Klaas, James P.

Background: High-grade intracranial atherosclerosis (ICAS) is associated with an elevated risk of recurrent ischemic stroke, particularly in patients with severe stenosis (70–99%). Identifying predictors of early recurrence can inform risk stratification and guide treatment strategies. Methods: The Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) study is a multicenter, international, retrospective cohort analysis pooling data from 35 comprehensive stroke centers. We included hospitalized adult patients with symptomatic ICAS, defined as 50–99% stenosis of an intracranial artery (intracranial vertebral, basilar, distal ICA, or M1 MCA), confirmed by vascular imaging and associated with a qualifying ischemic event. Patients with only high-grade stenosis (70-99%) were included in this analysis. The primary outcome was to determine predictors of recurrent ischemic stroke in the territory of the symptomatic artery within 90 days of the index event. Baseline demographic, clinical, and imaging characteristics were recorded. Multivariable Cox proportional hazards regression with stepwise selection (p < 0.1) was used to identify independent predictors of recurrence; model discrimination was assessed using Harrell’s C-statistics. Results: Among 2,050 patients, 1,476 had high-grade (70-99%) symptomatic ICAS. The mean age was 67 ± 12.5 years, and 767 (55%) were male. Most patients were non-Hispanic (90.1%), taking dual antiplatelet therapy (77.8%), and statins (94.5%). Recurrent stroke occurred in 160 patients (10.8%) within 90 days. In multivariable Cox model, independent predictors of recurrence included atrial fibrillation (HR 2.05; 95% CI, 1.26–3.33; p = 0.004), hyperlipidemia (HR 1.57; 95% CI, 1.10–2.24; p = 0.014), diabetes mellitus (HR 1.36; 95% CI, 0.98–1.88; p = 0.064), and home use of dual antiplatelet therapy (HR 1.60; 95% CI, 1.01–2.54; p = 0.043)(Harrell’s C-statistic=0.62). In patients who underwent perfusion(n=402), mistmatch >10seconds were associated with increased recurrence (HR 1.80; 95% CI 0.95-3.38, p=0.07) and atrial fibrillation (HR 2.06: 95% CI 0.03-4.60, p=0.78) though did not reach statistical significance. Conclusion: In this population, diabetes, hyperlipidemia, atrial fibrillation, and prior use of dual antiplatelet therapy were associated with increased risk of 90-day recurrent ischemic stroke. Perfusion imaging may help identify high-risk patients who could benefit from intensified secondary prevention.

Introduction: Intracranial atherosclerosis (ICAS) is a leading cause of ischemic stroke (IS) worldwide and carries a high risk of recurrence. Current guidelines favor 90 days of dual antiplatelet therapy (DAPT) for severe symptomatic ICAS, but recurrence remain high. Limited data suggest possible benefit of single antiplatelet plus anticoagulation (SAPT+AC). We compared the effectiveness and safety of DAPT versus SAPT+AC. We hypothesized that DAPT would lower 90-day recurrent IS risk without significantly increasing bleeding. Methods: This substudy of the Biomarkers and Recurrence Risk in Symptomatic Intracranial Arterial Stenosis (BIORISK-ICAS) included patients from 35 centers (Jan 2019–Jun 2024) with symptomatic 50–99% ICAS in the intracranial internal carotid, vertebral, basilar, or M1 segment of the MCA, presenting ≤72 hours from last known well. The primary efficacy outcome was recurrent IS in the same vascular territory at 90 days; the primary safety outcome was severe bleeding (symptomatic intracranial hemorrhage or major extracranial bleeding). Categorical variables were compared using χ 2 and continuous variables with the Student's t test; multivariable Cox regression adjusted for key covariates. Results: Of 2050 BIORISK-ICAS patients, 1658 met criteria (DAPT n=1499; SAPT+AC n=159). Mean age was 67 vs. 73 years, and 44% were women. At 90 days, recurrent IS occurred in 121 DAPT patients (8.07%) vs. 13 SAPT+AC patients (8.17%); unadjusted HR 0.83 (95% CI, 0.50–1.36; p=0.46). After adjustment for age, diabetes, coronary heart disease, atrial fibrillation, active smoking, and borderzone infarct, the adjusted HR was 0.99 (95% CI, 0.52–1.86; p=0.97). Severe bleeding occurred in 34 DAPT patients (2.26%) and 5 SAPT+AC patients (3.14%); unadjusted HR 0.79 (95% CI, 0.28–1.85; p=0.50), adjusted HR 0.66 (95% CI, 0.21–2.09; p=0.47). Conclusions: In patients with symptomatic ICAS, DAPT and SAPT+AC were associated with similar risks of 90-day recurrent ischemic stroke and severe bleeding. Well-powered randomized trials are needed to determine the optimal antithrombotic regimen in this high-risk population.

BACKGROUND: Intracranial atherosclerosis (ICAS) is associated with an increased risk of early recurrent ischemic stroke. We evaluated whether biomarkers of impaired distal perfusion—specifically, anterior circulation borderzone infarct, and hypoperfusion mismatch volume—were associated with recurrent ischemic stroke within 90 days. METHODS: The BIORISK ICAS (Biomarkers and Recurrence Risk in Symptomatic Intracranial Atherosclerosis) is a multicenter retrospective international study (35 sites) that included hospitalized patients with symptomatic ICAS (50%–99% luminal stenosis of the intracranial vertebral, basilar, distal internal carotid, or proximal middle cerebral artery) from January 2019 to June 2024. The primary outcome was recurrent ischemic stroke in the territory of the symptomatic artery within 90 days. In the primary analysis, the exposure was an acute anterior circulation borderzone infarct. In secondary analysis of the subset with presentation within 72 hours of last known normal and perfusion imaging completed, the exposure of interest was prespecified as hypoperfusion mismatch volume at T max (time to maximum) threshold of 6 seconds, dichotomized at the Youden index. We performed multivariable Cox regression to test associations between exposure variables and the outcome, adjusting for clinically relevant variables and those associated with the outcome ( P <0.1). RESULTS: Of 2050 patients with symptomatic ICAS, 1737 (84.7%) presented within 72 hours of symptom onset, among whom 509 (29.3%) underwent perfusion imaging. The primary analysis included 1891 patients; 174 (9.2%) patients had recurrent ischemic stroke in the symptomatic arterial territory. In adjusted Cox regression models, there was an association between anterior circulation borderzone infarct and recurrent ischemic stroke at 90 days (adjusted hazard ratio, 1.40 [95% CI, 1.02–1.93]). In the perfusion imaging analysis, hypoperfusion mismatch of ≥10 mL was associated with recurrent ischemic stroke (adjusted hazard ratio, 1.83 [95% CI, 1.03–3.28]). CONCLUSIONS: Biomarkers of impaired distal perfusion, anterior circulation borderzone infarct, and hypoperfusion mismatch were associated with increased risk of recurrent ischemic stroke. These findings support the use of perfusion imaging in ICAS as well as future trials investigating early reperfusion in high-risk patients with ICAS.

Abstract Introduction Moyamoya is characterized by idiopathic, progressive, large intracranial arterial steno-occlusion, affecting the anterior circulation of the brain. Common presentations include strokes, seizures, and headaches, which have been associated with poor sleep quality and sleep disorders in the general population. However, to our knowledge, sleep quality has not been previously investigated in Moyamoya disease. The aim of this study was to characterize self-reported sleep quality, sleepiness, sleep disorder diagnoses in patients with Moyamoya syndrome, and to explore possible association between sleep disturbance and quality of life in these patients. Methods We analyzed consecutive patients with Moyamoya evaluated at our institution who completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). We also abstracted the Patient-Reported Outcomes Measurement Information System (PROMIS) to measure person-centered physical, mental and social wellbeing. Results We studied 23 patients with mean age 41.8 ± 12.1 years old having disease duration of 3 ± 4.4 years. 15 (65.2%) had ischemic strokes. Mean total PSQI score was 6.9 ± 2.9, and 17 (73.9%) had poor sleep quality (PSQI&gt;5). Mean sleep efficiency was reduced at 80 ± 17%. Although Median ESS was 6 (IQR 3.25 – 8), most patients (91.3%) reported at least mild daytime dysfunction (Component 7≥1). Mean PSQI component scores (0 – 3 severity, 3 is worse) were 1.29 ± 0.62 (subjective quality), 1.1 ± 0.73 (sleep latency), 1.04 ± 0.83 (sleep duration), 0.87 ± 1.01 (sleep efficiency), 1.22 ± 0.52 (sleep disturbances), 0.3 ± 0.88 (sleep medication), and 1.1 ± 0.52 (daytime dysfunction). The total PSQI score was positively correlated with PROMIS score (r=0.47, p=0.044). Only one patient was diagnosed with obstructive sleep apnea and three with chronic insomnia. Conclusion Poor sleep quality appears to be a frequent problem in patients with Moyamoya disease. Sleep disturbance severity was similar to previous findings in clinical stroke populations. The apparent mismatch between subjective sleep disturbance and sleep disorder diagnoses suggest that sleep disorders are likely underdiagnosed in Moyamoya patients. The relationship between PSQI and PROMIS scores suggests that sleep disturbance may significantly affect quality of life in these patients. Support (if any)

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) have known cardiovascular benefits. We aimed to assess the efficacy of GLP1-RA or SGLT2i initiation in reducing mortality or cardiovascular events in a community-based cohort of adults with ischemic stroke. Methods: Patients ≥18 years old admitted for acute ischemic stroke between Jan 2000 and June 2022 were identified using the Rochester Epidemiology Project. Subjects were considered exposed to SGLT-2i or GLP1-RA if they were treated with either medication after the index stroke and before the primary (all-cause mortality) or secondary outcomes (MI, recurrent ischemic stroke or composite). Kaplan-Meier curves and Cox models are shown in the Figures . Results: We included 7044 subjects, mean age 72±14 yr, 52% male, 94% white, over a median follow-up of 3 [1-7] years, 416 subjects (6%) had a second stroke, 426 (6%) had an incident MI and 3738 (53%) died. Those on SGLT2i/GLP1-RA had a decreased risk for mortality, incident MI, and composite in the univariate analysis. These associations remained significant after multivariable adjustment and were not affected by minimum time of exposure Figure 1&2 . SGLT2i/GLP1-RA use was associated with recurrent ischemic stroke in the multivariate analysis Figure 2C . All associations remained significant in most sub-analyses of individual medications except for the association between GLP1-RA and recurrent stroke Figure 3 Conclusions: SGLT2i or GLP-1 RA use was associated with decreased mortality and risk of myocardial infarction and recurrent stroke in patients with ischemic stroke.

Introduction: Artificial Intelligence-enabled electrocardiogram (AI-ECG) can estimate the probability of having atrial fibrillation (AFib) while in sinus rhythm. Recurrent stroke in subjects without known AFib may be due to undiagnosed AFib. We evaluated the association between AI-ECG AFib and recurrent ischemic stroke and with incident AFib Methods: Consecutive adults admitted to a Mayo Clinic or Mayo Clinic Health System hospital or to Olmsted Community Hospital for ischemic stroke between January,1,2000 and June,30,2022 were identified using the Rochester Epidemiology Project. Recurrent ischemic strokes were identified after reviewing medical records and imaging studies. We excluded those with known AFib or without ECGs within 3 years prior to the first ischemic stroke. The AI-ECG network was previously developed using 649,931 ECGs from > 180,000 subjects. The primary endpoint was recurrent ischemic stroke; secondary endpoint was incident AFib. Cox model adjusted for age, sex, and CHA2DS2-VASc2 score variables. Results: We included 4,816 subjects, mean age 70±15 yr, 54% male, 92% white, median CHA2DS2-VASc2 score 4 [3-5], median follow-up 3 [1-7] yr. 280 subjects (6%) had a second stroke and 366 (8%) were diagnosed with incident AFib over follow-up. Those with a positive AI-ECG AFib had an increased risk for recurrent ischemic stroke(HR 1.54, 95% CI 1.21-1.96, P<0.001 Figure A) This association remained significant after adjustment for CHA2DS2-VASc2 score(HR 1.37 95% CI 1.07-1.76, P=0.01). These associations were not affected by anticoagulation use over follow-up. AI-ECG AFib was also associated with incident AFib(HR 2.42 95% CI 1.96-2.98, P<0.001 Figure B) Conclusions: AI-ECG AFib predicts recurrent ischemic stroke in the community, possibly reflecting undiagnosed AFib that can be detected by AI-ECG, as it also predicts incident AFib. These results underscore the potential utility of AI-ECG for risk stratification of patients with ischemic stroke.