A new era in the treatment of wide necked bifurcation aneurysms: Intrasaccular flow disruption

Abstract

Wide-necked bifurcation aneurysms (WNBAs) are challenging lesions to treat via both open surgical and endovascular techniques. Presently, there are 3 intrasaccular devices available to address many of the limitations of prior techniques, all of which are at different phases of approval for human use around the world. These devices include the Woven EndoBridge (WEB ^® ) made by MicroVention, the Artisse^™ Embolization Device made by Medtronic, and the Contour Neurovascular System^™ made by Cerus Endovascular. Although heterogenous in design, these devices rely on the principle of using fine mesh overlying the aneurysm neck to slow blood inflow, promoting stagnation and thrombosis that ultimately leads to healing across the neck and exclusion from the circulation. While our understanding improves as long-term occlusion rates from these devices continue to be studied, the safety profiles and short-term success rates demonstrated in recent studies provide optimism for these innovative intrasaccular devices for the treatment of WNBAs. In this paper, we review these 3 intra-saccular flow disruption devices for use in WNBAs and summarize recent literature and studies of their effectiveness and safety.

Introduction

Wide-necked bifurcation aneurysms (WNBAs) have posed a significant challenge for endovascular treatment since the advent of detachable coils.^1,2 An aneurysm with a neck greater than 4 mm or having an aspect ratio (dome-to-neck) of less than 1.6 is considered a WNBA. ³ At this size, coils tend to prolapse out of the aneurysm into the parent vessel, which can pose both embolic and thrombotic risk. In recent years, multiple adjunctive treatment methods have been developed to help mitigate these issues with WNBAs, including temporary techniques, such as balloon-assisted coiling or retrievable scaffolding devices, as well as implantable devices, such as stents. However, WNBAs add further difficulty as 2 vessels must be adequately protected. While complex stent constructs or deployments can be utilized or use of various balloon techniques can be used to protect both vessels, these measures increase the risk of the procedure.^2,4 With these concerns, other options, such as flow diversion or intra-saccular flow disruption devices, have been sought for the safe treatment of WNBAs.

Principles of flow diversion

In large aneurysms, blood flow is a complex co-existence between inflow and outflow from the neck, although predictable. ⁵ A small high-velocity inflow jet enters the aneurysm through the distal aspect of the neck; the blood swirls within the aneurysm and then exits via a broader, slower outflow area of the neck. ⁵ The path of blood is much like the path a wire takes when utilizing the “around the world” technique to access distal vessel during the treatment of large or giant aneurysms.

Flow diversion aims to modulate this balanced flow dynamic to initiate blood stagnation within the aneurysm and ultimately thrombosis. ⁶ With the increased resistance to flow caused by the low porosity of the flow diverting stent, the inflow jet decreases in velocity and increases in size. ⁷ As a result, the outflow region decreases in size and, therefore, blood pools within the aneurysm. This correlates with the contrast stasis seen within an aneurysm after flow diverter placement. ⁸ Interestingly, when radiolucent coils are deployed within a simulated aneurysm, a similar contrast stasis is seen.

Aneurysm healing by any endovascular treatment begins with an intervention causing flow disruption within the aneurysm dome that results in thrombus formation. ⁹ A process of neointimal formation across the face of the thrombus provides long term exclusion of the aneurysm from the arterial circulation. In the setting of a coil embolization, this process occurs due to the random alignment of coils within the aneurysm causing turbulence in flow, resulting in areas of stagnation. ⁹

Flow diverting stents can be an effective tool for branch vessel aneurysms, where the whole neck can be covered by deployment in a parent vessel to cause the flow disruption described above. ¹⁰ However, with the neck of WNBAs often involving both vessels, deployment in one vessel may not offer adequate neck coverage, and thus, alternative treatments need be selected. ¹

Intra-saccular flow disruption

Intra-saccular flow disruption devices were developed as an endovascular solution to a number of challenges that alternate treatment strategies for WNBA face.^11–13 These devices employ various designs to obtain a high fine mesh density at the interface between the aneurysm neck and parent vessel. This configuration facilitates the alteration of the inflow and outflow, much like a flow diverting stent, while limiting metal along the parent vessel(s) and not placing intraluminal metal, as needed in for Y-stent assisted coiling. The intra-aneurysmal position of the device does not require dual-antiplatelet therapy, as intra-luminal stents presently require. A lack of dual-antiplatelet therapy can be a significant advantage to intra-saccular devices, particularly in the setting of subarachnoid hemorrhage that may require ventriculostomy or other procedures. Another advantage to many of the intrasaccular devices over coils is preserved visualization within the aneurysm to assess contrast stasis and better evaluate for recurrence.

Presently, there are 3 intra-saccular flow disruption devices available worldwide.^11–13 Two are variations on self-expanding mesh balls, including the Woven EndoBridge (WEB ^® ) made by MicroVention (MicroVention, Inc, A Terumo Group Company, Aliso Viejo, California, USA) and the Artisse^™ Embolization Device (formerly known as the LUNA) made by Medtronic (Dublin, Ireland). The Contour Neurovascular System^™, made by Cerus Endovascular (Fremont, California, USA), is a mesh disk that nestles in the aneurysm covering the neck from the inside (Table 1, Figures 1 & 2).

Fig. 1.

Images of the Woven EndoBridge (WEB ^® ) made by MicroVention (A), the Contour Neurovascular System^™ made by Cerus Endovascular (B), and the Artisse^™ Embolization Device made by Medtronic (C).

Fig. 2.

(A) digital subtraction angiogram of a left middle cerebral artery aneurysm prior to treatment. (B) Unsubtracted cerebral angiogram following WEB placement. (C) Six-month follow-up angiography demonstrating complete aneurysm occlusion. (E) Digital subtraction angiogram of a left internal carotid artery terminus aneurysm prior to treatment. (B) Unsubtracted cerebral angiogram following Contour placement. (C) Six-month follow-up angiography demonstrating complete aneurysm occlusion.

Table 1.

Comparison of recently developed intra-saccular devices.

Device	Company	Sizes (mm)	Microcatheter Inner Diameter (Inches)	Detachment
WEB®	Microvention	3 × 2 to 11 × 9 (width by height)	0.017, 0.021, 0.027, 0.033	Electrolytic
Artisse™	Medtronic	4.5 to 8	0.021	Electrolytic
Contour™	Cerus Endovascular	2 to 8 neck	0.027	Electrolytic

Woven endoBridge (WEB^®)

The WEB ^® device is a single layer of between 114 and 216 nitinol/platinum wires braided together and bound at each end with a radiopaque platinum marker. On the walls of the device, the metal density is around 65% and increases to almost 100% at the binding end markers. With the proximal radiopaque marker at the neck of the aneurysm, the highest density overlies the neck of the aneurysm to disrupt flow and serves as a lattice for vessel healing at later stages. The device is afixed to a delivery wire and is electrolytically detached, much like many commercially available detachable coils. The nitinol of the braided wires gives the device the property of self-expansion to an intended size. For the cylindrical SL device, the sizes range from 3 mm x 2 mm (width by height) to 11 mm x 9 mm; for the more spherical SLS device, sizes range from 4 mm to 11 mm. Depending on the size of the device, they are delivered through 0.017 to 0.033-inch diameter VIA microcatheters (Microvention, Aliso Viejo, California, USA). The WEB ^® device is recommended to be oversized by adding 1–2 mm to the average width of the aneurysm in 2 dimensions to ensure adequate wall apposition, which is necessary for the WEB ^® to maintain its resistance to compressive forces of blood into the aneurysm. With the addition of a 1–2 millimeters to the width, a similar amount is recommended to be subtracted from the height of the aneurysm to adjust for the vertical growth of the device created by horizontal compression. Given the cylindrical and spherical shape of the WEB ^® , unilobular aneurysms with spherical, cylindrical, or ovoid shapes are best suited for this type of endosaccular treatment. However, multilobular WNBAs can also be treated with the WEB ^® device as long as adequate seal can be formed at the aneurysm neck by placing the device into the primary lobe, which would then induce thrombosis of secondary lobes. ¹⁴

Three European studies, the WEBCAST I & II and the “French Observatory study,” were the first large prospective series demonstrating the technical feasibility and occlusion outcomes of the WEB ^® device (Table 2).^15–19 They found complete aneurysm occlusion in 51.7–54% of patients, and residual neck filling in 26.0–27.6%. Together, this resulted in a total adequate occlusion rate of 79.3–85.4% between 6–12 months on follow-up angiography. These studies also showed a favorable safety profile with follow-up morbidity (modified Rankin Scale >1) rates from 0–4% and mortality rates between 0–3%. Importantly, the WEB ^® double-layer (DL) was replaced with the WEB ^® single-layer (SL) and single-layer sphere (SLS) midway through the “French Observatory study” enrollment; thus, while that study had all of the devices included, the first WEBCAST study included only the WEB ^® DL and WEBCAST II evaluated only WEB ^® SL and SLS. The 3-year follow-up for the WEBCAST I & II studies were published earlier this year and demonstrated adequate occlusion in 83.6%, a retreatment rate of 11.4%, and a nearly 10% rate of neck recurrence between years 1 and 3 in aneurysms that had previously been shown to be completely occluded. ²⁰

Table 2.

Recent WEB^® studies .

Study	Devices Used	Micro-catheters Used	TotalPatients	Unruptured	Successful Deployment	Occlusion	Residual Neck	Residual Dome	Morbidity (mRS >1)	Mortality
French Observatory Study18,19	WEB DL and SL/SLS	027 and 033	62	89%	98%	52%	28%	21%	0%	3%
WEBCAST 15	WEB DL		51	94%	94%	56%	29%	15%	2%	0%
WEBCAST II 16	WEB SL/SLS	021, 027, and 033	55	93%	96%	54%	26%	20%	4%	2%
WEB-IT 21	WEB DL and SL/SLS	021, 027, and 033	150	94%	99%	54%	31%	15%	1%	0%

Abbreviation: mRS = modified Rankin Scale.

The WEB-IT trial was a prospective, multi-center, core laboratory adjudicated, single arm study to evaluate the occlusion rates of WEB ^® treated aneurysms ²¹ (Table 2). Both ruptured (Hunt and Hess grade I and II) and unruptured, wide, or challenging neck bifurcation aneurysms were included, specifically those aneurysms at the basilar artery apex, middle cerebral artery, anterior communicating artery, and internal carotid artery terminus. One hundred and fifty patients were enrolled from 25 sites in the United States and 5 international sites. Primary endpoints included complete occlusion at 12 months, as well as no retreatment, recurrent subarachnoid hemorrhage, or significant parent artery stenosis greater than 50%. Primary safety endpoints included major stroke and all cause death through 30 days, as well as major ipsilateral stroke and neurological death at 12 months. The study demonstrated 53.8% complete occlusion and 84.6% adequate occlusion (including residual neck filling) at 1 year. ²² Eight patients were retreated within the 1-year study period, and an additional 6 patients were retreated 6 months thereafter, for a total 9.8% retreatment rate. One patient had parent artery stenosis that required stenting. There were no cases of recurrent subarachnoid hemorrhage. Only 1 primary safety event occurred (0.7%), which was a delayed ipsilateral intraparenchymal hemorrhage in a patient on postoperative day 22, and no deaths occurred during the study. These outcomes were similar to the previously published European studies. The safety profile of the WEB ^® is favorable compared to the published complication rates of other WNBA treatment modalities with major morbidity and mortality rates between 2.4–10% reported in large retrospective series of aneurysm stent-assisted coiling.^4,23–25 The long term follow-up data from the WEB-IT trial are expected to be published in the near future, which should shed additional light on the long term effectiveness of aneurysm occlusion with the WEB ^® device. Additional ongoing trials include the CLARYS study looking at WEB ^® treatment of ruptured aneurysms, the WEB-IT China study, and the CLEVER study evaluating the WEB ^® 17 devices.

Artisse^™ Embolization Device

The Artisse^™ Embolization Device (Medtronic, Dublin, Ireland) is a self-expanding, double-layered, braided mesh device that comes in 2 configurations: spheroid and flared, the latter of which is shaped like an acorn. ¹² The device is made of nitinol with platinum radio-opaque markers, ranges in diameter from 4.5–8.0 mm, is delivered through a 0.021 inch microcatheter, and is electrolytically detached. The largest clinical series (using its former name, LUNA) was conducted in Europe and published in 2018. ²⁶ Sixty-three patients were enrolled from 2011–2013. In contrast to the WEB ^® studies, nearly a quarter of the aneurysms in this study were side-wall aneurysms. There was a 95% successful deployment rate and a 78% adequate occlusion at 1-year follow-up. During the periprocedural and follow-up period, there were 2 major strokes (3.2%), 1 minor stroke (1.6%) and intracranial hemorrhages in 2 patients (3.2%). At 36-month follow-up, there was 1 mortality (1.6%).

Contour Neurovascular System^™

The Contour Neurovascular System^™ (Cerus Endovascular, Fremont, California, USA) is a another dual-layered mesh device. However, it is flat in its unconstrained form, akin to a mesh steamer basket. The device is deployed within an aneurysm and conforms to the aneurysm neck, forming a tulip shape. Another difference from the 2 prior devices is that the mesh itself is radio-opaque. The device is sized to treat aneurysm necks from 2 to 8 mm, delivered through an 0.027-inch microcatheter, and electrolytically detached. Two European single-center small case series have been published on the use of the device.^13,27 Of the 14 patients reported in these studies, 12 had one-year follow-up imaging, which demonstrated 7 (58%) aneurysms with complete occlusion, 4 (33%) with residual neck filling, and 1 (8%) with residual aneurysm filling attributed to a displaced device.^13,27 While there were no mortalities or major morbidities in these 2 studies, there were 3 minor strokes without lasting sequale.^13,27 The CERUS study, which began enrolling in 2018, will be prospectively evaluating the Contour device in 30 patients, and is yet to be completed.

Conclusion

WNBAs are challenging lesions to treat via both open surgical and endovascular techniques. A variety of intrasaccular endovascular devices have been developed in the past decade to address many of the limitations of prior methods of treatment. While our understanding of the long-term occlusion rates is being elucidated at various stages, the relatively good safety profiles and short-term success rates provide optimism for these innovative intrasaccular devices. A proposed multicenter randomized trail comparing intra-saccular flow disruption devices with best conventional management options (surgical or endovascular) would further help us understand the safety and efficacy profile of these intra-saccular devices in comparison to other available options. ²⁸