Large Artery Disease Research Articles

Intracranial atherosclerotic disease and neurodegeneration: a narrative review and plausible mechanisms

IntroductionIntracranial atherosclerotic disease (ICAD) of the large cerebral arteries, a leading cause of stroke worldwide, is increasingly implicated in cognitive impairment and neurodegeneration among the general population; however, the underlying pathophysiologic mechanisms in this relationship remain unknown. MethodsIn this narrative review, we aim to provide an overview of the epidemiology and pathophysiology of ICAD, the evidence that relates ICAD to neurodegeneration, putative mechanisms, and future research directions. We synthesized available evidence on PubMed up to August 2024. Results and ConclusionsICAD, a common cause of stroke, is characterized as a chronic, inflammatory, fibroproliferative disease of the cerebral large arteries. Numerous lines of evidence have related ICAD to clinical, neuroimaging, and pathology-based markers of cognitive impairment and Alzheimer's disease; however, little data exists on plausible pathophysiological links. Based on ongoing and adjacent work, we hypothesize hypoperfusion, arterial stiffness, and inflammation to play a role, but further research is needed. Conventional classification of ICAD often infers from symptomatic coronary artery disease and relies on degree of luminal stenosis, but unique anatomic features of the intracranial circulation may be relevant and a more comprehensive description that includes arterial wall features and plaque morphology may be needed to fully understand its relationship with cognitive impairment and neurodegeneration.

Association of intracranial large artery disease with long-term prognosis after ischaemic stroke.

Intracranial large artery disease (ICLAD) is a common cause of ischaemic stroke and is associated with the risk of recurrent vascular events in the short term. We compared the incidence of various long-term vascular outcomes between ischaemic stroke patients with and without ICLAD. This was a longitudinal observational study of acute ischaemic stroke patients who were followed up serially for recurrent stroke, myocardial infarction or vascular death up to a median of 86 months. Transcranial colour-coded Doppler was used in the diagnosis of ICLAD. Among the 581 ischaemic stroke patients studied (median age 63 ± 11 years, male 71%), 354 (60.9%) had ICLAD. In regression analyses adjusting for covariates, patients with ICLAD were more likely to have long-term composite vascular outcomes (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.02-2.03, P = 0.041), myocardial infarction (HR 2.89, 95% CI 1.71-4.91, P < 0.001) and vascular death (HR 3.52, 95% CI 1.67-7.52, P = 0.001) but not recurrent stroke (HR 1.10, 95% CI 0.72-1.70, P = 0.652), at a median of 86 months as compared to patients without ICLAD. Our findings of poor prognostic impact of ICLAD on long-term recurrent vascular events after ischaemic stroke provide evidence for the need of specific, emphasised screening and secondary prevention, especially for coronary artery disease in this high-risk group.

A risk prediction model for unexplained early neurological deterioration following intravenous thrombolysis

Background and objectivesEarly neurological deterioration (END) post-intravenous thrombolysis significantly impacts the long-term prognosis of stroke patients. This study aimed to establish a rapid risk prediction model for unexplained END following intravenous thrombolysis.MethodsThis prospective study consecutively enrolled patients with acute ischemic stroke treated with recombinant tissue plasminogen activator intravenous thrombolysis at the Department of Neurology, Third People’s Hospital of Hubei Province, and Yangluo Hospital District between June 2019 and December 2022. Unexplained END was defined as an increase of ≥ 4 points in the National Institutes of Health Stroke Scale (NIHSS) score between admission and 24 h. A nomogram was developed and assessed by calculating the area under the receiver operating characteristic curve (AUC-ROC). The calibration was assessed using the Hosmer–Lemeshow test.ResultsA total of 211 patients (130 males and 110 patients aged < 65 years) were included, with 66 experiencing unexplained END. Multivariate logistic regression analysis identified large arterial disease, transient ischemic attack, high blood glucose, high neutrophil/lymphocyte ratio, important perforator disease, and low the Alberta Stroke Program Early CT scores (APSECTS) as independent risk factors for END and established the nomogram used above indicators. The nomogram showed an AUC-ROC of 0.809 (95% CI 0.7429–0.8751), with a specificity of 0.862 and sensitivity of 0.712. The positive predictive value was 0.702, and the negative predictive value was 0.868. The Hosmer–Lemeshow goodness-of-fit test (χ2 = 1.069, P = 0.169) indicated acceptable model calibration.ConclusionThis study successfully established a risk prediction model for END following intravenous thrombolysis and the model demonstrates good stability and predictive capacity. Further validation through a prospective, multicenter study is necessary.

Drug-coated balloon versus drug-eluting stent for treating de novo large vessel coronary artery disease: a systematic review and meta-analysis of 13 studies involving 2888 patients.

Drug-coated balloon (DCB) is an established treatment option for in-stent restenosis and small vessel, de novo, coronary artery disease (CAD). Although the use of this tool is increasing in everyday practice, data regarding performance in the treatment of de novo, large vessel CAD (LV-CAD) is still lacking. A systematic review and meta-analysis were conducted to evaluate the efficacy and safety of DCB versus drug-eluting stent (DES) in this setting. A comprehensive literature search was performed including Medline, Embase, and Cochrane electronic databases up to January 24, 2024, for studies which compared the efficacy and safety of DCB versus DES in the treatment of de novo lesions in large vessels (≥ 2.5mm), reporting at least one clinical outcome of interest (PROSPERO ID: CRD42023470417). The analyzed outcomes were cardiovascular death (CVD), myocardial infarction (MI), target lesion revascularization (TLR), all-cause death (ACD), and late lumen loss (LLL) at follow-up. The effect size was estimated using a random effects model as risk ratio (RR) and mean difference (MD) and relative 95% confidence interval (CI). A total of 13 studies (6 randomized controlled trials and 7 observational studies) involving 2888 patients (DCB n = 1334; DES n = 1533) with de novo LV-CAD were included in this meta-analysis following our inclusion criteria. No differences were observed between DCB and DES in terms of CVD (RR 0.49; 95% CI [0.23-1.03]; p = 0.06), MI (RR 0.48; 95% CI [0.16-1.45]; p = 0.89), TLR (RR 0.73; 95% CI [0.40-1.34]; p = 0.32), ACD (RR 0.78; 95% CI [0.57-1.07]; p = 0.12), and LLL (MD - 0.14; 95% CI [- 0.30 to 0.02]; p = 0.10) at follow-up. DES proved a higher mean acute gain versus DCB [1.94 (1.73, 2.14) vs 1.31 (1.02, 1.60); p = 0.0006]. Our meta-analysis showed that DCB PCI might provide a promising option for the management of selected, de novo LV-CAD compared to DES. However, more focused RCTs are needed to further prove the benefits of a "metal-free" strategy in this subset of CAD.

Small-Vessel Disease and Intracranial Large Artery Disease in Brain MRI Predict Dementia and Acute Coronary Syndrome, Respectively: A Prospective, Observational Study in the Population at High Vascular Risk.

We aimed to clarify the predictive value of cerebral small-vessel disease and intracranial large artery disease (LAD) observed in magnetic resonance imaging of the brain and magnetic resonance angiography on future vascular events and cognitive impairment. Data were derived from a Japanese cohort with evidence of cerebral vessel disease on magnetic resonance imaging. This study included 862 participants who underwent magnetic resonance angiography after excluding patients with a modified Rankin Scale score >1 and Mini-Mental State Examination score <24. We evaluated small-vessel disease such as white matter hyperintensities and lacunes in magnetic resonance imaging and LAD with magnetic resonance angiography. Outcomes were incident stroke, dementia, acute coronary syndrome,and all-cause death. Over a median follow-up period of 4.5 years, 54 incident stroke, 39 cases of dementia, and 27 cases of acute coronary syndrome were documented. Both small-vessel disease (white matter hyperintensities and lacunes) and LAD were associated with stroke; however, only white matter hyperintensities were related to dementia. In contrast, only LAD was associated with acute coronary syndrome. Among the 357 patients with no prior history of stroke, coronary or peripheral artery disease, or atrial fibrillation, white matter hyperintensities emerged as the sole predictor of future stroke and dementia, while LAD was the sole predictor of acute coronary syndrome. Among cerebral vessels, small-vessel disease could underlie the cognitive impairment while LAD was associated with coronary artery disease as atherosclerotic vessel disease.

Cost-effectiveness of atrial fibrillation detection with insertable cardiac monitors in large-artery or small-vessel disease stroke in the United Kingdom

Abstract Background The randomised STROKE-AF trial demonstrated clinical effectiveness of continuous cardiac monitoring to detect atrial fibrillation (AF) with insertable cardiac monitors (ICMs) for patients with ischemic stroke attributed to large-artery or small-vessel disease (LAD/SVD). ICMs were ten-fold more effective at detecting AF compared to the standard of care (SoC). However, cost-effectiveness of this monitoring strategy is unknown. Purpose The aim of this economic evaluation was to assess the cost-effectiveness of long-term continuous cardiac monitoring via ICMs, for detection of AF (and, in event of AF diagnosis, subsequent anticoagulation), in patients with ischemic stroke attributed to large-or-small vessel disease compared to the SoC of conventional follow up in the United Kingdom. Methods We constructed a Markov model with a cycle length of three months and a lifetime horizon to conduct the cost-effectiveness analysis, from the National Health Service (NHS) perspective. Costs and health-related benefits were discounted at an annual rate of 3.5%. We expressed outcomes in terms of quality-adjusted life-years (QALYs). Patient characteristics in the analysis and detection probabilities were based on the STROKE-AF trial. Detection of AF resulted in a switch in treatment from antiplatelet to direct oral anticoagulant (DOAC). Risk of cerebrovascular events were dependent on a patient’s AF detection status and subsequent treatment. Scenario, deterministic, and probabilistic sensitivity analyses were conducted to test the robustness of the base-case incremental cost-effectiveness ratio (ICER) and account for uncertainties in the model. We stratified patients into risk groups based on CHA2DS2-VASc scores and risk of AF detection. Results The base case incremental cost-effectiveness ratio of the implantation of an ICM was £15,485 per QALY, substantially under the NICE willingness-to-pay threshold of £20,000-£30,000 per QALY. ICM implantations resulted in 0.139 QALYs gained per patient at an incremental cost of £2,147. There were 0.054 fewer stroke events per patient in the ICM arm versus SoC. Results were robust under sensitivity analysis. Conclusion ICMs were cost-effective compared to SoC for detection of AF in patients with LAD/SVD stroke in the United Kingdom driven largely by more stroke events avoided. Subgroup analysis showed that ICMs were more cost-effective in patients with higher CHA2DS2-VASc scores and those with a higher individual risk of AF.Markov Model SchematicSummary ICER Results and Events avoided

Literature Review on the Association between Cerebral Large Artery Disease and Cerebral Microbleeds

CMBs are small areas of hemorrhage in the brain, often seen on neuroimaging studies, that have been associated with various cerebrovascular pathologies. Large-artery atherosclerosis and resulting vascular stenosis are major contributors to ischemic stroke. Given the structural continuity between intracranial large and small vessels, their susceptibility to hemodynamic influences, and their shared risk factors, they may coexist in the same individual. This article reviews recent advances in understanding the interplay between large artery atherosclerosis (LAA) and cerebral microbleeds (CMB). Methods: A comprehensive search of electronic databases including PubMed, MEDLINE, and Google Scholar was conducted using relevant keywords such as "cerebral large artery disease," "cerebral microbleeds," "arterial stenosis," and "atherosclerosis." Articles published in English between [2010] and [2024] were considered for inclusion. Studies investigating the relationship between LAA and CMBs through neuroimaging, pathological examination, or clinical correlations were selected for review. Results: The review identified a range of studies exploring the association between LAA and CMBs. Several cross-sectional imaging studies have demonstrated a significant correlation between LAA severity and the presence, number, and distribution of CMBs. Histopathological investigations have revealed microvascular alterations in regions affected by LAA, potentially contributing to CMB formation. The evidence indicates a correlation between cerebrovascular microbleeds (CMBs) and large artery diseases, impacting the prognosis of individuals with cerebral infarction resulting from large artery atherosclerosis (LAA). Keywords: Cerebral infarction; Large-artery atherosclerosis; Cerebral microbleeds.

Common and distinct risk profiles of asymptomatic extra- and intracranial atherosclerosis in the Nagahama cohort

Background and purposeAtherosclerotic burden increases the risk of both extracranial internal carotid artery stenosis (ICS) and intracranial large artery disease (ICAD). However, the differences in risk profiles have not been thoroughly investigated. MethodsParticipants were recruited from the Nagahama study cohort in Japan. Individuals over 60 years old who underwent 1.5-T head and neck magnetic resonance angiography (MRA) between July 2013 and February 2017 were included. ICAD was defined as WASID ≥ 50 %, and ICS was defined as NSCET ≥ 30 %. The prevalence and association of risk factors, including proatherogenic and proinflammatory factors, and the p.R4810K variant in the RNF213 gene, were investigated. Multivariable logistic regression analyses were performed. ResultsA total of 3089 individuals participated in the study, with a mean age of 68.1 ± 5.3 years, and 36.0 % were males. Among them, 52 (1.7 %) had ICS, 119 (3.8 %) had ICAD, and 15 (0.49 %) had both conditions. Alopecia areata was an independent predictor for both ICS (Odds ratio [OR] 3.5; 95 % CI 1.3-8.3) and ICAD (OR 2.1; 95 % CI 1.0-3.9). Diabetes (OR 3.7; 95 % CI 2.0-7.0) and older age (OR 2.4; 95 % CI 1.2-4.5) were associated only with ICS, while the RNF213 variant was associated with only ICAD (OR 5.7; 95 % CI 1.6-16.0). ICS and ICAD were also independently associated with each other. ConclusionsIn this MRA-based large scale study, alopecia areata, known as a systemic inflammatory disease, was shown to be a common risk factor for ICS and ICAD. While conventional atherosclerotic factors were associated with ICS, non-atherosclerotic factors appear to contribute to ICAD in Japan.

Non-coronary peripheral arterial complications in people with type 2 diabetes: a Swedish retrospective cohort study

BackgroundFew studies have explored long-term trends and risk factors for peripheral arterial complications in type 2 diabetes compared to the general population. Our research focuses on identifying optimal risk factors, their significance, multifactorial control risks, and trends for these complications in diabetic patients versus general controls. MethodsThis study included persons with type 2 diabetes mellitus entered into the Swedish National Diabetes Register 2001-2019 and controls matched for age-, sex- and county of residence. Outcomes comprised of extracranial large artery disease, aortic aneurysm, aortic dissection, lower extremity arterial disease and diabetes foot disease. Standardized incidence rates and Cox regression were used for analyses. FindingsThe study comprises 655,250 persons with type 2 diabetes mellitus; average age 64.2; 43.8% women. Among persons with type 2 diabetes mellitus, the incidence rates per 100,000 person years for each non-coronary peripheral arterial complication event changed between 2001 and 2019 as follows: extracranial large artery disease 170.0 to 84.9; aortic aneurysm 40.6 to 69.2; aortic dissection 9.3 to 5.6; lower extremity artery disease from 338.8 to 190.8; and diabetic foot disease from 309.8 to 226.8. Baseline hemoglobin A1c (HbA1c), systolic blood pressure (SBP), smoking status and lipid levels were independently associated with all outcomes in the type 2 diabetes mellitus cohort. Within the cohort with type 2 diabetes mellitus, the risk for extracranial large artery disease and lower extremity artery disease increased in a stepwise fashion for each risk factor not within target. Excess risk for non-coronary peripheral arterial complications in the entire cohort for persons with type 2 diabetes mellitus, compared to matched controls, were as follows: extracranial large artery disease adjusted hazard ratio (HR) 1.69 (95% confidence interval (CI), 1.65-1.73), aortic aneurysm HR 0.89 (95% CI, 0.87-0.92), aortic dissection HR 0.51 (95% CI, 0.46-0.57) and lower extremity artery disease HR 2.59 (95% CI, 2.55-2.64). InterpretationsThe incidence of non-coronary peripheral arterial complications has declined significantly among persons with type 2 diabetes mellitus, with the exception of aortic aneurysm. HbA1c, smoking and blood pressure demonstrated greatest relative contribution for outcomes and lower levels of cardiometabolic risk factors are associated with reduced relative risk of outcomes.Funding: Swedish governmental and the county support of research and education of doctors, the Swedish Heart and Lung Foundation and Åke-Wibergs grant.

Sex differences in modifiable risk factors for stroke incidence and recurrence: the UCC-SMART study

Background and purposeRisk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort.MethodsWithin the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale.ResultsThe age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27–0.88; and RD 1.39; CI − 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23–0.80; and RD 9.05; CI 2.78–15.32).ConclusionsIn high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention.

A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches.

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

Abstract 138: Cost-Effectiveness of Insertable Cardiac Monitors to Identify Atrial Fibrillation After Stroke Attributed to Large-Artery or Small-Vessel Disease

Introduction: Identification of atrial fibrillation (AF) in patients with stroke is critical for secondary stroke prevention with guideline-recommended oral anticoagulation (OAC). The randomized STROKE AF trial evaluating patients with ischemic stroke attributed to large-artery or small-vessel disease (LAD/SVD) found that insertable cardiac monitors (ICMs) were more likely to detect AF than standard of care (SoC) using intermittent external ECG monitors. However, the cost-effectiveness of ICMs in this population is not known. This study aimed to evaluate the cost-effectiveness of ICMs to detect new AF in patients with LAD/SVD stroke in the U.S. Methods: Using patient data from STROKE AF (N=492, median CHA 2 DS 2 -VASc=5.0), a lifetime Markov model was developed to assess the cost-effectiveness of ICM vs. SoC from a payer perspective. SoC was based on the frequency of ECG/Holter monitoring observed in the trial. AF detection was assumed to result in a switch from aspirin to OAC, unless precluded by prior bleeds. Lifetime risks of stroke and bleeding events were based on underlying presence of AF and the safety and efficacy of the treatment received. Future costs/effects were discounted at 3% annually to adjust to present values. Sensitivity analyses were conducted to assess uncertainty. Results: ICM was associated with a gain of 0.17 quality-adjusted life years (QALYs) versus SoC (6.63 vs. 6.46), driven by higher incidence of OAC and consequent reduction in lifetime ischemic strokes, with 53 fewer strokes projected per 1,000 patients. Total lifetime per-patient costs were $65,989 and $59,703 in the ICM and SoC arms, respectively. The incremental cost-effectiveness ratio was $37,760 per QALY gained compared to SoC (under the $50,000/QALY threshold considered highly cost-effective in the U.S.). Cost-effectiveness improved further in the subset with CHA 2 DS 2 -VASc≥6. In the patients at highest risk of AF detection (left atrial enlargement, heart failure, obesity, or prolonged QRS), the cost/QALY was $22,016. Conclusions: ICMs are likely to be cost-effective in the U.S. for the diagnosis of AF in the population with stroke attributed to LVD or SVD. This strategy was most cost-effective in patients with high CHA 2 DS 2 -VASc scores and those at greatest risk of AF.

Abstract WP258: Younger Patients Have a Higher Likelihood of Recurrent Vessel Small Subcortical Infarct: A Post-Hoc Analysis of the SPS3 Trial

Introduction: Recurrent ischemic stroke due to intracranial large artery disease occurs in up to 20% of patients and is associated with uncontrolled cardiovascular risk factors. However less is known of recurrent vessel small subcortical infarcts (rvSSI), which may be related to branch atherosclerotic disease. The aim of this study was to describe the clinical risk factors associated with rvSSI. Methods: We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled participants between 2003 and 2007. All participants were ≥ 30 years old and had a SSI index event within the preceding 6 months of randomization, confirmed by MRI with a maximal diameter on diffusion weighted imaging (DWI) of ≤ 20 mm, and were without competing stroke mechanism (e.g. ipsilateral carotid stenosis ≥ 50%). Participants were followed over a mean duration of 4 years post-enrollment during which stroke recurrence was noted and characterized. rvSSI was defined as recurrent SSI within the same vascular distribution as an index enrolling infarct confirmed by brain MRI. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Adjusted logistic regression models were formed to calculate odds ratio. Statistical significance was ≤ 0.05. Results: Of the 3020 participants enrolled in SPS3, 1245 participants met inclusion criteria with 15 having a rvSSI (mean time post-enrollment: 427 days). Participants with rvSSI were younger (54.5 ± 10.2 years vs 61.2 ± 10.6 years, p = 0.008) and had enrollment diagnoses of obesity [BMI ≥ 30 kg/m2; 80% (12/15) vs 49% (598/1230), p = 0.016] and hyperlipidemia [87% (13/15) vs 58% (713/1230), p = 0.025]. Sex, former/current tobacco use, and known diagnoses of hypertension and diabetes mellitus did not differ. For every advancing decade of life, the likelihood of developing a rvSSI was 0.46 (95%CI 0.26 - 0.82, p = 0.008). Conclusions: Participants of the SPS3 trial who were younger in age had rvSSI more frequently with the likelihood decreasing by roughly half with advancing decade of life.

Cilostazol addition to aspirin may worsen the short-term outcome in patients with large artery disease: ADS subanalysis

Our previous acute dual study (ADS) reported that dual antiplatelet therapy (DAPT) using cilostazol and aspirin did not reduce the rate of neurological deterioration in non-cardioembolic stroke patients. In this post-hoc analysis, we investigated whether the impact of dual antiplatelet therapy (DAPT) may depend on neurological severity, as represented by large artery disease. Neurological deterioration was defined as neurological progression with an increment of the National Institutes of Health Stroke Scale (NIHSS) score of ≥2. NIHSS score subgroups were divided into that of 0-1, 2-4, 5-10, and >10. Among 1014 patients, 203 (20%) had the large artery disease, and 811 (80%) did not. In the total cohort, the rate of neurological deterioration was 10.8% in the DAPT group and 8.3% in the aspirin group (P=0.197). When we focused on the large artery disease group, DAPT group had a higher rate of neurological deterioration as 18.3% compared to 8.2% in the aspirin group (P=0.036). Among patients with NIHSS score of 0-1 and 2-4, the rates of neurological deterioration were not different between the two group (both, P=1.000). However, when NIHSS score elevated to 5-10, 45% in the DAPT group and 9.1% in the aspirin group deteriorated (P=0.013). Among the patients with NIHSS score of >10, 60% in the DAPT group and none (0%) in the aspirin group had the neurological deterioration (P=0.045). DAPT with aspirin and cilostazol was associated with higher rate of neurological deterioration when patients have large artery disease and not mild neurological deficits.

JAK2 V617F Mutation and Large Cerebral Artery Disease in Patients with Myeloproliferative Neoplasms.

The aim of the present study was to clarify the association between the Janus kinase 2 (JAK2) V617F mutation and large cerebral artery disease (LCAD) in patients with myeloproliferative neoplasms (MPNs). We retrospectively analysed patients diagnosed with MPNs between June 1992 and June 2022 who underwent brain magnetic resonance imaging. LCAD was defined as extracranial or intracranial large artery stenosis (≥ 50%) or occlusion on magnetic resonance angiography. A total of 86 patients (47 males; median age, 69 years old) were enrolled in this study. JAK2 V617F mutation was detected in 63 (73.3%) patients and LCAD in 35 (40.7%) patients. Univariate analysis showed that history of ischaemic stroke (LCAD, 62.9% vs. non-LCAD, 11.8%; P＜0.001), JAK2 V617F mutation (91.4% vs. 60.8%, P=0.002), and age ≥ 60 years (85.7% vs. 60.8%, P=0.016) were significantly associated with LCAD. Multiple logistic regression analysis showed that, in addition to ischaemic stroke, age ≥ 60 years and diabetes mellitus, JAK2 V617F mutation (odds ratio 29.2, 95% confidence interval 1.2-709.8, P=0.038) was independently associated with LCAD. LCAD was frequently observed in the intracranial carotid (14/35, 40.0%) and middle cerebral (13/35, 37.1%) arteries. This study revealed a significant association between the JAK2 V617F mutation and LCAD in patients with MPNs. This suggests that the JAK2 V617F mutation may promote cerebrovascular atherosclerosis and could be very important in determining therapeutic strategies for patients with not only JAK2 V617F-mutated MPNs but also LCAD-related stroke.

Atrial Fibrillation Detection and Load: Knowledge Gaps Related to Stroke Prevention.

Atrial fibrillation is a major cause of ischemic stroke. Technological advances now support prolonged cardiac rhythm monitoring using either surface electrodes or insertable cardiac monitors. Four major randomized controlled trials show that prolonged cardiac monitoring detects subclinical paroxysmal atrial fibrillation in 9% to 16% of patients with ischemic stroke, including in patients with potential alternative causes such as large artery disease or small vessel occlusion; however, the optimal monitoring strategy, including the target patient population and the monitoring device (whether to use an event monitor, insertable cardiac monitor, or stepped approach) has not been well defined. Furthermore, the clinical significance of very short duration paroxysmal atrial fibrillation remains controversial. The relevance of the duration of monitoring, burden of device-detected atrial fibrillation, and its proximity to the acute ischemic stroke will require more research to define the most effective methods for stroke prevention in this patient population.

Safety and effectiveness of emergency stenting for acute anterior circulation large artery disease

Objective: To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease. Methods: Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared. Result: A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05). Conclusion: For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.

Abstract 15381: Clinical Outcomes of Post-Drug-Coated Balloon Angioplasty Dissection in Large De-Novo Coronary Artery Disease

Introduction: Drug-coated balloon (DCB) may be an alternative to stents in the treatment of large native coronary artery disease. However, the complications of acute elastic recoil and coronary dissections confine the practical application of DCB. Little is known about the clinical outcomes of different types of dissection after DCB angioplasty with or without stenting. Aims: This study sought to investigate the clinical outcomes of post-DCB dissection in large de novo coronary artery disease. Methods: This was a retrospective observational study. A consecutive series of patients with large native coronary artery disease (reference diameter ≥ 3.0 mm) who occurred coronary dissections after the treatment of DCB angioplasty were included. These patients were divided into stented groups and non-stented groups depending on whether bail-out stents were employed. Post-angioplasty coronary artery dissections were classified into type A-F. The cumulative incidence of major adverse cardiac events (MACE) was compared between the two groups. Results: Between March 2017 and October 2022, 676 patients with large de novo coronary artery disease developed post-DCB angioplasty dissection, 554 of which treated with DCB only, 122 of which underwent bail-out stent implantation. These dissections were type A (60.5%), B (30.9%), C (6.5%), D (1.9%) and F (0.1%), respectively. During a mean follow-up of 1 year, MACE occurred in 60 patients (9 in the stented group and 51 in the non-stented group; 7.4% vs. 9.2%; p=0.522). For type B dissection, the rate of MACE was similar in the stented group than that in the non-stented group (11.1% vs. 8.2%; p=0.502). For type C dissection, the rate of MACE was numerically higher in the non-stented group than that in the stented group (9.5% vs. 0%; p=0.222). Conclusions: For post-DCB angioplasty dissection in large de-novo coronary artery disease, type B dissection requires no bail-out stent implantation and type C dissection deserves further investigation.

Atrial Fibrillation In Patients With Stroke Attributed to Large- or Small-Vessel Disease

The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown. To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD. This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded. ICM monitoring vs site-specific usual care. The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee. In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001). Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years. ClinicalTrials.gov Identifier: NCT02700945.

Emergent use of ticagrelor during endovascular reperfusion in large arterial occlusions

ObjectiveGiven many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes. MethodsThis was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any. Results73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03). ConclusionWe report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.