Luciano A. Sposato

Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis

BACKGROUND Among patients with atrial fibrillation, the risk of stroke is highest for those with a history of stroke; however, oral anticoagulants can lower the risk of recurrent stroke by two-thirds. No consensus has been reached about how atrial fibrillation should be investigated in patients with stroke, and its prevalence after a stroke remains uncertain. We did a systematic review and meta-analysis to estimate the proportion of patients newly diagnosed with atrial fibrillation after four sequential phases of cardiac monitoring after a stroke or transient ischaemic attack. METHODS We searched PubMed, Embase, and Scopus from 1980 to June 30, 2014. We included studies that provided the number of patients with ischaemic stroke or transient ischaemic attack who were newly diagnosed with atrial fibrillation. We stratified cardiac monitoring methods into four sequential phases of screening: phase 1 (emergency room) consisted of admission electrocardiogram (ECG); phase 2 (in hospital) comprised serial ECG, continuous inpatient ECG monitoring, continuous inpatient cardiac telemetry, and in-hospital Holter monitoring; phase 3 (first ambulatory period) consisted of ambulatory Holter; and phase 4 (second ambulatory period) consisted of mobile cardiac outpatient telemetry, external loop recording, and implantable loop recording. The primary endpoint was the proportion of patients newly diagnosed with atrial fibrillation for each method and each phase, and for the sequential combination of phases. For each method and each phase, we estimated the summary proportion of patients diagnosed with post-stroke atrial fibrillation using random-effects meta-analyses. FINDINGS Our systematic review returned 28,290 studies, of which 50 studies (comprising 11,658 patients) met the criteria for inclusion in the meta-analyses. The summary proportion of patients diagnosed with post-stroke atrial fibrillation was 7·7% (95% CI 5·0-10·8) in phase 1, 5·1% (3·8-6·5) in phase 2, 10·7% (5·6-17·2) in phase 3, and 16·9% (13·0-21·2) in phase 4. The overall atrial fibrillation detection yield after all phases of sequential cardiac monitoring was 23·7% (95% CI 17·2-31·0). INTERPRETATION By sequentially combining cardiac monitoring methods, atrial fibrillation might be newly detected in nearly a quarter of patients with stroke or transient ischaemic attack. The overall proportion of patients with stroke who are known to have atrial fibrillation seems to be higher than previously estimated. Accordingly, more patients could be treated with oral anticoagulants and more stroke recurrences prevented. FUNDING Heart and Stroke Foundation of Canada, and Natural Science and Engineering Research Council of Canada.

Quality of Ischemic Stroke Care in Emerging Countries The Argentinian National Stroke Registry (ReNACer)

Background and Purpose— Limited information is available on stroke management in developing countries. An accurate monitoring of quality of stroke care will become crucial, particularly with the emerging paradigm of pay-for-performance. Our aim was to explore the feasibility of measuring standardized indicators of quality of ischemic stroke care in acute care facilities in Argentina. Methods— ReNACer is a prospective, multicenter, countrywide, stroke registry comprising 74 academic and nonacademic institutions in Argentina. The registry includes patient-level information on demography, clinical characteristics, diagnostic procedures, treatment, and the selected key performance indicators of quality of ischemic stroke care (access to thrombolysis or aspirin use in the acute setting, admission to designated stroke units, length of stay, risk-adjusted in-hospital pneumonia, risk-adjusted in-hospital mortality, discharge on antithrombotics, and antihypertensive agents). Results— We included 1991 patients with ischemic stroke from 74 institutions in Argentina between November 2004 and October 2006. Seventy-nine per cent of the patients were prescribed antithrombotic therapy within 48 hours of admission, but only 1% received thrombolytics. No more than 5.7% were admitted to stroke units. In-hospital pneumonia was diagnosed in 14.3% of the patients and was higher in nonacademic facilities (16.4% versus 11.4%, P<0.02). The overall adjusted in-hospital mortality was 9.1%, also higher in nonacademic hospitals (10.6% versus 7.1%, P<0.008). At discharge, antithrombotics were prescribed in 90.2% and antihypertensive agents in 63.6% of the patients. Conclusions— In ReNACer, there was a limited access to stroke units and thrombolytics, and a relatively high incidence of in-hospital pneumonia. Differences in stroke care were observed between academic and nonacademic institutions. There is an urgent need to develop national stroke programs in Argentina.

Newly Diagnosed Atrial Fibrillation after Acute Ischemic Stroke and Transient Ischemic Attack: Importance of Immediate and Prolonged Continuous Cardiac Monitoring

Atrial fibrillation (AF) is the major cause of cardioembolic stroke. It often remains occult when asymptomatic and paroxysmal. We hypothesized that the detection of AF after acute ischemic stroke (AIS) or transient ischemic attack (TIA) could be improved by using continuous cardiac monitoring (CCM) immediately after admission. We sought to determine the detection rate of AF by immediate in-hospital CCM after cryptogenic and noncryptogenic AIS or TIA in patients without a previous diagnosis of AF. We retrospectively studied a cohort of 155 patients with cryptogenic and noncryptogenic AIS or TIA without known AF. We compared the detection rates of newly diagnosed AF (NDAF) in patients admitted to areas with CCM and those never admitted to these areas. We developed a multiple logistic regression model for identifying predictors of NDAF. We characterized NDAF episodes and analyzed how the availability of CCM data changed secondary prevention strategies. We detected NDAF in 21 patients (13.5%). Diagnostic rates of NDAF in patients who underwent CCM and those who did not undergo CCM were 18.2% and 2.2%, respectively (P = .005). The median time from admission to recognition of NDAF was 2.0 days. Most NDAFs were paroxysmal (95.2%) and lasted less than 1 hour (85.7%). Diabetes mellitus and infarct size were predictors of NDAF. Detection of NDAF prompted the initiation of anticoagulation therapy in 8.2% of the patients admitted to areas with CCM availability. Our findings suggest that immediate and prolonged CCM significantly improves the detection of NDAF after cryptogenic and noncryptogenic AIS or TIA, and that diabetes mellitus and infarct size are significantly associated with NDAF.

Insular networks for emotional processing and social cognition: Comparison of two case reports with either cortical or subcortical involvement

INTRODUCTION The processing of the emotion of disgust is attributed to the insular cortex (IC), which is also responsible for social emotions and higher-cognitive functions. We distinguish the role of the IC from its connections in regard to these functions through the assessment of emotions and social cognition in a double case report. These subjects were very rare cases that included a focal IC lesion and a subcortical focal stroke affecting the connections of the IC with frontotemporal areas. MATERIALS & METHODS Both patients and a sample of 10 matched controls underwent neuropsychological and affective screening questionnaires, a battery of multimodal basic emotion recognition tests, an emotional inference disambiguation task using social contextual clues, an empathy task and a theory of mind task. RESULTS The insular lesion (IL) patient showed no impairments in emotion recognition and social emotions and presented with a pattern of delayed reaction times (RTs) in a subset of both groups of tasks. The subcortical lesion (SL) patient was impaired in multimodal aversive emotion recognition, including disgust, and exhibited delayed RTs and a heterogeneous pattern of impairments in subtasks of empathy and in the contextual inference of emotions. CONCLUSIONS Our results suggest that IC related networks, and not the IC itself, are related to negative emotional processing and social emotions. We discuss these results with respect to theoretical approaches of insular involvement in emotional and social processing and propose that IC connectivity with frontotemporal and subcortical regions might be relevant for contextual emotional processing and social cognition.

Poststroke atrial fibrillation: Cause or consequence? Critical review of current views

Poststroke atrial fibrillation (AF) represents up to 1 of 4 overall AF cases in acute ischemic stroke. Current guidelines recommend oral anticoagulation for every ischemic stroke patient in whom AF is diagnosed. However, in some cases, AF detected after acute ischemic stroke may be short-lasting and perhaps a nonrecurrent autonomic and inflammatory epiphenomena of stroke. The autonomic regulation of cardiac rhythm constitutes an integrated relay system. The highest level of control is exerted by the cerebral cortex, particularly the insula. The onset of AF may be associated with an imbalance of sympathetic and parasympathetic activity, a common consequence of insular infarctions. This autonomic imbalance and an interruption in the cerebral regulation of the intrinsic cardiac autonomic system constitute the most likely mechanisms responsible for the autonomic pathway. The role of inflammation in the genesis of AF within the first few days after ischemic stroke may occur through inflammatory mediators stimulating the intrinsic autonomic system and by direct damage to atrial myocardium. To what extent poststroke AF is the cause or a consequence remains uncertain.

Comparing Moral Judgments of Patients With Frontotemporal Dementia and Frontal Stroke

IMPORTANCE Several clinical reports have stated that patients with prefrontal lesions or patients with the behavioral variant of frontotemporal dementia share social cognition impairments. Moral reasoning is impaired in both conditions but there have been few investigations that directly compare this domain in the 2 groups. OBSERVATIONS This work compared the moral judgments of these patient groups using a task designed to disentangle the contributions of intentions and outcomes in moral judgment. For both disorders, patients judged scenarios where the protagonists believed that they would cause harm but did not as being more permissible than the control group. Moreover, patients with frontotemporal dementia judged harmful outcomes in the absence of harmful intentions as less permissible than the control participants. There were no differences between the 2 conditions. CONCLUSIONS AND RELEVANCE Both disorders involved impairments in integrating intention and outcome information for moral judgment. This study was the first, to our knowledge, to directly compare a social cognition domain in 2 frontal pathologies with different etiology. Our results highlighted the importance of comparing patients with vascular lesions and patients with neurodegenerative diseases.

Sex Differences in Stroke Incidence, Prevalence, Mortality and DALYs: Results from the Global Burden of Disease Study 2013

Background: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time. Methods: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed. Findings: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women. Changes in global HS incidence were not statistically significant for males (1990 = 65.31 (95% UI 61.63-69.0), 2013 = 64.89 (95% UI 59.82-68.85)), but was significant for females (1990 = 64.892 (95% UI 59.82-68.85), 2013 = 45.48 (95% UI 42.427-48.53)). The number of DALYs related to IS rose from 1990 (male = 16.62 (95% UI 13.27-19.62), female = 17.53 (95% UI 14.08-20.33)) to 2013 (male = 25.22 (95% UI 20.57-29.13), female = 22.21 (95% UI 17.71-25.50)). The number of DALYs associated with HS also rose steadily and was higher than DALYs for IS at each time point (male 1990 = 29.91 (95% UI 25.66-34.54), male 2013 = 37.27 (95% UI 32.29-45.12); female 1990 = 26.05 (95% UI 21.70-30.90), female 2013 = 28.18 (95% UI 23.68-33.80)). Interpretation: Globally, men continue to have a higher incidence of IS than women while significant sex differences in the incidence of HS were not observed. The total health loss due to stroke as measured by DALYs was similar for men and women for both stroke subtypes in 2013, with HS higher than IS. Both IS and HS DALYs show an increasing trend for both men and women since 1990, which is statistically significant only for IS among men. Ongoing monitoring of sex differences in the burden of stroke will be needed to determine if disease rates among men and women continue to diverge. Sex disparities related to stroke will have important clinical and policy implications that can guide funding and resource allocation for national, regional and global health programs.

Declining Incidence of Stroke and Dementia: Coincidence or Prevention Opportunity?

Declining Incidence of Stroke and Dementia: Coincidence or Prevention Opportunity? Stroke and dementia pose significant threats to the adult brain and share the same treatable risk factors.1 Stroke incidence in high-income countries has been declining,2 coinciding with better risk-factor control. However, hitherto there have been encouraging trends, but no proof, of declining dementia incidence.3 To address this, we analyzed health care administrative data from the Canadian Institute for Health Information for the province of Ontario, Canada.

Atrial Fibrillation Detected after Acute Ischemic Stroke: Evidence Supporting the Neurogenic Hypothesis

BACKGROUND It is unknown whether atrial fibrillation (AF) detected after acute ischemic stroke is caused by neurogenic or cardiogenic mechanisms. Based on the potential damage to the autonomic nervous system, neurogenic mechanisms could be implicated in the pathophysiology of newly diagnosed AF. To test this hypothesis, we developed a mechanistic approach by comparing a prespecified set of indicators in acute ischemic stroke patients with newly diagnosed AF, known AF, and sinus rhythm. METHODS We prospectively assessed every acute ischemic stroke patient undergoing continuous electrocardiographic monitoring from 2008 through 2011. We compared newly diagnosed AF, known AF, and sinus rhythm patients by using 20 indicators grouped in 4 domains: vascular risk factors, underlying cardiac disease, burden of neurological injury, and in-hospital outcome. RESULTS We studied 275 acute ischemic stroke patients, 23 with newly diagnosed AF, 64 with known AF, and 188 with sinus rhythm. Patients with newly diagnosed AF had a lower proportion of left atrial enlargement (60.9% versus 91.2%, P=.001), a smaller left atrial area (22.0 versus 26.0 cm2, P=.021), and a higher frequency of insular involvement (30.4% versus 9.5%, P=.017) than participants with known AF. Compared with patients in sinus rhythm, those with newly diagnosed AF had a higher proportion of brain infarcts of 15 mm or more (60.9% versus 37.2%, P=.029) and a higher frequency of insular involvement (30.4% versus 7.3%, P<.001). CONCLUSIONS The low frequency of underlying cardiac disease and the strikingly high proportion of concurrent strategic insular infarctions in patients with newly diagnosed AF provide additional evidence supporting the role of neurogenic mechanisms in a subset of AF detected after acute ischemic stroke.

Ischemic Stroke Risk in Patients With Atrial Fibrillation and CHA2DS2-VASc Score of 1

Background and Purpose— The CHA 2 DS 2 -VASc score aims to improve risk stratification of ischemic stroke among patients with atrial fibrillation to identify those who can safely forego oral anticoagulation. Oral anticoagulation treatment guidelines remain uncertain for CHA 2 DS 2 -VASc score of 1. We conducted a systematic review and meta-analysis of the risk of ischemic stroke for patients with atrial fibrillation and CHA 2 DS 2 -VASc score of 0, 1, or 2 not treated with oral anticoagulation. Methods— We searched MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from the start of the database up until April 15, 2015. We included studies that stratified the risk of ischemic stroke by CHA 2 DS 2 -VASc score for patients with nonvalvular atrial fibrillation. We estimated the summary annual rate of ischemic stroke using random effects meta-analyses and compared the estimated stroke rates with published net-benefit thresholds for initiating anticoagulants. Results— 1162 abstracts were retrieved, of which 10 met all inclusion criteria for the study. There was substantial heterogeneity among studies. The summary estimate for the annual risk of ischemic stroke was 1.61% (95% confidence interval 0%–3.23%) for CHA 2 DS 2 -VASc score of 1, meeting the theoretical threshold for using novel oral anticoagulants (0.9%), but below the threshold for warfarin (1.7%). The summary incident risk of ischemic stroke was 0.68% (95% confidence interval 0.12%–1.23%) for CHA 2 DS 2 -VASc score of 0 and 2.49% (95% confidence interval 1.16%–3.83%) for CHA 2 DS 2 -VASc score of 2. Conclusions— Our meta-analysis of ischemic stroke risk in atrial fibrillation patients suggests that those with CHA 2 DS 2 -VASc score of 1 may be considered for a novel oral anticoagulant, but because of high heterogeneity, the decision should be based on individual patient characteristics.Background and Purpose— The CHA2DS2-VASc score aims to improve risk stratification of ischemic stroke among patients with atrial fibrillation to identify those who can safely forego oral anticoagulation. Oral anticoagulation treatment guidelines remain uncertain for CHA2DS2-VASc score of 1. We conducted a systematic review and meta-analysis of the risk of ischemic stroke for patients with atrial fibrillation and CHA2DS2-VASc score of 0, 1, or 2 not treated with oral anticoagulation. Methods— We searched MEDLINE, Embase, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science from the start of the database up until April 15, 2015. We included studies that stratified the risk of ischemic stroke by CHA2DS2-VASc score for patients with nonvalvular atrial fibrillation. We estimated the summary annual rate of ischemic stroke using random effects meta-analyses and compared the estimated stroke rates with published net-benefit thresholds for initiating anticoagulants. Results— 1162 abstracts were retrieved, of which 10 met all inclusion criteria for the study. There was substantial heterogeneity among studies. The summary estimate for the annual risk of ischemic stroke was 1.61% (95% confidence interval 0%–3.23%) for CHA2DS2-VASc score of 1, meeting the theoretical threshold for using novel oral anticoagulants (0.9%), but below the threshold for warfarin (1.7%). The summary incident risk of ischemic stroke was 0.68% (95% confidence interval 0.12%–1.23%) for CHA2DS2-VASc score of 0 and 2.49% (95% confidence interval 1.16%–3.83%) for CHA2DS2-VASc score of 2. Conclusions— Our meta-analysis of ischemic stroke risk in atrial fibrillation patients suggests that those with CHA2DS2-VASc score of 1 may be considered for a novel oral anticoagulant, but because of high heterogeneity, the decision should be based on individual patient characteristics.