Publications by authors named "Michael D Hill"

608 Publications

Predictors and clinical impact of infarct progression rate in the ESCAPE-NA1 trial.

J Neurointerv Surg 2021 Sep 7. Epub 2021 Sep 7.

Department of Diagnostic Imaging, University of Calgary, Calgary, Alberta, Canada

Background: Determining infarct progression rate in acute ischemic stroke (AIS) is important for patient triage, treatment decision-making, and outcome prognostication.

Objective: To estimate infarct progression rate in patients with AIS with large vessel occlusion (LVO) and determine its predictors and impact on clinical outcome.

Methods: Data are from the ESCAPE-NA1 Trial. Patients with AIS with time from last known well to randomization <6 hours and near-complete reperfusion following endovascular treatment were included. Infarct growth rate (mL/h) was estimated by dividing 24 hour infarct volume (measured by non-contrast CT or diffusion-weighted magnetic resonance imaging) by time from last known well to reperfusion. Multivariable linear regression was used to assess the association of patient baseline variables with log-transformed infarct progression rate. The association of infarct progression rate and good outcome (modified Rankin Scale score 0-2) was determined using multivariable logistic regression.

Results: Four hundred and nine patients were included in the study. Median infarct progression rate was 4.74 mL/h (IQR 1.25-14.84). Collateral status (β: -0.81 (95% CI -1.20 to -0.41)), Alberta Stroke Program Early CT Score (ASPECTS, β: -0.34 (95% CI -0.46 to -0.23)), blood glucose(β:0.09 (95% CI 0.02 to 0.16)), and National Institutes of Health Stroke Scale (NIHS score (β: 0.07 (95% CI 0.04 to 0.10)) were associated with log-transformed infarct progression rate. Clinical and imaging baseline variables explained 23% of the variance in infarct progression rate. Infarct progression rate was significantly associated with good outcome (aOR per 1 mL/h increase: 0.96 (95% CI 0.95 to 0.98)).

Conclusion: In this sample of patients presenting within the early time window with LVO and near-complete recanalization, infarct progression rate was significantly associated with good outcome. A significant association between ASPECTS, collateral status, blood glucose, and NIHSS score was observed, but baseline imaging and clinical characteristics explained only a small proportion of the interindividual variance. More research on measurable factors affecting infarct growth is needed.
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http://dx.doi.org/10.1136/neurintsurg-2021-017994DOI Listing
September 2021

Value of infarct location in the prediction of functional outcome in patients with an anterior large vessel occlusion: results from the HERMES study.

Neuroradiology 2021 Sep 3. Epub 2021 Sep 3.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, Location AMC, Amsterdam, The Netherlands.

Purpose: Follow-up infarct volume (FIV) is moderately associated with functional outcome. We hypothesized that accounting for infarct location would strengthen the association of FIV with functional outcome.

Methods: We included 252 patients from the HERMES collaboration with follow-up diffusion weighted imaging. Patients received endovascular treatment combined with best medical management (n = 52%) versus best medical management alone (n = 48%). FIV was quantified in low, moderate and high modified Rankin Scale (mRS)-relevant regions. We used binary logistic regression to study the relation between the total, high, moderate or low mRS-relevant FIVs and favorable outcome (mRS < 2) after 90 days. The strength of association was evaluated using the c-statistic.

Results: Small lesions only occupied high mRS-relevant brain regions. Lesions additionally occupied lower mRS-relevant brain regions if FIV expanded. Higher FIV was associated with a higher risk of unfavorable outcome, as were volumes of tissue with low, moderate and high mRS relevance. In multivariable modeling, only the volume of high mRS-relevant infarct was significantly associated with favorable outcome. The c-statistic was highest (0.76) for the models that included high mRS-relevant FIV or the combination of high, moderate and low mRS-relevant FIV but was not significantly different from the model that included only total FIV (0.75).

Conclusion: This study confirms the association of FIV and unfavorable functional outcome but showed no strengthened association if lesion location was taken into account.
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http://dx.doi.org/10.1007/s00234-021-02784-xDOI Listing
September 2021

Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) - study protocol for a randomised controlled trial.

Eur Stroke J 2021 Jun 18;6(2):222-228. Epub 2021 Jun 18.

Institute of Neuroscience, Newcastle University, Newcastle, UK.

Background: Inflammation contributes to unstable atherosclerotic plaque and stroke. In randomised trials in patients with coronary disease, canukinumab (an interleukin-1B antagonist) and colchicine (a tubulin inhibitor with pleiotropic anti-inflammatory effects) reduced recurrent vascular events.Hypothesis: Anti-inflammatory therapy with low-dose colchicine plus usual care will reduce recurrent vascular events in patients with non-severe, non-cardioembolic stroke and TIA compared with usual care alone.

Design: CONVINCE is a multi-centre international (in 17 countries) Prospective, Randomised Open-label, Blinded-Endpoint assessment (PROBE) controlled Phase 3 clinical trial in 3154 participants. The intervention is colchicine 0.5 mg/day and usual care versus usual care alone (antiplatelet, lipid-lowering, antihypertensive treatment, lifestyle advice). Included patients are at least 40 years, with non-severe ischaemic stroke (modified Rankin score ≤3) or high-risk TIA (ABCD2 > 3, or positive DWI, or cranio-cervical artery stenosis) within 72 hours-28 days of randomisation, with qualifying stroke/TIA most likely caused by large artery stenosis, lacunar disease, or cryptogenic embolism. Exclusions are stroke/TIA caused by cardio-embolism or other defined cause (e.g. dissection), contra-indication to colchicine (including potential drug interactions), or incapacity for participation in a clinical trial. The anticipated median follow-up will be 36 months. The primary analysis will be by intention-to-treat.

Outcome: The primary outcome is time to first recurrent ischaemic stroke, myocardial infarction, cardiac arrest, or hospitalisation with unstable angina (non-fatal or fatal).

Summary: CONVINCE will provide high-quality randomised data on the efficacy and safety of anti-inflammatory therapy with colchicine for secondary prevention after stroke.

Schedule: First-patient first-visit was December 2016. Recruitment to complete in 2021, follow-up to complete in 2023.
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http://dx.doi.org/10.1177/2396987320972566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8370082PMC
June 2021

Cerebral Edema in Patients With Large Hemispheric Infarct Undergoing Reperfusion Treatment: A HERMES Meta-Analysis.

Stroke 2021 Aug 13:STROKEAHA120033246. Epub 2021 Aug 13.

Department of Medicine and Neurology, Melbourne Brain Centre, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia. (F.C.N., N.Y., G.S., S.M.D., B.C.V.C.).

Background And Purpose: Whether reperfusion into infarcted tissue exacerbates cerebral edema has treatment implications in patients presenting with extensive irreversible injury. We investigated the effects of endovascular thrombectomy and reperfusion on cerebral edema in patients presenting with radiological evidence of large hemispheric infarction at baseline.

Methods: In a systematic review and individual patient-level meta-analysis of 7 randomized controlled trials comparing thrombectomy versus medical therapy in anterior circulation ischemic stroke published between January 1, 2010, and May 31, 2017 (Highly Effective Reperfusion Using Multiple Endovascular Devices collaboration), we analyzed the association between thrombectomy and reperfusion with maximal midline shift (MLS) on follow-up imaging as a measure of the space-occupying effect of cerebral edema in patients with large hemispheric infarction on pretreatment imaging, defined as diffusion-magnetic resonance imaging or computed tomography (CT)-perfusion ischemic core 80 to 300 mL or noncontrast CT-Alberta Stroke Program Early CT Score ≤5. Risk of bias was assessed using the Cochrane tool.

Results: Among 1764 patients, 177 presented with large hemispheric infarction. Thrombectomy and reperfusion were associated with functional improvement (thrombectomy common odds ratio =2.30 [95% CI, 1.32-4.00]; reperfusion common odds ratio =4.73 [95% CI, 1.66-13.52]) but not MLS (thrombectomy β=-0.27 [95% CI, -1.52 to 0.98]; reperfusion β=-0.78 [95% CI, -3.07 to 1.50]) when adjusting for age, National Institutes of Health Stroke Score, glucose, and time-to-follow-up imaging. In an exploratory analysis of patients presenting with core volume >130 mL or CT-Alberta Stroke Program Early CT Score ≤3 (n=76), thrombectomy was associated with greater MLS after adjusting for age and National Institutes of Health Stroke Score (β=2.76 [95% CI, 0.33-5.20]) but not functional improvement (odds ratio, 1.71 [95% CI, 0.24-12.08]).

Conclusions: In patients presenting with large hemispheric infarction, thrombectomy and reperfusion were not associated with MLS, except in the subgroup with very large core volume (>130 mL) in whom thrombectomy was associated with increased MLS due to space-occupying ischemic edema. Mitigating cerebral edema-mediated secondary injury in patients with very large infarcts may further improve outcomes after reperfusion therapies.
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http://dx.doi.org/10.1161/STROKEAHA.120.033246DOI Listing
August 2021

Poststroke Selective Serotonin Reuptake Inhibitors-Do They Work for Anything?

JAMA Neurol 2021 Sep;78(9):1053-1054

Department of Clinical Neurosciences (Neurology) and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1001/jamaneurol.2021.1907DOI Listing
September 2021

Standardized Nomenclature for Modified Rankin Scale Global Disability Outcomes: Consensus Recommendations From Stroke Therapy Academic Industry Roundtable XI.

Stroke 2021 Aug 29;52(9):3054-3062. Epub 2021 Jul 29.

Division of Stroke and Neurocritical Care, Department of Neurology and Neurological Sciences and the Stanford Stroke Center, Stanford University (C.V., G.W.A.).

The modified Rankin Scale (mRS), a 7-level, clinician-reported, measure of global disability, is the most widely employed outcome scale in acute stroke trials. The scale's original development preceded the advent of modern clinimetrics, but substantial subsequent work has been performed to enable the mRS to meet robust contemporary scale standards. Prior research and consensus recommendations have focused on modernizing 2 aspects of the mRS: operationalized assignment of scale scores and statistical analysis of scale distributions. Another important characteristic of the mRS still requiring elaboration and specification to contemporary clinimetric standards is the Naming of scale outcomes. Recent clinical trials have used a bewildering variety, often mutually contradictory, of rubrics to describe scale states. Understanding of the meaning of mRS outcomes by clinicians, patients, and other clinical trial stakeholders would be greatly enhanced by use of a harmonized, uniform set of labels for the distinctive mRS outcomes that would be used consistently across trials. This statement advances such recommended rubrics, developed by the Stroke Therapy Academic Industry Roundtable collaboration using an iterative, mixed-methods process. Specific guidance is provided for health state terms (eg, Symptomatic but Nondisabled for mRS score 1; requires constant care for mRS score 5) and valence terms (eg, excellent for mRS score 1; very poor for mRS score 5) to employ for 23 distinct numeric mRS outcomes, including: all individual 7 mRS levels; all 12 positive and negative dichotomized mRS ranges, positive and negative sliding dichotomies; and utility-weighted analysis of the mRS.
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http://dx.doi.org/10.1161/STROKEAHA.121.034480DOI Listing
August 2021

Endovascular Treatment Effect Diminishes With Increasing Thrombus Perviousness: Pooled Data From 7 Trials on Acute Ischemic Stroke.

Stroke 2021 Jul 20:STROKEAHA120033124. Epub 2021 Jul 20.

Radiology and Nuclear Medicine, Amsterdam University Medical Center, University of Amsterdam, the Netherlands. (M.K., M.L.T., K.M.T., B.G.D., H.A., G.Z., H.A.M., C.B.L.M.M.).

Background And Purpose: Thrombus perviousness estimates residual flow along a thrombus in acute ischemic stroke, based on radiological images, and may influence the benefit of endovascular treatment for acute ischemic stroke. We aimed to investigate potential endovascular treatment (EVT) effect modification by thrombus perviousness.

Methods: We included 443 patients with thin-slice imaging available, out of 1766 patients from the pooled HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke trials) data set of 7 randomized trials on EVT in the early window (most within 8 hours). Control arm patients (n=233) received intravenous alteplase if eligible (212/233; 91%). Intervention arm patients (n=210) received additional EVT (prior alteplase in 178/210; 85%). Perviousness was quantified by thrombus attenuation increase on admission computed tomography angiography compared with noncontrast computed tomography. Multivariable regression analyses were performed including multiplicative interaction terms between thrombus attenuation increase and treatment allocation. In case of significant interaction, subgroup analyses by treatment arm were performed. Our primary outcome was 90-day functional outcome (modified Rankin Scale score), resulting in an adjusted common odds ratio for a one-step shift towards improved outcome. Secondary outcomes were mortality, successful reperfusion (extended Thrombolysis in Cerebral Infarction score, 2B-3), and follow-up infarct volume (in mL).

Results: Increased perviousness was associated with improved functional outcome. After adding a multiplicative term of thrombus attenuation increase and treatment allocation, model fit improved significantly (=0.03), indicating interaction between perviousness and EVT benefit. Control arm patients showed significantly better outcomes with increased perviousness (adjusted common odds ratio, 1.2 [95% CI, 1.1-1.3]). In the EVT arm, no significant association was found (adjusted common odds ratio, 1.0 [95% CI, 0.9-1.1]), and perviousness was not significantly associated with successful reperfusion. Follow-up infarct volume (12% [95% CI, 7.0-17] per 5 Hounsfield units) and chance of mortality (adjusted odds ratio, 0.83 [95% CI, 0.70-0.97]) decreased with higher thrombus attenuation increase in the overall population, without significant treatment interaction.

Conclusions: Our study suggests that the benefit of best medical care including alteplase, compared with additional EVT, increases in patients with more pervious thrombi.
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http://dx.doi.org/10.1161/STROKEAHA.120.033124DOI Listing
July 2021

2021 Update on Safety of Magnetic Resonance Imaging: Joint Statement From Canadian Cardiovascular Society/Canadian Society for Cardiovascular Magnetic Resonance/Canadian Heart Rhythm Society.

Can J Cardiol 2021 Jun;37(6):835-847

Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis.
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http://dx.doi.org/10.1016/j.cjca.2021.02.012DOI Listing
June 2021

Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial.

CMAJ Open 2021 Apr-Jun;9(2):E693-E702. Epub 2021 Jun 18.

Division of Infectious Diseases (Schwartz, Mponponsuo), Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alta.; Alberta Strategy for Patient Oriented Research SUPPORT Unit (Boesen); Cumming School of Medicine (Boesen, Cerchiaro, Greenfield, Kenney, Ryckborst), University of Calgary; Section of Infectious Diseases (Edwards), Department of Medicine, and Department of Clinical Neurosciences (Doram, Ganesh, Karnik), Cumming School of Medicine, University of Calgary, Calgary, Alta.; Quality Management in Clinical Research Office (Jamieson, Stewart), University of Alberta, Edmonton, Alta.; Division of Respirology (Lim), Department of Medicine, Cumming School of Medicine, and Departments of Clinical Neurosciences and Community Health Sciences (Menon, Metz), Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alta.; Women and Children's Research Institute (Rathwell, Yaskina), and Department of Pediatrics (Richer), Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alta.; Departments of Clinical Neurosciences, Community Health Sciences, and Medicine (Hill), Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, Alta.

Background: Identification of therapies to prevent severe COVID-19 remains a priority. We sought to determine whether hydroxychloroquine treatment for outpatients with SARS-CoV-2 infection could prevent hospitalization, mechanical ventilation or death.

Methods: This randomized controlled trial was conducted in Alberta during the first wave of the COVID-19 pandemic without direct contact with participants. Community-dwelling individuals with confirmed SARS-CoV-2 infection (by reverse transcription polymerase chain reaction [RT-PCR] viral ribonucleic acid test) within the previous 4 days, and symptom onset within the previous 12 days, were randomly assigned to oral hydroxychloroquine or matching placebo for 5 days. Enrolment began Apr. 15, 2020. The primary outcome was the composite of hospitalization, invasive mechanical ventilation or death within 30 days. Secondary outcomes included symptom duration and disposition at 30 days. Safety outcomes, such as serious adverse events and mortality, were also ascertained. Outcomes were determined by telephone follow-up and administrative data.

Results: Among 4919 individuals with a positive RT-PCR test, 148 (10.2% of a planned 1446 patients) were randomly assigned, 111 to hydroxychloroquine and 37 to placebo. Of the 148 participants, 24 (16.2%) did not start the study drug. Four participants in the hydroxychloroquine group met the primary outcome (4 hospitalizations, 0 mechanical ventilation, 4 survived to 30 days) and none in the placebo group. Hydroxychloroquine did not reduce symptom duration (hazard ratio 0.77, 95% confidence interval 0.49-1.21). Recruitment was paused on May 22, 2020, when a since-retracted publication raised concerns about the safety of hydroxychloroquine for hospitalized patients with COVID-19. Although we had not identified concerns in a safety review, enrolment was slower than expected among those eligible for the study, and cases within the community were decreasing. Recruitment goals were deemed to be unattainable and the trial was not resumed, resulting in a study underpowered to assess the effect of treatment with hydroxychloroquine and safety.

Interpretation: There was no evidence that hydroxychloroquine reduced symptom duration or prevented severe outcomes among outpatients with proven COVID-19, but the early termination of our study meant that it was underpowered.

Trial Registration: ClinicalTrials.gov, no. NCT04329611.
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http://dx.doi.org/10.9778/cmajo.20210069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248582PMC
June 2021

The Brain in Motion II Study: study protocol for a randomized controlled trial of an aerobic exercise intervention for older adults at increased risk of dementia.

Trials 2021 Jun 14;22(1):394. Epub 2021 Jun 14.

Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada.

Background: There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months).

Methods: We will recruit 264 participants (aged 50-80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months).

Discussion: This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing.

Trial Registration: ClinicalTrials.gov NCT03035851 . Registered on 30 January 2017.
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http://dx.doi.org/10.1186/s13063-021-05336-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201462PMC
June 2021

Influence of cardiovascular risk-factors on morphological changes of cerebral arteries in healthy adults across the life span.

Sci Rep 2021 Jun 10;11(1):12236. Epub 2021 Jun 10.

Department of Radiology, Faculty of Medicine, University of Calgary, Calgary, Canada.

Cerebral artery morphological alterations have been associated with several cerebrovascular and neurological diseases, whereas these structures are known to be highly variable among healthy individuals. To date, the knowledge about the influence of cardiovascular risk factors on the morphology of cerebral arteries is rather limited. The aim of this work was to investigate the impact of cardiovascular risk factors on the regional cerebroarterial radius and density. Time-of-Flight magnetic resonance angiography from 1722 healthy adults (21-82 years) were used to extract region-specific measurements describing the main cerebral artery morphology. Multivariate statistical analysis was conducted to quantify the impact of cardiovascular risk factors, including clinical and life behavioural factors, on each region-specific artery measurement. Increased age, blood pressure, and markers of obesity were significantly associated with decreased artery radius and density in most regions, with aging having the greatest impact. Additionally, females showed significantly higher artery density while males showed higher artery radius. Smoking and alcohol consumption did not show any significant association with the artery morphology. The results of this study improve the understanding of the impact of aging, clinical factors, and life behavioural factors on cerebrovascular morphology and can help to identify potential risk factors for cerebrovascular and neurological diseases.
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http://dx.doi.org/10.1038/s41598-021-91669-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192575PMC
June 2021

Short- and Long-term Health Care Resource Utilization and Costs Following Intracerebral Hemorrhage.

Neurology 2021 08 9;97(6):e608-e618. Epub 2021 Jun 9.

From the Division of Critical Care (S.M.F., S.W.E., K.K.), Department of Medicine, and Department of Emergency Medicine (S.M.F.), University of Ottawa; ICES (D.Q., R.T., M.M.S., D.C.S., P.T.), Toronto; Clinical Epidemiology Program (D.Q., R.T., D.D., M.M.S., S.W.E., P.T., K.K.), Ottawa Hospital Research Institute; School of Epidemiology and Public Health (D.Q., D.D., M.M.S., S.W.E., P.T.), University of Ottawa; Bruyère Research Institute (D.Q., P.T.); Division of Palliative Care (D.Q., P.T., K.K.), Department of Medicine, Division of Neurology (D.D.), Department of Medicine, and Division of Nephrology (M.M.S.), Department of Medicine, University of Ottawa, Ontario; Calgary Stroke Program (E.E.S., M.D.H.), Hotchkiss Brain Institute, and Department of Clinical Neurosciences (E.E.S., M.D.H.), Cumming School of Medicine, University of Calgary, Alberta; Interdepartmental Division of Critical Care Medicine (V.A.M., D.C.S.), University of Toronto; Krembil Research Institute (V.A.M.), Toronto Western Hospital, University Health Network; Department of Critical Care Medicine (V.A.M., D.C.S.), Sunnybrook Health Sciences Centre; Li Ka Shing Knowledge Institute (D.C.S.), St. Michael's Hospital, Toronto; Department of Medicine (B.R.), Division of Critical Care and Department of Health Research Methods, Evidence, and Impact (B.R.), McMaster University, Hamilton; and Institut du Savoir Montfort (K.K.), Ottawa, Ontario, Canada.

Objective: We sought to evaluate the short- and long-term resource use and costs associated with intracerebral hemorrhage (ICH) taken from an entire population. We in addition sought to evaluate the association of oral anticoagulation (OAC) and health care costs.

Methods: This was a retrospective cohort study of adult patients (≥18 years) with ICH in the entire population of Ontario, Canada (2009-2017). We captured outcomes through linkage to health administrative databases. We used generalized linear models to identify factors associated with total cost. Analysis of OAC use was limited to patients ≥66 years of age. The primary outcome was total 1-year direct health care costs in 2020 US dollars.

Results: Among 16,248 individuals with ICH (mean age 71.2 years, male 52.3%), 1-year mortality was 46.0%, and 24.2% required mechanical ventilation. The median total 1-year cost was $26,886 (interquartile range [IQR] $9,641-$62,907) with costs for those who died in hospital of $7,268 (IQR $4,031-$14,966) vs $44,969 (IQR $20,264-$82,414, < 0.001) for survivors to discharge. OAC use (analysis limited to individuals ≥66 years old) was associated with higher total 1-year costs (cost ratio 1.06 [95% confidence interval 1.01-1.11]). Total 1-year costs for the entire cohort exceeded $120 million per year over the study period.

Conclusions: ICH is associated with significant health care costs, and the median cost of a patient with ICH is roughly 10 times the median inpatient cost in Ontario. Costs were higher among survivors than deceased patients. OAC use is independently associated with increased costs. To maximize cost-effectiveness, future therapies for ICH must aim to reduce disability, not only improve mortality.
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http://dx.doi.org/10.1212/WNL.0000000000012355DOI Listing
August 2021

Automated Prediction of Ischemic Brain Tissue Fate from Multiphase Computed Tomographic Angiography in Patients with Acute Ischemic Stroke Using Machine Learning.

J Stroke 2021 May 31;23(2):234-243. Epub 2021 May 31.

Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada.

Background And Purpose: Multiphase computed tomographic angiography (mCTA) provides time variant images of pial vasculature supplying brain in patients with acute ischemic stroke (AIS). To develop a machine learning (ML) technique to predict tissue perfusion and infarction from mCTA source images.

Methods: 284 patients with AIS were included from the Precise and Rapid assessment of collaterals using multi-phase CTA in the triage of patients with acute ischemic stroke for Intra-artery Therapy (Prove-IT) study. All patients had non-contrast computed tomography, mCTA, and computed tomographic perfusion (CTP) at baseline and follow-up magnetic resonance imaging/non-contrast-enhanced computed tomography. Of the 284 patient images, 140 patient images were randomly selected to train and validate three ML models to predict a pre-defined Tmax thresholded perfusion abnormality, core and penumbra on CTP. The remaining 144 patient images were used to test the ML models. The predicted perfusion, core and penumbra lesions from ML models were compared to CTP perfusion lesion and to follow-up infarct using Bland-Altman plots, concordance correlation coefficient (CCC), intra-class correlation coefficient (ICC), and Dice similarity coefficient.

Results: Mean difference between the mCTA predicted perfusion volume and CTP perfusion volume was 4.6 mL (limit of agreement [LoA], -53 to 62.1 mL; P=0.56; CCC 0.63 [95% confidence interval [CI], 0.53 to 0.71; P<0.01], ICC 0.68 [95% CI, 0.58 to 0.78; P<0.001]). Mean difference between the mCTA predicted infarct and follow-up infarct in the 100 patients with acute reperfusion (modified thrombolysis in cerebral infarction [mTICI] 2b/2c/3) was 21.7 mL, while it was 3.4 mL in the 44 patients not achieving reperfusion (mTICI 0/1). Amongst reperfused subjects, CCC was 0.4 (95% CI, 0.15 to 0.55; P<0.01) and ICC was 0.42 (95% CI, 0.18 to 0.50; P<0.01); in non-reperfused subjects CCC was 0.52 (95% CI, 0.20 to 0.60; P<0.001) and ICC was 0.60 (95% CI, 0.37 to 0.76; P<0.001). No difference was observed between the mCTA and CTP predicted infarct volume in the test cohort (P=0.67).

Conclusions: A ML based mCTA model is able to predict brain tissue perfusion abnormality and follow-up infarction, comparable to CTP.
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http://dx.doi.org/10.5853/jos.2020.05064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189856PMC
May 2021

Effect of Implantable vs Prolonged External Electrocardiographic Monitoring on Atrial Fibrillation Detection in Patients With Ischemic Stroke: The PER DIEM Randomized Clinical Trial.

JAMA 2021 06;325(21):2160-2168

Libin Cardiovascular Institute, University of Calgary, Calgary, Alberta, Canada.

Importance: The relative rates of detection of atrial fibrillation (AF) or atrial flutter from evaluating patients with prolonged electrocardiographic monitoring with an external loop recorder or implantable loop recorder after an ischemic stroke are unknown.

Objective: To determine, in patients with a recent ischemic stroke, whether 12 months of implantable loop recorder monitoring detects more occurrences of AF compared with conventional external loop recorder monitoring for 30 days.

Design, Setting, And Participants: Investigator-initiated, open-label, randomized clinical trial conducted at 2 university hospitals and 1 community hospital in Alberta, Canada, including 300 patients within 6 months of ischemic stroke and without known AF from May 2015 through November 2017; final follow-up was in December 2018.

Interventions: Participants were randomly assigned 1:1 to prolonged electrocardiographic monitoring with either an implantable loop recorder (n = 150) or an external loop recorder (n = 150) with follow-up visits at 30 days, 6 months, and 12 months.

Main Outcomes And Measures: The primary outcome was the development of definite AF or highly probable AF (adjudicated new AF lasting ≥2 minutes within 12 months of randomization). There were 8 prespecified secondary outcomes including time to event analysis of new AF, recurrent ischemic stroke, intracerebral hemorrhage, death, and device-related serious adverse events within 12 months.

Results: Among the 300 patients who were randomized (median age, 64.1 years [interquartile range, 56.1 to 73.7 years]; 121 were women [40.3%]; and 66.3% had a stroke of undetermined etiology with a median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score of 4 [interquartile range, 3 to 5]), 273 (91.0%) completed cardiac monitoring lasting 24 hours or longer and 259 (86.3%) completed both the assigned monitoring and 12-month follow-up visit. The primary outcome was observed in 15.3% (23/150) of patients in the implantable loop recorder group and 4.7% (7/150) of patients in the external loop recorder group (between-group difference, 10.7% [95% CI, 4.0% to 17.3%]; risk ratio, 3.29 [95% CI, 1.45 to 7.42]; P = .003). Of the 8 specified secondary outcomes, 6 were not significantly different. There were 5 patients (3.3%) in the implantable loop recorder group who had recurrent ischemic stroke vs 8 patients (5.3%) in the external loop recorder group (between-group difference, -2.0% [95% CI, -6.6% to 2.6%]), 1 (0.7%) vs 1 (0.7%), respectively, who had intracerebral hemorrhage (between-group difference, 0% [95% CI, -1.8% to 1.8%]), 3 (2.0%) vs 3 (2.0%) who died (between-group difference, 0% [95% CI, -3.2% to 3.2%]), and 1 (0.7%) vs 0 (0%) who had device-related serious adverse events.

Conclusions And Relevance: Among patients with ischemic stroke and no prior evidence of AF, implantable electrocardiographic monitoring for 12 months, compared with prolonged external monitoring for 30 days, resulted in a significantly greater proportion of patients with AF detected over 12 months. Further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness.

Trial Registration: ClinicalTrials.gov Identifier: NCT02428140.
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http://dx.doi.org/10.1001/jama.2021.6128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170545PMC
June 2021

Radiologic Patterns of Intracranial Hemorrhage and Clinical Outcome after Endovascular Treatment in Acute Ischemic Stroke: Results from the ESCAPE-NA1 Trial.

Radiology 2021 08 1;300(2):402-409. Epub 2021 Jun 1.

From the Department of Clinical Neurosciences and Diagnostic Imaging, University of Calgary Cumming School of Medicine, 29th St NW, 1079 A, Calgary, AB, Canada T2N 2T9 (J.M.O., W.Q., B.K.M., A.M., A.D., C.Z., M.A., M.D.H., M.G.); Department of Radiology, University Hospital of Basel, Basel, Switzerland (J.M.O.); Department of Radiology, University of Calgary, Calgary, Canada (B.K.M., A.D., M. Joshi, M.A., M.D.H., M.G.); Department of Interventional Radiology, Warren Alpert Medical School of Brown University, Providence, RI (R.M., M. Jayaraman); Department of Neurology, Emory University School of Medicine, Atlanta, Ga (R.G.N., D.H.); Department of Neurology (D.R.) and Neurosciences (A.Y.P.), Centre Hospitalier de l'Université de Montréal, Montréal, Canada; Department of Medicine, University of Alberta Hospital, Edmonton, Canada (B.B.); and NoNo, Toronto, Canada (M.T.).

Background Intracranial hemorrhage is a known complication after endovascular treatment in patients with acute ischemic stroke due to large vessel occlusion, but the association between radiologic hemorrhage severity and outcome is controversial. Purpose To investigate the prevalence and impact on outcome of intracranial hemorrhage and hemorrhage severity after endovascular stroke treatment. Materials and Methods The Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke (ESCAPE-NA1) trial enrolled participants with acute large vessel occlusion stroke who underwent endovascular treatment from March 1, 2017, to August 12, 2019. Evidence of any intracranial hemorrhage, hemorrhage multiplicity, and radiologic severity, according to the Heidelberg classification (hemorrhagic infarction type 1 [HI1], hemorrhagic infarction type 2 [HI2], parenchymal hematoma type 1 [PH1], and parenchymal hematoma type 2 [PH2]) was assessed at CT or MRI 24 hours after endovascular treatment. Good functional outcome, defined as a modified Rankin score of 0-2 at 90 days, was compared between participants with intracranial hemorrhage and those without intracranial hemorrhage at follow-up imaging and between hemorrhage subtypes. Poisson regression was performed to obtain adjusted effect size estimates for the presence of any intracranial hemorrhage and hemorrhage subtypes at good functional outcome. Results Of 1097 evaluated participants (mean age, 69 years ± 14 [standard deviation]; 551 men), any degree of intracranial hemorrhage was observed in 372 (34%). Good outcomes were less often achieved among participants with hemorrhage than among those without hemorrhage at follow-up imaging (164 of 372 participants [44%] vs 500 of 720 [69%], respectively; < .01). After adjusting for baseline variables and infarct volume, intracranial hemorrhage was not associated with decreased chances of good outcome (adjusted risk ratio [RR] = 0.91 [95% CI: 0.82, 1.02], = .10), but there was a graded relationship of radiologic hemorrhage severity and outcomes, whereby PH1 (RR = 0.77 [95% CI: 0.61, 0.97], = .03) and PH2 (RR = 0.41 [95% CI: 0.21, 0.81], = .01) were associated with decreased chances of good outcome. Conclusion Any degree of intracranial hemorrhage after endovascular treatment was seen in one-third of participants. A graded association existed between radiologic hemorrhage severity and outcome. Hemorrhagic infarction was not associated with outcome, whereas parenchymal hematoma was strongly associated with poor outcome, independent of infarct volume. © RSNA, 2021 Clinical trial registration no. NCT01778335
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http://dx.doi.org/10.1148/radiol.2021204560DOI Listing
August 2021

Prediction of Clinical Outcomes in Acute Ischaemic Stroke Patients: A Comparative Study.

Front Neurol 2021 6;12:663899. Epub 2021 May 6.

Depertment of Radiology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Clinical stroke rehabilitation decision making relies on multi-modal data, including imaging and other clinical assessments. However, most previously described methods for predicting long-term stroke outcomes do not make use of the full multi-modal data available. The aim of this work was to develop and evaluate the benefit of nested regression models that utilise clinical assessments as well as image-based biomarkers to model 30-day NIHSS. 221 subjects were pooled from two prospective trials with follow-up MRI or CT scans, and NIHSS assessed at baseline, as well as 48-hours and 30 days after symptom onset. Three prediction models for 30-day NIHSS were developed using a support vector regression model: one clinical model based on modifiable and non-modifiable risk factors (M) and two nested regression models that aggregate clinical and image-based features that differed with respect to the method used for selection of important brain regions for the modelling task. The first model used the widely accepted RreliefF (M) machine learning method for this purpose, while the second model employed a lesion-symptom mapping technique (M) often used in neuroscience to investigate structure-function relationships and identify eloquent regions in the brain. The two nested models achieved a similar performance while considerably outperforming the clinical model. However, M required fewer brain regions and achieved a lower mean absolute error than M while being less computationally expensive. Aggregating clinical and imaging information leads to considerably better outcome prediction models. While lesion-symptom mapping is a useful tool to investigate structure-function relationships of the brain, it does not lead to better outcome predictions compared to a simple data-driven feature selection approach, which is less computationally expensive and easier to implement.
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http://dx.doi.org/10.3389/fneur.2021.663899DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134662PMC
May 2021

A Detailed Analysis of Infarct Patterns and Volumes at 24-hour Noncontrast CT and Diffusion-weighted MRI in Acute Ischemic Stroke Due to Large Vessel Occlusion: Results from the ESCAPE-NA1 Trial.

Radiology 2021 07 11;300(1):152-159. Epub 2021 May 11.

From the Department of Clinical Neurosciences and Diagnostic Imaging, University of Calgary Cumming School of Medicine, 29th St NW, 1079 A, Calgary, AB, Canada T2N 2T9 (J.M.O., B.K.M., W.Q., N.K., A.M., N.S., P.C., M.M., A.M.D., C.Z., M.J., M.A.A., S.B.C., M.D.H., M.G.); Department of Radiology, University Hospital of Basel, Basel, Switzerland (J.M.O.); Department of Radiology, University of Calgary, Calgary, Alberta, Canada (B.K.M., N.K., A.M.D., C.Z., M.J., M.A.A., S.B.C., M.D.H., M.G.); Department of Medical Imaging, St Anne's University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic (P.C.); International Clinical Research Center, St Anne's University Hospital Brno, Czech Republic (P.C.); Department of Neurology, Emory University School of Medicine, Atlanta, Ga (R.G.N., D.H.); Department of Interventional Radiology, Warren Alpert Medical School of Brown University, Providence, RI (R.A.M.); Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada (A.Y.P., D.R., D.I.); Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI (S.C.); Department of Neuroradiology, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada (A.R.); and NoNo, Toronto, Ontario, Canada (M.T.).

Background The effect of infarct pattern on functional outcome in acute ischemic stroke is incompletely understood. Purpose To investigate the association of qualitative and quantitative infarct variables at 24-hour follow-up noncontrast CT and diffusion-weighted MRI with 90-day clinical outcome. Materials and Methods The Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke, or ESCAPE-NA1, randomized controlled trial enrolled patients with large-vessel-occlusion stroke undergoing mechanical thrombectomy from March 1, 2017, to August 12, 2019. In this post hoc analysis of the trial, qualitative infarct variables (predominantly gray [vs gray and white] matter involvement, corticospinal tract involvement, infarct structure [scattered vs territorial]) and total infarct volume were assessed at 24-hour follow-up noncontrast CT or diffusion-weighted MRI. White and gray matter infarct volumes were assessed in patients by using follow-up diffusion-weighted MRI. Infarct variables were compared between patients with and those without good outcome, defined as a modified Rankin Scale score of 0-2 at 90 days. The association of infarct variables with good outcome was determined with use of multivariable logistic regression. Separate regression models were used to report effect size estimates with adjustment for total infarct volume. Results Qualitative infarct variables were assessed in 1026 patients (mean age ± standard deviation, 69 years ± 13; 522 men) and quantitative infarct variables were assessed in a subgroup of 358 of 1026 patients (mean age, 67 years ± 13; 190 women). Patients with gray and white matter involvement (odds ratio [OR] after multivariable adjustment, 0.19; 95% CI: 0.14, 0.25; < .001), corticospinal tract involvement (OR after multivariable adjustment, 0.06; 95% CI: 0.04, 0.10; < .001), and territorial infarcts (OR after multivariable adjustment, 0.22; 95% CI: 0.14, 0.32; < .001) were less likely to achieve good outcome, independent of total infarct volume. Conclusion Infarct confinement to the gray matter, corticospinal tract sparing, and scattered infarct structure at 24-hour noncontrast CT and diffusion-weighted MRI were highly predictive of good 90-day clinical outcome, independent of total infarct volume. Clinical trial registration no. NCT02930018 © RSNA, 2021 See also the editorial by Mossa-Basha in this issue.
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http://dx.doi.org/10.1148/radiol.2021203964DOI Listing
July 2021

Management and outcome of patients with acute ischemic stroke and tandem carotid occlusion in the ESCAPE-NA1 trial.

J Neurointerv Surg 2021 May 4. Epub 2021 May 4.

Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada

Background: The optimal treatment and prognosis for stroke patients with tandem cervical carotid occlusion are unclear. We analyzed outcomes and treatment strategies of tandem occlusion patients in the ESCAPE-NA1 trial.

Methods: ESCAPE-NA1 was a multicenter international randomized trial of nerinetide versus placebo in 1105 patients with acute ischemic stroke who underwent endovascular treatment. We defined tandem occlusions as complete occlusion of the cervical internal carotid artery (ICA) on catheter angiography, in addition to a proximal ipsilateral intracranial large vessel occlusion. Baseline characteristics and outcome parameters were compared between patients with tandem occlusions versus those without, and between patients with tandem occlusion who underwent ICA stenting versus those who did not. The influence of tandem occlusions on functional outcome was analyzed using multivariable regression modeling.

Results: Among 115/1105 patients (10.4%) with tandem occlusions, 62 (53.9%) received stenting for the cervical ICA occlusion. Of these, 46 (74.2%) were stented after and 16 (25.8%) before the intracranial thrombectomy. A modified Rankin Score (mRS) of 0-2 at 90 days was achieved in 82/115 patients (71.3%) with tandem occlusions compared with 579/981 (59.5%) patients without tandem occlusions. Tandem occlusion did not impact functional outcome in the adjusted analysis (OR 1.5, 95% CI 0.95 to 2.4). Among the subgroup of patients with tandem occlusion, cervical carotid stenting was not associated with different outcomes compared with no stenting (mRS 0-2: 75.8% vs 66.0%, adjusted OR 2.0, 95% CI 0.8 to 5.1).

Conclusions: Tandem cervical carotid occlusion in patients with acute large vessel stroke did not lower the odds of good functional outcome in our study. Functional outcomes were similar irrespective of the management of the cervical ICA occlusion (stenting vs not stenting).
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http://dx.doi.org/10.1136/neurintsurg-2021-017474DOI Listing
May 2021

Deferral of Consent: Recent Lessons From Canadian Acute Stroke Trials.

Stroke 2021 Jul 5;52(7):e326-e327. Epub 2021 May 5.

Ottawa Hospital and Department of Medicine, University of Ottawa (M.S., D.D.), Ontario, Canada.

[Figure: see text].
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http://dx.doi.org/10.1161/STROKEAHA.121.034655DOI Listing
July 2021

Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke: A Meta-analysis of Individual Patient Data From 7 Randomized Clinical Trials.

JAMA Neurol 2021 Jun;78(6):709-717

Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles.

Importance: The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known.

Objective: To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO).

Data Sources: PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020.

Study Selection: All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included.

Data Extraction/synthesis: Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time.

Main Outcomes And Measures: Change in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics.

Results: Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP ≤4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours.

Conclusions And Relevance: In this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time period. The finding that every 1 second of delay was associated with loss of 2.2 hours of healthy life may encourage continuous quality improvement in door-to-treatment times.
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http://dx.doi.org/10.1001/jamaneurol.2021.1055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094030PMC
June 2021

Clinical impact of EVT with failed reperfusion in patients with acute ischemic stroke: results from the ESCAPE and ESCAPE-NA1 trials.

Neuroradiology 2021 Apr 29. Epub 2021 Apr 29.

Department of Clinical Neurosciences, University of Calgary, Calgary, Canada.

Background And Purpose: Endovascular treatment (EVT) is a powerful treatment for large vessel occlusion (LVO) stroke if reperfusion can be achieved, while in cases with failed reperfusion, EVT may cause harm, as procedure-related complications may occur. We hypothesized that EVT with failed recanalization does not result in worse outcomes compared to best medical management and compared clinical outcomes of LVO stroke patients who underwent EVT with failed reperfusion to those who were treated with best medical management.

Methods: We included patients with failed reperfusion from the control (EVT-only) arm of the ESCAPE-NA1 trial and the EVT arm of the ESCAPE trial and patients of the ESCAPE control arm who were treated with best medical management. Failed reperfusion following EVT was defined as modified thrombolysis in cerebral infarction score 0-2a. Proportions of good outcome (modified Rankin scale 0-2) were compared between patients who did and did not undergo EVT, and adjusted effect size estimates for EVT on outcomes were obtained.

Results: We included 260 patients (110 failed EVT and 150 non-EVT patients). Proportions of good outcome were 38/110 (34.6%) with failed EVT vs.43/147 (29.3%) without EVT (adjusted odds ratio[aOR]: 1.48 [95%CI: 0.81-2.68]). Mortality and proportions of sICH in the failed EVT group vs. patients treated with best medical management were 26/110 (23.6%) vs. 28/147 (19.1%), aOR: 1.12 (95%CI: 0.56-2.24), and 7/110 (6.4%) vs. 4/150 (2.7%), aOR: 2.34 (95%CI: 0.00-22.97).

Conclusion: Clinical outcomes of EVT patients with failed reperfusion did not differ significantly from patients treated with best medical management.
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http://dx.doi.org/10.1007/s00234-021-02723-wDOI Listing
April 2021

Will there be a rapid change towards an EVT-only paradigm?

Interv Neuroradiol 2021 Apr 22:15910199211011880. Epub 2021 Apr 22.

Calgary Stroke Program, Department of Clinical Neurosciences, University of Calgary, Calgary, Canada.

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http://dx.doi.org/10.1177/15910199211011880DOI Listing
April 2021

Protocol for LASER: A Randomized Evaluation and an Associated Registry of Early Anticoagulation With Edoxaban After Ischemic Stroke in Patients With Atrial Fibrillation.

Front Neurol 2021 31;12:645822. Epub 2021 Mar 31.

Department of Medicine, University of Alberta, Edmonton, AB, Canada.

The optimal timing of anticoagulation after stroke in patients with atrial fibrillation (AF) is unknown. Our primary aim is to demonstrate the safety of edoxaban initiation within 5 days of AF related stroke. Our secondary aim is to determine predictors of hemorrhagic transformation (HT) after AF related stroke. We hypothesize that the rate of radiological HT will not be increased in patients starting edoxaban within 5 days of AF related stroke, relative to those in whom initiation is delayed. We hypothesize that the risk of HT in patients treated with edoxaban can be predicted using RNA expressed in leukocytes at time of stroke. LASER (Lixiana Acute Stroke Evaluation Registry) is a randomized controlled trial with an associated registry (clinicaltrials.gov NCT03494530). One hundred and fifty patients with ischemic stroke and AF will undergo baseline Computed Tomography (CT) scan and will be randomized 2:1 within 5 days of symptom onset to early (≤5 days, = 100) or delayed (6-14 days, = 50) edoxaban initiation. Participants will undergo clinical assessment and repeat CT at 7 days and clinical assessment at 90 days. The primary outcome is the rate of incident radiological HT. Secondary outcomes include symptomatic HT, recurrent ischemic stroke, recurrent sub-clinical infarcts on follow up CT, systemic hemorrhagic complication rate, National Institute of Health Stroke Scale and modified Rankin Scale at day 7 and 90, mortality within 90 days, quality of life assessments at day 90, and predictors of HT, including RNA expression by 6 pre-selected candidate genes. Event rates for both HT and recurrent ischemic events, in patients treated with early vs. delayed edoxaban initiation are unknown. The primary study endpoint of LASER is an objective performance criterion relevant to clinical decision making in patients with AF related stroke. This study will provide data required for a definitive safety/efficacy study sample size power calculation.
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http://dx.doi.org/10.3389/fneur.2021.645822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044522PMC
March 2021

Iatrogenic Diffusion-Weighted Imaging Lesions: What Is Their Impact and How Can It Be Measured?

Stroke 2021 May 8;52(5):1929-1936. Epub 2021 Apr 8.

Department of Clinical Neurosciences (M.G., A.G., M.D.H., J.M.O.), University of Calgary, Canada.

Infarct volume in acute ischemic stroke is closely linked with clinical outcome, with larger infarct volumes being associated with a worse prognosis. Small iatrogenic infarcts, which can occur as a result of surgical or endovascular procedures, are often only seen on diffusion-weighted MR imaging. They often do not lead to any overtly appreciable clinical deficits, hence the term covert or silent infarcts. There is relative paucity of data on the clinical impact of periprocedural hyperintense diffusion-weighted MR imaging lesions, partly because they commonly remain undiagnosed. Clearly, a better understanding of iatrogenic periprocedural diffusion-weighted MR imaging lesions and their clinical significance is needed. In this article, we describe the current limitations of our understanding of the significance of iatrogenic diffusion-weighted MR imaging lesions using exemplary data from the ENACT trial (Safety and Efficacy of NA-1 in Patients With Iatrogenic Stroke After Endovascular Aneurysm Repair) and outline a framework for how to investigate their clinical impact.
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http://dx.doi.org/10.1161/STROKEAHA.120.033984DOI Listing
May 2021

In imaging-selected ischemic stroke with unknown onset, alteplase increases favorable outcomes and death at 90 d.

Authors:
Michael D Hill

Ann Intern Med 2021 04 6;174(4):JC42. Epub 2021 Apr 6.

University of Calgary and Hotchkiss Brain Institute & Foothills Medical Centre, Calgary, Alberta, Canada (M.D.H.).

Source Citation: Thomalla G, Boutitie F, Ma H, et al. Lancet. 2020;396:1574-84. 33176180.
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http://dx.doi.org/10.7326/ACPJ202104200-042DOI Listing
April 2021

Which Acute Ischemic Stroke Patients Are Fast Progressors?: Results From the ESCAPE Trial Control Arm.

Stroke 2021 May 5;52(5):1847-1850. Epub 2021 Apr 5.

Clinical Neurosciences (J.M.O., M.D.H., A.M.D., B.K.M., A.M., M.G.), University of Calgary, Canada.

Background And Purpose: Fast infarct progression in acute ischemic stroke has a severe impact on patient prognosis and benefit of endovascular thrombectomy. In this post hoc analysis of the ESCAPE trial (Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke), we identified acute ischemic stroke patients with rapid infarct growth and investigated their baseline clinical and imaging characteristics.

Methods: Control arm patients were included if they had follow-up imaging at 2-8 hours without substantial recanalization, and if their baseline Alberta Stroke Program Early CT Score was ≥9. Fast infarct progression was defined as Alberta Stroke Program Early CT Score decay ≥3 points from baseline to 2- to 8-hour follow-up imaging. Clinical and imaging baseline characteristics were compared between fast progressors and other patients, and occlusion site and collateral flow patterns were assessed in detail.

Results: Fast infarct progression occurred in 15 of 43 included patients (34.9%). Fast progressors had worse collaterals (poor in 3/15 [20%] versus 0/28 patients, =0.021) and more carotid-T or -L occlusions (8/15 [53.4%] versus 3/28[10.7%], =0.021). In 8 out of 15 (53.3%), occlusion site and circle of Willis configuration prevented collateral flow via the anterior or posterior cerebral artery.

Conclusions: Most patients with fast infarct progression had terminal carotid occlusions and impaired collateral flow via the anterior or posterior cerebral artery, indicating that occlusion location and intracranial vascular anatomy are relevant for infarct progression.
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http://dx.doi.org/10.1161/STROKEAHA.120.032950DOI Listing
May 2021

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

Stroke Vasc Neurol 2021 Mar 26. Epub 2021 Mar 26.

Department of Radiology, Beaumont Hospital, Dublin, Ireland.

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.

Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.

Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile.

Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
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http://dx.doi.org/10.1136/svn-2020-000695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006491PMC
March 2021
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