Hill, Michael D.

Introduction: Long-term cardiac monitoring studies have unveiled low-burden, occult atrial fibrillation (AF) in some patients with otherwise cryptogenic stroke (CS). But occult AF is also found in some normal individuals and patients with stroke of known cause (KS). Clinical management would be aided by estimates of how often occult AF in a patient with CS is causal versus incidental. Methods: Through systematic search, we identified all case-control and cohort studies applying identical long-term monitoring techniques to both CS and KS patients. We performed a random-effects meta-analyses across these studies to determine the best estimate of the differential frequency of occult AF in CS and KS among all patients, and across age subgroups. We then applied Bayes’ theorem (method of Alsheikh-Ali et al, Stroke 2009) to determine the probability that occult AF is causal or incidental. Results: The systematic search identified 3 case-control and cohort studies enrolling 575 patients (337 CS, 238 KS). Methods of long-term monitoring were implantable loop recorder in 191 (33.2%), extended mobile external cardiac monitor in 277 (48.2%), and patch/event/Holter monitoring in 107 (18.6%). In formal meta-analysis, the summary odds ratio for occult AF in CS vs KS in all patients was 1.72 (95%CI 0.91-3.25) (Figure). With application of Bayes theorem, the corresponding probabilities indicated that, when present, occult AF in CS patients is causal in 44.4% and incidental in 55.6%. Only one study reported age-specific subgroup data: these suggested occult AF in CS patients was causal in 93% of patients <65y vs 5.6% of patients ≥65y, but estimates had limited precision. Conclusions: In patients with cryptogenic stroke, when occult AF is found, it is likely causal in about 44% of patients, who may benefit from anticoagulation, and likely incidental in about 56% of patients, who may not benefit from anticoagulation. Figure

Introduction: Occurrence of stroke and myocardial infarction (MI) after carotid endarterectomy or stenting have each been associated with increased later mortality. Methods: In the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) 69 strokes, 37 protocol MIs, and 19 biomarker + only events occurred within 30 days among 2272 patients followed up to 10 years. Mortality was determined and compared for patients with stroke, MI, or biomarker + only to those without. Cox proportional hazard models adjusting for age, sex, symptomatic status and treatment were calculated to assess the relationship between mortality and stroke and mortality and MI status. Kaplan-Meier survival curves were plotted. Results: Patients with peri-procedural stroke had a 67% greater likelihood of long-term mortality compared to those without stroke (HR=1.67, 95% CI 1.15,2.43; p<0.007)(Figure A). Patients with a protocol MI had a 249% greater likelihood of mortality, and biomarker+ only patients had a 104% greater likelihood of mortality, compared to those without MI (HR=3.49; 95%CI 2.20,5.53, p<0.0001; and HR=2.04; 95% CI 1.09,3.83, p=0.03)(Figure B). Discussion: Stroke, MI, and biomarker + only events following CEA or CAS are associated with increased long-term mortality. The higher risk for MI may be a marker for patients with serious underlying heart disease, rather than causal, providing an opportunity to decrease long-term mortality through aggressive diagnostic evaluation and preventive treatment.

Background Since 2015, endovascular therapy has been established as a standard of care for acute stroke. This has caused major challenges regarding the organization of systems of care, which have to meet the increasing demand for thrombectomies. This study aims to evaluate how endovascular therapy decisions made by European and North American physicians under their current local resources differ from those made under assumed ideal conditions. Methods In an international, multidisciplinary survey, physicians involved in acute stroke care were asked to give their treatment decisions to 10 out of 22 randomly assigned stroke case-scenarios. Participants stated (a) their treatment approach under assumed ideal conditions (without any external limitations) and (b) the treatment they would pursue under their current local resources. Resources gaps (ideal minus current endovascular therapy rates) were calculated for different countries/states/provinces and correlated to economic and healthcare key metrics (gross domestic product-per-capita, public or private health insurance coverage, etc.). Results A total of 607 physicians, among them 218 from North America and 136 from 25 European countries, responded to the survey. Resources gaps in the majority of North American states/provinces and European countries were small (<5%). The highest gaps were observed among few European countries, namely Poland (30%) and the United Kingdom (33%). The magnitude of the resources gap did not correlate to national economic or healthcare metrics. Discussion and conclusion In the majority of North American states/provinces and European countries covered in this study, the discrepancy between endovascular therapy decisions under current local resources and assumed ideal conditions seems to be small, even in countries with a limited economic status and healthcare infrastructure.

Background and Purpose— The American Heart Association and the American Stroke Association guidelines for early management of patients with ischemic stroke offer guidance to physicians involved in acute stroke care and clarify endovascular treatment indications. The purpose of this study was to assess concordance of physicians’ endovascular treatment decision-making with current American Heart Association and the American Stroke Association stroke treatment guidelines using a survey-approach and to explore how decision-making in the absence of guideline recommendations is approached. Methods— In an international cross-sectional survey (UNMASK-EVT), physicians were randomly assigned 10 of 22 case scenarios (8 constructed with level 1A and 11 with level 2B evidence for endovascular treatment and 3 scenarios without guideline coverage) and asked to declare their treatment approach (1) under their current local resources and (2) assuming there were no external constraints. The proportion of physicians offering endovascular therapy (EVT) was calculated. Subgroup analysis was performed for different specialties, geographic regions, with regard to physicians’ age, endovascular, and general stroke treatment experience. Results— When facing level 1A evidence, participants decided in favor of EVT in 86.8% under current local resources and in 90.6% under assumed ideal conditions, that is, 9.4% decided against EVT even under assumed ideal conditions. In case scenarios with level 2B evidence, 66.3% decided to proceed with EVT under current local resources and 69.7% under assumed ideal conditions. Conclusions— There is potential for improving thinking around the decision to offer endovascular treatment, since physicians did not offer EVT even under assumed ideal conditions in 9.4% despite facing level 1A evidence. A majority of physicians would offer EVT even for level 2B evidence cases.

Background and purpose Thromboembolic events are recognized complications of aneurysm coiling. Objective To identify any protective effects of antiplatelet therapy use before coiling of unruptured aneurysms. Methods We conducted a meta-analysis of clinical studies published up to February 2019. We included studies reporting symptomatic thromboembolic events (defined as clinical stroke or transient ischemic attacks) in patients who received antiplatelet therapy before coiling of unruptured aneurysms using unassisted coiling, balloon assistance, or multiple microcatheters. We excluded ruptured aneurysms and those treated with stent coiling or flow diverters. Results We identified 14 studies (2486 patients). All were single-center studies and four were prospective. In three studies with a control (no treatment) arm, the pooled risk ratio for symptomatic thromboembolic events with versus without antiplatelet therapy was 0.33 (95% CI 0.17 to 0.92, p= 0.035). The cumulative risk of symptomatic thromboembolic events with single antiplatelet agents was 5.0% ‘56/1122’ (95% CI 1.6% to 8.4%, I283.63%), and with dual or multiple agents 2.7% ‘33/1237’ (95% CI 1.0% to 3.0%, I239.9%). The incidence of diffusion lesions was reported in seven studies. It was 50.5% ‘96/190’ (95% CI 7.3% to 93.9%, I294.4%) with single agents compared with 43.9% ‘196/446’ (95% CI 25.9% to 61.9%, I273.4%) with dual or multiple agents. Conclusion Periprocedural antiplatelet therapy was associated with a low symptomatic thromboembolic event after coiling-only for unruptured aneurysms. However, available evidence is of limited quality with significant heterogeneity, requiring evidence from randomized controlled trials.

Background and purpose Differences in the treatment practice of female and male physicians have been shown in several medical subspecialties. It is currently not known whether this also applies to endovascular stroke treatment. The purpose of this study was to explore whether there are differences in endovascular treatment decisions made by female and male stroke physicians and neurointerventionalists. Methods In an international survey, stroke physicians and neurointerventionalists were randomly assigned 10 case scenarios and asked how they would treat the patient: (A) assuming there were no external constraints and (B) given their local working conditions. Descriptive statistics were used to describe baseline demographics, and the adjusted OR for physician gender as a predictor of endovascular treatment decision was calculated using logistic regression. Results 607 physicians (97 women, 508 men, 2 who did not wish to declare) participated in this survey. Physician gender was neither a significant predictor for endovascular treatment decision under assumed ideal conditions (endovascular therapy was favored by 77.0% of female and 79.3% of male physicians, adjusted OR 1.03, P=0.806) nor under current local resources (endovascular therapy was favored by 69.1% of female and 76.9% of male physicians, adjusted OR 1.03, P=0.814). Conclusion Endovascular therapy decision making between male and female physicians did not differ under assumed ideal conditions or under current local resources.

Background and Purpose— Little is known about the real-life factors that clinicians use in selection of patients that would receive endovascular treatment (EVT) in the real world. We sought to determine patient, practitioner, and health system factors associated with therapeutic decisions around endovascular treatment. Methods— We conducted a multinational cross-sectional web-based study comprising of 607 clinicians and interventionalists from 38 countries who are directly involved in acute stroke care. Participants were randomly allocated to 10 from a pool of 22 acute stroke case scenarios. Each case was classified as either Class I, Class II, or unknown evidence according to the current guidelines. We used logistic regression analysis applying weight of evidence approach. Main outcome measures were multilevel factors associated with EVT, adherence to current EVT guidelines, and practice gaps between current and ideal practice settings. Results— Of the 1330 invited participants, 607 (45.6%) participants completed the study (53.7% neurologists, 28.5% neurointerventional radiologists, 17.8% other clinicians). The weighed evidence approach revealed that National Institutes of Health Stroke Scale (34.9%), level of evidence (30.2%), ASPECTS (Alberta Stroke Program Early CT Score) or ischemic core volume (22.4%), patient’s age (21.6%), and clinicians’ experience in EVT use (19.3%) are the most important factors for EVT decision. Of 2208 responses that met Class I evidence for EVT, 1917 (86.8%) were in favor of EVT. In case scenarios with no available guidelines, 1070 of 1380 (77.5%) responses favored EVT. Comparison between current and ideal practice settings revealed a small practice gap (941 of 6070 responses, 15.5%). Conclusions— In this large multinational survey, stroke severity, guideline-based level of evidence, baseline brain imaging, patients’ age and physicians’ experience were the most relevant factors for EVT decision-making. The high agreement between responses and Class I guideline recommendations and high EVT use even when guidelines were not available reflect the real-world acceptance of EVT as standard of care in patients with disabling acute ischemic stroke.