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Background and purposeThe presence of collaterals is associated with a reduced risk of stroke and transient ischemic attack in patients with steno-occlusive carotid artery disease. Although metabolic syndrome negatively impacts collateral status, it is unclear whether and to what extent type 2 diabetes mellitus affects cerebral collateral flow regulation during hypoperfusion.MethodsWe examined the spatial and temporal changes of the leptomeningeal collateral flow and the flow dynamics of the penetrating arterioles in the distal middle cerebral artery and anterior cerebral artery branches over 2 weeks after unilateral common carotid artery occlusion (CCAO) using optical coherent tomography in db/+ and db/db mice. We also assessed the temporal adaptation of the circle of Willis after CCAO by measuring circle of Willis vessel diameters.ResultsAfter unilateral CCAO, db/db mice exhibited diminished leptomeningeal collateral flow compensation compared with db/+ mice, which coincided with a reduced dilation of distal anterior cerebral artery branches, leading to reduced flow not only in pial vessels but also in penetrating arterioles bordering the distal middle cerebral artery and anterior cerebral artery. However, no apparent cell death was detected in either strain of mice during the first week after CCAO. db/db mice also experienced a more severe early reduction in the vessel diameters of several ipsilateral main feeding arteries in the circle of Willis, in addition to a delayed post-CCAO adaptive response by 1 to 2 weeks, compared with db/+ mice.ConclusionsType 2 diabetes mellitus is an additional risk factor for hemodynamic compromise during cerebral hypoperfusion, which may increase the severity and the risk of stroke or transient ischemic attack.

Patients with carotid occlusive disease express altered hemodynamics in the post-occlusive vasculature and lesions commonly attributed to cerebral small vessel disease (SVD). We addressed the question if cerebral perforating artery flow measures, using a novel 7T MRI technique, are altered and related to SVD lesion burden in patients with carotid occlusive disease.21 patients were included with a uni- (18) or bilateral (3) carotid occlusion (64±7 years) and 19 controls (65±10 years). Mean flow velocity and pulsatility in the perforating arteries in the semi-oval center (CSO) and basal ganglia (BG), measured with a 2D phase contrast 7T MRI sequence, were compared between patients and controls, and between hemispheres in patients with unilateral carotid occlusive disease. In patients, relations were assessed between perforating artery flow measures and SVD burden score and white matter hyperintensity (WMH) volume.CSO perforating artery flow velocity was lower in patients than controls, albeit non-significant (mean difference [95% confidence interval] 0.08 cm/s [0.00–0.16]; p = 0.053), but pulsatility was similar (0.07 [-0.04–0.18]; p = 0.23). BG flow velocity and pulsatility did not differ between patients and controls (velocity = 0.28 cm/s [-0.32–0.88]; p = 0.34; pulsatility = 0.00 [-0.10–0.11]; p = 0.97). Patients with unilateral carotid occlusive disease showed no significant interhemispheric flow differences. Though non-significant, within patients lower CSO (p = 0.06) and BG (p = 0.11) flow velocity related to larger WMH volume.Our findings suggest that carotid occlusive disease may be associated with abnormal cerebral perforating artery flow and that this relates to SVD lesion burden in these patients, although our observations need corroboration in larger study populations.

Background Despite thrombectomy having become the standard of care for large‐vessel occlusion strokes, acute endovascular management in tandem occlusions, especially of the cervical internal carotid artery lesion, remains uncertain. We aimed to compare efficacy and safety of acute carotid artery stenting to balloon angioplasty alone on treating the cervical lesion in tandem occlusions. Similarly, we aimed to explore those outcomes’ associations with technique approaches and use of thrombolysis. Methods and Results We performed a systematic review and meta‐analysis to compare functional outcomes (modified Rankin Scale), reperfusion, and symptomatic intracranial hemorrhage and 3‐month mortality. We explored the association of first approach (anterograde/retrograde) and use of thrombolysis with those outcomes as well. Two independent reviewers performed the screening, data extraction, and quality assessment. A random‐effects model was used for analysis. Thirty‐four studies were included in our systematic review and 9 in the meta‐analysis. Acute carotid artery stenting was associated with higher odds of modified Rankin Scale score ≤2 (odds ratio [OR], 1.95 [95% CI, 1.24–3.05]) and successful reperfusion (OR, 1.89 [95% CI, 1.26–2.83]), with no differences in mortality or symptomatic intracranial hemorrhage rates. Moreover, a retrograde approach was significantly associated with modified Rankin Scale score ≤2 (OR, 1.72 [95% CI, 1.05–2.83]), and no differences were found on thrombolysis status. Conclusions Carotid artery stenting and a retrograde approach had higher odds of successful reperfusion and good functional outcomes at 3 months than balloon angioplasty and an anterograde approach, respectively, in patients with tandem occlusions. A randomized controlled trial comparing these techniques with structured antithrombotic regimens and safety outcomes will offer definitive guidance in the optimal management of this complex disease.

Abstract Introduction We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI]). Methods We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi‐center Heart–Brain Study. We used pseudo‐continuous ASL to estimate whole‐brain and regional partial volume‐corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains. Results CBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning. Discussion We found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart–brain axis.

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.

Objective – to optimize imaging algorithms of preoperative evaluation and postoperative changes and complications in patients with occlusive carotid disease.Material and methods. Results of pre- and postoperative imaging of patients with occlusive carotid disease during 2012–2016 years were analyzed. Four groups were defined: assessment of CT-angiography (CTA) for preoperative planning (256 patients); the role of CTA for postoperative changes (51 patients); CT-perfusion (CTP) abilities in cerebral circulation assessment before and after surgery (103 and 76 patients); CT and MRI in diagnosis of postoperative neurologic complications (595 patients).Results. CTA employment in preoperative examination increased accuracy of occlusive process evaluation and changed management strategy in 6 patients. With CTA data we were able to define three variants of postoperative carotid changes: “expected” condition; changes that require further dynamic control studies; complications. The most reasonable was CTP employment for patients with combination of stenosis of one carotid artery and occlusion of contralateral artery. For diagnosis of neurologic complication first line examination was MRI, than for further assessment – CTA and CTP.Conclusion. Complex imaging algorithm for occlusive carotid disease assessment, defining of postoperative vascular status and possible neurologic complications provide necessary information for management strategy examination.

Cardiovascular disease is an important contributor to cognitive impairment. This likely involves prototypical vascular disease mechanisms like ischemia, but cardiovascular disease might also impact the brain by accelerating cerebral amyloid-β accumulation. We aimed to determine whether there is an association between heart disease or carotid occlusive disease (COD) and cerebral amyloid-β burden. We conducted a systematic review of studies investigating cerebral amyloid-β burden, measured with positron emission tomography, in adults with and without heart disease or COD. Where possible, we obtained standardized mean differences (SMD) of amyloid-β standardized uptake volume ratios (SUVr) for meta-analysis. Eight cross-sectional studies were identified (1478 participants, aged 60–81 years, 51% female). Three studies on heart disease (two on atrial fibrillation (AF) only, one on AF, coronary artery disease and heart failure) did not find a difference in amyloid-β burden between patients and controls. The pooled difference for 746 participants with and without AF did not reach significance (SMD SUVr 0.14, 95%CI -0.06–0.34). Of the five studies on COD (one on differences between participants with and without COD, four on differences between hemispheres in unilateral COD), four did not find a difference in amyloid-β between participants or hemispheres. The pooled difference in amyloid-β load between hemispheres in 24 patients with unilateral COD was not significant (SMD SUVr −0.13, 95%CI -0.70–0.43). Based on current studies, although limited and heterogeneous, there is insufficient evidence to support the hypothesis that heart disease or COD are associated with increased cerebral amyloid-β burden. • Cardiovascular disease is an important contributor to cognitive impairment. • Cardiovascular disease may impact the brain by accelerating amyloid-β accumulation. • We found no link between heart or carotid occlusive disease and amyloid-β load. [ABSTRACT FROM AUTHOR]

This study examined associations of neighbourhood walkability with cognitive functioning (i.e., global cognition, memory, language, attention-psychomotor speed, and executive functioning) in participants without or with either heart failure, carotid occlusive disease, or vascular cognitive impairment. Neighbourhood walkability at baseline was positively associated with global cognition and attention-psychomotor speed. These associations were stronger in patients with vascular cognitive impairment. Individuals who live in residential areas with higher walkability levels were less likely to have impairments in language and executive functioning at two-year follow-up. These findings highlight the importance of the built environment for cognitive functioning in healthy and vulnerable groups. • We assessed associations of neighbourhood walkability with cognitive functioning. • We did this in reference participants and various heart-brain axis patient groups. • Walkability was positively cross-sectionally associated with global cognition. • Higher walkability lowered the odds of impaired executive functioning at follow-up. • Some associations were stronger in patients with vascular cognitive impairment. [ABSTRACT FROM AUTHOR]

The carotid disease represents a long and malignant process that lasts for years before manifesting its clinic symptoms. This disease is in 30 out of 90% of cases the source of the embolus, that is, the cause of the cerebrovascular insult. The aim of the modern medicine is to diagnose the disease and to cure it in order to avoid the catastrophic consequences of the insult. The paper gives a description of the presenceof morphological and hemodynamic changes in 1205 patients. The examination of the carotid arteries was made by the radiologist at the Institute for Radiology in Niš by the linear probe of 7,5 MHz at the apparatus Acuson 128 xp. The results of the examination done in the time interval from January, 3, 1996 to November, 18, 1996 have been made; thus, 47,63% of the examined were of male, while 52,26% of female sex. The most present were the patients of the group from 45 to 65 years of age. In 469 (38,92%) there were morphological changes on the common carotid artery or to the accessible part of the branches. In 166 (35,38%) the atheromatic lesions was present at one side, while in 64,62% the changes were at both sides. In 6 (1,4%) of the patients the occlusion of one of the branches of the carotid artery was diagnosed, while in another one the occlusion of the common carotid artery was diagnosed.

The carotid disease represents a long and malignant process that lasts for years before manifesting its clinic symptoms. This disease is in 30 out of 90% of cases the source of the embolus, that is, the cause of the cerebrovascular insult. The aim of the modern medicine is to diagnose the disease and to cure it in order to avoid the catastrophic consequences of the insult. The paper gives a description of the presenceof morphological and hemodynamic changes in 1205 patients. The examination of the carotid arteries was made by the radiologist at the Institute for Radiology in Niš by the linear probe of 7,5 MHz at the apparatus Acuson 128 xp. The results of the examination done in the time interval from January, 3, 1996 to November, 18, 1996 have been made; thus, 47,63% of the examined were of male, while 52,26% of female sex. The most present were the patients of the group from 45 to 65 years of age. In 469 (38,92%) there were morphological changes on the common carotid artery or to the accessible part of the branches. In 166 (35,38%) the atheromatic lesions was present at one side, while in 64,62% the changes were at both sides. In 6 (1,4%) of the patients the occlusion of one of the branches of the carotid artery was diagnosed, while in another one the occlusion of the common carotid artery was diagnosed.

OBJECTIVES: Ischaemic stroke is a major complication of cardiac surgery. The optimal strategies for operating on patients with obstructive carotid and/or intracranial artery disease (CIAD) are controversial. We aimed to clarify whether single-photon emission computed tomography (SPECT) with acetazolamide, to quantify the cerebral perfusion reserve, could predict the risk of haemodynamic ischaemic stroke during cardiac surgery. METHODS: The incidence of stroke related to obstructive CIAD and the corresponding autoregulatory reserve were prospectively assessed in 514 consecutive patients who underwent elective cardiac surgery with cardiopulmonary bypass (n = 484) and off-pump coronary artery bypass grafting (n = 30) between 2009 and 2013. Preoperative cerebral blood flow and its reactivity to acetazolamide were quantitatively determined in patients (n = 88) with obstructive CIAD, diagnosed by carotid ultrasonography and/or magnetic resonance angiography. RESULTS: An impaired cerebral perfusion reserve was identified in 1 (1.1%) of the 88 patients. This patient underwent prophylactic superficial temporal artery to middle cerebral artery anastomosis 1 month before coronary artery bypass surgery. Subsequently, the patient underwent conventional coronary artery bypass surgery, without experiencing perioperative stroke. Seven (1.4%) patients died in-hospital mortality and 5 (1.0%) experienced perioperative stroke. However, no patients experienced perioperative haemodynamic ischaemic stroke. CONCLUSIONS: It is unusual for CIAD to affect the incidence of haemodynamic ischaemic stroke during cardiac surgery. Brain perfusion SPECT with acetazolamide is effective for narrowing down patients at high risk of ischaemic stroke during cardiac surgery. Meanwhile, the application of brain perfusion single-photon emission tomography should be confined only to patients with obstructive CIAD because it is an expensive examination tool. [ABSTRACT FROM AUTHOR]

We demonstrate the close relationship between a conspicuous ocular pulse amplitude and severe underlying cardiovascular disease. Two otherwise symptom-free glaucoma patients without any previously diagnosed underlying cardiovascular pathology but with a conspicuous ocular pulse amplitude and who underwent routine examinations in our glaucoma department were referred to the appropriate specialty for further diagnostic procedures. In both patients, the diagnosis of a tachyarrhythmia was made as suspected on dynamic contour tonometry measurements. In addition to medical treatment, one patient underwent electric cardioversion and the second patient was scheduled for pacemaker implantation. A third patient with an unexpected high ocular pulse amplitude despite severe cardiovascular pathology underwent major surgery due to an aortic aneurysm. Carotid stenosis was diagnosed due to side differences in ocular pulse amplitude as well. Ocular pulse amplitude might be a noninvasive and affordable screening tool and could be used to detect severe cardiovascular disease. A prospective study including a larger number of patients is needed to prove this hypothesis. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Irradiation induced extracranial carotid occlusive disease has been recognized as a potential cause of post-irradiation stroke in nasopharyngeal carcinoma (NPC) patients. Our study aims to investigate the prevalence of extracranial CA disease in post-irradiated Taiwanese NPC ischemic stroke patients. Methods: Forty-three NPC patients with ischemic stroke were retrospectively selected from the stroke registration of the study hospital and compared with 276 first-ever ischemic stroke patients from the same database, of which 31 patients underwent carotid duplex sonography (CDS). Significant atherosclerotic lesions of the carotid arteries were defined as a >50% stenosis or an occlusion according to CDS. Results: Significant carotid lesions occurred in 13 of 31 (42%) NPC patients. Stroke was more frequently caused by large artery disease (44% versus 23%; p <0.01) in NPC patients than in first-ever stroke patients without NPC. Carotid artery disease (odds ratio 7.22, 95% confidence interval 2.51–20.77; p <0.0001) and absence of diabetes mellitus (odds ratio 0.26, 95% confidence interval 0.07–0.93; p =0.039) were the strongest independent discriminators between NPC stroke patients and non-NPC stroke patients in a multivariate logistic regression analysis. Conclusion: Patients who received neck irradiation are at risk for the delayed development of diffused atherosclerosis but also for carotid occlusion within years, although the mechanism remains elusive and probably multifactorial. [ABSTRACT FROM AUTHOR]

Background and Objectives: The risk of stroke caused by a symptomatic high-grade carotid stenosis (CS) is high. Disturbed balance between the procoagulant and fibrinolytic activity in blood associated with unfavorable hemorheology could render CS symptomatic. We wanted to assess whether hemostatic and fibrinolytic plasma markers as well as basic indicators of hemorheology differentiate asymptomatic and symptomatic patients with a high-grade CS and whether they are associated with the macroscopic appearance of the plaque and the rate of microembolization. Methods: We recruited 92 consecutive consenting patients referred to the neurological or the surgical department of our university teaching hospital for treatment of their high-grade CS. Blood samples were collected before surgery for determination of prothrombin fragments F1 and 2, thrombin-antithrombin complex, tissue-type plasminogen activator (tPA) activity and antigen, plasminogen activator inhibitor-1 (PAI-1) activity and antigen, D-dimer, homocysteine, fibrinogen, in plasma, and hematocrit in blood, and the patients underwent transcranial Doppler ultrasonology for evaluation of microembolic signals (MES). Results: Patients with symptomatic plaques had higher hematocrit levels (p = 0.04), as well as trends for higher tPA antigen and MES rate (p = 0.07). Hematocrit, tPA antigen, and PAI-1 antigen and activity were positively correlated with the degree of stenosis. Ulceration was more common in symptomatic plaques but did not reflect variables of hemostasis or fibrinolysis. In multivariate analysis, tPA antigen and hematocrit were risk factors for a symptomatic high-grade stenosis. Conclusion: Mediators of fibrinolysis and unfavorable hemorheology may contribute to the development of a symptomatic disease in patients with a high-grade CS. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: To report the technique of carotid endarterectomy (CEA) combined with retrograde balloon angioplasty and stenting of proximal "tandem" lesions in the supra-aortic trunk. Technique: Intraoperative techniques in 34 patients with 23 left common carotid artery (CCA) and 11 innominate artery lesions included general anesthesia, low-dose dextran, prosthetic patching, selective shunting, 8-F sheath entry into the native CCA before the CEA, manual CCA sizing, and balloon-expandable stent placement after predilation. The technique has a high procedural success rate (97%) and appears durable. Over a mean 34-month follow-up, 2 >70% ostial CCA restenoses were found at 24 months. Conclusions: Intraoperative innominate or left CCA balloon angioplasty/stenting combined with carotid endarterectomy is safe, effective, and durable. [ABSTRACT FROM AUTHOR]

Patients with carotid occlusive disease express altered hemodynamics in the post-occlusive vasculature and lesions commonly attributed to cerebral small vessel disease (SVD). We addressed the question if cerebral perforating artery flow measures, using a novel 7T MRI technique, are altered and related to SVD lesion burden in patients with carotid occlusive disease. 21 patients were included with a uni- (18) or bilateral (3) carotid occlusion (64±7 years) and 19 controls (65±10 years). Mean flow velocity and pulsatility in the perforating arteries in the semi-oval center (CSO) and basal ganglia (BG), measured with a 2D phase contrast 7T MRI sequence, were compared between patients and controls, and between hemispheres in patients with unilateral carotid occlusive disease. In patients, relations were assessed between perforating artery flow measures and SVD burden score and white matter hyperintensity (WMH) volume. CSO perforating artery flow velocity was lower in patients than controls, albeit non-significant (mean difference [95% confidence interval] 0.08 cm/s [0.00-0.16]; p  = 0.053), but pulsatility was similar (0.07  [-0.04-0.18]; p  = 0.23). BG flow velocity and pulsatility did not differ between patients and controls (velocity = 0.28 cm/s [-0.32-0.88]; p  = 0.34; pulsatility = 0.00 [-0.10-0.11]; p  = 0.97). Patients with unilateral carotid occlusive disease showed no significant interhemispheric flow differences. Though non-significant, within patients lower CSO ( p  = 0.06) and BG ( p  = 0.11) flow velocity related to larger WMH volume. Our findings suggest that carotid occlusive disease may be associated with abnormal cerebral perforating artery flow and that this relates to SVD lesion burden in these patients, although our observations need corroboration in larger study populations., Competing Interests: The authors have no conflicts of interest to declare., (© 2022 Published by Elsevier B.V.)

Background Despite thrombectomy having become the standard of care for large-vessel occlusion strokes, acute endovascular management in tandem occlusions, especially of the cervical internal carotid artery lesion, remains uncertain. We aimed to compare efficacy and safety of acute carotid artery stenting to balloon angioplasty alone on treating the cervical lesion in tandem occlusions. Similarly, we aimed to explore those outcomes' associations with technique approaches and use of thrombolysis. Methods and Results We performed a systematic review and meta-analysis to compare functional outcomes (modified Rankin Scale), reperfusion, and symptomatic intracranial hemorrhage and 3-month mortality. We explored the association of first approach (anterograde/retrograde) and use of thrombolysis with those outcomes as well. Two independent reviewers performed the screening, data extraction, and quality assessment. A random-effects model was used for analysis. Thirty-four studies were included in our systematic review and 9 in the meta-analysis. Acute carotid artery stenting was associated with higher odds of modified Rankin Scale score ≤2 (odds ratio [OR], 1.95 [95% CI, 1.24-3.05]) and successful reperfusion (OR, 1.89 [95% CI, 1.26-2.83]), with no differences in mortality or symptomatic intracranial hemorrhage rates. Moreover, a retrograde approach was significantly associated with modified Rankin Scale score ≤2 (OR, 1.72 [95% CI, 1.05-2.83]), and no differences were found on thrombolysis status. Conclusions Carotid artery stenting and a retrograde approach had higher odds of successful reperfusion and good functional outcomes at 3 months than balloon angioplasty and an anterograde approach, respectively, in patients with tandem occlusions. A randomized controlled trial comparing these techniques with structured antithrombotic regimens and safety outcomes will offer definitive guidance in the optimal management of this complex disease.

Background The optimal approach to treat the cervical carotid artery lesion during endovascular thrombectomy (EVT) for acute strokes with tandem occlusions is unclear. While carotid artery stenting (CAS) might be a more definitive recanalization method, the potential risk of intracranial hemorrhage (ICH) limits its routine usage. In this study, we aimed to evaluate the safety outcomes of CAS and carotid artery angioplasty (CAA) in patients with acute tandem occlusions. Methods In this retrospective cohort study, data were obtained from the Nationwide Readmissions Database 2016–2017. The primary safety outcome was a composite of ICH and all-cause in-hospital mortality. Logistic regression analysis was used to compare the in-hospital outcomes. Survival analysis was used to estimate the 30-day readmissions. Results We identified 2042 hospitalizations meeting the study inclusion criteria (median age: 66 years, female 31.3%). Of these, 1391 (68.1%) had undergone CAS and 651 (31.9%) CAA alone. Baseline characteristics between the two groups were similar, except patients with CAS were more likely to be on anti-thrombotic medications and were less likely to have received intravenous thrombolysis. There was no significant difference in the clinical outcomes including ICH, in-hospital mortality, gastrostomy tube placement, prolonged mechanical ventilation, length of stay, hospital charges, and 30-day readmissions between the two groups, however, patients with CAS were more likely to be discharged home after adjusting for the confounding variables [odds ratio (OR) 1.49, 95% confidence interval (CI) 1.05–2.12, P 0.025]. Conclusion The emergent CAS-EVT approach appears to be safe with no adverse outcomes compared to CAA alone. • Acute carotid artery intervention in tandem occlusions involves stenting in most (68%) cases. • Carotid artery angioplasty and stenting for acute tandem occlusions have similar safety profile for in-hospital outcomes. • Patients with carotid artery stenting are more likely to be discharged home as compared to those with angioplasty alone. [ABSTRACT FROM AUTHOR]

Background: The clinical syndrome of chronic ocular ischaemia may be difficult to diagnose due to its wide range of non-specific presentations, and its diagnosis often implies the presence of underlying severe carotid occlusive disease. Colour Doppler imaging (CDI), a recent advance in ultrasonography that allows for colour-encoded blood flow data of a vascular structure to be displayed simultaneously on a conventional real-time gray-scale B mode image, has been used in the assessment of ocular and orbital vasculature. Method: Four patients with chronic ocular ischaemic syndrome whose diagnoses were aided by CDI are presented. Results: Orbital CDI was successful in confirming the diagnosis in all four cases. Reversal of blood flow in the ophthalmic arteries was demonstrated. Central retinal vessels were not detected with CDI in all four patients with complete occlusion of the ipsilateral internal carotid artery. One of the four patients had intermittent reversal of ophthalmic arterial flow ipsilateral to the 60% stenosed internal carotid artery. Conclusion: This non-invasive technique is an excellent alternative to invasive vascular studies such as angiography for the diagnosis and evaluation of the chronic ocular ischaemic syndrome. [ABSTRACT FROM AUTHOR]

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Purpose: The association of internal carotid artery disease (ICAD) with aortic valve stenosis (AVS) constitutes a very high-risk clinical occurrence in which combined surgery may increase the operative risks and carotid stenting before or after cardiac surgery may be a valuable option. Unfortunately, in patients with AVS, the evaluation of carotid arteries by Doppler ultrasound (DUS) may be inaccurate. The present retrospective study is aimed to evaluate the pitfalls of DUS and the role of carotid angiography before carotid stenting in evaluating ICAD in patients with AVS. Methods: We analyzed the clinical, hemodynamic, and angiographic findings of 200 patients with moderate to severe AVS (5.5% of 3600 patients underwent cardiac catheterization; mean age, 68.5+/-10.6 years) investigated in our institution over the past 2 years. Patients with moderate to severe AVS, candidates to open cardiac surgery, underwent carotid ultrasonography to assess ICAD and complete left and right catheterization with coronary artery angiography, and in case of doubtful carotid artery sonography, the patients underwent also carotid artery angiography at the time of complete cardiac catheterization before confirming the indication to carotid stenting or combined surgery. Results: Seventy patients with moderate to severe AVS and doubtful carotid ultrasonography underwent coincident carotid angiography. Reasons for suboptimal Doppler ultrasonographic examination are related to the anatomical or to the difficult evaluation of Doppler flow due to hemodynamic influences of AVS. On carotid angiography, 20 patients (28.5%, male/female, 8/12; mean age, 72.1+/-5.1 years) were diagnosed to have critical stenosis of one (16 patients) or both (4 patients) internal carotid arteries; in five patients, a significant ICAD was not diagnosed by DUS, whereas in seven patients, the stenosis was underestimated by DUS (mean luminal narrowing, 58+/-12.7% vs. 76.7+/-19.3%, P<.03), and in the other eight patients, DUS overestimated ICAD (77+/-12% vs. 62+/- 13.4%, P<.02). Out of this group, six patients underwent successful carotid stenting, six combined surgical treatments, and eight underwent simple cardiac surgery. Conclusions: Doppler ultrasound may be inconclusive in evaluating ICAD in patients with moderate to severe AVS candidates to cardiac surgery and endovascular carotid stenting. Carotid angiography may be proposed at the time of cardiac catheterization in patients with inconclusive DUS examination. [ABSTRACT FROM AUTHOR]

Introduction: We examined the role of hemodynamic dysfunction in cognition by relating cerebral blood flow (CBF), measured with arterial spin labeling (ASL), to cognitive functioning, in patients with heart failure (HF), carotid occlusive disease (COD), and patients with cognitive complaints and vascular brain injury on magnetic resonance imaging (MRI; ie, possible vascular cognitive impairment [VCI])., Methods: We included 439 participants (124 HF; 75 COD; 127 possible VCI; 113 reference participants) from the Dutch multi-center Heart-Brain Study. We used pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Neuropsychological tests covered global cognition and four cognitive domains., Results: CBF values were lowest in COD, followed by VCI and HF, compared to reference participants. This did not explain cognitive impairment, as we did not find an association between CBF and cognitive functioning., Discussion: We found that reduced CBF is not the major explanatory factor underlying cognitive impairment in patients with hemodynamic dysfunction along the heart-brain axis., Competing Interests: A.E. Leeuwis, A.M. Hooghiemstra, S. Kuipers, E.A. Oudeman, T. Kalay, H.P. Brunner La Rocca, R.J. van Oostenbrugge, W.J. Niessen, M.A. van Buchem, A.C. van Rossum: report no conflicts.E.E. Bron and J.P. Greving have been funded by the Dutch Heart Foundation.N.D. Prins serves on the advisory board of Boehringer Ingelheim and Probiodrug, and on the DSMB of Abbvie's M15‐566 trial. He has provided consultancy services for Sanofi, Takeda, and Kyowa Kirin Pharmaceutical Development. He also receives research support from Alzheimer Nederland (project number WE.03‐2012‐02) and is CEO and co‐owner of Brain Research Center, Amsterdam, the Netherlands.M.J.P. van Osch has received research funding from Philips, the Netherlands Organisation for Scientific Research (NWO), and European Union Horizon 2020 and serves on the editorial boards of JCBFM and NMR in Biomedicine.G.J. Biessels has been funded by the Dutch Heart Foundation (grant 2010T073), ZonMW (Vici grant 918.16.616), The Netherlands Organisation for Health Research and Development and European Union Horizon 2020 (grant agreement no. 666881, SVDs@target).F. Barkhof is supported by the NIHR biomedical research centre at UCLHF. Barkhof serves as a consultant for Biogen‐Idec, Janssen Alzheimer Immunotherapy, Bayer‐Schering, Merck‐Serono, Roche, Novartis, Genzyme, and Sanofi‐aventis.F. Barkhof has received sponsoring from EU‐H2020, NWO, SMSR, TEVA, Novartis, Toshiba, and Imi and serves on the editorial boards of Radiology, Brain, Neuroradiology, MSJ, and Neurology.Research programs of W.M. van der Flier have been funded by ZonMW, NWO, EU‐FP7, Alzheimer Nederland, Cardiovasculair Onderzoek Nederland, stichting Dioraphte, Gieskes‐Strijbis fonds, Pasman Stichting, Boehringer Ingelheim, Piramal Imaging, Roche BV, Janssen Stellar, Biogen, and Combinostics. All funding is paid to her institution., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)

Carotid revascularization has been recommended as the maximally beneficial treatment for stroke prevention in patients with recently symptomatic carotid stenosis (SCS). The appropriate timing for performing carotid endarterectomy (CEA) within the first 14 d after the occurrence of the index event remains controversial. We aim to provide a snapshot of the pertinent current literature related to the timing of CEA for patients with SCS. A systematic review of literature was conducted to study the timing of CEA for SCS. The guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) were followed. A total of 63 articles were identified as relevant to this topic. A summary of 15 articles favoring urgent CEA (within 48 h) for SCS within 48 h of index event and 9 articles not favoring urgent CEA is presented. A consensus is still to be achieved on the ideal timing of CEA for SCS within the 14-d window presently prescribed. The current literature suggests that patients who undergo urgent CEA (within 48 h) after nondisabling stroke as the index event have an increased periprocedural risk as compared to those who had transient ischemic attack (TIA) as the index event. Further prospective studies and clinical trials studying this question with separate groups classified as per the index event are required to shed more light on the subject. The current literature points to a changing paradigm towards early carotid surgery, specifically targeted within 48 h if the index event is TIA, and within 7 d if the index event is stroke., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Introduction: Symptomatic internal carotid artery occlusion (ICAO) can lead to neurologic decline, recurrent stroke, and mortality., Objective: We sought to evaluate the safety and feasibility of endovascular revascularization for ICAO without tandem intracranial large vessel occlusion (LVO)., Design, Setting, and Participants: This is a retrospective cohort analysis of all patients presenting to a single academic center with ischemic stroke and ipsilateral cervical ICAO from November 2003 through April 2016. Patients were excluded if pre-procedural angiography demonstrated tandem LVO or if patients were known to have chronic ICAO., Main Outcomes and Measures: Study endpoints included discharge neurologic examination, post-procedural infarct burden, 3-month functional outcomes, and treatment durability., Results: A total of 107 patients with symptomatic angiographically-confirmed cervical ICAO without tandem LVO were identified. Median admission NIH Stroke Scale (NIHSS) score was 8 (IQR 11). Baseline radiographic stroke severity was assessed by ASPECT score (median 9; IQR 2), perfusion mismatch (present in 93%), and clinical imaging mismatch (42%). Median time from symptom onset to treatment was 25 hours (IQR 61). Successful revascularization was achieved in 92% of patients. At discharge, 83% had stable/improved NIHSS score, while at 3 months 65% achieved independence (modified Rankin Scale score ≤2). The most common complication was distal embolization (22%) of which 16% required intra-arterial treatment. Rate of significant restenosis (≥70%) was 15% at 1 year., Conclusions: Stenting in selected patients at risk of neurologic deterioration due to symptomatic ICAO can be performed with high rates of technical success and good clinical outcomes. Because of significant peri-procedural risks and high rates of restenosis, randomized studies are necessary to understand the benefit of this approach., Competing Interests: Competing interests: TGJ has the following disclosures: Consultant, Neuravi (steering committee -modest), Codman Neurovascular (DSMB - modest), Stryker Neurovascular (PI DAWN - unpaid), Fundacio Ictus (PI REVASCAT unpaid); stock, Anaconda, Silk Road, Blockade Medical (modest). AFD has the following disclosure: Consultant, Medtronic (device proctor - modest)., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol., Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz-heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines., Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor., (© 2017 The Author(s). Published by S. Karger AG, Basel.)

Background and Purpose: Craniocervical fibromuscular dysplasia (FMD) is associated with dissections and with S-shaped curves in the internal carotid artery (ICA). We evaluated the occurrence of S-curves in patients presenting with acute strokes due to ICA steno-occlusive dissections., Methods: This was a retrospective review of the interventional databases of two academic tertiary-care institutions. The presence of ICA S-shaped curves, C-shaped curves, 360-degree loops, as well as classic FMD and atherosclerotic changes at the ICA bulb and curve/loop was determined. Cases of carotid dissections were compared with a control group (consecutive non-tandem anterior circulation strokes)., Results: Twenty-four patients with carotid dissections were compared to 92 controls. Baseline characteristics and procedural variables were similar, with the exception of younger age, less frequent history of hypertension, diabetes, atrial fibrillation and stent retriever use in patients with dissections. The rates of mTICI2b-3 reperfusion, parenchymal hematoma, good outcome and mortality were similar amongst groups. The frequency of S-curves (any side without superimposed atherosclerosis) was 29% in the dissection group versus 7% in controls (p < 0.01). S-curves were typically mirror images within the dissection group (85% had bilateral occurrence). The frequency of C-shaped and 360-degree curves was similar between groups. FMD changes within the craniocervical arteries were statistically more common in dissection patients. Ten patients (41%) of the dissection group had S-curves or classic FMD changes. Multivariate analysis indicated that S-curves were independently associated with the presence of dissections., Conclusion: S-shaped ICA curves are predictably bilateral, highly associated with carotid dissections in patients with moderate to severe strokes, and may suggest an underlying presence of FMD.

Objectives: Ischaemic stroke is a major complication of cardiac surgery. The optimal strategies for operating on patients with obstructive carotid and/or intracranial artery disease (CIAD) are controversial. We aimed to clarify whether single-photon emission computed tomography (SPECT) with acetazolamide, to quantify the cerebral perfusion reserve, could predict the risk of haemodynamic ischaemic stroke during cardiac surgery., Methods: The incidence of stroke related to obstructive CIAD and the corresponding autoregulatory reserve were prospectively assessed in 514 consecutive patients who underwent elective cardiac surgery with cardiopulmonary bypass (n = 484) and off-pump coronary artery bypass grafting (n = 30) between 2009 and 2013. Preoperative cerebral blood flow and its reactivity to acetazolamide were quantitatively determined in patients (n = 88) with obstructive CIAD, diagnosed by carotid ultrasonography and/or magnetic resonance angiography., Results: An impaired cerebral perfusion reserve was identified in 1 (1.1%) of the 88 patients. This patient underwent prophylactic superficial temporal artery to middle cerebral artery anastomosis 1 month before coronary artery bypass surgery. Subsequently, the patient underwent conventional coronary artery bypass surgery, without experiencing perioperative stroke. Seven (1.4%) patients died in-hospital mortality and 5 (1.0%) experienced perioperative stroke. However, no patients experienced perioperative haemodynamic ischaemic stroke., Conclusions: It is unusual for CIAD to affect the incidence of haemodynamic ischaemic stroke during cardiac surgery. Brain perfusion SPECT with acetazolamide is effective for narrowing down patients at high risk of ischaemic stroke during cardiac surgery. Meanwhile, the application of brain perfusion single-photon emission tomography should be confined only to patients with obstructive CIAD because it is an expensive examination tool., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Carotid artery stenting (CAS) was introduced in the United States nearly a decade ago as a novel treatment of severe carotid stenosis. Voluminous and high-quality prospective data permit analysis of longitudinal trends in CAS outcomes., Methods: Outcomes from all prospective trials with the Food and Drug Administration (FDA) oversight from 2000-2011 were reviewed, as were the subset of studies using a single CAS system. All studies shared common inclusion/exclusion criteria, endpoints, independent assessment/adjudication of neurological events, and were conducted in accordance with FDA regulations. Death and stroke (DS) rates from FDA-approved studies in high-surgical-risk patients were assessed., Results: Between 2000 and 2011, two distinct periods with clustered and differentiated outcomes in CAS IDE trials were observed, separated by FDA approval and Centers for Medicare and Medicaid Services (CMS) coverage in 2004-2005. The mean 30-day DS rate in the first wave (2000-2004) of CAS trials was 5.3% (95% CI: 4.6-6.2%), and fell significantly to 2.6% (95% CI: 1.9-3.7%; P = 0.0001) in the second wave (2006-2011). This decline occurred during a simultaneous, independent 24-fold increase in monitored CAS activity. This decline in DS rates was observed in symptomatic and asymptomatic patients, alike independent of device tested., Conclusions: Declines in periprocedural DS rates in CAS appear linked to regulatory and coverage approvals leading to increased operator experience along with continued regulatory oversight, and provide insight into the introduction of other novel therapies., (Copyright © 2013 Wiley Periodicals, Inc.)

Background and Purpose: In the Asymptomatic Carotid Surgery Trial-1 (ACST-1), 3120 patients with tight asymptomatic carotid stenosis were randomly assigned to medical treatment alone or to carotid endarterectomy and appropriate medication. Successful carotid endarterectomy significantly reduced 10-year stroke risk in younger patients. This study was undertaken to determine the risk of new occlusion and stroke during trial follow-up., Methods: Patients with contralateral occlusion at trial entry (n=276) or incomplete duplex follow-up (n=137) were excluded. Risk of occlusion and stroke in patients with occlusion was estimated by Kaplan-Meier analysis. Cox proportional hazard regression models were used to determine risk factors for developing new occlusion and stroke., Results: Median follow-up in 2707 patients was 80.0 months (interquartile range, 52.0-115.0). New occlusions occurred in 197 patients (1.1% per annum) but were more likely to occur in arteries with tight stenosis and in unoperated patients. Overall risk of stroke was 7.6% (95% confidence interval [CI], 6.6-8.7) and 15.5% (95% CI, 13.6-17.4) at 5 and 10 years, respectively; for patients with new occlusion, this significantly increased to 17.0% (95% CI, 11.6-22.4) and 20.8% (95% CI, 14.1-26.2), respectively (P<0.001). Stroke was significantly more likely to occur in patients developing occlusion (hazard ratio, 1.78; 95% CI, 1.26-2.51) irrespective of allocated treatment., Conclusions: New occlusions were uncommon after carotid endarterectomy in ACST-1. During long-term follow-up, occlusion and stroke were commoner among patients with ≥ 70% stenosis, most of whom had not undergone carotid endarterectomy. Occlusion was an independent prognostic risk factor for occurrence of stroke.