Apixaban vs. standard of care after transcatheter aortic valve implantation: the ATLANTIS trial.

AIMS: The respective roles of oral anticoagulation or antiplatelet therapy following transcatheter aortic valve implantation (TAVI) remain debated. ATLANTIS is an international, randomized, open-label, superiority trial comparing apixaban to the standard of care. METHODS AND RESULTS: After successful TAVI, 1500 patients were randomized (1:1) to receive apixaban 5 mg (2.5 mg if impaired renal function or concomitant antiplatelet therapy) (n = 749) twice daily, or standard of care (n = 751). Randomization was stratified by the need for chronic anticoagulation therapy. Standard-of-care patients received a vitamin K antagonist (VKA) (Stratum 1) or antiplatelet therapy (Stratum 2) if there was an indication for anticoagulation or not, respectively. The primary endpoint was the composite of death, myocardial infarction, stroke or transient ischaemic attack, systemic embolism, intracardiac or bioprosthesis thrombosis, deep vein thrombosis or pulmonary embolism, and life-threatening, disabling, or major bleeding over 1-year follow-up. The primary safety endpoint was major, disabling, or life-threatening bleeding. The primary outcome occurred in 138 (18.4%) and 151 (20.1%) patients receiving apixaban or standard of care, respectively [hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.73-1.16] and there was no evidence of interaction between treatment and stratum (Pinteraction = 0.57). The primary safety endpoint was similar in both groups (HR 1.02; 95% CI 0.72-1.44). In Stratum 1 (n = 451), an exploratory analysis showed no difference for all endpoints between apixaban and VKA. In Stratum 2 (n = 1049), the primary outcome and primary safety endpoint did not differ, but obstructive valve thrombosis was reduced with apixaban vs. antiplatelet therapy (HR 0.19; 95% CI 0.08-0.46), while a signal of higher non-cardiovascular mortality was observed with apixaban. CONCLUSION: After TAVI, apixaban was not superior to the standard of care, irrespective of an indication for oral anticoagulation.

Mechanical Thrombectomy in Perioperative Strokes: A Case-Control Study.

BACKGROUND AND PURPOSE: Perioperative strokes (POS) are rare but serious complications for which mechanical thrombectomy could be beneficial. We aimed to compare the technical results and patients outcomes in a population of POS versus non-POS (nPOS) treated by mechanical thrombectomy. METHODS: From 2010 to 2017, 25 patients with POS (ie, acute ischemic stroke occurring during or within 30 days after a procedure) who underwent mechanical thrombectomy (POS group) were enrolled and paired with 50 consecutive patients with nPOS (control group), based on the occlusion's site, National Institute of Health Stroke Scale, and age. RESULTS: Respectively, mean age was 68.3±16.6 versus 67.2±16.6 years (P=0.70), and median National Institute of Health Stroke Scale score at admission was 20 (interquartile range, 15-25) versus 19 (interquartile range, 17-25; P=0.79). Good clinical outcome (modified Rankin Scale score of 0-2 at 3 months) was achieved by 33.3% (POS) versus 56.5% (nPOS) of patients (P=0.055). Successful reperfusion (modified Thrombolysis In Cerebral Infarction score of ≥2b) was obtained in 76% (POS) versus 86% (nPOS) of cases (P=0.22). Mortality at 3 months was 33.3% in the POS group versus 4.2% (nPOS) (P=0.002). The rate of major procedural complications was 4% (POS) versus 6% (nPOS); none were lethal. Average time from symptoms' onset to reperfusion was 4.9 hours (±2.0) in POS versus 5.2 hours (±2.6). CONCLUSIONS: Successful reperfusion seems accessible in POS within a reasonable amount of time and with a good level of safety. However, favorable outcome was achieved with a lower rate than in nPOS, owing to a higher mortality rate.

Persistent perfusion abnormalities at day 1 correspond to different clinical trajectories after stroke.

BACKGROUND: Perfusion abnormalities after thrombolysis are frequent within and surrounding ischemic lesions, but their relative frequency is not well known. OBJECTIVE: To describe the different patterns of perfusion abnormalities observed at 24 hours and compare the characteristics of the patients according to their perfusion pattern. METHODS: From our thrombolysis registry, we included 226 consecutive patients with an available arterial spin labeling (ASL) perfusion sequence at day 1. We performed a blinded assessment of the perfusion status (hypoperfusion-h, hyperperfusion-H, or normal-N) in the ischemic lesion and in the surrounding tissue. We compared the time course of clinical recovery, the rate of arterial recanalization, and hemorrhagic transformations in the different perfusion profiles. RESULTS: We identified seven different perfusion profiles at day 1. Four of these (h/h, h/H, H/H, and H/N) represented the majority of the population (84.1%). The H/H profile was the most frequent (34.5%) and associated with 3-month good outcome (modified Rankin Scale (mRS): 63.5%). Patients with persistent hypoperfusion within and outside the lesion (h/h, 12.4%) exhibited worse outcomes after treatment (mRS score 0-2: 23.8%) than other patients, were less frequently recanalized (40.7%), and had more parenchymal hematoma (17.8%). The h/H profile had an intermediate clinical trajectory between the h/h profile and the hyperperfused profiles. CONCLUSION: ASL hypoperfusion within the infarct and the surrounding tissue was associated with poor outcome. A more comprehensive view of the mechanisms in the hypoperfused surrounding tissue could help to design new therapeutic approaches during and after reperfusion therapies.

Cognitive Status Predicts Return to Functional Independence After Minor Stroke: A Decision Tree Analysis.

About two-thirds of patients with minor strokes are discharged home. However, these patients may have difficulties returning to their usual living activities. To investigate the factors associated with successful home discharge, our aim was to provide a decision tree (based on clinical data) that could identify if a patient discharged home could return to pre-stroke activities and to perform an external validation of this decision tree on an independent cohort. Two cohorts of patients with minor strokes gathered from stroke registries at the Hôpital Pitié-Salpêtrière and University Hospital Bern were included in this study (n = 105 for the construction cohort coming from France; n = 100 for the second cohort coming from Switzerland). The decision tree was built using the classification and regression tree (CART) analysis on the construction cohort. It was then applied to the validation cohort. Accuracy, sensitivity, specificity, false positive, and false-negative rates were reported for both cohorts. In the construction cohort, 60 patients (57%) returned to their usual, pre-stroke level of independence. The CART analysis produced a decision tree with the Montreal Cognitive Assessment (MoCA) as the first decision point, followed by discharge NIHSS score or age, and then by the occupational status. The overall prediction accuracy to the favorable outcome was 80% in the construction cohort and reached 72% accuracy in the validation cohort. This decision tree highlighted the role of cognitive function as a crucial factor for patients to return to their usual activities after a minor stroke. The algorithm may help clinicians to tailor planning of patients' discharge.

Mechanical thrombectomy in acute ischemic stroke patients under venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) in adult patients to treat refractory cardiogenic shock has increased in recent years, and ischemic stroke is the most frequent VA-ECMO-induced cerebrovascular complication. No adult case of mechanical thrombectomy (MT) has been reported. METHODS: Retrospective observational study of hospital medical records of patients who received circulatory support with VA-ECMO with acute ischemic stroke treated with MT, from 2006 to 2018. RESULTS: Two adult patients on VA-ECMO with acute ischemic stroke treated with MT were found. Both cases were successfully treated. CONCLUSION: These cases illustrate the feasibility of performing MT in adult patients on ECMO.

The silver effect of admission glucose level on excellent outcome in thrombolysed stroke patients.

Higher admission glucose levels (AGL) are associated with less favorable outcome in thrombolysis. But, could AGL's impact on outcome vary by onset-to-treatment (OTT) time? Is hyperglycemia associated with a shorter therapeutic time window for excellent outcome for thrombolysed stroke patients? We assessed predictive values of AGL, baseline NIHSS, age, and OTT time quartiles on excellent outcome (3-month modified Rankin score of 0-1) in 773 patients treated by rt-Pa. We added the AGL × OTT time quartile interaction in the model and separately analyzed the predictive values of AGL, age, and NIHSS for each OTT time quartile if the interaction was significant. AGL, baseline NIHSS, age, and OTT time quartiles were significant predictors. When added in the model, the AGL × OTT interaction was significant (OR: 0.96, 95% CI: 0.94-0.99, p: 0.0009). AGL was predictive only during the third OTT time quartile (181-224 min). During this period, the predicted rate of excellent outcome was 16% for AGL = 6.5 mmol/L and 8% for AGL = 8 mmol/L. The rate of excellent outcome was not decreased in hyperglycemic patients for OTT time ≤ 180 min (20 vs. 24.5% p: 0.37), but was decreased for OTT time > 180 min (9.6 vs. 26.7% p: 0.00001). Similar results were found in patients with MCA recanalization, but not in patients without recanalization. The therapeutic time window for excellent outcome is shortened in hyperglycemic patients. This would support the design of "freezing penumbra" randomized trials based on ultra-early AGL control.

Hyperglycaemia, insulin therapy and critical penumbral regions for prognosis in acute stroke: further insights from the INSULINFARCT trial.

BACKGROUND: Recently, the concept of 'clinically relevant penumbra' was defined as an area saved by arterial recanalization and correlated with stroke outcome. This clinically relevant penumbra was located in the subcortical structures, especially the periventricular white matter. Our aims were to confirm this hypothesis, to investigate the impact of admission hyperglycemia and of insulin treatment on the severity of ischemic damages in this area and to study the respective contributions of infarct volume and ischemic damage severity of the clinically relevant penumbra on 3-month outcome. METHODS: We included 99 patients from the INSULINFARCT trial. Voxel-Based Analysis was carried on the Apparent Diffusion Coefficient (ADC) maps obtained at day one to localize the regions, which were more damaged in patients i) with poor clinical outcomes at three months and ii) without arterial recanalization. We determined the intersection of the detected areas, which represents the clinically relevant penumbra and investigated whether hyperglycemic status and insulin regimen affected the severity of ischemic damages in this area. We performed logistic regression to examine the contribution of infarct volume or early ADC decrease in this strategic area on 3-month outcome. FINDINGS: Lower ADC values were found in the corona radiata in patients with poor prognosis (p< 0.0001) and in those without arterial recanalization (p< 0.0001). The tracking analysis showed that lesions in this area interrupted many important pathways. ADC values in this area were lower in hyperglycemic than in normoglycemic patients (average decrease of 41.6 ± 20.8 x10(-6) mm2/s) and unaffected by the insulin regimen (p: 0.10). ADC values in the clinically relevant penumbra, but not infarct volumes, were significant predictors of 3-month outcome. CONCLUSION: These results confirm that the deep hemispheric white matter is part of the clinically relevant penumbra and show that hyperglycaemia exacerbates the apparition of irreversible ischemic damage within 24 hours in this area. However, early intensive insulin therapy fails to protect this area from infarction. TRIAL REGISTRATION: ClinicalTrials.gov NCT00472381.

Contribution of corticospinal tract and functional connectivity in hand motor impairment after stroke.

BACKGROUND: Motor outcome after stroke is associated with reorganisation of cortical networks and corticospinal tract (CST) integrity. However, the relationships between motor severity, CST damage, and functional brain connectivity are not well understood. Here, the main objective was to study the effect of CST damage on the relationship between functional motor network connectivity and hand motor function in two groups of stroke patients: the severely (n=8) and the mildly impaired (n=14). METHODS: Twenty-two carotid stroke patients with motor deficits were studied with magnetic resonance imaging (MRI) at 3 weeks, at 3 and 6 months. Healthy subjects (n=28) were scanned once. The CST injury was assessed by fractional anisotropy values. Functional connectivity was studied from a whole-hand grip task fMRI in a cortical and cerebellar motor network. Functional connectivity indexes were computed between these regions at each time point. The relationship between hand motor strength, ipsilesional CST damage and functional connectivity from the primary motor cortex (M1) was investigated using global and partial correlations. FINDINGS: In mildly impaired patients, cortico-cortical connectivity was disturbed at three weeks but returned to a normal pattern after 3 months. Cortico-cerebellar connectivity was still decreased at 6 months. In severely impaired patients, the cortico-cortical connectivity tended to return to a normal pattern, but the cortico-cerebellar connectivity was totally abolished during the follow-up. In the entire group of patients, the hand motor strength was correlated to the ipsilesional functional connectivity from M1. Partial correlations revealed that these associations were not anymore significant when the impact of CST damage was removed, except for the ipsilesional M1-contralateral cerebellum connectivity. CONCLUSION: Functional brain connectivity changes can be observed, even in severely impaired patients with no recovery. Upper limb function is mainly explained by the CST damage and by the ipsilesional cortico-cerebellar connectivity.

Detection of brain functional-connectivity difference in post-stroke patients using group-level covariance modeling.

Functional brain connectivity, as revealed through distant correlations in the signals measured by functional Magnetic Resonance Imaging (fMRI), is a promising source of biomarkers of brain pathologies. However, establishing and using diagnostic markers requires probabilistic inter-subject comparisons. Principled comparison of functional-connectivity structures is still a challenging issue. We give a new matrix-variate probabilistic model suitable for inter-subject comparison of functional connectivity matrices on the manifold of Symmetric Positive Definite (SPD) matrices. We show that this model leads to a new algorithm for principled comparison of connectivity coefficients between pairs of regions. We apply this model to comparing separately post-stroke patients to a group of healthy controls. We find neurologically-relevant connection differences and show that our model is more sensitive that the standard procedure. To the best of our knowledge, these results are the first report of functional connectivity differences between a single-patient and a group and thus establish an important step toward using functional connectivity as a diagnostic tool.