Distribution of atrial cardiomyopathy markers and association with atrial fibrillation detected after ischaemic stroke in the SAFAS study.

BACKGROUND: Atrial cardiomyopathy (AC) is an emerging concept explaining the pathophysiology of cardioembolic strokes in absence of atrial fibrillation (AF). A definition based on the presence of electrical abnormality (P-wave terminal force in lead V1 (PTFV1) >5000 µV×ms), N-Terminal pro-B-type natriuretic peptide (NT pro BNP) >250 pg/mL and/or indexed left atrial diameter (LADI) >3 cm/m² is currently tested in the ARCADIA (AtRial Cardiopathy and Antithrombotic Drugs In prevention After cryptogenic stroke) trial. We set out to estimate the prevalence of AC as defined in the ARCADIA trial, its determinants and its association with AF detected after stroke (AFDAS). METHODS: Stepwise screening for silent Atrial Fibrillation After Stroke (SAFAS) study prospectively included 240 ischaemic stroke patients. AC markers were complete for 192 of them and 9 were not included in this analysis because AF had been diagnosed on admission. RESULTS: A total of 183 patients were analysed, of whom 57% (104 patients) met the AC criteria (79 NT-proBNP, 47 PTFV1, 4 LADI). In the multivariate logistic regression, C reactive protein >3 mg/L (OR (95% CI) 2.60 (1.30 to 5.21), p=0.007) and age (OR (95% CI) 1.07 (1.04 to 1.10), p<0.001) were found to be independently associated with AC. After 6 months of follow-up, AFDAS was detected in 33% of AC patients and in 14% of the remaining ones (p=0.003). However, AC was not independently associated with AFDAS, contrary to left atrial volume index (>34 mL/m2, OR 2.35 (CI 1.09 to 5.06) p=0029). CONCLUSION: AC as defined in ARCADIA is mostly based on NT pro BNP elevation (76% of patients) and is associated with age and inflammation. Moreover, AC was not independently associated with AFDAS at follow-up. The ARCADIA trial, which compares aspirin to apixaban in patients with embolic strokes of undetermined source with AC markers and must, therefore be analysed in the light of these limitations. TRIAL REGISTRATION NUMBER: NCT03570060.

Multimodal Approach for the Prediction of Atrial Fibrillation Detected After Stroke: SAFAS Study.

Background: Intensive screening for atrial fibrillation (AF) has led to a better recognition of this cause in stroke patients. However, it is currently debated whether AF Detected After Stroke (AFDAS) has the same pathophysiology and embolic risk as prior-to-stroke AF. We thus aimed to systematically approach AFDAS using a multimodal approach combining clinical, imaging, biological and electrocardiographic markers. Methods: Patients without previously known AF admitted to the Dijon University Hospital (France) stroke unit for acute ischemic stroke were prospectively enrolled. The primary endpoint was the presence of AFDAS at 6 months, diagnosed through admission ECG, continuous electrocardiographic monitoring, long-term external Holter during the hospital stay, or implantable cardiac monitor if clinically indicated after discharge. Results: Of the 240 included patients, 77 (32%) developed AFDAS. Compared with sinus rhythm patients, those developing AFDAS were older, more often women and less often active smokers. AFDAS patients had higher blood levels of NT-proBNP, osteoprotegerin, galectin-3, GDF-15 and ST2, as well as increased left atrial indexed volume and lower left ventricular ejection fraction. After multivariable analysis, galectin-3 ≧ 9 ng/ml [OR 3.10; 95% CI (1.03-9.254), p = 0.042], NT-proBNP ≧ 290 pg/ml [OR 3.950; 95% CI (1.754-8.892, p = 0.001], OPG ≥ 887 pg/ml [OR 2.338; 95% CI (1.015-5.620), p = 0.046) and LAVI ≥ 33.5 ml/m2 [OR 2.982; 95% CI (1.342-6.625), p = 0.007] were independently associated with AFDAS. Conclusion: A multimodal approach combining imaging, electrocardiography and original biological markers resulted in good predictive models for AFDAS. These results also suggest that AFDAS is probably related to an underlying atrial cardiopathy. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03570060].

Assessment of Clinical Scales for Detection of Large Vessel Occlusion in Ischemic Stroke Patients from the Dijon Stroke Registry.

(1) Background: The limited availability of thrombectomy-capable stroke centres raises questions about pre-hospital triage of patients with suspected stroke (IS) due to large vessel occlusion (LVO). Aims: This study aimed to evaluate the diagnostic accuracy of clinical stroke severity scales available for LVO detection. (2) Methods: Patients with IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). Clinical signs and arterial imaging data were collected. LVO was defined as an occlusion site affecting the terminal intracranial internal carotid artery, the M1 segment of the middle cerebral artery (MCA), or the basilar artery (restricted definition). A wide definition of LVO also included the M2 segment of the MCA. For each of the 16 evaluated scales, a receiver operator characteristic (ROC) analysis was performed, and the c-statistic representing the area under the ROC curve was evaluated to assess discrimination for predicting LVO. (3) Results: 971 patients were registered, including 123 patients (12.7%) with an LVO according to the restricted definition. The c-statistic for LVO detection ranged between 0.66 and 0.80 according to the different scales, with a sensibility varying from 70% to 98% and a specificity from 33% to 86%. According to the wide definition of LVO (174 patients, 17.9%), the c-statistic was slightly lower, ranging between 0.64 and 0.79. The sensitivity was 59% to 93%, and the specificity was 34% to 89%. (4) Conclusion: The clinical scales failed to combine a high sensitivity and a high specificity to detect LVO. Further studies are needed to determine the best strategy for pre-hospital triage of IS patients.

Temporal Trends in the Incidence of Ischemic Stroke in Young Adults: Dijon Stroke Registry.

INTRODUCTION: Stroke is associated with major consequences in terms of socioeconomic impact and lost disability-adjusted life in young victims, thus justifying a careful surveillance of epidemiological trends. This study aimed to assess changes in the incidence of ischemic stroke in young adults over a long period. METHODS: All cases of first-ever ischemic stroke that occurred among adults aged 18-55 years were prospectively recorded using the population-based Dijon Stroke Registry, from 1985 to 2017. Sex-specific annual incidence rates were calculated and were presented according to 6 time periods. Incidence rate ratios (IRRs) were determined to assess sex differences in stroke incidence. RESULTS: Over the whole study period, 4,451 patients suffered a first-ever ischemic stroke. Among these patients, 469 (10.5%) were young adults (median age: 46 years, IQR: 39-50; 53.9% men). Incidence rates rose from the study period 2003 to 2007 compared with previous periods and remained stable thereafter, both in men and women. Hence, incidence per 100,000 per year was globally 11.0 (95% CI: 9.4-12.7) before 2003 and 22.9 (20.3-25.6) thereafter. In individuals aged 18-45 years, incidence rates were 5.4 (4.3-6.9) overall, 4.1 (2.7-6.0) in men, and 6.7 (4.9-9.0) in women, before 2003. After 2003, incidence rates rose to 12.8 (10.7-15.1) overall, 12.0 (9.2-15.4) in men, and 13.6 (10.6-17.0) in women. In this age group, the men/women IRR was 0.78 (95% CI: 0.62-1.26, p = 0.08), although sex differences decreased over time (IRR = 0.62; 95% CI: 0.36-1.02, p = 0.046 before 2003, vs. IRR = 0.88; 95% CI: 0.62-1.26, p = 0.48 after 2003). In individuals aged 45-55 years, incidence rates before 2003 were 47 (37-61) in men and 25 (17-35) in women (IRR = 1.90; 95% CI: 1.24-2.97, p < 0.001), and they increased to 82 (67-100) in men and 46 (35-59) in women (IRR = 1.79; 95% CI: 1.29-2.49, p < 0.001) after 2003. CONCLUSIONS: The incidence of ischemic stroke in young adults increased during the early 2000s and remained stable thereafter. These results highlight the priority need for dedicated prevention strategies for the young to reduce the burden of stroke.

Current characteristics and early functional outcome of older stroke patients: a population-based study (Dijon Stroke Registry).

BACKGROUND: the ongoing growing and ageing population is associated with an increase in older patients suffering a stroke. We aimed to assess the current profile of these patients in a population-based setting. METHODS: all patients with acute stroke were prospectively identified among residents of Dijon, France, between 2013 and 2017, using a population-based registry. Characteristics and early outcome of patients were compared according to age groups. RESULTS: 1,288 stroke cases were recorded (median age: 81.1 years, interquartile range: 66.1-86.7, 54% women). Patients aged 75-85 years and those >85 years accounted for 27.6 and 33.9% of overall cases. Increasing age was associated with a greater prevalence of vascular risk factors, pre-existing cognitive impairment and handicap, higher initial severity, more frequent cardioembolic ischemic stroke, post-stroke pulmonary infection and delirium. Only 41% of patients aged 75-85 years and 18% of those aged >85 years had a good early recovery. Compared with patients aged <75 years, patients aged 75-85 years [adjusted odds ratio (OR) = 2.61; 95% confidence interval (CI): 1.74-3.93, P < 0.001] and those aged >85 years (adjusted OR = 7.18; 95% CI: 4.58-11.3, P < 0.001) had an increased risk of poor post-stroke functional outcome. Among survivors, the proportion of patients discharged to home was 60% in age group <75 years, compared with 49% in patients aged 75-85 years and 29% in those aged >85 years. Thirty per cent of patients >85 years old required a long-term care institution. CONCLUSION: the increasing burden of stroke in older people has major implications for future treatment strategies and need for dedicated care facilities.

Incidence of Acute Ischemic Stroke With Visible Arterial Occlusion: A Population-Based Study (Dijon Stroke Registry).

BACKGROUND AND PURPOSE: Because of several methodological limitations, previous studies focusing on the prevalence of large vessel occlusion in ischemic stroke (IS) patients provided conflicting results. We evaluated the incidence of IS with a visible arterial occlusion using a comprehensive population-based registry. METHODS: Patients with acute IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). All arterial imaging exams were reviewed to assess arterial occlusion. Annual incidence rates of IS (first-ever and recurrent events) and IS with a visible occlusion were calculated. RESULTS: One thousand sixty cases of IS were recorded (mean age: 76.0±15.8 years, 53.9% women). Information about arterial imaging was available in 971 (91.6%) of them, and only preexisting dementia was independently associated with having missing information (odds ratio=0.34 [95% CI, 0.18-0.65], P=0.001). Among these patients, 284 (29.2%) had a visible arterial occlusion. Occlusion site was the anterior circulation in 226 patients (23.3% of overall patients with available data) and the posterior circulation in 58 patients (6.0%). A proximal occlusion of the anterior circulation was observed in 167 patients (17.2%). The crude annual incidence rate of total IS per 100 000 was 138 (95% CI, 129-146). Corresponding standardized rates were 66 (95% CI, 50-82) to the World Health Organization and 141 (95% CI, 118-164) to the 2013 European populations. The crude annual incidence rate of IS with a visible arterial occlusion per 100 000 was 37 (95% CI, 33-41) and that of IS with a proximal occlusion of the anterior circulation was 22 (95% CI, 18-25). Corresponding standardized rates were 18 (95% CI, 10-26) and 10 (95% CI, 8-13) to the World Health Organization population, and 38 (95% CI, 26-50) and 23 (95% CI, 19-26) to the 2013 European population, respectively. CONCLUSIONS: These results will be helpful to plan the need for thrombectomy-capable stroke center resources.

Influence of Preexisting Cognitive Impairment on Clinical Severity of Ischemic Stroke: The Dijon Stroke Registry.

Background and Purpose- The ongoing ageing population is associated with an increasing number of patients with stroke who have preexisting cognitive impairment. This study aimed to evaluate clinical severity in patients with ischemic stroke according to prestroke cognitive status. Methods- Patients with ischemic stroke were prospectively identified among residents of Dijon, France using a population-based registry (2013-2017). Prestroke cognitive status (no impairment, mild cognitive impairment [MCI], or dementia) was recorded, and severity at stroke onset was measured using the National Institutes of Health Stroke Scale (NIHSS) score. Association between prestroke cognitive status and severity was evaluated using ordinal regression analysis models in which the NIHSS score was considered as a categorical variable. Results- Among the 1048 patients (mean age, 76.3±15.2 years; 54.0% women), a greater severity was observed in those with MCI (n=132; median NIHSS: 6; interquartile range, 2-15), and those with dementia (n=164; median NIHSS: 7; interquartile range, 3-16), than in patients without cognitive impairment (n=752; median NIHSS: 3; interquartile range, 1-9). MCI (odds ratio [OR], 1.70 [95% CI, 1.21-2.38]; P=0.002) and dementia (OR, 2.24 [95% CI, 1.65-3.04]; P<0.001) were both associated with a greater severity at onset. The association was still observed after adjustment for clinical variables and proximal arterial occlusion (OR, 1.52 [95% CI, 1.02-2.28]; P=0.04 for MCI; OR, 2.16 [95% CI, 1.45-3.22]; P<0.001 dementia). Further adjustment for prestroke handicap slightly reduced the magnitude of the association (OR, 1.49 [95% CI, 0.98-2.25]; P=0.06 for MCI, and OR, 1.98 [95% CI, 1.26-3.12]; P=0.02 for dementia). The greater severity in patients with prestroke cognitive impairment was not specifically driven by a more severe impairment of either motor or language function. Conclusions- Patients with preexisting cognitive impairment suffered more severe ischemic stroke. This result could reflect a lower brain tolerance of acute ischemia. Further studies are needed to explore the underlying mechanisms that could be targeted from therapeutic perspectives focusing on neuroprotection.

Influence of Pre-Existing Mild Cognitive Impairment and Dementia on Post-Stroke Mortality. The Dijon Stroke Registry.

OBJECTIVE: We assessed the association between pre-stroke cognitive status and 90-day case-fatality. METHODS: Patients with ischemic stroke (IS) or spontaneous intracerebral hemorrhage (ICH) were prospectively identified among residents of Dijon, France, between 2013 and 2015, using a population-based registry. Association between pre-stroke cognitive status and case-fatality at 90 days was evaluated using Cox regression. RESULTS: Seven hundred sixty-two patients were identified, and information about pre-stroke cognitive status was obtained for 716 (92.6%) of them, including 603 IS (84.2%) and 113 ICH (15.8%). Before stroke, 99 (13.8%) patients had mild cognitive impairment (MCI) and 98 (13.7%) had dementia. Patients with cognitive impairment were older, had a higher prevalence of several risk factors, more severe stroke, more frequent ICH, and less admission to stroke unit. Case-fatality rate at 90 days was 11.7% in patients without cognitive impairment, 32.3% in MCI patients, and 55.1% in patients with dementia. In multivariable analyses, pre-existing MCI (hazard ratio [HR] 2.22, 95% CI 1.21-4.05, p = 0.009) and dementia (HR 4.35, 95% CI 2.49-7.61, p < 0.001) were both associated with 90-day case-fatality. CONCLUSION: Pre-stroke MCI and dementia were both associated with increased mortality. These associations were not fully explained by baseline characteristics, pre-stroke dependency, stroke severity or patient management, and underlying reasons need to be investigated.

Association Between Fatigue and Cognitive Impairment at 6 Months in Patients With Ischemic Stroke Treated With Acute Revascularization Therapy.

Background: Fatigue is a frequent symptom after stroke. We aimed to determine the association between fatigue and cognitive performance in patients with ischemic stroke who received acute revascularization therapy (IV thrombolysis and/or mechanical thrombectomy). Methods: Seventy patients were prospectively included in the stroke unit of the University Hospital of Dijon, France. A follow-up was performed at 6 months with clinical examination, fatigue assessment by the Fatigue Severity Scale (FSS), and a comprehensive neuropsychological evaluation. Patients with fatigue (FSS score >4) were compared with patients without fatigue. Neuropsychological factors associated with fatigue at 6 months were analyzed using multivariable logistic regression models. Results: Fatigue was reported by 34.3% of patients. Patients with fatigue were older, had more frequent residual handicap, depressive symptoms, and impaired quality of life. They had more frequently low score (<26) on the MoCA scale (79.2 vs. 47.8%, OR = 4.15; 95% CI: 1.32-13, p = 0.015), memory impairment (60 vs. 30.6%, OR = 3.41; 95% CI: 1.09-10.7, p = 0.035), and executive dysfunction (65 vs. 30.8%, OR = 4.18; 95% CI: 1.33-13.1, p = 0.014). In multivariable logistic regression analysis, only memory impairment was independently associated with fatigue (OR = 5.70; 95% CI: 1.09-29.6, p = 0.039). Further analyses restricted to non-depressed patients (n = 58, 84.1%) showed in multivariable models that a score < 26 on MoCA scale (OR 5.12; 95% CI: 1.00-26.2, p = 0.05), and a memory impairment (OR = 6.17; 95% CI: 1.06-35.9, p = 0.043) were associated with fatigue. There was also a non-significant trend toward an association between divided attention deficit and fatigue (OR = 6.79; 95% CI: 0.80-57.6, p = 0.079). Conclusion: The association between fatigue and subtle cognitive impairment including memory or attention deficits could be of interest in elaborating future interventional studies to evaluate the impact of therapeutic strategies, including cognitive rehabilitation, on fatigue.

Impact of the Ageing Population on the Burden of Stroke: The Dijon Stroke Registry.

BACKGROUND: We aimed to evaluate the impact of the ageing population on temporal trends in burden of stroke and to provide projections for the coming years. METHODS: Stroke cases (ischemic strokes, spontaneous intracerebral hemorrhages, or undetermined strokes) were prospectively identified between 1987 and 2015 in Dijon, France, using a population-based registry. Age-standardized incidence rates of first-ever and recurrent stroke were calculated, and their temporal trends were assessed using age- and sex-adjusted annual incidence rate ratios (RR). RESULTS: The population of Dijon increased by 3.8% over time, with an increase by 28% in the number of residents aged ≥75 years. We recorded 5,899 strokes including 5,101 patients with a first-ever event. Incidence of first-ever stroke was stable both in people < 75 and ≥75 years old, but an increase in standardized incidence rates of total strokes was noted due to a rise in the incidence of recurrent stroke (from 4.7/100,000/year in 1987-1994 to 12.3/100,000/year in 2009-2015 in people < 75 years old, RR 1.036; p < 0.001; from 74/100,000/year in 1987-1994 to 200/100,000/year in 2009-2015 in people ≥75 years, RR 1.040; p < 0.001). The absolute number of first-ever strokes increased by 43%, and that of total stroke events rose by 58% over time, with a more pronounced increase in people ≥75 years old (+47 and +65% respectively). The annual number of patients who survived > 90 days after a first-ever stroke increased by 90%. According to demographic projections, the total number of strokes will increase by 55% (+65% patients ≥75 years, and +25% patients < 75 years) by 2,030 in Dijon. CONCLUSIONS: Ageing and growth of the population led to a rise in the absolute number of strokes, especially in the elderly, that is expected to increase dramatically in the coming years. Improved stroke care was accompanied with an increase in stroke survivors that contributed to a rise in recurrent events. Urgent action is needed to meet this epidemiological challenge.

Increasing Burden of Stroke: The Dijon Stroke Registry (1987-2012).

BACKGROUND: We aimed to provide a representation of the global burden of stroke. METHODS: All cases of stroke were prospectively identified through the population-based registry of Dijon, France (1987-2012). Attack rates and mortality rates (defined as stroke leading to death within 30 days) were standardized to the European standard. Sex differences and temporal trends were evaluated by calculating rate ratios (RRs). RESULTS: In all, 5,285 stroke cases (52.7% women) were recorded. The standardized attack rate was 98.2/100,000/year and the mortality rate was 12/100,000/year, and both were lower in women than in men (RR 0.67, p < 0.001, and RR 0.70, p < 0.001, respectively). Attack rates increased over time (RR 1.016; 95% CI 1.013-1.020) irrespective of the stroke subtype. In contrast, mortality rates declined (RR 0.985; 95% CI 0.976-0.995) with decreasing rates for ischemic stroke but no change for intracerebral hemorrhage and subarachnoid hemorrhage. The sex gap in both attack and mortality rates remained stable. Between the first (1987-1991) and the last (2007-2012) study periods, the annual number of stroke patients who survived beyond 30 days rose by 55%, Conclusions: Increasing attack rates and decreasing mortality have led to a rise in the number of stroke survivors in the population, thus indicating a growing need for the implementation of dedicated services.

Contemporary Epidemiology of Transient Ischemic Attack in Dijon, France (2013-2015).

BACKGROUND: We aimed to evaluate the epidemiological features of transient ischemic attack (TIA). METHODS: All TIAs were prospectively collected in Dijon, France, using a population-based registry (2013-2015). TIAs were considered the first-ever in patients who had no previous cerebrovascular events (CVEs); otherwise they were considered recurrent TIAs. Annual incidence (first-ever TIAs) and attack rates (first-ever and recurrent TIAs) were calculated. RESULTS: Four hundred twenty TIAs were registered (255 first-ever and 165 recurrent TIAs, mean age: 74.1 ± 15.7 years). The age-standardized incidence rate (to the 2013 European population) was 61 (95% CI 46-76) and the attack rate was 81 (95% CI 64-99) per 100,000/year. Patients with TIA as a recurrent event had a greater prevalence of risk factors and preventive treatments. However, one third of them were not receiving antithrombotic agents or antihypertensive treatments, and half were not treated with statins at the time of their recurrence. The mean ABCD2 score was 4.3 ± 1.3, and 72% of patients had a high risk of recurrence (score ≥4). In patients with available MRI (23%), an infarct lesion was seen in 15.5%. CONCLUSIONS: TIA is a frequent occurrence and a large proportion of patients have a high risk of recurrence, thus highlighting the need to establish dedicated emergency services to administer prompt secondary prevention.