Faculty Bibliography

BACKGROUND:The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS:We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS:We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS:The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.

OBJECTIVE:Prolonged post-stroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of ischemic stroke (IS) patients with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We aim to evaluate the association between PCM and the institution of stroke preventive strategies and stroke recurrence. METHODS:We searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or transient ischemic attack (TIA) receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random-effects model. To explore for differences between the monitoring strategies we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT). RESULTS:We included 8 studies (5 RCTs, 3 observational; 2994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in both RCTs (RR=3.91, 95%CI:2.54-6.03 & RR=2.16, 95%CI:1.66-2.80) and observational studies (RR=2.06, 95%CI:1.57-2.70 & RR=2.01; 95%CI:1.43-2.83), respectively. PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR=0.29; 95%CI:0.15-0.59), but not in RCTs (RR=0.72, 95%CI:0.49-1.07). In the indirect analyses of RCTs the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with both Holter monitors and external loop recorders. CONCLUSIONS:PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. Currently, there is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

Importance/UNASSIGNED:In the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, acute treatment with clopidogrel-aspirin was associated with significantly reduced risk of recurrent stroke. There may be specific patient groups who are more likely to benefit from this treatment. Objective/UNASSIGNED:To investigate whether the association of clopidogrel-aspirin with stroke recurrence in patients with minor stroke or high-risk transient ischemic attack (TIA) is modified by the presence of infarct on imaging attributed to the index event (index imaging) among patients enrolled in the POINT Trial. Design, Setting, and Participants/UNASSIGNED:In the POINT randomized clinical trial, patients with high-risk TIA and minor ischemic stroke were enrolled at 269 sites in 10 countries in North America, Europe, Australia, and New Zealand from May 28, 2010, to December 19, 2017. In this post hoc analysis, patients were divided into 2 groups according to whether they had an acute infarct on index imaging. All POINT trial participants with information available on the presence or absence of acute infarct on index imaging were eligible for this study. Univariable Cox regression models evaluated associations between the presence of an infarct on index imaging and subsequent ischemic stroke and evaluated whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Data were analyzed from July 2020 to May 2021. Exposures/UNASSIGNED:Presence or absence of acute infarct on index imaging. Main Outcomes and Measures/UNASSIGNED:The primary outcome is whether the presence of infarct on index imaging modified the association of clopidogrel-aspirin with subsequent ischemic stroke risk. Results/UNASSIGNED:Of the 4881 patients enrolled in POINT, 4876 (99.9%) met the inclusion criteria (mean [SD] age, 65 [13] years; 2685 men [55.0%]). A total of 1793 patients (36.8%) had an acute infarct on index imaging. Infarct on index imaging was associated with ischemic stroke during follow-up (hazard ratio [HR], 3.68; 95% CI, 2.73-4.95; P < .001). Clopidogrel-aspirin vs aspirin alone was associated with decreased ischemic stroke risk in patients with an infarct on index imaging (HR, 0.56; 95% CI, 0.41-0.77; P < .001) compared with those without an infarct on index imaging (HR, 1.11; 95% CI, 0.74-1.65; P = .62), with a significant interaction association (P for interaction = .008). Conclusions and Relevance/UNASSIGNED:In this study, the presence of an acute infarct on index imaging was associated with increased risk of recurrent stroke and a more pronounced benefit from clopidogrel-aspirin. Future work should focus on validating these findings before targeting specific patient populations for acute clopidogrel-aspirin treatment.

OBJECTIVE:Chronic subdural hematoma (CSDH) is a serious problem with an incidence of 20.6/100,000/year in North America and is posited to grow as the population ages. Middle Meningeal Artery (MMA) embolization is an upcoming therapy for treatment of CSDH. Among patients with CSDH who undergo MMA embolization outcomes are no different in patients who resume the antithrombotic (AT) after MMA embolization as compared to patients who don't resume AT. METHODS:We did retrospective review of all cases of MMA embolization in the setting of CSDH done over 2.5 years in 2 centers. Comparison of cases in which AT was resumed vs controls with no AT was performed. A successful outcome was defined as reduction of at least 50% volume in CSDH. Univariate analysis regarding all outcome measures for baseline variables was performed using Fisher exact test or t-test. Multivariate logistic regression with controlling for age, surgical evacuation of the hematoma. RESULTS:There were a total of 56 MMA embolization cases, 33 of them had no AT started and 23 of them had AT resumption at a mean of 2.4 days. About 40% of patients had surgical evacuation done prior to MMA embolization. There was no significant difference in hematoma reduction or volume even after adjusting for surgical evacuation (OR 1.00 95%CI 0.60- 1.67). Patients who had AT resumption had more CAD (71%vs 21% p= 0.001) and Afib (58% vs 18% p=0.002) necessitating AT. CONCLUSION/CONCLUSIONS:AT therapy can be safely resumed in CSDH after MMA embolization as there is no significant difference in CSDH volume reduction and recurrence.

Background One-quarter of all strokes are subsequent events. It is not known whether higher levels of blood glucose are associated with an increased risk of subsequent stroke after high-risk transient ischemic attack or minor ischemic stroke. Methods and Results We performed a secondary analysis of the POINT (Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke) trial to evaluate the relationship between serum glucose hyperglycemia (≥180 mg/dL) versus normoglycemia (<180 mg/dL) before enrollment in the trial and outcomes at 90 days. The primary end point was subsequent ischemic stroke modeled by a multivariable Cox model with adjustment for age, sex, race, ethnicity, study treatment assignment, index event, and key comorbidities. Of 4878 patients included in this study, 267 had a recurrent stroke. There was a higher hazard of subsequent stroke in patients with hyperglycemia compared with normoglycemia (adjusted hazard ratio [HR], 1.50 [95% CI, 1.05-2.14]). Treatment with dual antiplatelet therapy was not associated with a reduced hazard of subsequent stroke in patients with hyperglycemia (HR, 1.18 [95% CI, 0.69-2.03]), though the wide confidence interval does not exclude a treatment effect. When modeled as a continuous variable, there was evidence of a nonlinear association between serum glucose and the hazard of subsequent stroke (P<0.001). Conclusions Hyperglycemia on presentation is associated with an increased risk of subsequent ischemic stroke after high-risk transient ischemic attack or minor stroke. A rapid, simple assay of serum glucose may be a useful biomarker to identify patients at particularly high risk of subsequent ischemic stroke. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT0099102.

OBJECTIVE:To explore the association between blood pressure (BP) levels after endovascular thrombectomy (EVT) and the clinical outcomes of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO). METHODS:A study was eligible if it enrolled AIS patients older than 18 years, with an LVO treated with either successful or unsuccessful EVT, and provided either individual or mean 24-hour systolic BP values after the end of the EVT procedure. Individual patient data from all studies were analyzed using a generalized linear mixed-effects model. RESULTS:A total of 5874 patients (mean age: 69±14 years, 50% women, median NIHSS on admission: 16) from 7 published studies were included. Increasing mean systolic BP levels per 10 mm Hg during the first 24 hours after the end of the EVT were associated with a lower odds of functional improvement (unadjusted common OR=0.82, 95%CI:0.80-0.85; adjusted common OR=0.88, 95%CI:0.84-0.93) and modified Ranking Scale score≤2 (unadjusted OR=0.82, 95%CI:0.79-0.85; adjusted OR=0.87, 95%CI:0.82-0.93), and a higher odds of all-cause mortality (unadjusted OR=1.18, 95%CI:1.13-1.24; adjusted OR=1.15, 95%CI:1.06-1.23) at 3 months. Higher 24-hour mean systolic BP levels were also associated with an increased likelihood of early neurological deterioration (unadjusted OR=1.14, 95%CI:1.07-1.21; adjusted OR=1.14, 95%CI:1.03-1.24) and a higher odds of symptomatic intracranial hemorrhage (unadjusted OR=1.20, 95%CI:1.09-1.29; adjusted OR=1.20, 95%CI:1.03-1.38) after EVT. CONCLUSION/CONCLUSIONS:Increased mean systolic BP levels in the first 24 hours after EVT are independently associated with a higher odds of symptomatic intracranial hemorrhage, early neurological deterioration, three-month mortality, and worse three-month functional outcomes.

Background Vasospasm is a treatable cause of deterioration following aneurysmal subarachnoid hemorrhage. Cerebral computed tomography perfusion mean transit times have been proposed as a predictor of vasospasm but suffer from well-known technical limitations. We evaluated fully automated, thresholded time-to-maxima of the tissue residue function (T

BACKGROUND:Post-acute sequelae of COVID-19 (PASC) includes a heterogeneous group of patients with variable symptomatology, who may respond to different therapeutic interventions. Identifying phenotypes of PASC and therapeutic strategies for different subgroups would be a major step forward in management. METHODS:In a prospective cohort study of patients hospitalized with COVID-19, 12-month symptoms and quantitative outcome metrics were collected. Unsupervised hierarchical cluster analyses were performed to identify patients with: (1) similar symptoms lasting ≥4 weeks after acute SARS-CoV-2 infection, and (2) similar therapeutic interventions. Logistic regression analyses were used to evaluate the association of these symptom and therapy clusters with quantitative 12-month outcome metrics (modified Rankin Scale, Barthel Index, NIH NeuroQoL). RESULTS:Among 242 patients, 122 (50%) reported ≥1 PASC symptom (median 3, IQR 1-5) lasting a median of 12-months (range 1-15) post-COVID diagnosis. Cluster analysis generated three symptom groups: Cluster1 had few symptoms (most commonly headache); Cluster2 had many symptoms including high levels of anxiety and depression; and Cluster3 primarily included shortness of breath, headache and cognitive symptoms. Cluster1 received few therapeutic interventions (OR 2.6, 95% CI 1.1-5.9), Cluster2 received several interventions, including antidepressants, anti-anxiety medications and psychological therapy (OR 15.7, 95% CI 4.1-59.7) and Cluster3 primarily received physical and occupational therapy (OR 3.1, 95%CI 1.3-7.1). The most severely affected patients (Symptom Cluster 2) had higher rates of disability (worse modified Rankin scores), worse NeuroQoL measures of anxiety, depression, fatigue and sleep disorder, and a higher number of stressors (all P<0.05). 100% of those who received a treatment strategy that included psychiatric therapies reported symptom improvement, compared to 97% who received primarily physical/occupational therapy, and 83% who received few interventions (P = 0.042). CONCLUSIONS:We identified three clinically relevant PASC symptom-based phenotypes, which received different therapeutic interventions with varying response rates. These data may be helpful in tailoring individual treatment programs.

BACKGROUND:Studies demonstrate an association between visit-to-visit blood pressure variability (BPV) and cardiovascular events and death. We aimed to determine the long-term cardiovascular and mortality effects of BPV in midlife in participants with and without cardiovascular risk factors. METHODS:This is a post-hoc analysis of the Atherosclerosis Risk in the Community study. Long-term BPV was derived utilizing mean systolic blood pressure at Visits 1-4 (Visit 1: 1987-89, Visit 2: 1990-1992, Visit 3: 1993-95, Visit 4: 1996-98). The primary outcome was mortality from Visit 4 to 2016 and secondary outcome was cardiovascular events (fatal coronary heart disease, myocardial infarction, cardiac procedure, or stroke). We fit Cox proportional hazards models and also performed the analysis in a subgroup of cardiovascular disease-free patients without prior stroke, myocardial infarction, congestive heart failure, hypertension, or diabetes. RESULTS:We included 9,578 participants. The mean age at the beginning of follow-up was 62.9±5.7 years, and mean follow-up was 14.2±4.5 years. During follow-up, 3,712 (38.8%) participants died and 1,721 (n=8,771, 19.6%) had cardiovascular events. For every standard deviation higher in systolic residual standard deviation (range 0-60.5 mm Hg, standard deviation = 5.6 mm Hg), the hazard ratio for death was 1.09 (95% CI 1.05-1.12) and for cardiovascular events was 1.00 (95% CI 0.95-1.05). In the subgroup of cardiovascular disease-free participants (n=4,452), the corresponding hazard ratio for death was 1.12 (95% CI 1.03-1.21) and for cardiovascular events was 1.01 (95% CI 0.89-1.14). CONCLUSION/CONCLUSIONS:Long-term BPV during midlife is an independent predictor of later life mortality but not cardiovascular events.

BACKGROUND:Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes. METHODS:In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models. RESULTS:Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01). CONCLUSIONS:aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.