Article Text
Abstract
Background Stent-assisted coiling is commonly used to treat wide-necked and fusiform cerebral aneurysms. We evaluated our institutional experience with stent-assisted coiling of cerebral aneurysms to elucidate potential risk factors for recurrence.
Methods A retrospective analysis of patients undergoing stent-assisted coiling of cerebral aneurysms from 2005 to 2012 resulted in 122 patients with 122 aneurysms. Demographic, peri-procedural, medical comorbidity, and follow-up data were collected. Primary outcomes of interest were procedural safety, efficacy, and aneurysm recurrence. Univariate and multivariate logistic regression and χ2 tests determined the statistical significance of the risk factors.
Results All 122 stent-assisted coiling procedures led to satisfactory obliteration of the aneurysm (3.3% complication rate). Twenty-one (17.2%) patients experienced recurrence at average follow-up of 297 days. Fifteen (71.4%) clinically significant recurrences required retreatment. Eleven of 30 (36.7%) procedures using Enterprise stents had recurrence compared with only 10 of 92 (10.9%) procedures using Neuroform stents (p=0.001). Average coiling packing density (PD) was 20.3% with Enterprise stents and 22.5% with Neuroform stents (p=0.8). In multivariate logistic regression, recurrences requiring recoiling were significantly associated with Enterprise stents (OR 8.57, 95% CI 1.97 to 37.19; p=0.004), females (OR 0.19, 95% CI 0.04 to 1.00; p=0.05), and postoperative dextran use (OR 8.42, 95% CI 1.40 to 50.58; p=0.02). Aneurysms with <20% PD were more likely to have a clinically significant recurrence than aneurysms with >20% PD (19% vs 5.1%; p=0.02).
Conclusions Stent-assisted coiling for wide-necked cerebral aneurysms has a high therapeutic success rate with low procedure-related morbidity and mortality. Clinically significant recurrences may occur more frequently with Enterprise stents, in aneurysms with low PD, and with post-procedural dextran use.
- Aneurysm
- Coil
- Endoscopy
- Stent
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Introduction
Stent-assisted coiling is a common endovascular technique used to treat wide-necked and fusiform cerebral aneurysms.1 ,2 Stenting allows improved coil packing and maintains vessel patency by preventing herniation of coils into the parent vessel.3 ,4 In addition, the metal surface across the aneurysm neck provides scaffolding for endothelialization, thus encouraging permanent aneurysmal healing.5–7 Stent-assisted coiling provides high rates of complete occlusion and low rates of recurrence, sustaining its role as a mainstay in the therapy of wide-necked intracranial aneurysms.8
However, the available literature is controversial regarding risk factors for recurrence following stent-assisted coiling. Some studies argue that, while recurrence rates may be lower with stent-assisted coiling than with coiling without stents, the technical difficulty of the procedure increases the complication rate or makes the complications that do occur more serious. Other studies suggest that complication rates are within acceptable limits and that stent-assisted coiling for wide-necked and fusiform cerebral aneurysms is the preferred method of treatment. The purpose of this study was to evaluate our institutional experience with stent-assisted coiling of intracranial aneurysms and to identify predictors of recurrence including differences in clinical and radiographic outcomes between patients undergoing Neuroform (Stryker, Kalamazoo, Michigan, USA) versus Enterprise (Johnson & Johnson, New Brunswick, New Jersey, USA) stent placement.
Methods
Study design
We performed a retrospective analysis via medical record review of patients undergoing stent-assisted coiling of cerebral aneurysms at our institution. This study was approved by our local Institutional Review Board.
Patient selection
All patients who underwent stent-assisted coiling for the treatment of cerebral aneurysms for the period 1 January 2005 to 10 January 2012 at our institution, with Current Procedural Terminology (CPT) codes 61624, 61626, 61635, 37215, and 37216, were included in this study. Four patients treated with the Pipeline device (Medtronic, Dublin, Republic of Ireland) or Wallstents (Boston Scientific, Marlborough, Massachusetts, USA) were excluded from the study. Patients with <6 months of clinical follow-up were also excluded.
Clinical data
Demographic and clinical data included age, sex, obesity (body mass index >30), history of diabetes, hypercoagulable state, history of coronary artery disease, and active tobacco use. Peri-procedural data included aneurysm location, aneurysm neck size (mm), aneurysm volume (mm3), coil packing density (PD; %), type of stent used (Enterprise vs Neuroform), intraoperative rupture, postoperative dextran use, postoperative CNS bleed, aneurysmal recurrence, and treatment for recurrence. These data were obtained from review of the comprehensive inpatient and outpatient medical records and correlated with imaging including digital subtraction angiography, CT angiography (CTA), and both two-dimensional (2D) and three-dimensional (3D) magnetic resonance angiography (MRA). Neurological complications were considered in this study. Recurrences were determined by angiographic imaging during follow-up appointments. PD was determined by dividing coiling volume by aneurysm volume. Coiling volume and aneurysm volume were calculated using AngioCalc (http://www.angiocalc.com). Aneurysm volume was assessed using diagnostic angiography reports as well as CTA and both 2D and 3D MRA imaging. PD was classified as either low PD or high PD, according to previous studies that reported a clinical difference at 20% PD. Thus, low PD is <20% and high PD is ≥20%.1
Surgical procedure
All patients undergoing elective stent-assisted coil embolization were pretreated with dual antiplatelet agents (aspirin (ASA) and clopidogrel) for 1 week. Beginning in 2007, platelet inhibition was assessed with the VerifyNow (VN) ASA and VN P2Y12 assays (Accumetrics, San Diego, California, USA) in ASA reaction units and P2Y12 reaction units (PRU). Patients were considered responsive if ASA reaction units were ≤550 and PRU ≤237. Therapeutic platelet inhibition with both aspirin and clopidogrel was confirmed either the day before or the day of the intervention. Non-responders were placed on ticlopidine, prasugrel, or ticagrelor, depending on surgeon preference. Stent selection was based on operator preference as well as configuration of the parent vessel and more proximal vascular anatomy. In cases with a narrow landing zone or a tortuous parent vessel, the Neuroform stent was given preference secondary to its segmental deployment, which allows for immediate apposition of the stent along the vessel wall providing for an overall more stable deployment. In cases with significant proximal tortuosity in which stent deployment was expected to be challenging, the Enterprise stent was favored secondary to its re-sheathability.
Percutaneous retrograde common femoral artery access was obtained using ultrasound guidance and a modified Seldinger technique with a 4 Fr micropuncture kit (Cook Medical, Bloomington, Indiana, USA). Patients were heparinized based on body weight (60–100 IU/kg) to maintain an activated clotting time between 250 and 300 s. Following arterial access and 6 Fr sheath placement, a guide catheter was placed into the ipsilateral distal cervical carotid artery (anterior circulation aneurysm) or the distal V2 segment of the vertebral artery (posterior circulation aneurysm). A stent-specific microcatheter was then used to catheterize the parent vessel distal to the aneurysm. If a jailing technique was to be used, a second microcatheter was advanced through the guide catheter in parallel and used to catheterize the aneurysm. A coil was partially deployed through the second microcatheter. The stent was then deployed across the aneurysm neck and the aneurysm was coiled through the jailed microcatheter until satisfactory occlusion of the aneurysm was achieved (Raymond-Roy class I or II). If jailing was not used, the stent was deployed in the parent vessel across the aneurysm neck and the microcatheter was removed. An Sl-10 microcatheter (Stryker Neurovascular, Fremont, California, USA) and a synchro 14 wire (Stryker Neurovascular) were then used to cross the stent tines into the aneurysm sac. The aneurysm was then coiled until Raymond-Roy class I or II occlusion was achieved.
Perioperative care
Patients were monitored in the neurosurgical intensive care unit for 24 hours post-procedure. In some cases, postoperative care included heparin infusion intravenously at 500 units/hour and/or dextran-40 infusion intravenously at 25 mL/hour, depending on surgeon preference.9 Patients were maintained on dual antiplatelet therapy for 3–6 months, after which clopidogrel was discontinued. Aspirin therapy was maintained indefinitely. All patients underwent cerebral angiography to evaluate aneurysm stability and evidence of recurrence 6 months post-coiling. If no recurrence was documented, the patient was followed with contrast-enhanced MRI of the brain and MRA of the circle of Willis at 12 and 24 months.
Follow-up
Aneurysm filling was graded using the Raymond-Roy classification.10 Class I aneurysms were those that remained completely occluded, class II aneurysms were those that had residual contrast filling at the aneurysm neck, and class III aneurysms were those that had residual contrast filling centrally within the coil mass beyond the neck or along the aneurysm wall beyond the neck. Class III aneurysms were deemed clinically significant and were retreated. Class II aneurysms were watched with follow-up imaging.
Statistical analysis
Demographic data were compared between those patients with a recurrence and those without a recurrence using χ2, Fisher exact, or t-tests, depending on sample size and whether the variable was continuous or categorical. Univariate logistic regressions were performed with covariates in order to determine their relative contributions to recurrence status. All variables with p<0.20 were included in a multivariate logistic regression. We considered a two-sided p≤0.05 to be statistically significant. All data were analyzed using SPSS software (IBM SPSS Statistics for Windows, V.22.0, Armonk, New York, USA).
Results
Data for 122 patients who underwent stent-assisted coiling of their aneurysm was obtained (122 aneurysms in total). At the time of surgery all 122 aneurysms were coiled to satisfactory occlusion (Raymond-Roy class I or II). There were 97 women and 25 men with an average age of 57.2±11.0 years treated with stent-assisted coiling. Demographic data (table 1) demonstrated that female patients were less likely to have a recurrence of their aneurysm after stent-assisted coiling than male patients (57.1% vs 84.2%; p=0.01). Obesity, diabetes, hypertension, hypercoagulable state, history of coronary artery disease, and active smoking status did not demonstrate statistically significant differences between those patients who developed a recurrence and those without recurrence (table 1).
Peri-procedural data (table 2) demonstrated that aneurysms with a larger volume and neck size were associated with recurrences. The average aneurysm volume with recurrence was 812.8±946.9 mm3, compared with 365.2±918.5 mm3 without recurrence (p=0.05). The average neck size for an aneurysm with recurrence was 5.9±1.5 mm compared with 4.8±2.3 mm without recurrence (p=0.04). In 30 (24.6%) procedures Enterprise stents were used, while Neuroform stents were used in the remaining 92 (75.4%) procedures. Eleven of the 30 (36.7%) procedures that used Enterprise stents had a recurrence compared with only 10 of the 92 (10.9%) procedures that used Neuroform stents (p=0.001). Emergent or elective procedure, location of the aneurysm (anterior or posterior circulation), aneurysm PD, and postoperative dextran use were not significantly different in patients with a recurrence and those without recurrence (table 2).
One (0.8%) of the 122 patients experienced an intraoperative rupture, in another patient (0.8%) the treatment was complicated by an intracranial hemorrhage, and two (1.6%) patients developed embolic events following stent-assisted coiling. There were therefore a total of four (3.3%) procedure-related complications in the patient population. Two complications occurred with Enterprise stents (2/30; 6.7%) and two occurred with Neuroform stents (2/92; 2.2%). There were no statistically significant differences in these groups (p=0.25).
Twenty-one (17.2%) of the 122 treated patients experienced recurrence at an average follow-up of 297 days. Univariate analysis was performed to determine the significance of covariates. Age, female sex, elective procedures, aneurysm volume, aneurysm neck size, PD, use of Enterprise stents, and administration of postoperative dextran all had a p value <0.20 and were subsequently used in the multivariate analysis. Of these variables, female sex (p=0.01) and the use of Enterprise stents (p=0.002) were significantly related to recurrence. Multivariate logistic regression demonstrated that Enterprise stents (OR 5.81, 95% CI 1.73 to 19.57; p=0.004) and female sex (OR 0.25, 95% CI 0.07 to 0.90; p=0.03) were significantly associated with recurrence.
Fifteen (71.4%) of the 21 recurrences were determined to be clinically significant (Raymond-Roy class III), requiring retreatment. A similar univariate analysis was performed (table 3). Age, female sex, obesity, history of diabetes, elective procedures, aneurysm neck size, PD, use of Enterprise stents, and administration of postoperative dextran all had p values <0.20. With these covariates, multivariate analysis demonstrated that recurrences requiring recoiling were significantly associated with Enterprise stents (OR 8.57, 95% CI 1.97 to 37.19; p=0.004), female sex (OR 0.19, 95% CI 0.04 to 1.00; p=0.05), and postoperative dextran use (OR 8.42, 95% CI 1.40 to 50.58; p=0.02).
PD was also assessed in this study (table 4). More patients with a comorbid hypercoagulable state tended to have low PD compared with high PD (20.6% vs 6.8%; p=0.03). In addition, only 5.1% of cases with high PD resulted in recurrences requiring retreatment compared with 19.0% of cases with low PD (p=0.02). There was no significant difference in the complication rate between high and low PD.
Discussion
Stent-assisted coiling is safe and effective in the treatment of wide-necked intracranial aneurysms. In this series we achieved satisfactory occlusion (Raymond-Roy class I or II) in 100% of our cases and had a low neurologic complication rate of 3.3%. Twenty-one (17.2%) of the 122 treated patients experienced recurrence at an average follow-up of 297 days. Multivariate logistic regression demonstrated that Enterprise stents and female sex were significantly associated with recurrence.
In this series there was a significant increase in recurrence rate in patients treated with the Enterprise stent, which is in contradiction to other series in the literature.2 ,11 Izar et al 11 described a higher success rate with Enterprise stents than with Neuroform stents (95.8% vs 82.3%), while King et al 2 reported an increased incidence of recanalization after use of Neuroform stents compared with Enterprise stents. There are several possible explanations for these findings. We found similar packing densities in both groups, so this was an unlikely contributor. In addition, the difference was not related to differences in aneurysm size between groups. Similarly, both the Enterprise and Neuroform stents are made of nitinol with approximately 5% metal coverage, so these factors are unlikely contributors to the differences we found. The most notable differences between the stent constructs is their cell structure (open vs closed). The Enterprise stent has a closed cell structure, which creates a more rigid longitudinal profile. This increased rigidity hinders apposition of the stent to the vessel wall, particularly in tortuous anatomy, potentiating the risk of endoleak.12 ,13 The rigid structure can also lead to kinking, making recrossing the stent for coiling very difficult.13 ,14
Another notable difference between the Enterprise and Neuroform stents is the parylene coating on the Enterprise stent. Parylene is a biologically inert polymer that provides a slick surface when it is applied to materials.15 The coating is applied to the Enterprise stent to prevent sticking in the microcatheter during deployment. Previous studies have hypothesized a potential role of the parylene coating in the increased risk of embolic complications with the Enterprise stent.16 However, we did not find a difference in the thromboembolic rate between patients undergoing stenting with Enterprise versus Neuroform stents. Nonetheless, it is conceivable that the coating could prevent stent endothelialization or could inhibit platelet aggregation on the coil mass, increasing the chance of recurrence. Further studies may help to elucidate the effects caused by the unique properties of the Enterprise stent in the aneurysm microenvironment.
Our analysis was notable for a statistically significant increase in recurrences requiring treatment in patients without high PD (<20%). Although some have questioned the importance of high PD, the general consensus that PD >20% decreases recurrence is supported by our findings.1 ,17–20 Each of these studies demonstrates that increasing the PD decreases the rate of recurrence. They each use slightly different cut-offs for PD, but all are consistent in the fact that recurrences of aneurysms are decreased as PD increases.
Finally, in our series the use of postoperative dextran correlated with clinically significant recurrences. Dextran is a mild antithrombotic agent that expands intravascular volume, promotes fibrinolysis, and inhibits platelet aggregation.21 Although the clinical effectiveness of dextran is the subject of some controversy, its use has been correlated with fewer thromboembolic complications in aneurysm coiling and in carotid endarterectomy.9 ,22 We hypothesize that the mildly antithrombotic effects of dextran may have inhibited thrombosis of the aneurysm sac in the immediate postoperative period, thus preventing permanent intra-aneurysmal healing. Our findings advocate the judicious use of post-procedural dextran, particularly in cases that are at increased risk of future recurrence (ie, those with low PD).
Our study is limited by its retrospective nature and relatively small number of patients. Furthermore, our analysis spanned several device iterations, thereby limiting generalizability of the results. Additionally, our cohort may be susceptible to an inherent selection bias, as the type of stent used was not chosen at random and was based on surgeon preference and specific anatomic and pathologic considerations. Despite these limitations, our findings are thought-provoking and warrant further exploration. Larger prospective randomized studies are needed to further corroborate our findings.
Conclusions
Stent-assisted coiling of wide-necked cerebral aneurysms has a high therapeutic success rate with low procedure-related morbidity and mortality. In our series, aneurysmal recurrence was more common in female patients and those treated with the Enterprise stent. Furthermore, cases with low PD or those in whom post-procedural dextran is used may have an increased risk of clinically significant recurrence.
References
Footnotes
Contributors All authors contributed to writing, data gathering, data analysis, manuscript review, and approval for submission.
Competing interests None declared.
Ethics approval Ethics approval was obtained from the University of Michigan Institutional Review Board.
Provenance and peer review Not commissioned; externally peer reviewed.