Is COVID-19 Infection a Multiorganic Disease? Focus on Extrapulmonary Involvement of SARS-CoV-2.

First described in December 2019 in Wuhan (China), COVID-19 disease rapidly spread worldwide, constituting the biggest pandemic in the last 100 years. Even if SARS-CoV-2, the agent responsible for COVID-19, is mainly associated with pulmonary injury, evidence is growing that this virus can affect many organs, including the heart and vascular endothelial cells, and cause haemostasis, CNS, and kidney and gastrointestinal tract abnormalities that can impact in the disease course and prognosis. In fact, COVID-19 may affect almost all the organs. Hence, SARS-CoV-2 is essentially a systemic infection that can present a large number of clinical manifestations, and it is variable in distribution and severity, which means it is potentially life-threatening. The goal of this comprehensive review paper in the series is to give an overview of non-pulmonary involvement in COVID-19, with a special focus on underlying pathophysiological mechanisms and clinical presentation.

Atrial fibrillation and preexisting cognitive impairment in ischemic stroke patients: Dijon Stroke Registry.

BACKGROUND: Atrial Fibrillation (AF) is a common cause of ischemic stroke (IS), and is associated with cognitive impairment in the general population. We aimed to compare the prevalence of preexisting cognitive impairment between IS patients with and without AF, and to assess whether prior brain damage could contribute to the observed differences. METHODS: Patients with acute IS were prospectively identified from the population-based Dijon Stroke Registry, France. Patients who had a CT-scan as brain imaging modality were included in this analysis to assess the presence of preexisting leukoaraiosis, old vascular brain lesions, and cerebral atrophy. Characteristics of patients including prior-to-stroke cognitive status (normal cognition, mild cognitive impairment (MCI), or dementia) were compared between those with and without AF. RESULTS: Among 916 IS patients, 288 (31.4 %) had AF, of whom 88 had newly diagnosed AF. AF patients had more frequent prior MCI (17.8 % versus 10.2 %) or dementia (22.4 % versus 13.1 %) (p = 0.001), vascular risk factors, and preexisting brain damage. In unadjusted model, preexisting cognitive impairment was associated with AF (OR=2.24; 95 % CI: 1.49-3.37, p < 0.001 for MCI; OR=2.20; 95 % CI: 1.52-3.18, p < 0.001 for dementia). After adjustment for clinical and imaging variables, preexisting mild cognitive impairment (OR=1.87; 95 % CI: 1.06-3.32, p = 0.032) and dementia (OR=1.98; 95 % CI: 1.15-3.40, p = 0.013) were independently associated with AF. CONCLUSION: AF is a common condition in IS patients and is associated with preexisting cognitive impairment. Brain lesions visible on imaging did not seem to fully account for this association that may involve other mechanisms yet to be elucidated.

Prevalence and characteristics of known versus newly detected atrial fibrillation in ischemic stroke: a population-based study.

BACKGROUND: Atrial fibrillation (AF) is frequently diagnosed during the acute stage of ischemic (IS), and it may reflect undiagnosed AF before stroke, thus representing a missed opportunity for stroke prevention. This population-based study aimed to assess the prevalence of known AF (KAF) and AF diagnosed early after IS (AFDAS), and to compare clinical and brain/arterial imaging characteristics between patients. METHODS: Among patients with acute IS recorded in the population-based Dijon Stroke Registry, France (2013-2020), we identified those with KAF or AFDAS. AFDAS was considered when AF was diagnosed during the initial work-up based on electrocardiograms, in-hospital continuous electrocardiographic and/or Holter monitoring. Clinical and imaging characteristics on brain CT-scan or angio-CT-scan when available including old parenchymal lesions, arterial territory of the index IS, and aortic arch, cervical and intracranial arteries atheroma were compared between groups (KAF versus AFDAS). Regression logistic models were used to assess factors associated with AFDAS (compared to KAF). RESULTS: Among 1756 IS patients, 550 (31.3%) had AF (mean age: 83.6 ±10.3 years old, 60.5% women), of whom 367 (66.7%) presented with KAF and 183 (33.3%) had AFDAS. In multivariable model, hypertension (OR=0.37; 95% CI: 0.21-0.64, p<0.001), chronic heart failure (OR=0.34; 95% CI: 0.18-0.67, p=0.002), previous stroke (OR=0.42; 95% CI: 0.26-0.67, p<0.001), and preexisting dementia (OR=0.36; 95% CI: 0.21-0.63, p<0.001), were inversely associated with AFDAS, whereas NIHSS score was associated with AFDAS (OR=1.02; 95% CI: 1.00-1.05, p=0.012). CONCLUSIONS: Our findings indicate a more advanced stage of the atrial cardiomyopathy in KAF as compared with AFDAS patients, and may thus contribute to the fact that in these latter patients AF had not been diagnosed prior to stroke. This group of patients undeniably represents a missed opportunity for stroke prevention.

Prevalence of major embolic findings and incidental findings on early cardiac CT in patients with suspected ischemic stroke.

PURPOSE: The purpose of this study was to assess the type and prevalence of stroke and non-stroke-related findings diagnosed on early cardiac computed tomography (CT) in patients with suspected stroke. The secondary objective was to assess the clinical consequences on the management of patients with non-stroke-related conditions identified by early cardiac CT. MATERIALS AND METHODS: This single-center, retrospective, observational study included 1111 consecutive patients with suspected ischemic stroke between November 2018 and March 2020 who underwent cardiac CT examination in addition to the usual brain CT protocol (i.e., non-enhanced brain CT, perfusion brain CT when needed, aortic arch and supra-aortic CT angiography, and post contrast brain CT). There were 562 women and 549 men with a median age of 74 years (range: 60-85 years). Of these, 415 (415/1111; 37.4%) patients had ischemic stroke and 692 (692/1111; 62.3%) had no stroke. Cardiac CT examinations were retrospectively reviewed for cardiac CT findings at high embolic risk and clinically significant extracardiac incidental findings. RESULTS: Among 1111 included patients, 89 (89/1111; 8.0%) had a stroke-related condition identified on early cardiac CT. This was significantly more frequent in patients with ischemic stroke (66/415; 15.9%) by comparison with those without ischemic stroke (23/696; 3.3%) (P < 0.001), with 41 patients (41/415; 9.9%) diagnosed with left atrial thrombus. Cardiac CT revealed a clinically significant non-stroke-related finding in 173 patients (173/1111; 15.6%), including 17 pulmonary embolisms (1.5%), seven suspicious pulmonary lesions (0.6%), and three breast lesions suspected to be malignant (0.3%). Twenty out of 173 patients (20/173; 11.5%) with incidental findings on early cardiac CT had a change in their management. CONCLUSION: This study shows that adding early cardiac CT to brain CT during the acute phase of an ischemic stroke leads to a higher rate of etiological diagnoses and highlights the major interest of looking at the bigger picture.

Value of HAVOC and Brown ESUS-AF scores for atrial fibrillation on implantable cardiac monitors after embolic stroke of undetermined source.

OBJECTIVES: Up to 20 % of ischemic strokes are associated with overt atrial fibrillation (AF). Furthermore, silent AF was detected by an implantable cardiac monitor (ICM) in 1 in 3 cryptogenic strokes in the CRYSTAL AF study. An ESC position paper has suggested a HAVOC score ≥ 4 or a Brown ESUS-AF score ≥ 2 as criteria for ICM implantation after cryptogenic stroke, but neither of these criteria has been developed or validated in ICM populations. We assessed the performance of HAVOC and Brown ESUS-AF scores in a cohort of ICM patients implanted after embolic stroke of undetermined source (ESUS). METHODS: All patients implanted with an ICM for ESUS between February 2016 and February 2022 at two French University Hospitals were retrospectively included. Demographic data, cardiovascular risk factors, and clinical and biological data were collected after a review of electronic medical records. HAVOC and Brown ESUS-AF scores were calculated for all patients. FINDINGS: Among the 384 patients included, 106 (27 %) developed AF during a mean follow-up of 33 months. The scores performances for predicting AF during follow-up were: HAVOC= AUC: 68.5 %, C-Index: 0.662, and Brown ESUS-AF=AUC: 72.9 %, C-index 0.712. Compared with the CHA2DS2-VASc score, only the Brown ESUS-AF score showed significant improvement in NRI/IDI. Furthermore, classifying patients according to the suggested HAVOC and Brown ESUS-AF thresholds, only 24 % and 31 % of the cohort, respectively, would have received an ICM, and 58 (55 %) and 47 (44 %) of the AF patients, respectively, would not have been implanted with an ICM. CONCLUSION: HAVOC and Brown ESUS-AF scores showed close and moderate performance in predicting AF on ICM after cryptogenic stroke, with a significant lack of sensitivity. Specific risk scores should be developed and validated in large ICM cohorts.

Long-Term Survival of Ischemic Stroke Patients according to Prior Cognitive Status: Dijon Stroke Registry.

INTRODUCTION: Understanding the influence of preexisting cognitive impairment on the poststroke outcome is a critical challenge in the context of current aging and growing population. This study aimed to assess long-term survival of patients with acute ischemic stroke (IS) according to their premorbid cognitive status and to identify contributing factors of death. METHODS: Patients with IS were prospectively identified among residents of Dijon, France, using a population-based registry (2013-2017). The association between case fatality at 5 years and prestroke cognitive status was assessed by multivariable Cox models adjusted for other clinical characteristics and preexisting brain damage on the initial CT scan including leukoaraiosis, old vascular brain lesions, and cortical and central brain atrophy, as well as major arterial occlusion. RESULTS: 1,049 patients were included (mean age ± SD: 76.3 ± 15.2 years old, 54% women). Case fatality rates at 5 years were 38.1% in patients without cognitive impairment, 65.9% in patients with prior mild cognitive impairment (MCI, n = 132, 12.6%), and 86.6% in patients with dementia (n = 164, 15.6%) (p < 0.001). MCI (HR = 1.39; 95% CI: 1.06-1.81, p = 0.016) and dementia (HR = 1.89; 95% CI: 1.45-2.46, p < 0.001) were both independently associated with higher case fatality after adjustment for clinical variables. The association remained significant after further adjustment for preexisting brain damage and major arterial occlusion (HR = 1.47; 95% CI: 1.10-1.98, p = 0.009, for MCI and HR = 1.90; 95% CI: 1.43-2.53, p < 0.001, for dementia) among patients with available data on the CT scan (n = 916). Factors associated with death were roughly similar across groups. CONCLUSION: This study highlighted a poor long-term survival of IS patients with preexisting cognitive impairment, independently of other contributing factors of death. It is critical to better understand the trajectory of IS patients with preexisting cognitive impairment and to identify prognostic markers to guide clinicians in their management strategies.

Functional outcomes of ischemic stroke patients aged over 80 years treated with acute revascularization therapy according to pre-morbid disability: a PARADISE study.

Introduction: Aging population leads to changes in the profile of patients with acute ischemic stroke (IS), and older adults were largely excluded from randomized clinical trials of acute revascularization therapy. This study aimed to assess functional outcomes of treated IS patients > 80 years old according to prior disability and identify associated factors. Methods: Consecutively older patients with acute IS treated with either IV thrombolysis and/or mechanical thrombectomy were enrolled between 2016 and 2019. Pre-morbid disability was assessed using the modified Rankin Scale (mRS) score, and patients were classified as being independent (mRS score, 0-2) or having pre-existing disability (mRS score, 3-5). A multivariable logistic regression analysis was performed to assess factors associated with a poor functional outcome (mRS score > 3) at 3 and 12 months in each group of patients. Results: Among 300 included patients (mean age: 86.3 ± 4.6 years, 63% women, median NIHSS score: 14, IQR: 8-19), 100 had a pre-existing disability. In patients with a pre-morbid mRS score of 0-2, 51% had mRS >3 including 33% of deaths at 3 months. At 12 months, 50% had a poor outcome including 39% of deaths. In patients with a pre-morbid mRS score of 3-5, 71% had a poor outcome at 3 months including 43% of deaths, and at 12 months, 76% had mRS >3 including 52% of deaths. In multivariable models, the NIHSS score at 24 h was independently associated with poor outcomes at 3 and 12 months in both patients with (OR = 1.32; 95% CI: 1.16-1.51, p < 0.001 for 12 months outcome) or without (OR = 1.31; 95% CI: 1.19-1.44, p < 0.001 for 12 months outcome) pre-morbid disability. Conclusion: Although a large proportion of older patients with a pre-existing disability had a poor functional outcome, they did not differ from their non-impaired counterparts regarding prognostic factors. This means that there were no factors in our study that would help clinicians identify patients at risk of poor functional outcomes after revascularization therapy among those with prior disability. Further studies are needed to better understand the post-stroke trajectory of older IS patients with a pre-morbid disability.

Symptomatic Intracranial Hemorrhage after Ischemic Stroke Treated with Bridging Revascularization Therapy.

(1) Background: bridging revascularization therapy is now the standard of care in patients with ischemic stroke due to large vessel occlusion. This study aimed to determine the frequency of symptomatic intracranial hemorrhage (sICH) related to this treatment, and to assess contributing factors and patients' outcomes. (2) Methods: consecutive ischemic stroke patients treated with bridging therapy were prospectively enrolled. sICH (intracranial hemorrhage with an increase in NIHSS score of ≥4 points) was assessed on imaging at 24 h. The functional status of patients was measured at 6 months using the mRS score; (3) Results: 176 patients were included (mean age 68.7 ± 1.2 years, 52.3% women), among whom 15 (8.5%) had sICH. Patients with sICH had more frequent alcohol abuse (30.1% versus 9.7%, p = 0.023), prestroke use of dual antiplatelet therapy (14.3% versus 1.3%, p = 0.002), higher NIHSS scores at admission (median score 20.5 versus 15, p = 0.01), greater systolic blood pressure upon admission, more frequent vascular intracranial calcifications (p = 0.004), leukoaraiosis (p = 0.001), and intracranial atheroma (p = 0.02), and higher neutrophil-to-lymphocyte ratios (p = 0.02) and neutrophil-to-platelet ratios (p = 0.04). At 6-month follow-up, 9 (60%) patients with sICH died, versus 18% of patients without sICH (p < 0.001). Only 1 (7%) patient with sICH had a good functional outcome, defined as an mRS score of 0 to 2, versus 51% of patients without sICH. (4) Conclusions: one in twelve ischemic stroke patients treated with bridging therapy suffered sICH. Given the observed poor outcomes after sICH, further studies are required to better identify patients at risk to help clinicians in guiding therapeutic strategies.

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.

Comparison of Stroke Recurrence, Cardiovascular Events, and Death Among Patients With Pregnancy-Associated vs Non-Pregnancy-Associated Stroke.

Importance: Women with pregnancy-associated stroke might have different risks of stroke recurrence, including during subsequent pregnancies, and other cardiovascular events due to pregnancy-specific stroke risk factors, such as gestational hypertension, preeclampsia, or gestational diabetes. Objective: To estimate the rate of stroke recurrence, cardiovascular hospitalization, and death in women with pregnancy-associated stroke compared with women with non-pregnancy-associated stroke. Design, Setting, and Participants: This cohort study included all women aged 15 to 49 years in France who were affiliated with the general scheme of French health care insurance (94% of women) and had a first hospitalization for stroke between January 1, 2010, and December 31, 2018. Women were followed up until December 31, 2020, with the registration of stroke recurrence, hospitalization for cardiovascular conditions, and death. Data were from the French health care database Système National des Données de Santé. Statistical analyses were conducted between December 2021 and September 2022. Exposure: Pregnancy status at the time of stroke. Main Outcomes and Measures: Poisson regressions were used to estimate incidence rates of these events with 95% CIs. We used Cox proportional hazards regression models to estimate the hazard ratios (HRs) of each event during the follow-up for women with a pregnancy-associated stroke vs women with a non-pregnancy-associated stroke. Results: Among women aged between 15 and 49 years between 2010 and 2018 and living in France, 1204 had a pregnancy-associated stroke at a mean (SD) age of 31.5 (5.8) years, and 31 697 had a non-pregnancy-associated stroke at a mean age of 39.6 (8.2) years. Among the 1204 women with a pregnancy-associated stroke, the incidence rate was 11.4 (95% CI, 9.0-14.3) per 1000 person-years, with 2 recurrent events during a subsequent pregnancy. Compared with women with non-pregnancy-associated stroke, women with pregnancy-associated stroke had lower risks of ischemic stroke (adjusted HR, 0.53; 95% CI, 0.36-0.77), cardiovascular events (adjusted HR, 0.58; 95% CI, 0.49-0.69), and death (adjusted HR, 0.42; 95% CI, 0.22-0.79). In contrast, the risk of recurrent intracerebral hemorrhage and cerebral venous thrombosis did not differ significantly, whereas the risks of venous thromboembolism (HR, 2.02; 95% CI, 1.14-3.58) and acute coronary syndrome with ST-segment elevation (HR, 3.93; 95% CI, 1.10-14.0) were increased. Conclusions and Relevance: In this cohort study, although the risks of ischemic stroke, overall cardiovascular events, and mortality were lower after a pregnancy-associated stroke than after a non-pregnancy-associated stroke, the risks of venous thromboembolism and acute coronary syndrome with ST-segment elevation were higher. Recurrent stroke during a subsequent pregnancy remained rare.

Nationwide projections of ischemic stroke with large vessel occlusion of the anterior circulation by 2050: Dijon Stroke Registry.

Introduction: Data on the epidemiology of ischemic stroke (IS) with large vessel occlusion (LVO) are scarce although there is a need to better assess future demands for dedicated facilities in an aging population. This study aimed to estimate the number of expected cases of IS with LVO of the anterior circulation in the French population by 2050. Methods: IS were retrieved from the population-based registry of Dijon, France (2013-2017). Patients with LVO were identified and age-and sex-standardized incidence rates were calculated to estimate the number of expected cases in the whole French population by 2050 according three scenarios: stable incidence; a decrease in incidence rates of 0.5%/year in people >65 years old; a decrease in incidence rates of 0.5%/year in overall population. Results: 1,067 cases of IS with LVO were recorded in Dijon over the study period, corresponding to crude incidence rate of 22/100,000/year (95% CI: 18-25). By 2050, the number of cases is expected to increase by 51 to 81% according to the various scenarios, to reach between 22,457 cases (95% CI: 10,839 - 43,639) and 26,763 cases (95% CI: 12,918 - 52,008) annually. This increase will be mainly driven by patients >80 years old, with a rise of cases between +103% and +42% in this age group. The proportion of patients >80 years old among overall IS with LVO will increase from 43 to 57% approximately. Conclusion: The expected massive increase in IS with LVO highlights the need for a rapid action to cover stroke care requirements.

Acute revascularization therapy for ischemic stroke during pregnancy and post-partum in France.

INTRODUCTION: Intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in women with ischemic stroke (IS) during pregnancy/post-partum is challenging, and recent guidelines claimed for additional information to better argue its effectiveness and safety. This observational national study aimed to describe characteristics, rates and outcomes of pregnant/post-partum women receiving acute revascularization therapy for IS compared to their non-pregnant counterparts, and pregnant women with IS not receiving such therapy. PATIENTS AND METHODS: In this cross-sectional study, all women aged 15-49 years hospitalized in France for IS between 2012 and 2018 were retrieved from the French hospital discharge databases. Pregnant or post-partum (⩽6 weeks after delivery) women were identified. Data about patients' characteristics, risk factors, revascularization therapy, delivery, post-stroke survival, and recurrent vascular events during follow-up were recorded. RESULTS: Over the study period, 382 women with pregnancy-related IS were registered. Among them, 7.3% (n = 28) received a revascularization therapy, including nine cases during pregnancy, one the same day as delivery, and 18 during the post-partum period, compared with 8.5% (n = 1285) in women with non-pregnancy-related IS (n = 15,084). Treated pregnant/post-partum women had more severe IS than not-treated pregnant/post-partum. Compared with treated not-pregnant women, they were younger, but did not differ regarding other characteristics including stroke severity. There were no differences in systemic or intracranial hemorrhages or in the length of hospital stay between pregnant/post-partum women compared with treated not-pregnant women. All women receiving revascularization during pregnancy had a live baby. After a mean follow-up of 4.3 years, all pregnant/post-partum women were alive, one had recurrent IS and none had other vascular events. DISCUSSION AND CONCLUSION: Only a few women with pregnancy-related IS were treated with acute revascularization therapy, but this was proportionately similar to their non-pregnant counterparts, from whom they did not differed regarding characteristics, survival, and risk of recurrent events. These findings suggest that stroke physicians applied treatment strategies of IS in a similar way regardless of pregnancy in France, and this attitude was an anticipation but consistent with the recently published guidelines on the topic.

Efficiency and effectiveness of intensive multidisciplinary follow-up of patients with stroke/TIA or myocardial infarction compared to usual monitoring: protocol of a pragmatic randomised clinical trial. DiVa (Dijon vascular) study.

INTRODUCTION: The ongoing ageing population is associated with an increase in the number of patients suffering a stroke, transient ischaemic attack (TIA) or myocardial infarction (MI). In these patients, implementing secondary prevention is a critical challenge and new strategies need to be developed to close the gap between clinical practice and evidence-based recommendations. We describe the protocol of a randomised clinical trial that aims to evaluate the efficiency and effectiveness of an intensive multidisciplinary follow-up of patients compared with standard care. METHODS AND ANALYSIS: The DiVa study is a randomised, prospective, controlled, multicentre trial including patients >18 years old with a first or recurrent stroke (ischaemic or haemorrhagic) or TIA, or a type I or II MI, managed in one of the participating hospitals of the study area, with a survival expectancy >12 months. Patients will be randomised with an allocation ratio of 1:1 in two parallel groups: one group assigned to a multidisciplinary, nurse-based and pharmacist-based 2-year follow-up in association with general practitioners, neurologists and cardiologists versus one group with usual follow-up. In each group for each disease (stroke/TIA or MI), 430 patients will be enrolled (total of 1720 patients) over 3 years. The primary outcome will be the incremental cost-utility ratio at 24 months between intensive and standard follow-up in a society perspective. Secondary outcomes will include the incremental cost-utility ratio at 6 and 12 months, the incremental cost-effectiveness ratio at 24 months, reduction at 6, 12 and 24 months of the rates of death, unscheduled rehospitalisation and iatrogenic complications, changes in quality of life, net budgetary impact at 5 years of the intensive follow-up on the national health insurance perspective and analysis of factors having positive or negative effects on the implementation of the project in the study area. ETHICS AND DISSEMINATION: Ethical approval was obtained and all patients receive information about the study and give their consent to participate before randomisation. Results of the main trial and each of the secondary analyses will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04188457. Registered on 6 December 2019.

Incremental value of the combined brain-cardiac CT protocol on prediction of atrial fibrillation after stroke.

Introduction: Atrial fibrillation (AF) is one of the most common causes of ischemic stroke. It is essential to target patients at highest risk of AF detected after stroke (AFDAS), who should benefit from a prolonged rhythm screening strategy. Cardiac-CT angiography (CCTA) was added to the stroke protocol used in our institution in 2018. We sought to assess, for AFDAS, the predictive value of atrial cardiopathy markers by a CCTA performed on admission for acute ischemic stroke. Patients and Methods: From November 2018 to October 2019, consecutive stroke patients with no history of AF were included. Let atrial volume (LAV), epicardial adipose tissue (EAT) attenuation and volume, and LAA characteristics were measured on CCTA. The primary endpoint was the presence of AFDAS at follow-up, diagnosed by continuous electrocardiographic monitoring, long-term external Holter monitoring during hospital stay, or implantable cardiac monitor (ICM). Results: Sixty of the 247 included patients developed AFDAS. Multivariable analysis shows independent predictors of AFDAS: age >80 years (HR 2.46; 95%CI (1.23-4.92), p = 0.011), indexed LAV >45 mL/m2 (HR 2.58; 95%CI (1.19-5.62), p = 0.017), EAT attenuation > -85HU (HR 2.16; 95%CI (1.13-4.15), p = 0.021) and LAA thrombus (HR 2.50; 95%CI (1.06-5.93), p = 0.037). Added consecutively to AFDAS prediction AS5F score (combining age and NIHSS >5), these markers had an incrementally better predictive value compared with the global Chi2 of the initial model (p = 0.001, 0.035, and 0.015 respectively). Discussion and conclusion: Adding CCTA to the acute stroke protocol to assess markers of atrial cardiopathy associated with AFDAS may help to better stratify the AF screening strategy, including the use of an ICM.

Plasma growth differentiation factor - 8 / Myostatin level as prognostic biomarker of patients with ischemic stroke and acute revascularization therapy. PARADISE study.

BACKGROUND: Identifying biological markers of ischemic stroke (IS) is an important research approach to develop innovative therapeutic strategies. This study aimed to assess the association between plasma Growth Differentiation Factor-8 (GDF-8)/Myostatin levels and outcome of IS patients. METHODS: Consecutive patients with acute IS treated with either intravenous thrombolysis and/or mechanical thrombectomy at Dijon University Hospital, France were prospectively included. Clinical variables were recorded, and plasma GDF-8 was collected just after the revascularization procedure. Primary endpoint was functional outcome at 3 months assessed by the modified Rankin Scale (mRS) score. Secondary endpoints included mRS scores at 6 and 12 months, and overall mortality over 1-year of follow-up. RESULTS: Among the 173 included patients (median age: 76 years, Interquartile range (IQR): 66-85; 49% women), median plasma GDF-8 levels at admission were significantly lower in those with a poor outcome at 3 months defined as a mRS score > 2 (2073 (IQR: 1564-2757) pg/mL versus 1471 (1192-2241) pg/mL, p < 0.001). Lower GDF-8 levels at admission were associated with higher 3-months mRS score in multivariable ordinal logistic regression analysis (OR = 0.9995; 95% CI: 0.9991-0.9999, p = 0.011). The association was also observed with 6- and 12-month mRS scores. Although mortality was higher in patients with lower GDF-8 levels, the association was not significant in multivariable Cox analysis. CONCLUSION: Lower plasma GDF-8 levels were associated with a poorer functional outcome in IS patients treated with acute revascularization therapy. Underlying pathophysiological mechanisms involving GDF-8 in post-stroke outcome remain to be elucidated.

Pre-existing brain damage and association between severity and prior cognitive impairment in ischemic stroke patients.

BACKGROUND: We evaluated whether pre-existing brain damage may explain greater severity in cognitively-impaired patients with ischemic stroke (IS). METHODS: IS patients were retrieved from the population-based registry of Dijon, France. Pre-existing damage (leukoaraiosis, old vascular brain lesions, cortical and central brain atrophy) was assessed on initial CT-scan. Association between prestroke cognitive status defined as no impairment, mild cognitive impairment (MCI), or dementia, and clinical severity at IS onset assessed with the NIHSS score was evaluated using ordinal regression analysis. Mediation analysis was performed to assess pre-existing brain lesions as mediators of the relationship between cognitive status and severity. RESULTS: Among the 916 included patients (mean age 76.8 ± 15.0 years, 54.3% women), those with pre-existing MCI (n = 115, median NIHSS [IQR]: 6 [2-15]) or dementia (n = 147, median NIHSS: 6 [3-15]) had a greater severity than patients without (n = 654, median NIHSS: 3 [1-9]) in univariate analysis (OR=1.69; 95% CI: 1.18-2.42, p = 0.004, and OR=2.06; 95% CI: 1.49-2.84, p < 0.001, respectively). Old cortical lesion (OR=1.53, p = 0.002), central atrophy (OR=1.41, p = 0.005), cortical atrophy (OR=1.90, p < 0.001) and moderate (OR=1.41, p = 0.005) or severe (OR=1.84, p = 0.002) leukoaraiosis were also associated with greater severity. After adjustments, pre-existing MCI (OR=1.52; 95% CI: 1.03-2.26, p = 0.037) or dementia (OR=1.94; 95% CI: 1.32-2.86, p = 0.001) remained associated with higher severity at IS onset, independently of confounding factors including imaging variables. Association between cognitive impairment and severity was not mediated by pre-existing visible brain damages. CONCLUSION: Impaired brain ischemic tolerance in IS patients with prior cognitive impairment could involve other mechanisms than pre-existing visible brain damage.

Impact of the First COVID-19 Wave on French Hospitalizations for Myocardial Infarction and Stroke: A Retrospective Cohort Study.

The COVID-19 pandemic modified the management of myocardial infarction (MI) and stroke. We aimed to evaluate the effect of the COVID-19 pandemic on the volume and spatial distribution of hospitalizations for MI and stroke, before, during and after the first nationwide lockdown in France in 2020, compared with 2019. Hospitalization data were extracted from the French National Discharge database. Patient's characteristics were compared according to COVID-19 status. Changes in hospitalization rates over time were measured using interrupted time series analysis. Possible spatial patterns of over or under-hospitalization rates were investigated using Moran's indices. We observed a rapid and significant drop in hospitalizations just before the beginning of the lockdown with a nadir at 36.5% for MI and 31.2% for stroke. Hospitalization volumes returned to those seen in 2019 four weeks after the end of the lockdown, except for MI, which rebounded excessively. Older age, male sex, elevated rate of hypertension, diabetes, obesity and mortality characterized COVID-19 patients. There was no evidence of a change in the spatial pattern of over- or under-hospitalization clusters over the three periods. After a steep drop, only MI showed a significant rebound after the first lockdown with no change in the spatial distribution of hospitalizations.

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].

Quality of Life in the First Year after Ischemic Stroke Treated with Acute Revascularization Therapy.

(1) Background: we aimed to describe the disease-specific quality of life (QoL) of ischemic stroke patients treated with acute revascularization therapy, its evolution from 6 months to 12 months, and associated factors. (2) Methods: QoL was assessed with the SS-QoL in consecutive patients treated with either intravenous thrombolysis (IVT) and/or mechanical thrombectomy (MT). Variables associated with QoL scores and its evolution were studied using multivariate mixed models, and interaction with time. Analyses were performed in four domains of SS-QoL: self-care, mobility, mood, and social roles. (3) Results: Among the 501 included patients (mean (sd) age 68.9 (14.5), 49% women), lower post-stroke QoL was independently related to lower level of school education, prestroke mRS > 2, and 24 h NIHSS score > 4. Independent predictors of unfavorable evolution of QoL over time were age <75 years (Mobility p = 0.0194 and Mood p = 0.0015), NIHSS score ≤ 4, (Self-care p = 0.0053 and Mood p = 0.0048), and modified Rankin Scale score ≤ 2 (Social roles, p = 0.0006). Revascularization therapy had no significant effect on the QoL scores, but patients treated with MT (alone or as bridging therapy) had significantly greater improvement in mobility score between 6 and 12 months than patients treated with IVT alone (p = 0.0072). (4) Conclusion: QoL evolution over one year had only slight variation and was associated with the modalities of acute treatment, age, and stroke severity.

Patients Hospitalized for Ischemic Stroke and Intracerebral Hemorrhage in France: Time Trends (2008-2019), In-Hospital Outcomes, Age and Sex Differences.

BACKGROUND: Rates of patients hospitalized for stroke increased among people aged under 65 years in France, as has been found in other countries. METHODS: To analyze time trends in the rates of patients hospitalized for ischemic stroke (IS) and intracerebral hemorrhage (ICH) in France between 2008 and 2019 and determine related short-term outcomes mainly, we selected all patients hospitalized for stroke using the French national hospital database. RESULTS: The average annual percentage change in the rates of patients hospitalized for IS increased significantly in men and women aged 50-64 years (+2.0%) and in men aged 18-34 years (+1.5%) and 35-44 years (+2.2%). A decrease in the average annual percentage change was observed for IS among people aged over 75 years and among those over 50 years for ICH. After adjustment on confounding factors, women were less likely to die in hospital. Case fatality rates decreased overtime in all age groups for both sexes, with a more pronounced decrease for IS than ICH. CONCLUSIONS: The increasing trend of IS among adults under 65 years is ongoing, highlighting the urgent need for stroke prevention programs in that age. For the first time, we recorded a decrease in the rates of patients hospitalized for ICH among the population over 50 years.