WHAT IS ALREADY KNOWN ON THIS TOPICHOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICYIntroduction

Endovascular aneurysm treatment has become the standard of care for certain anatomic locations and geometries.1 Limitations of coiling2 have been overcome by balloon3 and stent use.4 Flow-diverting techniques5–7 aim at fluid dynamic disruption of the aneurysm from the parent vessel.8 Intraluminal structures such as stents, and especially flow diverters, may cover the aneurysm orifice and also neighboring branches, potentially resulting in branch occlusion,9 and therefore require long-term antiplatelet medication.10

Recent data suggest that flow diversion at the neck, but inside the aneurysm,11–13 decreases the risk of branch occlusion and, potentially, the need for antiaggregation.14 One such device, the Contour Neurovascular System (Cerus Endovascular, Ltd), has recently been shown to have beneficial effectiveness and safety in an international study.15 Platinum coils as stand-alone treatment are known to have their limitations in large and wide-neck aneurysms with coil protrusion into the parent artery having been shown to induce a risk of thromboembolic complications.16 A strategy to overcome this limitation, introduced even before the widespread use of stent-assisted coiling first described in 2001 in vivo17 and in patients,18 followed by systematic reviews in wide-neck aneurysms,19 was an intrasaccular structure consisting of three overlapping circular struts (TriSpan) that was first placed at the level of the neck, then traversed with a second microcatheter used for coil packing, and finally, electrolytically detached. This treatment allowed for better packing near the neck and prevented protrusion of coils into the parent artery. However, it did not contribute to hemodynamic separation of the aneurysm due to its very limited metallic coverage.

With the introducion of the Neqstent coil-assisted flow diverter (NQS; Cerus Endovascular, Ltd) in 2018 and its approval under CE mark in 2020, a woven neck bridging device that exhibits flow-diverting properties, but can also be penetrated with a microcatheter for subsequent coiling (figure 1), has become available and has been described in some initial series.20 The aim of our study was to evaluate the safety and efficacy of the NQS in a multicenter trial of endovascular treatment of unruptured wide-neck bifurcation aneurysms.

Figure 1

Overview of the Neqstent coil-assisted flow diverter (NQS) for coil occlusion in a wide-necked bifurcation aneurysm. Dashed lines represent the aneurysm and the parent vessels. Left-to-right: The NQS is self-expanding at the level of the occlusion plane and traversed by a microguidewire and microcatheter. Finally, after removal of the guidewire, coils can be introduced into the aneurysm as needed and without a potential risk of protrusion through the mesh.

Methods

A single-arm, prospective, multicenter trial to evaluate procedural, short-term and mid-term safety and effectiveness of NQS in unruptured saccular wide-neck bifurcation aneurysms was conducted at six sites in Austria, Canada, Denmark, Germany, and Switzerland in accordance with the declaration of Helsinki, approved by the ethics committee of the University of Kiel and all local ethics committees. The trial has been registered at clinicaltrials.gov under NCT04187573.

Inclusion criteria: age 18–80, unruptured wide-neck aneurysm in anterior or posterior circulation, untreated or recurrent after treatment if the previously placed coils did not interfere with the opening of the device at the neck. Patients were selected by local principal investigators without interference from the sponsor.

Primary endpoints: Technical success, occlusion at 6 months, death or disabling stroke within 30 days/6 months. Secondary endpoints: Procedure time, number of deployment attempts, and re-treatment rate. Follow-up modified Rankin Scale (mRS) score and National Institutes of Health Stroke Scale score obtained at discharge, 1 month, and 6 months. Angiographic status at the end of the procedure and at 6 months. The images were evaluated by an independent core laboratory (Eppdata, Hamburg, Germany).

The NQS

The NQS is a circular, dual-layered structure of 48 drawn filled tube wires (figure 1), with one proximally located platinum marker at the detachment site. It is radiopaque and retrievable until electrolytically detached. On deployment through a microcatheter it adapts to the lower half of the aneurysm, covering the neck. Sizing is made to the aneurysm neck width only, disregarding aneurysm maximum width and height. NQS was available in 7, 9, and 11 mm diameters during the study.

Material and anticoagulation

All procedures were performed via a transfemoral approach. Long sheath or standard guiding catheters were used in combination with Rebar 27 (Medtronic Neurovascular, Irvine, California, USA) or Headway 27 microcatheters (Microvention/Terumo, Aliso Viejo, California, USA). The periprocedural use of heparin was at the discretion of the interventionalist; however, all procedures were performed under an initial bolus, typically 5000 units, followed by aliquots of 500 to 1000 units per hour. Antiaggregation is not mandatory with NQS, but all patients were receiving single antiplatelet therapy (APT), or even dual APT, at the time of treatment, which was discontinued between 6 weeks and 6 months.

Data collection

Each center collected an electronic patient file. Adverse events were recorded even if no treatment was needed and without clinical worsening. Image evaluation and its results were recorded using an integrated computerized system compliant with good clinical practice (Eppdata, Hamburg, Germany). Preoperative and postoperative, 6- and 12- month images were rated using the Raymond-Roy Scale21 and an adaptation of the Bicetre refined WEB Occlusion Scale.22 In addition, device stability was rated for the marker position, movement, migration, and tilting of the NQS.

Statistics

The statistical evaluation is purely descriptive, using mean and median values and was performed with SPSS version 28.0.1.

Results

Between January 2020 and November 2021, 38 patients were recruited at six centers in Austria, Canada, Denmark, Germany, and Switzerland, of whom 36 were treated with the study device. The mean patient age was 61.1±10.5 (median 61.5) years, 27/36 patients were female. Full patient demographics, baseline aneurysm and procedural characteristics are shown in table 1.

Table 1

Demographics: 36 patients

The procedures were performed on biplane angiosuites under general anesthesia via a transfemoral approach. Periprocedural medication was managed autonomously at each center and no antiplatelet pre-medication was required by the study protocol. However, all treatments were performed under heparinization and applying single or dual APT to allow for emergency stent deployment.

The per protocol (PP) analysis, including follow-up, was based on 36 complete datasets. Two patients in the intention-to-treat (ITT) group were not implanted with the study device. In one patient, the NQS could not be introduced because of anatomical issues during catheterization, in the other patient with a recurrent aneurysm, an implant from a previous treatment (WEB, Microvention, Aliso Viejo, USA) prevented opening and correct positioning of the NQS. Both patients were followed up to 1 month and disregarded from the PP analysis with respect to efficacy outcome.

Procedure

Technical success was achieved in 36/38 (94.7%). In 32/36 (88.9%) NQS was successfully implanted and detached at the first attempt, in 3/36 (8.3%), two attempts and in 1/36, three attempts were needed. The most common NQS sizes used were 7 and 9 mm.

Clinical outcome

The primary safety endpoint was met in 4/38 patients in the ITT group as there were two disabling strokes at postoperative days 19 and 106, respectively, one of which was unrelated to the treatment while the other was probably caused by treatment and possibly related to the study device. Both patients had ongoing symptoms at 6 months. Two more ischemic strokes occurred at 116 days and at 399 days (thus past the observation period) and were regarded as unrelated to treatment with the study device. Visible distal emboli in one patient were successfully removed with a stent retriever and by direct aspiration, and the patient showed no clinical correlate thereafter. One aneurysm rupture was possibly related to the use of the study device and resolved without any clinical sequelae, while another vessel perforation required decompression craniectomy but was distal to the aneurysm and unrelated to the study device. The primary safety outcome is thus 10.5% among ITT patients (table 2).

At 6 months 31/36 patients in the PP analysis had an mRS score of 0–2, 1/36 had an mRS score of 3, and 4/36 patients missed their 6-month follow-up visit due to COVID-19 restrictions or refused to come to the hospital. However, all four had an mRS score of 0 at discharge.

Efficacy

Independent core laboratory occlusion status evaluation at the end of the procedure and at 6 months used the Raymond-Roy Scale21 and the Bicetre refined WEB Occlusion Scale.22 Complete occlusion was reached in 26/36 patients, a neck remnant was seen in 2/36, a residual aneurysm with contrast inside the coils in 1/36 patient and contrast along the wall in 3/36, while 4/36 PP patients could not be followed up at 6 months. The detailed results are shown in table 3. A satisfactory occlusion (RR1 and 2) was seen in 9/36 immediately post-treatment (25%) which progressed to 31/36 (86.2%) at 6 months. Complete occlusion (RR1) was achieved in 80.6% at the last available angiogram (3/36 were post procedure only). One case of device movement led to a neck remnant at follow-up.

Table 3

Aneurysm occlusion

Discussion

Aneurysm coil occlusion is a proven treatment, but occasionally limited owing to geometrical properties of the aneurysm. Wide-neck aneurysms make effective occlusion in the neck plane challenging and have an increased risk of coil protrusion into the parent artery, potentially resulting in thromboembolism.16 Filling the aneurysm cavity with coils to induce thrombus formation, on the one hand, has been applied for decades with success. To overcome the limitations of coiling in wide-neck aneurysms, stent-assisted coiling was introduced in 2000 and has since been linked to increased packing density and thus, a lower recurrence rate, but also to a higher rate of severe complications23 24—one potential downside being the need for long-term APT. This has been a matter of debate especially in the treatment of ruptured aneurysms.25

Flow diversion and flow disruption, on the other hand, have more recently been applied to aneurysm treatment since the advent of braiding technology. Stent-type flow diverters can achieve high long-term occlusion rates,26 exceeding 90%.27 However, they may result in parent artery luminal reduction, thromboembolism,28 or branch occlusion7 29 and typically mandate long-term APT.10 Insufficient damping of the pulse pressure wave may result in rupture before thrombosis or neointima formation—a limitation in ruptured aneurysms.29 Therefore, in very large and symptomatic aneurysms, flow diverter use in conjunction with coils has been advocated.30

Intra-aneurysmal flow diverters aim to create an equivalent border at the level of the neck, but from the sac and with no implant in the parent artery. So far, three different intrasaccular devices have been introduced into the field: WEB, LUNA/AED, and Contour. Existing evidence is very good for WEB with several good clinical practice studies,11–13 and for Contour,15 31 32 which has recently also been described in combination with coils in a single-center experience from 15 aneurysm treatments (10 ruptured) with both Contour and NQS, following a concept termed ‘intrasaccular flow disruptor-assisted coiling’.20 The authors conclude that this approach is valuable, especially in the ruptured cases, in part because it does not mandate antiplatelet medication. This reflects the general concept that also led to development of the NQS, which is not dissimilar from the TriSpan coil.17–19 TriSpan is no longer commercially available, but it too provided a barrier to prevent coil protrusion below the level of the neck, which remains controlled by the operator until deliberate detachment and that can be crossed with a microcatheter. The density of the mesh of the NQS differs from that of TriSpan, but does also give it the potential to obtain, or at least to enhance, hemodynamic separation of the aneurysm sac and the parent artery. This may make it superior in obtaining long-term occlusion, in comparison with a less dense structure like TriSpan, a laser cut stent, and most braided stents. Indeed, some of the aneurysms treated in this study have shown complete absence of contrast filling or significant stagnation after just placing the NQS and prior to coil delivery (figure 2).

Another finding that underscores the potential for the NQS acting as a sufficient flow disruptor is that the percentage of complete occlusion without residual flow progressed from 22.2% at the end of the procedure to 80.6% at follow-up. This would be a rare finding both with stand-alone coiling and stent-assisted coiling but was seen with stent-type flow diverters26 and the Contour15 in previous studies. In the CERUS study, 50% of aneurysms that showed residual filling at 6 months progressed to complete occlusion at 12 months.15 Even if the concept of flow disruption and coils can technically also be followed with the use of Contour, which exhibits a more pronounced effect on intrasaccular flow due to a higher mesh density, the ability to cross the NQS with the catheter and to introduce coils within the cavity of the mesh without having to the jail the microcatheter might potentially have some advantages—particularly with regard to the achievable packing density and also to treatment flexibility. With Contour, once a secure microcatheter position beyond the implant is lost during treatment, it might be difficult or even impossible to re-enter a partially coiled aneurysm, whereas the NQS can be reselected through the mesh. These differences and their impact on treatment success remain to be shown once both implants are used on a larger scale, making a comparison more justified.

The results of our series emphasize the potential hybrid position of the NQS between stent-assisted coiling and flow diversion, but without a need for long-term APT. The fact that all patients in the study were receiving APT is due to the limited experience with this new implant, aiming at a potential requirement for alternative or additional stent use.

Figure 2

Neqstent coil-assisted flow diverter (NQS) introduced into a paraophthalmic artery aneurysm. When brought to the level of the neck, complete hemodynamic separation was seen as contrast filling ceased (second), the NQS was then traversed with an.017” microcatheter (third) and additional coils were placed inside the aneurysm (right). At follow-up, stable occlusion was seen (fourth); The proximal aneurysm had been coiled.

The rate of adverse events that could potentially be attributed to use of the NQS reached 10.5% in our series. This figure is lower than that previously reported for the treatment of wide-neck aneurysms overall,33 but considerably higher than in the most recent studies on WEB 17, especially in the WEB-IT trial with less than 1% of patients meeting the safety endpoint.13 We hope that this difference is a result of the small sample size, but this remains to be proved in future trials or larger registries and case series.

Limitations

The main limitations are the sample size, non-randomization and that patients were not excluded because of previous treatment of the aneurysm. This is, however, a realistic scenario for the future use of NQS, and previously coiled recurrences might benefit from this technology. At least one patient could not be treated with the study device, because a previously placed WEB interfered with the opening of the NQS. Furthermore, there was no case selection, which, on the one hand, represents a realistic scenario and, on the other, might make these results reproducible outside a study.

Conclusion

We conducted the first multicenter trial on NQS for intracranial wide-neck bifurcation aneurysms at centers in Europe and Canada. The results of this study, when viewed in the light of the existing literature showed an acceptable safety record for the NQS, comparable to, or better than, for stent-assisted coil occlusion, but worse than the latest results with WEB. Four patients in the ITT group met the safety endpoint but only one of the serious adverse events was possibly attributable to the study device. Of the four adverse events that could be attributed to the study device, three were thromboembolic, one hemorrhagic. Three of those patients had recovered or were not symptomatic in the first place. Thus, procedural and long-term safety of the NQS will need to be determined with experience from larger series in the future. The core laboratory results of the last available follow-ups/at 6 months were 86.2%/77.8% adequate and 80.6%/72.2% complete occlusion and compared favorably with previous series of wide-neck bifurcation aneurysms, both surgically and endovascular.33 These results encourage the conduct of further trials with the aim of allocating this new instrument to the correct place within the existing technologies for aneurysm treatment.

Data availability statement

Data are available upon reasonable request. All data are kept on file and will be made available upon request.

Ethics statementsPatient consent for publication

Not applicable.

Ethics approval

This study involves human participants and was approved by the ethics committee of the University of Kiel, UKSH, Kiel, Germany. The ID is A 112/19 (EC of CAU). Participants gave informed consent to participate in the study before taking part.