The left atrial appendage exclusion for prophylactic stroke reduction (leaaps) trial: rationale and design.

INTRODUCTION: Left atrial appendage exclusion (LAAE) has been shown in randomized trials to reduce ischemic stroke risk in patients undergoing cardiac surgery with known atrial fibrillation (AF). Many patients undergoing cardiac surgery without pre-existing AF are at risk of stroke and may benefit from LAAE. METHODS: Left Atrial Appendage Exclusion for Prophylactic Stroke Reduction (LeAAPS) is an international, prospective, randomized, multicenter, blinded trial evaluating the effectiveness of LAAE in preventing ischemic stroke or systemic embolism in patients undergoing cardiac surgery at increased risk of AF and ischemic stroke. The trial will enroll 6500 patients at increased risk of stroke in whom a cardiac surgery is planned at 250 sites worldwide. Eligible patients are ≥18 years old, have no pre-existing AF but are at increased risk for AF and stroke (based on age, CHA2DS2-VASc score, left atrium size or brain natriuretic peptide). Patients are randomized 1:1 to receive either LAAE with AtriClip or no LAAE during cardiac surgery. Healthcare providers outside of the operating room and the patient will be blinded to allocation. The primary effectiveness endpoint is the first occurrence of ischemic stroke, systemic arterial embolism, or surgical or endovascular LAA closure. The powered secondary effectiveness endpoint is ischemic stroke or systemic arterial embolism. The primary safety endpoint is the occurrence of one of the following events (through 30 days): pericardial effusion requiring percutaneous or surgical treatment, peri-operative major bleeding, deep sternal wound infection, or myocardial infarction. Other endpoints include mortality, rehospitalizations, clinically diagnosed AF, transient ischemic attack, and cognitive and quality of life assessments. Follow-up is every 6 months for a minimum of 5 years; primary analysis occurs when 469 patients have had an ischemic stroke or systemic embolism. CONCLUSION: The results of the LeAAPS trial will demonstrate whether LAAE with AtriClip at the time of other routine cardiac surgery reduces stroke or systemic arterial embolism during long-term follow-up in patients at high risk of stroke without pre-existing AF. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT05478304, https://clinicaltrials.gov/study/NCT05478304?term=%20NCT05478304&rank=1.

Late device-related thrombus associated with occult malignancy years after left atrial appendage closure.

INTRODUCTION: The use of Left Atrial Appendage (LAA) occluder devices has been on the rise in patients with atrial fibrillation. Studies regarding the long-term risks of occluder devices remain sparse. MATERIALS & METHODS: In this brief report, we discuss the unusual case of an 85-year-old female with long-term complication from Left Atrial Appendage (LAA) closure: Device-Related Thrombus (DRT) about two years after insertion. RESULTS: Compared to the expected stroke rate without anticoagulation, patients with DRT on their LAAO device still had a 28 % relative reduction in ischemic stroke. This suggests that these strokes may have emanated from alternate etiologies other than the DRT. CONCLUSIONS: Patients with active or known history of cancer appears to have a higher risk of DRT. More data is needed on this topic to augment awareness and understanding of LAAO complications and DRT management strategies.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

Nationally Certified Stroke Centers Outperform Self-Attested Stroke Centers in the Florida Stroke Registry.

BACKGROUND: The Florida Stroke Act, signed into law in 2004, set criteria for Comprehensive Stroke Centers (CSC). For a set time period, Florida hospitals were permitted to either receive national certification (NC) or could self-attest (SA) as fulfilling CSC criteria. The aim of this project was to evaluate the quality of ischemic stroke care in NC versus SA stroke centers in Florida, using well-known, guideline-driven ischemic stroke outcome metrics. METHODS: A total of 37 CSCs (74% of Florida CSCs) in the Florida Stroke Registry from January 2013 through December 2018 were analyzed, including 19 SA CSCs and 18 NC (13 CSCs and 5 Thrombectomy-Capable Stroke Center). Hospital- and patient-level characteristics and stroke metrics were evaluated, adjusting for demographics, medical comorbidities, and stroke severity. RESULTS: A total of 78 424 acute ischemic stroke cases, 36 089 from SA CSCs and 42 335 from NC CSC/Thrombectomy-Capable Stroke Centers were analyzed. NC centers had older patients (73 [61-83] versus 71 [60-81]; P<0.001) with more severe strokes (median National Institutes of Health Stroke Scale score of 5 versus 4; P<0.001). NC had higher intravenous tissue-type plasminogen activator utilization (15% versus 13%; P<0.001), endovascular treatment (10% versus 7%; P<0.001) and faster median door-to-computed tomography (23 minutes [11-73] versus 31 [12-78]; P<0.001), door-to-needle (37 minutes [26-50] versus 45 [34-58]; P<0.001) and door-to-puncture times (77 minutes [50-113] versus 93 [62-140]; P<0.001). In adjusted analysis, patients arriving to NC hospitals by 3 hours were more likely to get intravenous tissue-type plasminogen activator in the 3- to 4.5-hour window (adjusted odds ratio, 1.87 [95% CI, 1.30-2.68]; P=0.001) and more likely to be treated with intravenous tissue-type plasminogen activator within 45 minutes (adjusted odds ratio, 1.61 [95% CI, 1.04-2.50]; P=0.04) compared with SA CSCs. CONCLUSIONS: Among Florida-Stroke Registry CSCs, acute ischemic stroke performance and treatment measures at NC centers are superior to SA CSCs. These findings have implications for stroke systems of care in Florida and support legislation updates requiring NC and removal of SA claims.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

Preexisting Depression and Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. METHODS: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. RESULTS: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. CONCLUSIONS: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.

Early Apixaban Use Following Stroke in Patients With Atrial Fibrillation: Results of the AREST Trial.

BACKGROUND AND PURPOSE: It is unknown when to start anticoagulation after acute ischemic stroke (AIS) from atrial fibrillation (AF). Early anticoagulation may prevent recurrent infarctions but may provoke hemorrhagic transformation as AF strokes are typically larger and hemorrhagic transformation-prone. Later anticoagulation may prevent hemorrhagic transformation but increases risk of secondary stroke in this time frame. Our aim was to compare early anticoagulation with apixaban in AF patients with stroke or transient ischemic attack (TIA) versus warfarin administration at later intervals. METHODS: AREST (Apixaban for Early Prevention of Recurrent Embolic Stroke and Hemorrhagic Transformation) was an open-label, randomized controlled trial comparing the safety of early use of apixaban at day 0 to 3 for TIA, day 3 to 5 for small-sized AIS (<1.5 cm), and day 7 to 9 for medium-sized AIS (≥1.5 cm, excluding full cortical territory), to warfarin, in a 1:1 ratio at 1 week post-TIA, or 2 weeks post-AIS. RESULTS: Although AREST ended prematurely after a national guideline focused update recommended direct oral anticoagulants over warfarin for AF, it revealed that apixaban had statistically similar yet generally numerically lower rates of recurrent strokes/TIA (14.6% versus 19.2%, P=0.78), death (4.9% versus 8.5%, P=0.68), fatal strokes (2.4% versus 8.5%, P=0.37), symptomatic hemorrhages (0% versus 2.1%), and the primary composite outcome of fatal stroke, recurrent ischemic stroke, or TIA (17.1% versus 25.5%, P=0.44). One symptomatic intracerebral hemorrhage occurred on warfarin, none on apixaban. Five asymptomatic hemorrhagic transformation occurred in each arm. CONCLUSIONS: Early initiation of anticoagulation after TIA, small-, or medium-sized AIS from AF does not appear to compromise patient safety. Potential efficacy of early initiation of anticoagulation remains to be determined from larger pivotal trials. Registration: URL: https://www.clinicaltrials.gov/; Unique identifier: NCT02283294.

Antithrombotic Treatment of Embolic Stroke of Undetermined Source: RE-SPECT ESUS Elderly and Renally Impaired Subgroups.

Background and Purpose- The RE-SPECT ESUS trial (Randomized, Double-Blind, Evaluation in Secondary Stroke Prevention Comparing the Efficacy and Safety of the Oral Thrombin Inhibitor Dabigatran Etexilate Versus Acetylsalicylic Acid in Patients With Embolic Stroke of Undetermined Source) tested the hypothesis that dabigatran would be superior to aspirin for the prevention of recurrent stroke in patients with embolic stroke of undetermined source. This exploratory subgroup analysis investigates the impact of age, renal function (both predefined), and dabigatran dose (post hoc) on the rates of recurrent stroke and major bleeding. Methods- RE-SPECT ESUS was a multicenter, randomized, double-blind trial of dabigatran 150 or 110 mg (for patients aged ≥75 years and/or with creatinine clearance 30 to <50 mL/minute) twice daily compared with aspirin 100 mg once daily. The primary outcome was recurrent stroke. Results- The trial, which enrolled 5390 patients from December 2014 to January 2018, did not demonstrate superiority of dabigatran versus aspirin for prevention of recurrent stroke in patients with embolic stroke of undetermined source. However, among the population qualifying for the lower dabigatran dose, the rate of recurrent stroke was reduced with dabigatran versus aspirin (7.4% versus 13.0%; hazard ratio, 0.57 [95% CI, 0.39-0.82]; interaction P=0.01). This was driven mainly by the subgroup aged ≥75 years (7.8% versus 12.4%; hazard ratio, 0.63 [95% CI, 0.43-0.94]; interaction P=0.10). Stroke rates tended to be lower with dabigatran versus aspirin with declining renal function. Risks for major bleeding were similar between treatments, irrespective of renal function, but with a trend for lower bleeding rates with dabigatran versus aspirin in older patients. Conclusions- In subgroup analyses of RE-SPECT ESUS, dabigatran reduced the rate of recurrent stroke compared with aspirin in patients qualifying for the lower dose of dabigatran. These results are hypothesis-generating. Aspirin remains the standard antithrombotic treatment for patients with embolic stroke of undetermined source. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02239120.

Cryptogenic Intracranial Hemorrhagic Strokes Associated with Hypervitaminosis E and Acutely Elevated α-Tocopherol Levels.

OBJECTIVES: Up to 41% of intracerebral hemorrhages (ICH) are considered cryptogenic despite a thorough investigation to determine etiology. Certain over-the-counter supplements may increase proclivity to bleeding, and we hypothesize that specifically vitamin E may have an association with ICH and acutely elevated serum levels of α-tocopherol. Our aim is to report 3 cases of recently admitted patients with hypervitaminosis E and otherwise cryptogenic ICH. METHODS: At our institution between January and December 2018, 179 patients were admitted with ICH with 73 imputed to be "cryptogenic" (without clear etiology as per Structural vascular lesions, Medication, Amyloid angiopathy, Systemic disease, Hypertension, or Undetermined and Hypertension, Amyloid angiopathy, Tumor, Oral anticoagulants, vascular Malformation, Infrequent causes, and Cryptogenic criteria). Of these, we found 3 (4.1%) clearly admitted to consistent use of vitamin E supplementation for which α-tocopherol levels were checked. We describe the clinical presentation and course of these patients and their etiologic and diagnostic evaluations including neuroimaging and α-tocopherol laboratory data. RESULTS: All patients in this series were consistently consuming higher than recommended doses of vitamin E and developed acute ICH. The first 2 patients both had subcortical (thalamic) intraparenchymal hemorrhages while the third had an intraventricular hemorrhage. Serum α-tocopherol levels in patient A, B, and C were elevated at 30.8, 46.7, and 23.3 mg/L, respectively (normal range 5.7-19.9 mg/L) with a mean of 33.6 mg/L. No clear alternate etiologies to their ICH could be conclusively determined despite thorough workups. CONCLUSIONS: In patients with cryptogenic ICH, clinicians should consider hypervitaminosis E and check serum α-tocopherol level during admission. Reviewing the patient's pharmacologic history, including over-the-counter supplements such as vitamin E, may help identify its association, and its avoidance in the future may mitigate risk. With its known vitamin K antagonism, hypo-prothrombinemic effect, cytochrome p-450 interaction, and antiplatelet activity, vitamin E may not be as benign as presumed. Its consumption in nonrecommended doses may increase ICH risk, which may be underestimated and under-reported.

Disparities and Temporal Trends in the Use of Anticoagulation in Patients With Ischemic Stroke and Atrial Fibrillation.

Background and Purpose- Ischemic stroke (IS) secondary to atrial fibrillation (AF) is largely preventable with the use of anticoagulation. We sought to identify race-ethnicity and sex disparities with the use of direct oral anticoagulants (DOACs), aspirin, and warfarin in IS patients with AF and to identify temporal trends in the utilization of these medications. Methods- The FLiPER-AF Stroke Study (Florida Puerto Rico Atrial Fibrillation) included 24 040 IS cases enrolled in the Florida-Puerto Rico Collaboration to Reduce Stroke Registry from 2010 to 2016. Multivariable logistic regression models were performed to evaluate the effect of race-ethnicity and sex on utilization of DOACs, aspirin, and warfarin for stroke prevention in AF after adjustment for sociodemographic, hospital, and clinical factors. Results- Among 24 040 IS cases, 54% were women and 10% black, 12% FL-Hispanics, 4% PR-Hispanic, and 74% whites. From 2010 to 2016, DOAC use increased from 0% to 36%, warfarin use decreased from 51% to 17%, and aspirin use remained relatively stable (42%-40%). After adjustment, blacks had higher odds of warfarin (odds ratio, 1.22; 95% CI, 1.07-1.40) prescription at discharge compared with whites. Men had higher rates of aspirin (42.1% versus 38.8%), warfarin (33.6% versus 28.9%), and DOAC (21.3% versus 19.3%) use compared with women. After adjustment, women had lower odds of being discharged on aspirin (odds ratio, 0.92; 95% CI, 0.86-0.98) or warfarin (odds ratio, 0.91; 95% CI, 0.84-0.99). There was no sex difference in use of DOACs. Conclusions- Our study confirmed the increasing use of DOACs, downtrending use of warfarin, whereas aspirin use remained similar over the years. There are sex and race-ethnicity disparities in anticoagulation use in IS patients with AF. It is critical to understand underlying drivers of these disparities to develop better practice strategies for stroke prevention in patients with AF. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT03627806.

Relearning functional and symmetric walking after stroke using a wearable device: a feasibility study.

BACKGROUND: Gait impairment is a common consequence of stroke and typically involves a hemiparetic or asymmetric walking pattern. Asymmetric gait patterns are correlated with decreased gait velocity and efficiency as well as increased susceptibility to serious falls and injuries. RESEARCH QUESTION: This paper presents an innovative device worn on a foot for gait rehabilitation post stroke. The device generates a backward motion to the foot, which is designed to exaggerate the existing step length asymmetry while walking over ground. We hypothesize this motion will decrease gait asymmetry and improve functional walking in individuals with chronic stroke. METHODS: Six participants with chronic stroke, more than one year post stroke, received four weeks of gait training with three sessions per week. Each session included 30 min of walking over ground using the wearable device. Gait symmetry and functional walking were assessed before and after training. RESULTS: All participants improved step length symmetry, and four participants improved double limb support symmetry. All participants improved on all three functional outcomes (gait velocity, Timed Up and Go Test, and 6-Minute Walk Test), and five participants improved beyond the minimal detectable change or meaningful change in at least one functional outcome. CONCLUSION: The results indicate that the presented device may help improve stroke patients' walking ability and warrant further study. A gait training approach using this new device may enable and expand long-term continuous gait rehabilitation outside the clinic following stroke. TRIAL REGISTRATION: NCT02185404. Registered July 9, 2014, https://clinicaltrials.gov/ct2/show/NCT02185404.

Predictors of Thrombolysis Administration in Mild Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

BACKGROUND AND PURPOSE: Mild stroke is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable among different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). METHODS: Among 73 712 prospectively enrolled patients with a final diagnosis of ischemic stroke or TIA from January 2010 to April 2015, we identified 7746 cases with persistent neurological symptoms and National Institutes of Health Stroke Scale ≤5 who arrived within 4 hours of symptom onset. Multilevel logistic regression analysis with generalized estimating equations was used to identify independent predictors of thrombolytic administration in the subgroup of patients without contraindications to thrombolysis. RESULTS: We included 6826 cases (final diagnosis mild stroke, 74.6% and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3% white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior vascular disease (myocardial infarction, peripheral vascular disease, and previous stroke), and had a higher presenting median National Institutes of Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early hospital arrival (arrive by 0-2 hours versus ≥3.5 hours; odds ratio [OR], 8.16; 95% confidence interval [CI], 4.76-13.98), higher National Institutes of Health Stroke Scale (OR, 1.87; 95% CI, 1.77-1.98), aphasia at presentation (OR, 1.35; 95% CI, 1.12-1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI, 1.53-2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39-2.95) were independent predictors of thrombolysis administration. CONCLUSIONS: Mild acutely presenting stroke patients are more likely to receive thrombolysis if they are young, white, or Hispanic and arrive early to the hospital with more severe neurological presentation. Identification of predictors of thrombolysis is important in design of future studies to assess the use of thrombolysis for mild stroke.

Disparities and Trends in Door-to-Needle Time: The FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities).

BACKGROUND AND PURPOSE: In the United States, about half of acute ischemic stroke patients treated with tPA (tissue-type plasminogen activator) receive treatment within 60 minutes of hospital arrival. We aimed to determine the proportion of patients receiving tPA within 60 minutes (door-to-needle time [DTNT] ≤60) and 45 minutes (DTNT ≤45) of hospital arrival by race/ethnicity and sex and to identify temporal trends in DTNT ≤60 and DTNT ≤45. METHODS: Among 65 654 acute ischemic stroke admissions in the National Institute of Neurological Disorders and Stroke-funded FL-PR CReSD study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities) from 2010 to 2015, we included 6181 intravenous tPA-treated cases (9.4%). Generalized estimating equations were used to determine predictors of DTNT ≤60 and DTNT ≤45. RESULTS: DTNT ≤60 was achieved in 42% and DTNT ≤45 in 18% of cases. After adjustment, women less likely received DTNT ≤60 (odds ratio, 0.81; 95% confidence interval, 0.72-0.92) and DTNT ≤45 (odds ratio, 0.73; 95% confidence interval, 0.57-0.93). Compared with Whites, Blacks less likely had DTNT ≤45 during off hours (odds ratio, 0.68; 95% confidence interval, 0.47-0.98). Achievement of DTNT ≤60 and DTNT ≤45 was highest in South Florida (50%, 23%) and lowest in West Central Florida (28%, 11%). CONCLUSIONS: In the FL-PR CReSD, achievement of DTNT ≤60 and DTNT ≤45 remains low. Compared with Whites, Blacks less likely receive tPA treatment within 45 minutes during off hours. Treatment within 60 and 45 minutes is lower in women compared with men and lowest in West Central Florida compared with other Florida regions and Puerto Rico. Further research is needed to identify reasons for delayed thrombolytic treatment in women and Blacks and factors contributing to regional disparities in DTNT.

Phantom-based standardization of CT angiography images for spot sign detection.

PURPOSE: The CT angiography (CTA) spot sign is a strong predictor of hematoma expansion in intracerebral hemorrhage (ICH). However, CTA parameters vary widely across centers and may negatively impact spot sign accuracy in predicting ICH expansion. We developed a CT iodine calibration phantom that was scanned at different institutions in a large multicenter ICH clinical trial to determine the effect of image standardization on spot sign detection and performance. METHODS: A custom phantom containing known concentrations of iodine was designed and scanned using the stroke CT protocol at each institution. Custom software was developed to read the CT volume datasets and calculate the Hounsfield unit as a function of iodine concentration for each phantom scan. CTA images obtained within 8 h from symptom onset were analyzed by two trained readers comparing the calibrated vs. uncalibrated density cutoffs for spot sign identification. ICH expansion was defined as hematoma volume growth >33%. RESULTS: A total of 90 subjects qualified for the study, of whom 17/83 (20.5%) experienced ICH expansion. The number of spot sign positive scans was higher in the calibrated analysis (67.8 vs 38.9% p < 0.001). All spot signs identified in the non-calibrated analysis remained positive after calibration. Calibrated CTA images had higher sensitivity for ICH expansion (76 vs 52%) but inferior specificity (35 vs 63%) compared with uncalibrated images. CONCLUSION: Normalization of CTA images using phantom data is a feasible strategy to obtain consistent image quantification for spot sign analysis across different sites and may improve sensitivity for identification of ICH expansion.

Sex Disparities in Ischemic Stroke Care: FL-PR CReSD Study (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities).

BACKGROUND AND PURPOSE: Sex-specific disparities in stroke care including thrombolytic therapy and early hospital admission are reported. In a large registry of Florida and Puerto Rico hospitals participating in the Get With The Guidelines-Stroke program, we sought to determine sex-specific differences in ischemic stroke performance metrics and overall thrombolytic treatment. METHODS: Around 51 317 (49% women) patients were included from 73 sites from 2010 to 2014. Multivariable logistic regression with generalized estimating equations evaluated sex-specific differences in the prespecified Get With The Guidelines-Stroke metrics for defect-free care in ischemic stroke, adjusting for age, race-ethnicity, insurance status, hospital characteristics, individual risk factors, and the presenting stroke severity. RESULTS: As compared with men, women were older (73±15 versus 69±14 years; P<0.0001), more hypertensive (67% versus 63%, P<0.0001), and had more atrial fibrillation (19% versus 16%; P<0.0001). Defect-free care was slightly lower in women than in men (odds ratio, 0.96; 95% confidence interval, 0.93-1.00). Temporal trends in defect-free care improved substantially and similarly for men and women, with a 29% absolute improvement in women (P<0.0001) and 28% in men (P<0.0001), with P value of 0.13 for time-by-sex interaction. Women were less likely to receive thrombolysis (odds ratio, 0.92; 95% confidence interval, 0.86-0.99; P=0.02) and less likely to have a door-to-needle time <1 hour (odds ratio, 0.83; 95% confidence interval, 0.71-0.97; P=0.02) as compared with men. CONCLUSIONS: Women received comparable stroke care to men in this registry as measured by prespecified Get With The Guidelines metrics. However, women less likely received thrombolysis and had door-to-needle time <1 hour, an observation that calls for the implementation of interventions to reduce sex disparity in these measures.

Constitutional Chromoanagenesis of Distal 13q in a Young Adult with Recurrent Strokes.

Constitutional chromoanagenesis events, which include chromoanasynthesis and chromothripsis and result in highly complex rearrangements, have been reported for only a few individuals. While rare, these phenomena have likely been underestimated in a constitutional setting as technologies that can accurately detect such complexity are relatively new to the mature field of clinical cytogenetics. G-banding is not likely to accurately identify chromoanasynthesis or chromothripsis, since the banding patterns of chromosomes are likely to be misidentified or oversimplified due to a much lower resolution. We describe a patient who was initially referred for cytogenetic testing as a child for speech delay. As a young adult, he was referred again for recurrent strokes. Chromosome analysis was performed, and the rearrangement resembled a simple duplication of 13q32q34. However, SNP microarray analysis showed a complex pattern of copy number gains and a loss consistent with chromoanasynthesis involving distal 13q (13q32.1q34). This report emphasizes the value of performing microarray analysis for individuals with abnormal or complex chromosome rearrangements.

Minimally invasive epicardial surgical left atrial appendage exclusion for atrial fibrillation patients at high risk for stroke and for bleeding.

BACKGROUND: Atrial fibrillation (AF) patients at high risk for stroke and for bleeding may be unsuitable for either oral anticoagulation or endocardial left atrial appendage (LAA) occlusion. However, minimally invasive, epicardial left atrial appendage exclusion (LAAE) may be an option. OBJECTIVE: The purpose of this study was to evaluate outcomes of LAAE in high-risk AF patients not receiving oral anticoagulation. METHODS: A retrospective analysis of Medicare claims data was conducted to evaluate thromboembolic events in AF patients who underwent LAAE compared to a 1:4 propensity score-matched group of patients who did not receive LAAE (control). Neither group was receiving any oral anticoagulation at baseline or follow-up. Fine-Gray models estimated hazard ratios and evaluated between-group differences. Bootstrapping was applied to generate 95% confidence intervals (CIs). RESULTS: The LAAE group (n = 243) was 61% male (mean age 75 years). AF was nonparoxysmal in 70% (mean CHA2DS2-VASc score 5.4; mean HAS-BLED score 4.2). The matched control group (n = 972) had statistically similar characteristics. One-year adjusted estimates of thromboembolic events were 7.3% (95% CI 4.3%-11.1%) in the LAAE group and 12.1% (95% CI 9.5%-14.8%) in the control group. Absolute risk reduction was 4.8% (95% CI 0.6%-8.9%; P = .028). Adjusted hazard ratio for thromboembolic events for LAAE vs non-LAAE was 0.672 (95% CI 0.394-1.146). CONCLUSION: In AF patients not taking oral anticoagulation who are at high risk for stroke and for bleeding, minimally invasive, thoracoscopic, epicardial LAAE was associated with a lower rate of thromboembolic events.

Cerebral Protection in Trans-Catheter Aortic Valve Replacement: Review and Contemporary Assessment of Randomized Trial Data.

As the population has aged and as aortic valve therapies have evolved, the use of trans-catheter aortic valve replacement (TAVR) has grown dramatically over the past decade. A well-known complication of percutaneous cardiac intervention is embolic phenomena, and TAVR is among the highest risk procedures for clinical and subclinical stroke. As indications for TAVR expand to lower-risk and ultimately younger patients, the long-term consequences of stroke are amplified. Cerebral embolic protection (CEP) devices have taken a on unique preventative role following the Food and Drug Administration approval of the SentinelTM Cerebral Protection System (CPS). More recently, the PROTECTED TAVR study has spurred extensive debate in the neuro-cardiac community. In this review we describe the contemporary literature regarding stroke risk associated with TAVR, the history and role of CEP devices, a PROTECTED TAVR sub-group analysis, and implications for next steps in the field. Lastly, we explore the unique need for CEP in a younger TAVR population, as well as directions for future research.

Transcranial laser therapy and infarct volume.

BACKGROUND AND PURPOSE: Two randomized trials suggested that transcranial laser therapy (TLT) may benefit patients with acute ischemic stroke, although efficacy has not been confirmed. Supportive proof of concept could be demonstrated if TLT reduces the volume of cortical infarction. METHODS: The NeuroThera Efficacy and Safety Trial-2 (NEST-2) was a randomized trial of TLT versus sham in patients with acute ischemic stroke treated within 24 hours of onset. Infarct volumes were measured quantitatively and semiquantitatively on all protocol-required computed tomography (or MRI, if clinically indicated) scans performed on day 5 (±2). Two approaches assessed treatment effects on cortex: (1) indirectly, by analyzing total infarct volume among patients with clinical presentations suggesting cortical involvement; and (2) directly, by assessing the cortical Alberta Stroke Program Early CT Score (cASPECTS) components (M1-M6, anterior, posterior) on a 0- to 8-point modified scale. RESULTS: A total of 640 subjects had scans (576 computed tomography, 64 MRI) on day 5. The reliability of ASPECTS (intraclass correlation coefficient=0.85) and cASPECTS (intraclass correlation coefficient=0.82) was excellent, and total ASPECTS was correlated with total infarct volume (r=0.71). In the overall study population, there was no impact of TLT on total infarct volume (P=0.30), total ASPECTS (P=0.85), or cASPECTS (P=0.89). Similarly, no effect was seen in any of the following prespecified subgroups selected to indicate cortical involvement: baseline National Institutes of Health Stroke Scale score >10, Oxfordshire Total Anterior Circulation Syndrome, subjects with aphasia or extinction at baseline, or subjects with radiographic involvement of cortex. CONCLUSIONS: TLT was not associated with a reduction in overall or cortical infarct volume as measured on computed tomography in the subacute phase.