment. The Woven EndoBridge (WEB) device is an intrasaccular braided device, recently approved by the FDA for treatment of WNBAs. While treatment of intracranial aneurysms with the WEB device has been shown to yield an adequate occlusion rate of 85% at 1 year, few data have been published for patients with ruptured aneurysms.
Objective To present a multi-institutional series depicting the safety and efficacy of using the WEB device as the primary treatment modality in ruptured intracranial aneurysms.
Methods A multi-institutional retrospective analysis was conducted, assessing patients presenting with aneurysmal subarachnoid hemorrhage treated with the WEB between January 2014 and April 2020. Baseline demographics, aneurysm characteristics, adverse events, and long-term outcomes (occlusion, re-treatment, functional status) were collected. A descriptive analysis was performed, and variables potentially associated with aneurysm recurrence or re-treatment were assessed.
Results Forty-eight patients were included. Anterior communicating artery aneurysms were the most common (35.4%) location for treatment, followed by middle cerebral artery (20.8%) and basilar apex (16.7%). Procedural success was noted in 95.8% of patients, and clinically significant periprocedural adverse events occurred in 12.5%. After a median follow-up of 5.5 months, 54.2% of patients had follow-up angiographic imaging. Complete occlusion was seen in 61.5% of cases with adequate occlusion in 92.3%. Re-treatment was required in only 4.2% of patients during the study period. Tobacco use was significantly higher in patients with aneurysm recurrence (88.9% vs 35.7%; p=0.012). No other characteristics were associated with recurrence/re-treatment. At 30 days, 81.1% were functionally independent (modified Rankin Scale score ≤2).
Conclusion Treatment of acutely ruptured aneurysms with the WEB device demonstrates both safety and efficacy on par with rates of conventional treatment strategies.
- aneurysm
- device
- embolic
- hemorrhage
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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Introduction
The incidence of aneurysmal subarachnoid hemorrhage in North America is 6.9 per 100 000 person-years.1 Treatment modalities for aneurysm obliteration include clipping, coil embolization, stent or balloon-assisted coiling, and flow diversion. Flow diversion has historically used intraluminal devices, such as the Pipeline Embolization Device (PED; Medtronic Inc, Minneapolis, Minnesota, USA), although these unfortunately require antiplatelet therapies, which are problematic in the setting of acutely ruptured aneurysms. Moreover, flow diversion results in aneurysm occlusion over time rather than providing immediate resolution. The Woven EndoBridge (WEB) (WEB; Microvention, Aliso Viejo, California, USA) is an intrasaccular braided wire device (sometimes termed a 'flow disruptor') that effectively treats intracranial aneurysms.2 3 The WEB device alters flow at the ostium of the aneurysm and provides a scaffold for neointimal growth, resulting in progressive occlusion. Recently, the WEB device has shown significant promise in the treatment of wide-necked bifurcation aneurysms (WNBAs).2–4
As the treatment of intracranial aneurysms has shifted increasingly to endovascular procedures, the need for advances in the available devices has become evident. WNBAs present unique technical challenges for endovascular approaches due to limitations in conventional treatment modalities. The treatment goal is complete occlusion of the aneurysm without compromising the patency of parent vasculature. Owing to aneurysm morphology, these aneurysms are typically not amenable to primary endovascular coil embolization as the dome-to-neck ratio is unfavorable. A variety of devices have been developed to meet these challenging circumstances, with the WEB device receiving FDA approval for use in the internal carotid artery terminus, middle cerebral artery bifurcation, anterior communicating artery complex, or basilar apex aneurysms, based on findings from the WEB Intra-saccular Therapy (WEB-IT) study.2 3
The WEB-IT study included 150 patients with WNBAs who were prospectively enrolled. Of the patients enrolled, 148 received a WEB device, and at 12 month follow-up, there was a 53.8% complete occlusion rate and an adequate occlusion rate of 84.6%.2 3 A subsequent study retrospectively reviewed 42 cases of patients treated with a WEB device, including those with five ruptured aneurysms, finding an adequate occlusion rate of 97% with no treatment related morbidity or mortality.5 Additional series evaluating the use of the WEB device in both ruptured and unruptured aneurysms have continued to demonstrate adequate occlusions rates of over 90%,6–8 including one single-center study that reviewed 100 cases of ruptured aneurysms treated with the WEB device.4 Herein, we present a multi-institutional series depicting the safety and efficacy of using the WEB device as the primary treatment modality in ruptured intracranial aneurysms.
Methods
Study design
A multi-institutional retrospective analysis was conducted in three US centers. All patients included in the study presented with aneurysmal subarachnoid hemorrhage (SAH), in which the WEB device was initially used as the primary means of treatment. Review and approval of the study protocol was obtained from the local institutional review boards of all involved centers.
Patient population
Data were included from patients presenting with aneurysmal SAH and treated with the WEB device within 15 days from hemorrhage over a 6-year period between January 1, 2014 and April 1, 2020. Indications for aneurysm treatment with a WEB device were at the discretion of the treating physician. Baseline demographics—including age, sex, race, baseline modified Rankin scale (mRS) score, hypertension, hyperlipidemia, diabetes mellitus, tobacco use, and prerupture anticoagulation use—were collected from the medical record and included in the analysis.
Clinical and radiological assessments
Data collection and reporting was performed by each individual center. Clinical hospitalization data collected included Hunt and Hess grade, modified Fisher grade, time from rupture to treatment, periprocedural adverse events, length of stay, hospitalization adverse events, and mRS score at discharge. Angiographic and aneurysm-specific information included aneurysm location, aneurysm width, aneurysm height, aneurysm neck, device used, degree of stasis, and vasospasm within the first 2 weeks. Degree of stasis was measured with the O’Kelly-Marotta angiographic grading scale.9 Long-term data included time to follow-up imaging, Raymond-Roy occlusion grade, recurrence or residual after treatment, need for re-treatment, and mRS score at 30 days. All neurological, ischemic, hemorrhagic, and access site complications were recorded, regardless of whether they resulted in a clinical deficit.
Statistical analysis
Descriptive analysis was performed for baseline demographics, aneurysm and treatment characteristics, and patient outcome metrics, and results are presented as frequencies, means with SD, and medians with IQR, where appropriate. Independent t-test, Pearson chi-square, and Wilcoxon rank sum analyses were used to assess correlations between continuous, categorical, and ordinal independent variables, respectively, with aneurysm recurrence or re-treatment. All statistical analyses were performed with SPSS version 26 (IBM Corp., Armonk, New York, USA). P values less than 0.05 were considered statistically significant.
Results
Baseline demographics
This study included a total of 48 patients who underwent WEB device placement as the primary treatment for a ruptured intracranial aneurysm. Average age in this cohort was 57.8±15.2 years. Women comprised 66.7% of the cohort. In this cohort, Hunt-Hess grade 2 was seen most frequently (37.5%), followed by grade 3 (22.9%), and grade 4 (22.9%), with modified Fisher grade of 3/4 in 72.9% of the patients. Further patient demographics can be found in table 1.
Baseline patient demographics
Aneurysm and treatment characteristics
Median time from rupture to treatment was 1 day, with anterior communicating artery aneurysms being the most common (35.4%) location for treatment in this cohort, followed by middle cerebral artery (20.8%) and basilar apex (16.7%). Over a quarter (27.1%) of the aneurysms treated were off-label with respect to location. Procedural success was noted in 95.8% (46/48) of the patient population (table 2). In two cases, the WEB device was unable to be deployed safely into the aneurysm and another treatment modality was employed. Periprocedural adverse events were noted in 18.8% (9/48), consisting of thrombus formation (n=5), intraoperative ruptures (n=2), device mal-positioning that required secondary stent placement (n=1), and femoral artery dissection (n=1). Only six of these patients had clinical sequelae from these adverse events (three ischemic stroke, two worsened SAH/intraventricular hemorrhage, and one femoral dissection), yielding a 12.5% rate of clinically significant adverse events in this cohort. Over a quarter of the patients (27.1%) required treatment for symptomatic vasospasm, and the entire cohort required hospitalization for 18.6±10.6 days.
Aneurysm and treatment characteristics
Patient outcomes
Three patients died following withdrawal of care after presenting with Hunt and Hess grades of 4, 5, and 5, respectively, for a mortality rate of 6.3% (table 3). With median follow-up of 5.5 months (IQR 1–6), 54.2% (26/48) of patients in this cohort had follow-up angiographic imaging. Complete occlusion of the ruptured aneurysm was noted in 61.5% of cases, with adequate occlusion (complete occlusion or neck remnant) in 92.3%. Only 4.2% (2/48) of patients required re-treatment during the study period. Both patients required stent-assisted coiling of a significant aneurysm recurrence at 2 and 4 months, respectively, with no adverse sequelae associated with the second treatment. At 30 days after the procedure, 77.1% (37/48) had clinical follow-up, at which 81.1% were functionally independent (mRS score ≤2).
Patient outcomes
Further assessment of this cohort analyzed factors associated with aneurysm recurrence/residual (n=10) or re-treatment (n=2), compared with patients with complete occlusion (n=15). No baseline demographics, aneurysm characteristics or treatment variables were associated with re-treatment. The use of tobacco was significantly higher in patients with aneurysm recurrence/residual (88.9% vs 35.7%; p=0.012), although no other metrics reached statistical significance (table 4).
Factors associated with aneurysm recurrence/residual
Discussion
Endovascular treatment of ruptured wide-necked bifurcation aneurysms is complicated by the need to secure the aneurysm and the unsuitable morphology for primary coil embolization. When flow diverters or intracranial stents are used, it is generally recommended that patients should be given dual antiplatelet therapy (DAPT) for at least 3–5 days prior to the procedure, although this is clearly problematic in the setting of SAH. Although there are recommended regimens for platelet inhibition with either glycoprotein IIb/IIIa inhibitors or antiplatelet medications when emergent stent placement is needed,10 there are no current randomized clinical trials that support a specific regimen to reduce the risk of thromboembolic complications. The WEB device is advantageous in that it can be placed emergently without the need for DAPT due to its intrasaccular nature. It is suitable for treatment of many aneurysms, including bifurcation and broad-necked aneurysms, which would otherwise not be amenable to primary coiling.
The WEB-IT trial, which included 150 patients treated with the WEB device, demonstrated safety of the device with only one primary safety event (0.7%) and no mortality at the 30-day follow-up.2 3 In their study, the authors found a 4.7% rate of minor ischemic stroke (five of which resolved without sequelae), a 2.7% rate of transient ischemic attacks, and 2% rate of arterial thrombosis (which resolved after treatment with stenting or eptifibatide infusion).2 3 Two cases of asymptomatic subarachnoid hemorrhage were seen.
A systematic review and meta-analysis of patients treated with the WEB device found a 4% risk of perioperative morbidity and 1% risk of mortality among 565 patients with 588 aneurysms, including 127 ruptured aneurysms.11 There was no significant difference in morbidity or mortality between ruptured and unruptured aneurysms. An 8% rate of thromboembolic complications was seen overall.11 A recent study evaluated use of the WEB device in acutely ruptured aneurysms of nine patients, finding no treatment-related mortalities or re-rupture following device placement.12 A systematic review of stent-assisted coiling for treatment of ruptured intracranial aneurysms found an 11.2% rate of thromboembolism, 5.4% rate of intraprocedural hemorrhage, and 3.6% rate of postprocedural hemorrhage.13 The overall rate of clinically significant complications in this study (12.5%) compares favorably with stent-assisted coil embolization. Further, in this cohort, 6.3% of patients had a thromboembolic complication while only 4.2% experienced intraprocedural hemorrhage. Several studies have previously investigated flow diversion in acute SAH.14–22 Pooled favorable outcomes, defined as mRS score ≤2, in those studies were seen in 71% (range 27–92%). In our study, good functional outcomes (ie, mRS score ≤2) were observed in 81.1% of the population. Thus, rates of morbidity and mortality appear to be similar among patients treated with the WEB embolization device and those having other endovascular treatments.
As mentioned previously, the treatment of WNBAs is particularly challenging. A recent meta-analysis evaluating treatment of WNBAs found long-term complete occlusion rates to be 39.8% for endovascular therapy and 52.5% following surgical clip ligation, with a 46.3% occlusion rate for all therapies.23 Adequate occlusion in this study was seen in 43.8% of patients treated by endovascular means, 69.7% following surgical clipping, and 59.4% for all therapies.23 In the present study, short-term follow-up identified complete occlusion rates of 61.5% and adequate occlusion (complete occlusion or neck remnant) rates of 92.3%, replicating those observed in the WEB-IT trial and presenting significant advantages over other methodologies. This increased efficacy may be due to the ability to improve coverage at the aneurysm neck with less concern for compromise of the parent vessel. Nonetheless, given the new nature of this device, follow-up in this study is limited and future studies will be needed to assess long-term aneurysm occlusion.
Intraoperative rupture rates may continue to decrease as operator experience with this new device increases. As more ruptured aneurysms are treated with a WEB device, technical prowess and expertise will increase and improved outcomes are expected to follow. It is important to note that the intraprocedural rupture risk (4.2%) and rate of thromboembolic complications (6.3%) is on par with that documented with other endovascular means of treatment for acutely ruptured aneurysms, including a recent retrospective study identifying a 4.1% rate of intraprocedural rupture associated with primary coil embolization.24 Furthermore, no patients experienced delayed hemorrhage following treatment despite the use of this novel flow disruption device.
In primary coil embolization of an aneurysm, the vector force of the coil as it exits the microcatheter and enters the aneurysm is typically directed towards the point of rupture. With this, there is a theoretically increased risk of intraoperative rupture from the coil pushing through the thrombosed dome. In contrast, with proper use the WEB device is deployed in a manner in which it is unsheathed within the aneurysm. When this technique is used, the device has vector forces that are directed in a lateral direction toward the walls of the aneurysm rather than the dome.
Posterior circulation aneurysms can be especially challenging to treat in the context of WNBAs and acute SAH. The surgical approach is less favorable due to technical challenges with proximal control and working angles. Various endovascular techniques are typically used, although each has potential drawbacks, particularly with WNBAs. Incomplete treatment and residual aneurysm filling are often seen with primary coiling, increased morbidity is a concern with balloon-assisted coil embolization, and the need for DAPT with stent placement raises the risk of hemorrhage. The WEB device provides an effective alternative treatment with a minimal risk profile in these particularly challenging aneurysms.
This study has numerous limitations. The retrospective, self-reported nature of the study lends itself to inherent biases. Most important, because this is a case series evaluating a new endovascular device, there is no control arm for comparison of adverse events and outcomes, and comparisons are, as such, limited to historical controls. Further studies directly comparing the use of the WEB device with surgical clipping and other endovascular means will be needed to identify the ideal treatment for acutely ruptured WNBAs. Finally, with this device recently gaining FDA approval and being used to a substantial degree only over the past year, follow-up is still ongoing and longer-term angiographic and clinical follow-up will need to continue to be evaluated to identify the true safety and efficacy of this treatment modality. Despite the fact that some patients were treated in 2014, a substantial portion of patients in this study were treated within the past 6–12 months, underlining the limited and short follow-up in this study. Future studies will be needed to assess the long-term efficacy of WEB embolization for ruptured aneurysms.
Conclusion
This study represents a single-arm analysis, but we found that use of the WEB device in the treatment of acutely ruptured intracranial aneurysms was both safe and efficacious. Further studies evaluating its use in direct comparison with other treatment modalities, and a longer follow-up to assess aneurysm occlusion, are warranted and will further elucidate best treatment practices for these difficult aneurysm subtypes.
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
Ethics statements
Ethics approval
Ohio State University, Columbus, OH # A2020-2107 Baptist Memorial Hospital, Memphis, TN # 20-46 UTHSC, Memphis, TN 20-07324-XP Thomas Jefferson, Philadelphia, PA # 12D.534.
Acknowledgments
The authors thank Andrew J Gienapp (Neuroscience Institute, Le Bonheur Children’s Hospital and Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN, USA) for copy editing, preparation of the manuscript and tables for publishing, and publication assistance.
References
Footnotes
Twitter @PatrickPYoussef, @DornbosIII_MD, @AhmadSweidMD, @PascalJabbourMD, @AdamArthurMD
Contributors All authors of this work met ICMJE criteria for authorship and made substantial contributions to the conception and design, acquisition of data, analysis and interpretation of data, drafting, critical revising, and final approval of this manuscript.
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 PJ is a consultant for Medtronic and MicroVention. ASA is a consultant for Johnson and Johnson, Medtronic, Microvention, Penumbra, Scientia, Siemens, and Stryker; receives research support from Balt, Cerenovus, Medtronic, Microvention, Penumbra, Siemens, and Stryker; and is a shareholder in Bendit, Cerebrotech, Endostream, Magneto, Marblehead, Neurogami, Serenity, Synchron, Triad Medical, Vascular Simulations.
Provenance and peer review Not commissioned; externally peer reviewed.