Citations

Abstract The severe acute respiratory syndrome coronavirus 2 pandemic of 2019 to 2020 has resulted in multiple hospitalizations, deaths, and economic hardships worldwide. Although respiratory involvement in patients with coronavirus disease 2019 ( COVID ‐19) is well known, the potential cardiovascular and cerebrovascular manifestations are less understood. We performed a PubMed and Google Scholar search and reviewed relevant literature on COVID ‐19 and cardiovascular system involvement. Severe acute respiratory syndrome coronavirus 2 possesses high affinity for angiotensin‐converting enzyme 2 receptor, which is highly concentrated in the lungs and cardiovascular tissue, thereby provoking concern for cardiovascular involvement in COVID ‐19 cases. Preexisting cardiovascular and cerebrovascular disease has been shown in previous reports to be a risk factor for severe infection. On the basis of our review of published studies, COVID ‐19 patients may be more likely to experience acute cardiac injury, arrhythmia, coagulation defects, and acute stroke and are likely to have poorer outcomes as a result. As the COVID ‐19 pandemic continues, more data about potential cardiovascular and cerebrovascular manifestations of the disease are required.

Abstract Flow diverters have drastically changed the landscape of intracranial aneurysm treatment and are now considered first-line therapy for select lesions. Their mechanism of action relies on intrinsic alteration in hemodynamic parameters, both at the parent artery and within the aneurysm sac. Moreover, the device struts act as a nidus for endothelial cell growth across the aneurysm neck ultimately leading to aneurysm exclusion from the circulation. In silico computational analyses and investigations in preclinical animal models have provided valuable insights into the underlying biological basis for flow diverter therapy. Here, we review the present understanding pertaining to flow diverter biology and mechanisms of action, focusing on stent design, induction of intra-aneurysmal thrombosis, endothelialization, and alterations in hemodynamics.

Background/objective: Reduction of brain temperature remains the most common method of neuroprotection against ischemic injury employed during cardiac surgery. However, cooling delivered via the cardiopulmonary bypass circuit is brief and cooling the body core along with the brain has been associated with a variety of unwanted effects. This study investigated the feasibility and safety of a novel selective brain cooling approach to induce rapid, brain-targeted hypothermia independent of the cardiopulmonary bypass circuit. Methods: This first-in-human feasibility study enrolled five adults undergoing aortic valve replacement with cardiopulmonary bypass support. During surgery, the NeuroSave system circulated chilled saline within the pharynx and upper esophagus. Brain and body core temperature were continuously monitored. Adverse effects, cardiopulmonary function, and device function were noted. Results: Patient 1 received cooling fluid for an insignificant period, and Patients 2-5 successfully underwent the cooling procedure using the NeuroSave system for 56-89 minutes. Cooling fluid was 12°C for Patients 1-3, 6°C for Patient 4, and 2°C for Patient 5. There were no NeuroSave-related adverse events and no alterations in cardiopulmonary function during NeuroSave use. Brain temperature decreased by 3°C within 15 minutes and remained at least 3.5°C colder than the body core. During a brief episode of hypotension in one patient, the brain cooled an additional 4°C in 2 minutes, briefly reaching 27.4°C. Conclusion: The NeuroSave system can induce rapid brain-targeted hypothermia and simultaneously maintain a favorable body–brain temperature gradient, even during hypotension. Further studies are required to evaluate the function of the system during longer periods of use.

Background Clot perviousness in large vessel occlusion has been shown to be associated with improved recanalization outcomes with mechanical thrombectomy and intravenous thrombolysis. Objective To evaluate the association between clot perviousness based on thrombus attenuation increase (TAI) on CT, and histologic composition of clots in acute ischemic stroke (AIS). Methods A retrospective review was completed of patients with AIS secondary to large vessel occlusion, non-contrast CT (NCCT) and CT angiography (CTA) images, and histologic analysis of the retrieved clot. TAI was measured by subtracting clot attenuation on NCCT from the attenuation on CTA. Up to 3 regions of interest (ROIs) were evaluated on each clot; the average attenuation was used for analysis if multiple ROIs were assessed. Pervious clots were defined as TAI ≥10 Hounsfield units (HUs); impervious clots had TAI <10 HU. Histopathologic analyses of clots were assessed for relative compositions of red blood cells (RBCs), white blood cells (WBCs), fibrin, and platelets/other. Results 57 patients were included. Pervious clots were more likely to be RBC rich (p=0.04); impervious clots were more likely to be fibrin and WBC rich (p=0.01 for both). Pervious clots also had greater RBC density than impervious clots (49.8% and 33.0%, respectively; p=0.006); fibrin density of pervious clots was lower than that of impervious clots (17.8% and 23.2%, respectively; p=0.02). Conclusion Clot perviousness, assessed on NCCT and CTA imaging, is associated with higher RBC density and lower fibrin density, offering a possible explanation for the higher rates of successful thrombectomy and favorable clinical outcome seen in such patients.

Background and Purpose— Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods— As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results— One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P =0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P =0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P =0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P =0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions— High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.

Objectives Remote ischemic preconditioning has been proposed as a possible potential treatment for ischemic stroke. However, neuroprotective benefits of the pre-procedural administration of remote ischemic preconditioning have not been investigated in patients undergoing an elective endovascular intracranial aneurysm repair procedure. This study investigated the safety and feasibility of remote ischemic preconditioning in patients with an unruptured intracranial aneurysm who undergo elective endovascular treatment. Methods In this single-center prospective study, patients with an unruptured intracranial aneurysm undergoing elective endovascular treatment with flow diverters or coiling were recruited. Patients received three intermittent cycles of 5 minutes arm ischemia followed by reperfusion using manual blood cuff inflation/deflation less than 5 hours prior to endovascular treatment. Patients were monitored and followed up for remote ischemic preconditioning-related adverse events and ischemic brain lesions by diffusion -weighted magnetic resonance imaging within 48 hours following endovascular treatment. Results A total of seven patients aged 60 ± 5 years with an unruptured intracranial aneurysm successfully completed a total of 21 sessions of remote ischemic preconditioning and the required procedures. Except for two patients who developed skin petechiae over their arms, no other serious procedure-related adverse events were observed as a result of the remote ischemic preconditioning procedure. On follow-up diffusion -weighted magnetic resonance imaging, a total of 19 ischemic brain lesions with a median (interquartile range) volume of 245 (61–466) mm 3 were found in four out of seven patients. Conclusions The application of remote ischemic preconditioning prior to endovascular intracranial aneurysm repair was well tolerated, safe and clinically feasible. Larger sham-controlled clinical trials are required to determine the safety and efficacy of this therapeutic strategy in mitigating ischemic damage following endovascular treatment of intracranial aneurysms.

Background Bacteria and bacterial components have been associated with the activation of coagulation factors and initiating the blood clot formation. The aim of this study was to investigate whether bacterial populations are present in clots retrieved from patients that have suffered a large vessel occlusion acute ischemic stroke (AIS). Materials and methods Clot samples were collected from 20 AIS patients who underwent clot retrieval with mechanical thrombectomy. Patient clinical demographic details were noted. Expression of bacterial 16S rDNA was analyzed by standard and real-time polymerase chain reaction (PCR). Gram staining was performed to identify Gram-positive and Gram-negative bacteria. Results Both the real-time and standard PCR demonstrated no expression of 16S rDNA in any of the 20 clots samples from AIS patients. Gram staining results showed no expression of Gram-positive or Gram-negative bacteria present in the clot samples. Conclusion Our current study found no bacteria populations in the clots of AIS patients.

AbstractModeling the flow dynamics in cerebral aneurysms after the implantation of intrasaccular devices is important for understanding the relationship between flow conditions created immediately posttreatment and the subsequent outcomes. This information, ideally available a priori based on computational modeling prior to implantation, is valuable to identify which aneurysms will occlude immediately and which aneurysms will likely remain patent and would benefit from a different procedure or device.In this report, a methodology for modeling the hemodynamics in intracranial aneurysms treated with intrasaccular flow diverting devices is described. This approach combines an image‐guided, virtual device deployment within patient‐specific vascular models with an immersed boundary method on adaptive unstructured grids. A partial mesh refinement strategy that reduces the number of mesh elements near the aneurysm dome where the flow conditions are largely stagnant was compared with the full refinement strategy that refines the mesh everywhere around the device wires.The results indicate that using the partial mesh refinement approach is adequate for analyzing the posttreatment hemodynamics, at a reduced computational cost. The results obtained on a series of four cerebral aneurysms treated with different intrasaccular devices were in good qualitative agreement with angiographic observations.Promising results were obtained relating posttreatment flow conditions and outcomes of treatments with intrasaccular devices, which need to be confirmed on larger series.

AbstractShape memory polymer (SMP) foam‐coated coils (FCCs) are new embolic coils coated with porous SMP designed to expand for increased volume filling and enhanced healing after implantation. The purpose of this study was to compare chronic aneurysm healing after treatment with SMP FCCs to bare platinum coil (BPC) controls in the rabbit elastase aneurysm model. BPCs or SMP FCCs were implanted in rabbit elastase‐induced aneurysms for follow‐up at 30 days (n = 10), 90 days (n = 5), and 180 days (n = 12 for BPCs; n = 14 for SMP FCCs). Aneurysm occlusion and histologic healing, including a qualitative healing score, neointima thickness, collagen deposition, and inflammation were compared between the two groups. The mean neointima thickness was significantly greater in groups treated with SMP FCCs for all three time points. Histologic healing scores and collagen deposition quantification suggested that aneurysms treated with SMP FCCs experience more complete healing of the dome by 90 days, but the differences were not statistically significant. More progressive occlusion and recanalization were observed in aneurysms treated with SMP FCCs, but neither difference was statistically significant. Additionally, the SMP foam used in the FCCs was found to degrade faster in the rabbit elastase model than expected based on previous studies in a porcine sidewall aneurysm model. This study suggests that SMP FCCs can promote neointima formation along the aneurysm neck, and may lead to more complete healing of the dome and neck. These findings indicate potential benefits of this device for aneurysm occlusion procedures. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2466–2475, 2019.

Background: Flow diverters (FD) are increasingly used in the treatment of intracranial aneurysms. The risk of distal thromboembolic complications with FD is high, even in patients treated with dual antiplatelet therapy. The aim of the study was to understand the downstream vascular wall changes, by measuring the pulse wave velocity and vascular contractility following flow diverter treatment in a rabbit model. Methods: FD (Pipeline Embolic Device, Medtronic) were implanted in normal rabbits and sham-operated aorta were used as controls (n=5 for each group). Pulse wave imaging with ultra-fast ultrasound at 1600 frames per second (Vantage, Verasonics, Inc.) was performed in the vessel wall distal to FD, prior to device implantation and at 8 weeks follow up to measure the pulse wave propagation. Force contraction studies were conducted in the aortic rings using organ bath to assess the vascular functions. Results: The difference in pulse wave velocity (PWV) in the follow-up compared to pre-implantation was significantly higher (p=0.03,Fig 1A) in the distal vessels compared to sham controls (mean difference of PWV was 1.18 m/s and -0.37m/s, respectively as shown in Fig 1B). Conversely, the distal aortic segments to FD exhibited 55% increase in the level of vascular contractility compared to that of proximal segments (p=0.002). There is a significant positive correlation between mean PWV and mean vascular contractility. Conclusion: Our study found changes in the PWV after implantation of the FD, which correlated with vascular contractility. These results could explain vascular wall changes downstream following FD implantation.