Objective
Elevated levels of cardiac troponin, and especially their relative changes over time, indicate acute myocardial injury. They are also frequently observed after acute ischemic stroke (AIS), ...indicating poor functional outcome and increased mortality. However, recent evidence showed that, in most AIS patients, myocardial injury is not caused by coronary ischemia. Instead, stroke lesion location has been suggested to precipitate myocardial injury.
Methods
Voxel‐based lesion‐symptom mapping (VLSM) was used in 299 patients who had a magnetic resonance imaging–confirmed acute ischemic stroke within the anterior circulation and a high‐sensitivity cardiac troponin T (hs‐cTnT) acquired on the day of admission. Of these, 228 had a second troponin measurement during the acute phase. The absolute hs‐cTnT levels above the 99th percentile of a healthy reference population (≥14ng/l) as well as their relative temporal changes were used as continuous variables of interest in the VLSM model, including a multiple regression analysis adjusted for confounding variables.
Results
The anterior insular cortex of the right hemisphere, in particular its dorsal subregion, was significantly associated with the relative temporal changes of hs‐cTnT (p < 0.01, corrected for multiple comparisons). In contrast, the baseline hs‐cTnT levels on admission were not related to lesion location anywhere within the anterior circulation.
Interpretation
Our results amplify recent evidence from functional neuroimaging, which suggests a prominent role of dorsal anterior insular cortex in the parasympathetic control of cardiac and autonomic function. Acute vascular damage of this insular subregion might lead to autonomic dysbalance and an upregulation of sympathetic function, thereby resulting in myocardial injury. Ann Neurol 2017;81:502–511
Cardiac troponin is a specific and sensitive biomarker to identify and quantify myocardial injury. Myocardial injury is frequently detected after acute ischemic stroke and strongly associated with ...unfavorable outcomes. Concomitant acute coronary syndrome is only one of several possible differential diagnoses that may cause elevation of cardiac troponin after stroke. As a result, there are uncertainties regarding the correct interpretation and optimal management of stroke patients with myocardial injury in clinical practice. Elevation of cardiac troponin may occur as part of a ‘Stroke-Heart Syndrome’. The term ‘Stroke-Heart Syndrome’ subsumes a clinical spectrum of cardiac complications after stroke including cardiac injury, dysfunction, and arrhythmia which may relate to disturbances of autonomic function and the brain–heart axis. In this review, we provide an up-to-date overview about prognostic implications, mechanisms, and management of elevated cardiac troponin levels in patients with acute ischemic stroke.
Cerebral microbleeds (CMBs) have been established as an independent predictor of cerebral bleeding. There are contradictory data regarding the potential association of CMB burden with the risk of ...symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT).
To investigate the association of high CMB burden (>10 CMBs on a pre-IVT magnetic image resonance MRI scan) with the risk of sICH following IVT for AIS.
Eligible studies were identified by searching Medline and Scopus databases. No language or other restrictions were imposed. The literature search was conducted on October 7, 2015. This meta-analysis has adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology (MOOSE) proposal.
Eligible prospective study protocols that reported sICH rates in patients with AIS who underwent MRI for CMB screening prior to IVT.
The reported rates of sICH complicating IVT in patients with AIS with pretreatment MRI were extracted independently for groups of patients with 0 CMBs (CMB absence), 1 or more CMBs (CMB presence), 1 to 10 CMBs (low to moderate CMB burden), and more than 10 CMBs (high CMB burden). An individual-patient data meta-analysis was also performed in the included studies that provided complete patient data sets.
Symptomatic intracerebral hemorrhage based on the European Cooperative Acute Stroke Study-II definition (any intracranial bleed with ≥4 points worsening on the National Institutes of Health Stroke Scale score).
We included 9 studies comprising 2479 patients with AIS. The risk of sICH after IVT was found to be higher in patients with evidence of CMB presence, compared with patients without CMBs (risk ratio RR, 2.36; 95% CI, 1.21-4.61; P = .01). A higher risk for sICH after IVT was detected in patients with high CMB burden (>10 CMBs) when compared with patients with 0 to 10 CMBs (RR, 12.10; 95% CI, 4.36-33.57; P < .001) or 1 to 10 CMBs (RR, 7.01; 95% CI, 3.20-15.38; P < .001) on pretreatment MRI. In the individual-patient data meta-analysis, high CMB burden was associated with increased likelihood of sICH before (unadjusted odds ratio, 31.06; 95% CI, 7.12-135.44; P < .001) and after (adjusted odds ratio, 18.17; 95% CI, 2.39-138.22; P = .005) adjusting for potential confounders.
Presence of CMB and high CMB burdens on pretreatment MRI were independently associated with sICH in patients with AIS treated with IVT. High CMB burden may be included in individual risk stratification scores predicting sICH risk following IVT for AIS.
Cervical artery dissection is a major cause of stroke in young people (aged <50 years). Historically, clinicians have preferred using oral anticoagulation with vitamin K antagonists for patients with ...cervical artery dissection, although some current guidelines—based on available evidence from mostly observational studies—suggest using aspirin. If proven to be non-inferior to vitamin K antagonists, aspirin might be preferable, due to its ease of use and lower cost. We aimed to test the non-inferiority of aspirin to vitamin K antagonists in patients with cervical artery dissection.
We did a multicentre, randomised, open-label, non-inferiority trial in ten stroke centres across Switzerland, Germany, and Denmark. We randomly assigned (1:1) patients aged older than 18 years who had symptomatic, MRI-verified, cervical artery dissection within 2 weeks before enrolment, to receive either aspirin 300 mg once daily or a vitamin K antagonist (phenprocoumon, acenocoumarol, or warfarin; target international normalised ratio INR 2·0–3·0) for 90 days. Randomisation was computer-generated using an interactive web response system, with stratification according to participating site. Independent imaging core laboratory adjudicators were masked to treatment allocation, but investigators, patients, and clinical event adjudicators were aware of treatment allocation. The primary endpoint was a composite of clinical outcomes (stroke, major haemorrhage, or death) and MRI outcomes (new ischaemic or haemorrhagic brain lesions) in the per-protocol population, assessed at 14 days (clinical and MRI outcomes) and 90 days (clinical outcomes only) after commencing treatment. Non-inferiority of aspirin would be shown if the upper limit of the two-sided 95% CI of the absolute risk difference between groups was less than 12% (non-inferiority margin). This trial is registered with ClinicalTrials.gov, NCT02046460.
Between Sept 11, 2013, and Dec 21, 2018, we enrolled 194 patients; 100 (52%) were assigned to the aspirin group and 94 (48%) were assigned to the vitamin K antagonist group. The per-protocol population included 173 patients; 91 (53%) in the aspirin group and 82 (47%) in the vitamin K antagonist group. The primary endpoint occurred in 21 (23%) of 91 patients in the aspirin group and in 12 (15%) of 82 patients in the vitamin K antagonist group (absolute difference 8% 95% CI −4 to 21, non-inferiority p=0·55). Thus, non-inferiority of aspirin was not shown. Seven patients (8%) in the aspirin group and none in the vitamin K antagonist group had ischaemic strokes. One patient (1%) in the vitamin K antagonist group and none in the aspirin group had major extracranial haemorrhage. There were no deaths. Subclinical MRI outcomes were recorded in 14 patients (15%) in the aspirin group and in 11 patients (13%) in the vitamin K antagonist group. There were 19 adverse events in the aspirin group, and 26 in the vitamin K antagonist group.
Our findings did not show that aspirin was non-inferior to vitamin K antagonists in the treatment of cervical artery dissection.
Swiss National Science Foundation, Swiss Heart Foundation, Stroke Funds Basel, University Hospital Basel, University of Basel, Academic Society Basel.
Objectives
To investigate the association between acute and chronic ischaemic lesions in a multiple territory lesion pattern (MTLP) detected by 3-Tesla MRI and stroke aetiology, specifically atrial ...fibrillation-associated stroke.
Methods
We analysed data from the 1000+ study – a prospective, observational 3-Tesla MRI cohort study of consecutively included acute stroke patients. Acute and chronic lesions were detected by DWI and fluid-attenuated inversion recovery, respectively. Observers blinded to clinical data allocated lesions to the right anterior, left anterior or posterior circulation. Lesion pattern was categorised as MTLP
a/c
when more than one territory was affected by either acute or chronic lesions or as MTLP
a
when more than one territory was affected by acute lesions alone.
Results
Of the 1,000 included patients, an MTLP
a/c
was found in 43% and MTLP
a
in 24%. Advanced age (aOR=1.21 per 10 years, 95% CI 1.06–1.39), atrial fibrillation (aOR=1.44, 95% CI 1.06–1.94), aortic arch atherosclerosis (aOR=2.52, 95% CI 1.10–5.77), malignant disease (aOR=1.99, 95% CI 1.25–3.16) and lower estimated glomerular filtration rate (eGFR) (aOR=0.90 per 10 ml, 95% CI 0.84–0.97) were associated with MTLP
a/c
. Only malignant disease (aOR=2.03, 95% CI 1.27–3.23) and lower eGFR (aOR=0.91 per 10 ml, 95% CI 0.85–0.97) were associated with MTLP
a
.
Conclusions
An MRI-detected multiple territory lesion pattern of acute and chronic ischaemic lesions is frequent and more often present in older patients and patients with atrial fibrillation, aortic arch atherosclerosis, malignant disease and lower eGFR. Considering not only acute but also chronic ischaemic lesions may facilitate identifying atrial fibrillation-associated or aorto-embolic stroke.
Key Points
• Brain imaging with MRI may help to determine the aetiology of stroke.
• Of 1,000 stroke patients undergoing 3-Tesla MRI, 43% had acute and chronic ischaemic lesions in multiple cerebral vascular territories.
• Atrial fibrillation, aortic arch atherosclerosis and malignant disease were associated with a multiple territory lesion pattern.
Women have a worse outcome after stroke compared with men, although in intravenous thrombolysis (IVT)-treated patients, women seem to benefit more. Besides sex differences, age has also a possible ...effect on functional outcome. The interaction of sex on the functional outcome in IVT-treated patients in relation to age remains complex. The purpose of this study was to compare outcome after IVT between women and men with regard to age in a large multicenter European cohort reflecting daily clinical practice of acute stroke care.
Data were obtained from IVT registries of 12 European tertiary hospitals. The primary outcome was poor functional outcome, defined as a modified Rankin scale score of 3 to 6 at 3 months. We stratified outcome by age in decades. Safety measures were symptomatic intracranial hemorrhage and mortality at 3 months.
In this cohort, 9495 patients were treated with IVT, and 4170 (43.9%) were women with a mean age of 71.9 years. After adjustments for baseline differences, female sex remained associated with poor functional outcome (odds ratio, 1.15; 95% confidence interval, 1.02-1.31). There was no association between sex and functional outcome when data were stratified by age. Symptomatic intracranial hemorrhage rate was similar in both sexes (adjusted odds ratio, 0.93; 95% confidence interval, 0.73-1.19), whereas mortality was lower among women (adjusted odds ratio, 0.83; 95% confidence interval, 0.70-0.99).
In this large cohort of IVT-treated patients, women more often had poor functional outcome compared with men. This difference was not dependent on age.
Background The best strategy to identify patients with suspected acute ischemic stroke and unknown vessel status (large vessel occlusion) for direct transport to a comprehensive stroke center instead ...of a nearer primary stroke center is unknown. Methods and Results We used mathematical modeling to estimate the impact of 10 increasingly complex prehospital triage strategy paradigms on the reduction of population-wide stroke-related disability. The model was applied to suspected acute ischemic stroke patients in (1) abstract geographies, and (2) 3 real-world urban and rural geographies in Germany. Transport times were estimated based on stroke center location and road infrastructure; spatial distribution of emergency medical services calls was derived from census data with high spatial granularity. Parameter uncertainty was quantified in sensitivity analyses. The mothership strategy was associated with a statistically significant population-wide gain of 8 to 18 disability-adjusted life years in the 3 real-world geographies and in most simulated abstract geographies (net gain -4 to 66 disability-adjusted life years). Of the more complex paradigms, transportation of patients with clinically suspected large vessel occlusion based on a dichotomous large vessel occlusion detection scale to the nearest comprehensive stroke center yielded an additional clinical benefit of up to 12 disability-adjusted life years in some rural but not in urban geographies. Triage strategy paradigms based on probabilistic conditional modeling added an additional benefit of 0 to 4 disability-adjusted life years over less complex strategies if based on variable cutoff scores. Conclusions Variable stroke severity cutoff scores were associated with the highest reduction in stroke-related disability. The mothership strategy yielded better clinical outcome than the drip-'n'-ship strategy in most geographies.
A relevant proportion of patients with acute ischemic stroke (AIS) have elevated levels of cardiac troponins (cTn). However, the frequency of coronary ischemia as the cause of elevated cTn is ...unknown. The aim of our study was to analyze coronary vessel status in AIS patients with elevated cTn compared with patients presenting with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS).
Among 2123 consecutive patients with AIS prospectively screened at 2 tertiary hospitals, 13.7% had cTn elevation (>50 ng/L). According to a prespecified sample size estimation, 29 patients with AIS (median age, 76 years first-third quartiles, 70-82 years; 52% male) underwent conventional coronary angiography and were compared with age- and sex-matched patients with NSTE-ACS. The primary end point was presence of coronary culprit lesions on coronary angiograms as analyzed by independent interventional cardiologists blinded for clinical data. Median cTn on presentation did not differ between patients with AIS or NSTE-ACS (95 versus 94 ng/L; P=0.70). Compared with patients with NSTE-ACS, patients with AIS were less likely to have coronary culprit lesions (7 of 29 versus 23 of 29; P<0.001) or any obstructive coronary artery disease (15 of 29 versus 25 of 29; P=0.02; median number of vessels with >50% stenosis, 1 first-third quartiles, 0-2 versus 2 first-third quartiles, 1-3; P<0.01).
Coronary culprit lesions are significantly less frequent in AIS patients compared with age- and sex-matched patients with NSTE-ACS despite similar baseline cTn levels. Half of all AIS patients had no angiographic evidence of coronary artery disease. Further studies are needed to clinically identify the minority of patients with AIS and angiographic evidence of a culprit lesion.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT01263964.
To investigate the aetiology, subsequent preventive strategies and outcomes of stroke despite anticoagulation in patients with atrial fibrillation (AF).
We analysed consecutive patients with AF with ...an index imaging-proven ischaemic stroke despite vitamin K-antagonist (VKA) or direct oral anticoagulant (DOAC) treatment across 11 stroke centres. We classified stroke aetiology as: (i) competing stroke mechanism other than AF-related cardioembolism; (ii) insufficient anticoagulation (non-adherence or low anticoagulant activity measured with drug-specific assays); or, (iii) AF-related cardioembolism despite sufficient anticoagulation. We investigated subsequent preventive strategies with regard to the primary (composite of recurrent ischaemic stroke, intracranial haemorrhage, death) and secondary endpoint (recurrent ischaemic stroke) within 3 months after index stroke.
Among 2946 patients (median age 81 years; 48% women; 43% VKA, 57% DOAC), stroke aetiology was competing mechanism in 713 patients (24%), insufficient anticoagulation in 934 (32%) and cardioembolism despite sufficient anticoagulation in 1299 (44%). We found high rates of the primary (27% of patients; completeness 91.6%) and secondary endpoint (4.6%; completeness 88.5%). Only DOAC (vs VKA) treatment after index stroke showed lower odds for both endpoints (primary: adjusted OR (aOR) (95% CI) 0.49 (0.32 to 0.73); secondary: 0.44 (0.24 to 0.80)), but not switching between different DOAC types. Adding antiplatelets showed higher odds for both endpoints (primary: aOR (95% CI) 1.99 (1.25 to 3.15); secondary: 2.66 (1.40 to 5.04)). Only few patients (1%) received left atrial appendage occlusion as additional preventive strategy.
Stroke despite anticoagulation comprises heterogeneous aetiologies and cardioembolism despite sufficient anticoagulation is most common. While DOAC were associated with better outcomes than VKA, adding antiplatelets was linked to worse outcomes in these high-risk patients. Our findings indicate that individualised and novel preventive strategies beyond the currently available anticoagulants are needed.
ISRCTN48292829.
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