Citations

Background The extent, rate, and source of endothelialization following coil embolization of saccular aneurysms remains poorly understood. We performed a whole tissue mount, dual immunohistochemical analysis of experimental aneurysms to characterize the state of endothelialization over time after platinum coil embolization. Method and material Elastase-induced rabbit aneurysms were created and treated with bare platinum coils. Samples were harvested at 4 and 8 weeks (n=6 for each). En face whole tissue mount staining with antibodies to CD31 and α-smooth muscle actin was used to identify endothelial cells and smooth muscle cells, respectively. Sytox green stain was used to demonstrate nuclear morphology for identification of inflammatory cells. The extent of endothelialization was measured in relation to the aneurysm neck–parent artery interface. Results At 4 weeks after coil embolization, very localized membranous tissue and neoendothelial cells were detected on the coil loops immediately adjacent to the parent artery–neck interface, but the remainder of the coil loops remained devoid of endothelial cells. At 8 weeks neoendothelial cells were more confluent over the coils than at 4 weeks, and extended up to 900 µm from the parent artery–neck interface. However, the surfaces of the coils farther away than this region harbored no endothelial cells. Scattered inflammatory cells, including neutrophils and monocytes, were seen on the coil surface at the neck central area, where the coil surface was bare at the 4 and 8 weeks’ follow-up. Conclusions Platinum coil embolization supports gradual but limited endothelialization, where endothelial cells migrate directly from the adjacent parent artery.

Objective Several definitions have been proposed to distinguish the daughter sac when treating unruptured intracranial aneurysms. The aim of this study was to evaluate interobserver variability of aneurysm morphology, including the daughter sac, using criteria from the International Study of Unruptured Intracranial Aneurysms (ISUIA) and the Unruptured Cerebral Aneurysm Study of Japan (UCAS). Materials and methods After approval by the institutional review board, we analyzed three morphological features (daughter sac, lobulation, and irregular margin) from the ISUIA and UCAS using angiographic images from 102 saccular aneurysms. Four independent readers interpreted each morphological criterion using dichotomized scales (existence or not). The κ statistic was used to measure interobserver agreement, and κ>0.6 was considered substantial agreement. Results For discrimination of the daughter sac, interobserver agreement among the four readers was substantial using the UCAS criteria (k=0.626 for two-dimensional (2D) and 0.659 for three-dimensional (3D) images) but not for the ISUIA criteria (k=0.487 for 2D and 0.473 for 3D images; significant difference). Irrespective of the images used, pairwise pooled κ values for the UCAS were >0.6, except for one case (score of 0.54 between readers A and B). Regarding the proportion of positive reads, there was a significant difference between reads for the daughter sac using the UCAS and ISUIA criteria. Conclusions For discrimination of the daughter sac, the UCAS definition showed a higher reliability than the ISUIA. However, a further prospective study is necessary to validate this definition as the treatment standard for unruptured intracranial aneurysms.

OBJECT Tobacco smoking is one of the most important risk factors for the formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhages. Smoking has also been suggested to contribute to the recurrence of aneurysms after endovascular coiling. To improve the understanding of the impact of smoking on long-term outcomes after coil embolization of intracranial aneurysms, the authors studied a consecutive contemporary series of patients treated at their institution. The aims of this study were to determine whether smoking is an independent risk factor for aneurysm recurrence and retreatment after endovascular coiling. METHODS All patients who had received an intrasaccular coil embolization of an intracranial aneurysm, who had undergone a follow-up imaging exam at least 6 months later, and whose smoking history had been recorded from January 2005 through December 2012 were included in this study. Patients were stratified according to smoking status into 3 groups: 1) never a smoker, 2) current smoker (smoked at the time of treatment), and 3) former smoker (quit smoking before treatment). The 2 primary outcomes studied were aneurysm recurrence and aneurysm retreatment after treatment for endovascular aneurysms. Kruskal-Wallis and chi-square tests were used to test statistical significance of differences in the rates of aneurysm recurrence, retreatment, or of both among the 3 groups. A multivariate logistic regression analysis controlling for smoking status and for several characteristics of the aneurysm was also performed. RESULTS In total, 384 patients with a combined total of 411 aneurysms were included in this study. The aneurysm recurrence rate was not significantly associated with smoking: both former smokers (OR 1.00, 95% CI 0.61–1.65; p = 0.99) and current smokers (OR 0.58, 95% CI 0.31–1.09; p = 0.09) had odds of recurrence that were similar to those who were never smokers. Former smokers (OR 0.78, 95% CI 0.46–1.35; p = 0.38) had odds of retreatment similar to those of never smokers, and current smokers had a lower odds of undergoing retreatment (OR 0.44, 95% CI 0.21–0.91; p = 0.03) than never smokers. Moreover, an analysis adjusting for aneurysm rupture, diameter, and initial occlusion showed that former smokers (OR 0.65, 95% CI 0.33–1.28; p = 0.21) and current smokers (OR 1.04, 95% CI 0.60–1.81; p = 0.88) had odds of aneurysm recurrence similar to those who were never smokers. Adjusting the analysis for aneurysm rupture, diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23–1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46–1.46; p = 0.50) had odds of retreatment similar to those of patients who were never smokers. CONCLUSIONS The results show that smoking was not an independent risk factor for aneurysm recurrence and aneurysm retreatment among patients receiving endovascular treatment for intracranial aneurysms at the authors' institution. Nonetheless, patients with intracranial aneurysms should continue to be counseled about the risks of tobacco smoking.

Background and purpose Mechanisms of both healing and complications, including spontaneous aneurysm rupture, remain unclear following flow diverter treatment. The aim of this study was to compare gene expression of various key molecules involved in the healing of aneurysms, between aneurysms treated with microcoils and flow diverters. Methods Saccular aneurysms were created in rabbits. Aneurysms were treated with coils (n=6) or flow diverters (n=6). Aneurysms were harvested at 4 weeks following treatment and used for gene expression and zymography experiments. Genes with a fold change of 1.2 or more were considered upregulated whereas those with a fold change of 0.8 or less were considered downregulated. Results All coil embolized aneurysms were completely occluded at follow-up. Two aneurysms were occluded and the remaining four samples were incompletely occluded in the flow diverter treated group. The following genes were expressed at lower levels in the flow diverter group compared with the coiled aneurysm group: proteinases (matrix metalloproteinases 2 and 9), cellular markers (endothelial nitric oxide synthase and smooth muscle actin), and structural proteins (collagens and fibronectin). Genes related to inflammation (tumor necrosis factor α and monocyte chemoattractant protein 1) were upregulated in flow diverter treated aneurysms compared with coil embolized aneurysms. Notably, the enzymatic activity of active matrix metalloproteinase 9 was high in aneurysms treated with flow diverters. Conclusions Our findings may provide improved understanding of rupture risk and healing following aneurysm treatment and inform development of therapies aimed at lowering rupture risk and accelerating healing.

Background and Purpose— Clinical equipoise of carotid revascularization therapies remains controversial. We sought to determine whether adverse outcomes after carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS) were similar using propensity score–matched analysis of retrospective data from a large hospital discharge database. Methods— All CEA and CAS cases were identified from the 2006 to 2011 Premier Perspective Database and subjected to 1:1 propensity score matching using 33 clinical covariates associated with carotid revascularization. A primary composite end point of peri- or postoperative mortality, stroke, or acute myocardial infarction and a modified composite end point excluding acute myocardial infarction were used to compare our findings with recent prospective controlled trials. Multivariate regression and Cox-proportional hazard ratio survival analysis were performed to compare revascularization therapy outcomes. Results— After 1:1 propensity score matching, 24 004 (12 002 CEA and CAS) asymptomatic and 3506 (1753 CEA and CAS) symptomatic procedures were included. The risk of the primary composite end point was significantly higher after CAS than CEA in both asymptomatic (odds ratio, 1.40 [1.19–1.65]; P <0.0001) and symptomatic (odds ratio=2.31 [1.78–3.00]; P <0.0001) presentations, irrespective of age ( P =0.28) or sex ( P =0.35). Similar findings were observed using the modified composite end point for both asymptomatic (odds ratio, 1.49 [1.25–1.78]; P <0.0001) and symptomatic (odds ratio, 3.02 [2.25–4.07]; P <0.0001) presentations. Acute myocardial infarction risk was not significantly different between revascularization therapies, regardless of clinical presentation ( P =0.71 and 0.24). Conclusions— Among individuals undergoing carotid artery revascularization from a large sample of US hospitals, CAS was associated with higher risk of perioperative mortality, stroke, and unfavorable discharges compared with CEA for all ages and clinical presentations.

Object Flow diversion has emerged as a promising treatment alternative for cerebral aneurysms. As a new device, treatment-related events and complications are currently being characterized. Methods Data on 100 consecutive procedures with the intention to use flow diversion were prospectively collected and analyzed retrospectively. Results Ninety-five aneurysms were treated in 93 patients during 100 consecutive procedures in which the intention was to treat an intracranial aneurysm with flow diversion. Death occurred in 1% and permanent morbidity in 1%. However, periprocedural technical complications occurred in 35% of the procedures and included proximal device migration in 12%, incomplete device expansion in 9%, catheter-induced vasospasm in 6%, and artery perforation from the wire in 3%. Perioperative clinical events were seen in 28% (thromboembolism and access site complications were the most common, being observed in 6.5% of patients). Worsened extraocular motility was seen in 5.4% and resolved in 4/5 patients. Mean clinical follow-up was 17 months. There were no late clinical or technical issues resulting in permanent deficits, although one patient suffered worsening ataxia. Overall, using very strict angiographic criteria, complete angiographic obliteration was 50% at 6 months and 69% after 1 year. Conclusions Flow diversion for intracranial aneurysms is a safe and effective treatment. Technical and clinical events are common in the perioperative period. Careful perioperative care and proper management of technical and clinical events encountered is key to achieving low morbidity and mortality. Late clinical events can occur but are unlikely to result in permanent complications.

SUMMARYUnderstanding the flow alteration in side branches during flow diversion treatment of cerebral aneurysms is important to prevent ischemic complications and improve device designs. Flow diverters were placed in the aorta of four rabbits crossing the origin of side arteries. Subject‐specific computational models were constructed from 3D angiographies and Doppler ultrasounds (DUSs). Flow simulations were run before and after virtually deploying the flow diverters, assuming distal resistances remained unchanged after treatment. All jailed arteries remained patent angiographically 8 weeks after treatment. The computational models estimated decreases compared to pretreatment in the mean flow rates between 2% and 20% and in peak flow rates between 5% and 36%. The major changes were observed during systole. Flow patterns did not exhibit recirculation zones before treatment. Implantation of the flow diverters altered the flow structure only locally near the device wires. No major recirculation regions were created or destroyed. Flow diverters seem safe with respect to perforator or side branch occlusion. Relatively small changes in flow rates through jailed arteries are expected, even for moderate to large degrees of coverage of their origins. These results seem consistent with previous clinical experiences where no or very few complications related to perforator occlusion have been reported.Copyright © 2014 John Wiley & Sons, Ltd.

SUMMARY Quantification and characterization of the hemodynamic environment created after flow diversion treatment of cerebral aneurysms is important to understand the effects of flow diverters and their interactions with the biology of the aneurysm wall and the thrombosis process that takes place subsequently. This paper describes the construction of multi‐modality image‐based subject‐specific CFD models of experimentally created aneurysms in rabbits and subsequently treated with flow diverters. Briefly, anatomical models were constructed from 3D rotational angiography images, flow conditions were derived from Doppler ultrasound measurements, stent models were created and virtually deployed, and the results were compared with in vivo digital subtraction angiography and Doppler ultrasound images. The models were capable of reproducing in vivo observations, including velocity waveforms measured in the parent artery, peak velocity values measured in the aneurysm, and flow structures observed with digital subtraction angiography before and after deployment of flow diverters. The results indicate that regions of aneurysm occlusion after flow diversion coincide with slow and smooth flow patterns, whereas regions still permeable at the time of animal sacrifice were observed in parts of the aneurysm exposed to larger flow activity, that is, higher velocities, more swirling, and more complex flow structures. Copyright © 2014 John Wiley & Sons, Ltd.

Background Expansion of the endovascular and surgical workforce in the USA might lead to carotid revascularization procedures being carried out at low volume centers. Objective To evaluate trends in the treatment of carotid stenosis at high volume centers in the USA and compare outcomes by hospital volume. Methods Using the Nationwide Inpatient Sample, we evaluated trends in the proportion of carotid revascularization procedures performed at high volume centers in the USA from 2005 to 2011. High volume was defined as combined endarterectomy/stenting volume ≥130 patients/year, carotid endarterectomy volume ≥117 cases/year and carotid stenting volume ≥38 cases/year. In-hospital mortality, discharge to a long-term facility, intracranial hemorrhage, and postoperative stroke rates were compared between high and low volume centers. Results A total of 181 972 patients were included in this study. Overall, 63 442 patients (34.9%) were treated at high volume centers. The proportion of patients treated at high volume carotid revascularization centers decreased from 38.3% in 2005–2006 to 30.2% in 2010–2011. The proportion of patients treated at high volume centers decreased from 35.7% to 30.0% for carotid endarterectomy (p<0.0001) and 45.2% to 35.1% for carotid stenting. Patients treated at low volume centers had significantly higher rates of discharge to a long-term facility than high volume center patients (6.3% vs 5.0%, p<0.0001). The same was true for endarterectomy patients (6.0% vs 4.7%, p<0.0001) and stenting patients (8.3% vs 6.5%, p<0.0001). Conclusions A trend toward a lower proportion of patients with carotid stenosis being treated in high volume centers from 2005 to 2011 is concerning as these high volume centers had lower complication rates.

Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. In-vitro studies have demonstrated a correlation between the magnitude and distribution of wall shear stress (WSS) and biological response of both endothelial cells and smooth muscle cells [1–3]. In elastase induced saccular aneurysms, low WSS (below 0.5 Pa) was found to have a correlation with altered expression of biological markers [4]. Localized regions of rapid aneurysm growth in-vivo have been shown to be associated with regions where WSS is below a critical value of 0.1 Pa [5]. Further, aspect ratio (AR), the ratio of the maximum diameter of the aneurysm to the width of the aneurysm neck, has been correlated with elevated risk of rupture [6]. The purpose of the current study is to explore the possibility of creating elastase induced aneurysms in rabbits with a range of aspect ratios (ratio of aneurysm height/neck) and evaluate the existence of a correlation between aspect ratio and WSS distribution. Aneurysms with ARs from 0.98 to 2.8 were created at the origin of the right common carotid artery (n = 30). Qualitative differences in WSS distribution were found in the high AR aneurysms (HARA) (AR>1.6) and low AR aneurysms (LARA) (AR<1.6) [7].