Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Importance of Sex and Gender Differences in Enrollment and Interpretation of Stroke Clinical Trials.

OBJECTIVES: This review aims to reinforce the importance of improving sex balance in preclinical trials and sex and gender diversity and proportional balance in clinical trials enrollment and how this influences interpretation of stroke clinical trials. It also aims to identify strategies for improvement in data collection. MATERIALS AND METHODS: A PubMed search was conducted of publications in English, using MeSH terms sex, sex characteristics, gender identity, transgender, gender-nonconforming persons, clinical trials as topic, stroke. Of 249 search results, 217 were human or animal studies related to stroke, the majority of which were reviews, secondary analyses of stroke clinical trials, meta analyses, or retrospective studies, subject to the methods of sex and gender acquisition per the primary data source. Articles were reviewed, noting inclusion or absence of sex and gender definitions and trial design. Selected articles were supplemented with United States Food and Drug Administration, National Institutes of Health, and National Academy of Science, Engineering, and Medicine publications. RESULTS: The majority of preclinical studies continue to report sex as a binary variable, and the majority of stroke clinical trials report sex and gender as interchangeable and binary. Mindful trial design and statistical analysis can improve accuracy in the interpretation of sex and gender differences. Guidance exists to improve reporting on currently accepted sex and gender definitions, recommended data collection instruments, and appropriate statistical analyses. CONCLUSIONS: Despite acknowledgement of having failed to achieve diverse and proportionally balanced enrollment, sex and gender imbalance across the research continuum remains prevalent. Responsible incorporation of sex and gender in stroke clinical trials can be achieved through thoughtful study design, use of contemporary sex and gender definitions, inclusive prospective data collection, balanced enrollment with prespecified goals, and appropriate statistical analysis.

Predictors of hospital length of stay and long-term care facility placement in aneurysmal subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is frequently associated with complications, extended hospital length of stay (LOS) and high health care related costs. We sought to determine predictors for hospital LOS and discharge disposition to a long-term care facility (LTCF) in aSAH patients. Methods: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic referral center from 2016 to 2021. Multiple linear regression was performed to identify predictors for hospital LOS. We then created a 10-point scoring system to predict discharge disposition to a LTCF. Results: In a cohort of 318 patients with confirmed aSAH, mean age was 57 years (SD 13.7), 61% were female and 70% were white. Hospital LOS was longer for survivors (median 19 days, IQR 14-25) than for non-survivors (median 5 days, IQR 2-8; p < 0.001). Main predictors for longer LOS for this cohort were ventriculoperitoneal shunt (VPS) requirement (p < 0.001), delayed cerebral ischemia (p = 0.026), and pneumonia (p = 0.014). The strongest predictor for LTCF disposition was age older than 60 years (OR 1.14, 95% CI 1.07-1.21; p < 0.001). LTCF score had high accuracy in predicting discharge disposition to a LTCF (area under the curve [AUC] 0.83; 95% CI 0.75-0.91). Forty-one percent of patients who were discharged to a LTCF had significant functional recovery at 3 months post-discharge. Conclusions: VPS requirement and aSAH related complications were associated with longer hospital LOS compared to other factors. LTCF score has high accuracy in predicting discharge disposition to a LTCF.

IV Thrombolysis for central retinal artery occlusion - Real-world experience from a comprehensive stroke center.

OBJECTIVES: Central retinal artery occlusion (CRAO) is a stroke of the retina potentially amenable to intravenous thrombolysis (IVT). We aimed to determine feasibility of an emergency treatment protocol and risk profile of IVT for CRAO in a comprehensive stroke center (CSC). METHODS: We performed a retrospective, observational cohort study including patients with acute CRAO admitted to a CSC over 4 years. Patients are offered IVT if they present with acute vision loss of ≤ 20/200 in the affected eye, have no other cause of vision loss (incorporating a dilated ophthalmologic exam), and meet criteria akin to acute ischemic stroke. We collected socio-demographic data, triage data, time from onset to presentation, IVT candidacy, and rates of symptomatic intracranial hemorrhage (sICH)- or extracranial hemorrhage. RESULTS: 36 patients presented within the study period, mean (standard deviation (SD)) age of 70.7 (10), 52 % female, and median time (Q1, Q3) to ED presentation of 13.5 (4.3, 18.8) h. Patients within 4.5 h from onset presented more commonly directly to our ED (66.6 % vs 37.1 %, p = 0.1). Nine patients (25 %) presented within the 4.5 h window. Of those eligible, 7 (77 %) received IVT. There were no events of intracranial or extracranial hemorrhage. CONCLUSIONS: Our study confirmed that IVT for acute CRAO is feasible. We found a high rate of treatment with IVT of those eligible. However, because 75 % of patients presented outside the treatment window, continued educational efforts are needed to improve rapid triage to emergency departments to facilitate evaluation for possible candidacy with IVT.

Comparison of the Effects of Blood Pressure Parameters on Rebleeding and Outcomes in Unsecured Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Elevated systolic blood pressure (SBP) has been linked to preprocedural rebleeding risk and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study seeks to compare the effects of SBP and mean arterial pressure (MAP) on rebleeding and functional outcomes in aSAH patients. METHODS: We performed a retrospective study of a prospectively collected cohort of consecutive patients with aSAH admitted to an academic center in 2016-2023. Binary regression analysis was used to determine the association between BP parameters and outcomes including rebleeding and poor outcome defined as modified Rankin Scale 4-6 at 3 months postdischarge. RESULTS: The cohort included 324 patients (mean age 57 years [standard deviation 13.4], 61% female). Symptomatic rebleeding occurred in 34 patients (11%). Higher BP measurements were recorded in patients with rebleeding and poor outcome, however, only MAP met statistical significance for rebleeding (odds ratio {OR} 1.02 for 1 mmHg increase in MAP, 95% confidence interval {CI}: 1.001-1.03, P = 0.043; OR 1 per 1 mmHg increase in SBP, 95% CI 0.99-1.01; P = 0.06)) and for poor outcome (OR 1.01 for 1 mmHg increase in MAP, 95% CI: 1.002-1.025, P = 0.025; OR 1 for 1 mmHg increase in SBP, 95% CI: 0.99-1.02, P = 0.23) independent of other predictors. CONCLUSIONS: MAP may appear to be slightly better correlated with rebleeding and poor outcomes in unsecured aSAH compared to SBP. Larger prospective studies are needed to identify and mitigate risk factors for rebleeding and poor outcome in aSAH patients.

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association.

Cerebral venous thrombosis accounts for 0.5% to 3% of all strokes. The most vulnerable populations include young individuals, women of reproductive age, and patients with a prothrombotic state. The clinical presentation of cerebral venous thrombosis is diverse (eg, headaches, seizures), requiring a high level of clinical suspicion. Its diagnosis is based primarily on magnetic resonance imaging/magnetic resonance venography or computed tomography/computed tomographic venography. The clinical course of cerebral venous thrombosis may be difficult to predict. Death or dependence occurs in 10% to 15% of patients despite intensive medical treatment. This scientific statement provides an update of the 2011 American Heart Association scientific statement for the diagnosis and management of cerebral venous thrombosis. Our focus is on advances in the diagnosis and management decisions of patients with suspected cerebral venous thrombosis. We discuss evidence for the use of anticoagulation and endovascular therapies and considerations for craniectomy. We also provide an algorithm to optimize the management of patients with cerebral venous thrombosis and those with progressive neurological deterioration or thrombus propagation despite maximal medical therapy.

A reassessment of hemoglobin and hematoma expansion in intracerebral hemorrhage.

BACKGROUND: In patients with spontaneous intracerebral hemorrhage (ICH), prior studies identified an increased risk of hematoma expansion (HE) in those with lower admission hemoglobin (Hgb) levels. We aimed to reproduce these findings in an independent cohort. METHODS: We conducted a cohort study of patients admitted to a Comprehensive Stroke Center for acute ICH within 24 hours of onset. Admission laboratory and CT imaging data on ICH characteristics including HE (defined as >33% or >6 mL), and 3-month outcomes were collected. We compared laboratory data between patients with and without HE and used multivariable logistic regression to determine associations between Hgb, HE, and unfavorable 3-month outcomes (modified Rankin Scale 4-6) while adjusting for confounders including anticoagulant use, and laboratory markers of coagulopathy. RESULTS: Among 345 patients in our cohort (mean [SD] age 72.9 [13.7], 49% male), 71 (21%) had HE. Patients with HE had similar Hgb versus those without HE (mean [SD] 13.1 [1.8] g/dl vs. 13.1 [1.9] g/dl, p=0.92). In fully adjusted multivariable models, Hgb was not associated with HE (OR per 1g/dl 1.01, 95% CI 0.86 -1.17, p = 0.94), however higher admission Hgb levels were associated with lower odds of unfavorable 3-month outcome (OR 0.83 per 1 g/dl Hgb, 95% CI 0.72-0.96, p=0.01). CONCLUSION: We did not confirm a previously reported association between admission Hgb and HE in patients with ICH, although Hgb and HE were both associated with poor outcome. These findings suggest that the association between Hgb and poor outcome is mediated by other factors.

Subsequent ischemic stroke and tobacco smoking: A secondary analysis of the POINT trial.

Background: The aim of this study was to determine the effect of smoking status on subsequent stroke risk in patients with minor ischemic stroke or TIA and to determine whether smoking modifies the effect of clopidogrel-based DAPT on subsequent stroke risk. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial, which had a 90-day follow-up period. We used multivariable Cox regression and subgroup interaction analysis to determine the effect of smoking on the risk of subsequent ischemic stroke and major hemorrhage, respectively. Results: Data from 4877 participants enrolled in the POINT trial were analyzed. Among these, 1004 were current smokers and 3873 were non-smokers at the time of index event. Smoking was associated with a non-significant trend toward an increased risk of subsequent ischemic stroke during follow up (adjusted HR, 1.31 (95% CI, 0.97-1.78), p = 0.076). The effect of clopidogrel on ischemic stroke did not differ between non-smokers (HR, 0.74 (95% CI, 0.56-0.98), p = 0.03) and smokers (HR, 0.63 (95% CI, 0.37-1.05), p = 0.078), p for interaction = 0.572. Similarly, the effect of clopidogrel on major hemorrhage did not differ between non-smokers (hazard ratio, 1.67 (95% CI, 0.40-7.00), p = 0.481) and smokers (HR, 2.59 (95% CI, 1.08-6.21), p = 0.032), p for interaction = 0.613. Conclusions: In this post-hoc analysis of the POINT trial we found that the effect of clopidogrel on reducing subsequent ischemic stroke as well as risk of major hemorrhage did not depend on smoking status, indicating that smokers benefit to a similar degree from DAPT as non-smokers.

Highs and Lows: Dysnatremia and Patient Outcomes in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Disturbances in serum sodium concentration (dysnatremia) are common following aneurysmal subarachnoid hemorrhage (aSAH), but its direct impact on outcomes is not well understood. This study aimed to examine the association between dysnatremia following aSAH and patient outcomes. METHODS: A retrospective cohort study of consecutive patients with aSAH who were admitted to an academic referral center between 2015 and 2021 was performed. Multivariate logistic regression was used to test the association of dysnatremia and outcomes including modified Rankin Scale score at 3 months after discharge and vasospasm. Multiple linear regression was used to test the association of hospital length of stay and dysnatremia. RESULTS: We included 320 patients with confirmed aneurysmal etiology (mean [SD] age = 57.8 [14.3] years; 61% female; 70% White). No independent associations were found between hyponatremia or hypernatremia and functional outcome or vasospasm. However, hospital length of stay was longer in patients with hypernatremia (7 more days; 95% confidence interval = 4.4-9.6, P < 0.001) independent of age, Hunt and Hess grade, modified Fisher score, delayed cerebral ischemia, and other hospital complications. CONCLUSIONS: Although dysnatremia may not directly impact functional outcome or vasospasm risk, hypernatremia may prolong hospital length of stay. Judicious use of hypertonic saline solutions and avoidance of unnecessary dysnatremia in patients with aSAH should be considered.

Radiographic predictors of aneurysmal etiology in patients with aneurysmal pattern subarachnoid hemorrhage.

OBJECTIVE: Spontaneous angiogram-negative nonperimesencephalic subarachnoid hemorrhage (an-NPSAH) can represent a diagnostic and management dilemma. The authors sought to determine radiographic predictors of aneurysmal etiology based on admission noncontrast head CT scans. METHODS: The authors performed a retrospective cohort study of prospectively collected data from consecutive patients who were admitted for spontaneous subarachnoid hemorrhage (SAH) with suspected aneurysmal etiology to an academic center from 2016 to 2021. They compared blood thickness in the basal cisterns and sylvian fissures and modified Graeb scores on admission head CT scans between the two groups and subsequently developed a predictive model to identify aneurysmal etiology. RESULTS: Of 259 included patients (mean age 56 years [SD 12.7 years]; 55% female), 209 had aneurysmal SAH (aSAH) and 50 had an-NPSAH. The median modified Graeb scores were similar for aSAH and an-NPSAH (6 [IQR 2-10] vs 3.5 [IQR 0-8.5], p = 0.33). The mean blood thickness was greater in the sylvian fissure (p = 0.010) and interhemispheric cisterns (p = 0.002), and there was a greater median degree of extension of blood in the sylvian fissures (p = 0.001) in aSAH than in an-NPSAH patients, but the mean blood thickness was less in the prepontine cistern (p = 0.014). The authors' scoring model was constructed based on differences in radiographic features. Receiver operating characteristic curve analysis showed acceptable accuracy in predicting aneurysmal etiology (area under the curve 0.71, 95% CI 0.62-0.79). CONCLUSIONS: There are differences in radiographic features on admission head CT between an-NPSAH and aSAH patients. The authors' proposed risk stratification model may be considered for further development and use in clinical practice in the future.

Cisternal Score: A Radiographic Score to Predict Ventriculoperitoneal Shunt Requirement in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Persistent hydrocephalus requiring a ventriculoperitoneal shunt (VPS) can complicate the management of aneurysmal subarachnoid hemorrhage (aSAH). Identification of high-risk patients may guide external ventricular drain management. OBJECTIVE: To identify early radiographic predictors for persistent hydrocephalus requiring VPS placement. METHODS: In a 2-center retrospective study, we compared radiographic features on admission noncontrast head computed tomography scans of patients with aSAH requiring a VPS to those who did not, at 2 referral academic centers from 2016 through 2021. We quantified blood clot thickness in the basal cisterns including interpeduncular, ambient, crural, prepontine, interhemispheric cisterns, and bilateral Sylvian fissures. We then created the cisternal score (CISCO) using features that were significantly different between groups. RESULTS: We included 229 survivors (mean age 55.6 years [SD 13.1]; 63% female) of whom 50 (22%) required VPS. CISCO was greater in patients who required a VPS than those who did not (median 4, IQR 3-6 vs 2, IQR 1-4; P < .001). Higher CISCO was associated with higher odds of developing persistent hydrocephalus with VPS requirement (odds ratio 1.6 per point increase, 95% CI 1.34-1.9; P < .001), independent of age, Hunt and Hess grades, and modified GRAEB scores. CISCO had higher accuracy in predicting VPS requirement (area under the curve 0.75, 95% CI 0.68-0.82) compared with other predictors present on admission. CONCLUSION: Cisternal blood clot quantification on admission noncontrast head computed tomography scan is feasible and can be used in predicting persistent hydrocephalus with VPS requirement in patients with aSAH. Future prospective studies are recommended to further validate this tool.

Association of hemoglobin trend and outcomes in aneurysmal subarachnoid hemorrhage: A single center cohort study.

BACKGROUND: Anemia has been linked to delayed cerebral ischemia (DCI) and worse outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the association of hemoglobin (Hb) trend and outcomes is not well studied. We investigated predictors of Hb trend and its association with outcomes in patients with aSAH. Our hypothesis was that a negative Hb trend is associated with poorer outcomes independent of Hb values. METHODS: We conducted a retrospective study of a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center (2016-2021). We tested the association of Hb trend and values with measures including DCI and poor functional outcome defined as modified Rankin scale 4-6 at 3 months after discharge. Multiple linear regression analysis was used to identify factors associated with Hb difference from admission to discharge. RESULTS: We included 310 patients with confirmed aneurysmal etiology (mean age 57 years, SD13.6; 62 % female). Greater Hb decrement from admission to discharge was independently associated with higher likelihood of both DCI (OR 1.28 per 1 g/dl decrease in Hb, 95 % CI 1.08-1.47; p = 0.003) and poor functional outcome (OR 1.27 per 1 g/dl decrease in Hb, 1.03-1.53; p = 0.026) independent of any absolute Hb values. Predictors of Hb decrement from admission to discharge were hospital length of stay, Hunt and Hess grades, female sex and age. CONCLUSION: Greater Hb decrement can be associated with higher likelihood of DCI and poor functional outcome in aSAH. More evidence is needed to use Hb trend to guide transfusion threshold in aSAH patients.

A Pilot Study of the Fluctuating Mental Status Evaluation: A Novel Delirium Screening Tool for Neurocritical Care Patients.

BACKGROUND: Delirium occurs frequently in patients with stroke and neurocritical illness but is often underrecognized. We developed a novel delirium screening tool designed specifically for neurocritical care patients called the fluctuating mental status evaluation (FMSE) and aimed to test its usability and accuracy in a representative cohort of patients with intracerebral hemorrhage (ICH). METHODS: We performed a single-center prospective study in a pilot cohort of patients with ICH who had daily delirium assessments throughout their admission. Reference-standard expert ratings were performed each afternoon using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and were derived from bedside assessments and clinical data from the preceding 24 h. Paired FMSE assessments were performed by patients' clinical nurses after receiving brief one-on-one training from research staff. Nursing assessments were aggregated over 24-h periods (including day and night shifts), and accuracy of the FMSE was analyzed in patients who were not comatose to determine optimal scoring thresholds. RESULTS: We enrolled 40 patients with ICH (mean age 71.1 ± 12.2, 55% male, median National Institutes of Health Stroke Scale score 16.5 [interquartile range 12-20]), of whom 85% (n = 34) experienced delirium during their hospitalization. Of 308 total coma-free days with paired assessments, 208 (68%) were rated by experts as days with delirium. Compared with expert ratings, FMSE scores ≥ 1 had 86% sensitivity and 73% specificity on a per-day basis, whereas FMSE scores ≥ 2 had 68% sensitivity and 82% specificity. Accuracy remained high in patients with aphasia (FMSE scores ≥ 1: 83% sensitivity, 77% specificity; FMSE scores ≥ 2: 68% sensitivity, 85% specificity) and decreased arousal (FMSE scores ≥ 1: 80% sensitivity, 100% specificity; FMSE scores ≥ 2: 73% sensitivity, 100% specificity). CONCLUSIONS: In this pilot study, the FMSE achieved a high sensitivity and specificity in detecting delirium. Follow-up validation studies in a larger more diverse cohort of neurocritical care patients will use score cutoffs of ≥ 1 as "possible" delirium and ≥ 2 as "probable" delirium.

A quantitative model to differentiate nonaneurysmal perimesencephalic subarachnoid hemorrhage from aneurysmal etiology.

OBJECTIVE: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (pmSAH) is considered to have a lower-risk pattern than other types of subarachnoid hemorrhage (SAH). However, a minority of patients with pmSAH may harbor a causative posterior circulation aneurysm. To exclude this possibility, many institutions pursue exhaustive imaging. In this study the authors aimed to develop a novel predictive model based on initial noncontrast head CT (NCHCT) features to differentiate pmSAH from aneurysmal causes. METHODS: The authors retrospectively reviewed patients admitted to an academic center for treatment of a suspected aneurysmal SAH (aSAH) during the period from 2016 to 2021. Patients with a final diagnosis of pmSAH or posterior circulation aSAH were included. Using NCHCT, the thickness (continuous variable) and location of blood in basal cisterns and sylvian fissures (categorical variables) were compared between groups. A scoring system was created using features that were significantly different between groups. Receiver operating characteristic curve analysis was used to measure the accuracy of this model in predicting aneurysmal etiology. A separate patient cohort was used for external validation of this model. RESULTS: Of 420 SAH cases, 48 patients with pmSAH and 37 with posterior circulation aSAH were identified. Blood thickness measurements in the crural and ambient cisterns and interhemispheric and sylvian fissures and degree of extension into the sylvian fissure were all significantly different between groups (all p < 0.001). The authors developed a 10-point scoring model to predict aneurysmal causes with high accuracy (area under the curve [AUC] 0.99; 95% CI 0.98-1.00; OR per point increase 10; 95% CI 2.18-46.4). External validation resulted in persistently high accuracy (AUC 0.97; 95% CI 0.92-1.00) of this model. CONCLUSIONS: A risk stratification score using initial blood clot burden may accurately differentiate between aneurysmal and nonaneurysmal pmSAH. Larger prospective studies are encouraged to further validate this quantitative tool.

Association of asymptomatic cerebral vasospasm with outcomes in survivors of aneurysmal subarachnoid hemorrhage.

BACKGROUND: Cerebral vasospasm (cVSP) is a common complication in aneurysmal subarachnoid hemorrhage (aSAH) and is associated with worse outcomes. However, clinical significance of asymptomatic cVSP is poorly understood. We sought to determine the association of asymptomatic cVSP with functional outcome and hospital length of stay (LOS). METHODS: We performed a retrospective study of a prospectively collected cohort of patients with aSAH who survived hospitalization at an academic center between 2016 and 2021. We defined cVSP based on transcranial Doppler criteria. Multivariate logistic and multiple linear regression analyses were used to determine the association of asymptomatic cVSP with poor functional outcome (defined as modified Rankin scale 3-6 at 3 months after discharge) and hospital length of stay (LOS). RESULTS: The cohort consisted of 201 aSAH patients with a mean age 54.9 years (SD 13.6) and 60% were female. One hundred nine patients (54%) experienced cVSP, of whom 43 patients (39%) were asymptomatic. Patients with asymptomatic cVSP were younger (mean 50.5 years [SD 10.6] vs 61 years [SD12.5]; p < 0.001) and had longer ICU LOS (median 13 days [IQR12-20] vs median 12 days [IQR9-15], p = 0.018) compared to those without cVSP. However, after adjusting with other variables asymptomatic cVSP was not associated with longer ICU or hospital LOS. Asymptomatic cVSP was not associated with poor outcome either (p = 0.14). CONCLUSION: Asymptomatic cVSP, which was more common in younger patients, was neither associated with poor functional outcome nor hospital LOS.  Larger prospective studies are needed to assess the significance of asymptomatic cVSP on long-term outcomes.

Association of pre-admission antihypertensive agents and outcomes in aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) and poor functional outcome are common complications in patients who suffer from aneurysmal subarachnoid hemorrhage (aSAH). It has been proposed that pre-admission beta-blocker therapy may lower cerebral vasospasm (cVSP) risk after aSAH; however, this association with other antihypertensives is unknown. We sought to determine the association between antihypertensives and clinical outcomes in aSAH patients. METHODS: We performed a retrospective study on a prospectively collected cohort of consecutive patients with aSAH who were admitted to an academic center from 2016 to 2021. Association between pre-admission use of antihypertensives and patient outcomes was determined. Primary outcomes included DCI and poor functional outcome at 3 months after discharge defined as modified Rankin scale [mRS] 4-6. The secondary outcome was cVSP identified using transcranial Doppler (TCD). RESULTS: The cohort consisted of 306 aSAH patients with mean age 57.1 (SD 13.6) years with 187 females (61 %). Although pre-admission use of beta-blockers (OR 0.40, 95 % CI 0.21-80, p = 0.02), calcium channel blockers (OR 0.43, 95 % CI 0.19-0.93, p = 0.035), and thiazide (OR 0.31, 95 % CI 0.11-0.86, p = 0.025) were associated with lower risk of cVSP in univariate analysis, we did not find any association in a multivariate model after adjusting for age. There was no association between any class of antihypertensives and DCI or functional outcome. CONCLUSION: Pre-admission use of antihypertensive agents may affect TCD findings, however, none of them appear to be independently associated with DCI or functional outcome. Larger prospective studies are needed to establish any potential association.

Central vs site outcome adjudication in the IRIS trial.

BACKGROUND: Central adjudication of outcome events is the standard in clinical trial research. We examine the benefit of central adjudication in the Insulin Resistance Intervention after Stroke (IRIS) trial and show how the benefit is influenced by outcome definition and features of the adjudicated events. METHODS: IRIS tested pioglitazone for prevention of stroke and myocardial infarction in patients with a recent transient ischemic attack or ischemic stroke. We compared the hazard ratios for study outcomes classified by site and central adjudication. We repeated the analysis for an updated stroke definition. RESULTS: The hazard ratios for the primary outcome were identical (0.76) and statistically significant regardless of adjudicator. The hazard ratios for stroke alone were nearly identical with site and central adjudication, but only reached significance with site adjudication (HR, 0.80; p = 0.049 vs. HR, 0.82; p = 0.09). Using the updated stroke definition, all hazard ratios were lower than with the original IRIS definition and statistically significant regardless of adjudication method. Agreement was higher when stroke type was certain, subtype was large vessel or cardioembolic, signs or symptoms lasted > 24 h, imaging showed a stroke, and when NIHSS was ≥3. DISCUSSION: Central stroke adjudication caused the hazard ratio for a main secondary outcome in IRIS (stroke alone) to be higher and lose statistical significant compared with site review. The estimate of treatment effects were larger with the updated stroke definition. There may be benefit of central adjudication for events with specific features, such as shorter symptom duration or normal brain imaging.

Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study.

BACKGROUND: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. METHODS: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. RESULTS: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA2DS2-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0-1.3] for each point increase; P=0.05) and hypertension (OR, 2.3 [95% CI, 1.0-5.1]; P=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0-1.2] for each year increase; P=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4-14.2]; P=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4-5.5]; P=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8-1.7]). CONCLUSIONS: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

The impact of perioperative stroke and delirium on outcomes after surgical aortic valve replacement.

OBJECTIVE: The effects of stroke and delirium on postdischarge cognition and patient-centered health outcomes after surgical aortic valve replacement (SAVR) are not well characterized. Here, we assess the impact of postoperative stroke and delirium on these health outcomes in SAVR patients at 90 days. METHODS: Patients (N = 383) undergoing SAVR (41% received concomitant coronary artery bypass graft) enrolled in a randomized trial of embolic protection devices underwent serial neurologic and delirium evaluations at postoperative days 1, 3, and 7 and magnetic resonance imaging at day 7. Outcomes included 90-day functional status, neurocognitive decline from presurgical baseline, and quality of life. RESULTS: By postoperative day 7, 25 (6.6%) patients experienced clinical stroke and 103 (28.5%) manifested delirium. During index hospitalization, time to discharge was longer in patients experiencing stroke (hazard ratio, 0.62; 95% confidence interval [CI], 0.42-0.94; P = .02) and patients experiencing delirium (hazard ratio, 0.68; 95% CI, 0.54-0.86; P = .001). At day 90, patients experiencing stroke were more likely to have a modified Rankin score >2 (odds ratio [OR], 5.9; 95% CI, 1.7-20.1; P = .01), depression (OR, 5.3; 95% CI, 1.6-17.3; P = .006), a lower 12-Item Short Form Survey physical health score (adjusted mean difference -3.3 ± 1.9; P = .08), and neurocognitive decline (OR, 7.8; 95% CI, 2.3-26.4; P = .001). Delirium was associated with depression (OR, 2.2; 95% CI, 0.9-5.3; P = .08), lower 12-Item Short Form Survey physical health (adjusted mean difference -2.3 ± 1.1; P = .03), and neurocognitive decline (OR, 2.2; 95% CI, 1.2-4.0; P = .01). CONCLUSIONS: Stroke and delirium occur more frequently after SAVR than is commonly recognized, and these events are associated with disability, depression, cognitive decline, and poorer quality of life at 90 days postoperatively. These findings support the need for new interventions to reduce these events and improve patient-centered outcomes.