Citations

Background Left ventricular assist devices (LVADs) are used as definitive therapy or as a bridge to heart transplant in patients with advanced heart failure. Thromboembolic complications such as acute ischemic stroke (AIS) are common among patients with LVAD support. This study aims to evaluate the current evidence on the efficacy and safety of mechanical thrombectomy (MT) in patients with AIS due to large vessel occlusions (LVO) and LVAD-support. Methods A comprehensive systematic review was conducted in PubMed, Embase, and Scopus to find observational studies with reports of ≥5 MTs in adult patients with LVAD support (PROSPERO registration code CRD42024597541). Rates of successful and complete reperfusion, favorable functional outcomes at 90 days (modified Rankin Scale (mRS) 0–2 or equal to pre-stroke mRS), mortality at 90 days, any intracerebral hemorrhage (ICH) and symptomatic ICH (sICH) were pooled using generalized linear mixed models. Results Eight studies were included with data from 51 patients and 62 MTs. The rate of successful reperfusion was 87.4% (95% CI 62.5% to 96.6%) and complete reperfusion rate was 57.3% (95% CI 35.1% to 76.9%). Rate of favorable functional recovery was 62.5% (95% CI 42.2% to 79.2%). Rate of sICH was 6.4% (95% CI 0.9% to 34.0%). Mortality rate was 16.7% (95% CI 7.1% to 34.7%). Between 25–40% of patients who were waiting for a heart transplant before their stroke received a heart transplant after MT. Conclusions MT for the emergent treatment of AIS in the setting of LVAD is relatively safe and efficacious for achieving successful reperfusion and good functional recovery.

Background The impact of certain comorbidities on mechanical thrombectomy (MT) outcomes remains largely unexplored. Diabetes mellitus (DM) and admission hyperglycemia have been associated with poor clinical outcomes for patients treated with MT. In this study, we sought to investigate the effects of DM and admission hyperglycemia on MT outcomes. Methods Following PRISMA guidelines, a systematic literature search was conducted in Medline, Embase, Scopus, and Web of Science databases. Data regarding successful recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] ≥2b), functional independence (modified Rankin Scale [mRS] 0–2), excellent outcomes (mRS 0–1), symptomatic intracranial hemorrhage (sICH), and mortality were extracted from the included studies. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated using random effects model. Results Twenty-one studies comprising 9708 patients were included. A total of 2311 patients (24%) had a history of DM, and 2026 patients (21%) had admission hyperglycemia. Admission hyperglycemia was associated with significantly lower odds of mTICI ≥2b (OR = 0.7, 95% CI = 0.55–0.89), mRS 0–2 (OR = 0.47, 95% CI = 0.41–0.53), and mRS 0–1 (OR = 0.43, 95% CI = 0.34–0.55) as compared to normoglycemic state. Patients with hyperglycemia had significantly higher rates of sICH (OR = 2.05, 95% CI = 1.66–2.54) and mortality (OR = 1.99, 95% CI = 1.58–2.52) than normoglycemic patients. Diabetes mellitus was associated with significantly high rates of mortality (OR = 1.74, 95% CI = 1.31–2.3) and lower rates of mRS 0–2 (OR = 0.60, 95% CI = 0.48–0.76) in sensitivity analyses. Conclusion Our results indicate that admission blood glucose levels and DM can negatively affect MT outcomes. Further research should focus on optimizing MT outcomes for these patients.

Background: Symptomatic intracranial hemorrhage (sICH) is the most dreaded complication after reperfusion therapy for acute ischemic stroke. We performed a meta-analysis of randomized controlled trials to estimate and compare risks of sICH after mechanical thrombectomy (MT) depending on the location of the large vessel occlusion, concomitant use of intravenous thrombolysis, timing of treatment, and core size. Methods: Randomized controlled trials were included, following a comprehensive search of different databases from inception to 1 March 2024. Random-effect models in a meta-analysis were employed to obtain the pooled risk ratios (RRs) and their corresponding 95% confidence intervals (95% CI) for sICH with MT, and were then compared to other reperfusion treatment regimens, including best medical treatment and intravenous thrombolysis (IVT). Results: MT in the anterior circulation was associated with a significantly higher risk of sICH as compared with no-MT (RR: 1.46; 95%CI: 1.03–2.07; p = 0.037). The risk of sICH was comparable between the MT and MT+IVT groups (RR: 0.77; 95%CI: 0.57–1.03; p = 0.079). There was no difference in sICH risk with MT as compared with no-MT within 6 h of last known well (RR: 1.14; 95%CI: 0.78–1.66; p = 0.485) and beyond that time (RR: 1.29; 95%CI: 0.80–2.08; p = 0.252); the risk of sICH was also comparable between MT conducted within 6 h of last known well and MT conducted beyond that time (p = 0.512). The sICH risk for MT in the posterior circulation (RR: 7.48; 95%CI: 2.27–24.61) was significantly higher than for MT in the anterior circulation (RR: 1.18; 95%CI: 0.90–1.56) (p = 0.003). MT was also associated with a significantly higher sICH risk than no-MT among patients with large core strokes (RR: 1.71; 95%CI: 1.09–2.66, p = 0.018). Conclusions: When evaluating cumulative evidence from randomized controlled trials, the risk of sICH is increased after MT compared with patients not treated with MT. Yet, the difference is largely driven by the greater risk of sICH in patients treated with MT for posterior circulation occlusions and, to a lesser degree, large core strokes. Concomitant use of intravenous thrombolysis and the use of MT in the extended therapeutic window do not raise the risk of sICH.

ABSTRACT As the number of cerebral aneurysms treated with flow diverters continues to increase, it is important to understand what factors influence not only thrombus formation within the aneurysm cavity but also fibrin accumulation across the device and its associated disruption and blockage of the inflow stream. Both processes contribute to the eventual occlusion of the aneurysm or its continued patency and incomplete occlusion which may require future re‐treatment. To investigate fibrin accumulation on flow diverters placed across the neck of cerebral aneurysms, a previously developed computational model that couples flow and fibrin dynamics is used in combination with experimental in vitro models of cerebral aneurysms treated with flow diverters. Fibrin accumulation was previously investigated in four glass models of cerebral aneurysms with varying parent artery geometries placed in a flow loop at different flow rates. Corresponding computational models were constructed and compared with the experimental findings. The computational model based on fibrin production stimulated from flow shear stress and subsequent adhesion to device wires was able to reproduce and explain the fibrin accumulation patterns observed in the experimental aneurysms treated with flow diverters. Specifically, these models indicated that increasing vessel curvature, flow rate, and thrombin concentration induced faster fibrin accumulation and associated aneurysm inflow disruption and blockage. The models described and tested in this paper are valuable to understand the detailed mechanisms leading to aneurysm occlusion and healing or incomplete occlusions after treatment with flow diverting devices.

Background As the use of flow diverters has expanded in recent years, predicting successful outcomes has become more challenging for certain aneurysms. Objective To provide neurointerventionalists with an understanding of the available machine learning algorithms for predicting the success of flow diverters in occluding aneurysms. Methods This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the four major medical databases (PubMed, Embase, Scopus, Web of Science) were screened. The study included original research articles that evaluated the predictive abilities of various machine learning algorithms for determining the success of flow diverters in achieving aneurysm occlusion. Results Five studies out of 217 were included based on our criteria. The included studies used various variables (patient demographics, aneurysm and parent artery characteristics, flow diverter and hemodynamic-related features, and angiographic parametric imaging) to predict flow diverter treatment outcomes. The machine learning algorithms used, along with their respective accuracy rates, were as follows: logistic regression (61% and 85%), support vector machine (88%), Gaussian support vector machine (90%), linear support vector machine (85%), decision tree (80%), random forest (87%), k-nearest neighbors (83% and 85%), XGBoost (87%), CatBoost (86%), deep neural networks (77.9%), and recurrent neural networks (74%).Two studies trained the machine learning models with both all features and the most significant features. Both studies observed that the accuracy of machine learning models decreased by removing the insignificant features. Conclusion The current literature indicates that machine learning algorithms can be trained to predict the success of flow diverters with an accuracy of up to 90%.

Background Aneurysm treatments are crucial to minimize the rupture risk. The underlying molecular processes mediating cellular remodeling, endothelialization, and aneurysm healing following endovascular treatment are poorly understood. The current study aims to explore circulating miRNA as a treatment and outcome-associated biomarkers in patients undergoing endovascular treatment. Methods Patients undergoing endovascular interventions for unruptured intracranial aneurysms, using either flow diverter placement or coil embolization, were enrolled. Blood samples were collected before the intervention and during a follow-up period between 6 and 18 months. Total mRNA/miRNA was isolated from plasma, followed by RNA-seq analysis. Gene Ontology analysis was used to identify pathways linked to altered miRNA expression. Results Twenty-three patients participated, with 13 (56.5%) undergoing flow diversion and 10 (43.5%) coil embolization. The median follow-up sample collection time was 10.70 months (SEM ± 1.32). No significant differences in angiographic occlusion were noted between intervention groups. Differentially expressed miRNAs were not identified between groups at baseline. However, at follow-up, 39 miRNAs were upregulated and 41 were downregulated, independent of intervention. Notably, three miRNAs (miR-4746-5p, miR-4685-3p, and miR-490-3p) were downregulated in the flow diversion group compared to the coil embolization group. Bioinformatics analysis revealed associations with upregulated fluid shear stress, p53, adherens junction pathways, along with downregulated apoptosis pathways. Conclusions This study suggests that fluid shear stress and apoptosis may influence aneurysm healing or thromboembolic events in flow diverter-treated patients. Further research is warranted to elucidate the functional significance of these findings in treatment outcomes, providing valuable insights for improved patient care in intracranial aneurysm management.

Introduction: Intracranial aneurysms are associated with local degradation of the vessel wall resulting in the formation of a blood-filled sac. Approximately 6 million people are estimated to have intercranial saccular aneurysms in the US alone. Most aneurysms remain undetected until rupture, resulting in hemorrhage which carries a high mortality rate (>50%). Flow diverters are placed across the aneurysm neck to divert blood flow away from the sac, preventing rupture once occluded. However, flow diverters carry significant risk for thromboembolism, which is a major cause of morbidity. The elevated risk of thromboembolism is likely due to endothelial injury of the parent artery at the neck of the aneurysm. We hypothesize that the bionanomatrix can promote faster endothelialization and aneurysm occlusion thereby reducing the risk of thromboembolism after flow diverter treatment. Methods: The bionanomatrix is composed of peptide amphiphiles containing endothelial cell adhesive ligand (YIGSR) and a nitric oxide (NO) donor (KKKKK), both components critical for recruiting and retaining endothelial cells on the device. The NO releasing bionanomatrix was coated onto the flow diverters using ultrasonic spray coating, and the NO effects on endothelial cell (EC) and smooth muscle cell (SMC) proliferation on the coated devices was assessed, in vitro, using calcien-AM staining. For the in vivo study, an elastase-induced rabbit aneurysm model was created. The bionanomatrix coated and uncoated flow diverters were implanted into the rabbit aneurysm model for 4 weeks. The coated and uncoated flow diverters were then analyzed for endothelialization, smooth muscle cell proliferation, and aneurysm occlusion by angiography, gross image, and immunohistochemistry analyses. Results: In vitro , the bionanomatrix coated flow diverters significantly enhanced endothelial cell proliferation as well as reduced smooth muscle cell proliferation on the flow diverters compared to the uncoated device. In vivo, after 4 weeks, the bionanomatrix coated flow diverters demonstrated enhanced neck coverage, more complete endothelialization, and reduced smooth muscle thickness on the coated flow diverters compared to the uncoated devices as seen by gross image analysis and histology. Conclusions: The bionanomatrix coated flow diverters can successfully promote faster endothelialization and brain aneurysm occlusion which is critical for reducing the risk of thromboembolism after neurointervention.

Background: Acute ischemic stroke (AIS) imposes a major healthcare burden. It is hypothesized that bacterial infection could influence atherosclerosis and thrombus formation, potentially contributing to AIS. Objectives: We aim to systematically review all studies that have investigated the presence of bacterial signatures within thrombi retrieved following mechanical thrombectomy (MT) procedures in patients with AIS. Design: This systematic review is designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 checklist. Data sources and methods: A comprehensive search was conducted in the Web of Sciences, PubMed, Scopus, and Embase databases to identify relevant studies. Results: The literature search and screening included 11 studies involving 674 patients, with 414 (61.4%) being male and 260 (38.6%) females. Among all the patients, 393 (58.3%) were positive for bacterial presence in their retrieved thrombi. The most utilized technique for bacterial signature detection was bacterial DNA extraction followed by polymerase chain reaction amplification of the 16S rRNA gene sequence. Staphylococcus aureus was the most studied bacteria among the studies analyzed. Conclusion: Bacterial infections and the presence of bacteria within thrombi may significantly contribute to AIS by initiating or exacerbating atherosclerosis or thrombosis. Understanding the mechanisms by which bacteria affect vascular health is crucial for developing effective preventive and therapeutic strategies for stroke patients.

ABSTRACT The mechanisms leading to aneurysm occlusion after treatment with flow‐diverting devices are not fully understood. Flow modification induces thrombus formation within the aneurysm cavity, but fibrin can simultaneously accumulate and cover the device scaffold, leading to further flow modification. However, the interplay and relative importance of these processes are not clearly understood. A computational model of fibrin accumulation and flow modification after flow diversion treatment of cerebral aneurysms has been developed under the guidance of in vitro experiments and observations. The model is based on the loose coupling of flow and transport‐reaction equations that are solved separately by independent codes. Interaction or reactive terms account for thrombin production from prothrombin stimulated by thrombogenic metallic wires and inhibition by antithrombin as well as fibrin production from fibrinogen stimulated by thrombin and flow shear stress, and fibrin adhesion to device wires and already attached fibrin. The computational model was demonstrated and tested on idealized vessel and aneurysm geometries. The model was able to reproduce the salient features of fibrin accumulation after the deployment of flow‐diverting devices in idealized in vitro models of cerebral aneurysms. Namely, fibrin production in regions of high shear stress, initial accumulation at the inflow zone, and progressive occlusion of the device and corresponding flow attenuation. The computational model linking flow dynamics to fibrin production, transport, and adhesion can be used to investigate and better understand the effects that lead to fibrin accumulation and the resulting aneurysm inflow reduction and intra‐aneurysmal flow modulation.