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BACKGROUND Warfarin for the prevention of non-valvular atrial fibrillation related thromboembolic stroke in patients on maintenance haemodialysis is controversial. Despite the exclusion of haemodialysis patients in randomised control trials, the American Heart Association/American College of Cardiology has recommended warfarin in high-risk AF patients. AIM We retrospectively examined the utility of warfarin anticoagulation therapy in our prevalent haemodialysis patients over 10 years of follow-up. METHODS Eligible patients were retrospectively identified and stratified to two cohorts based on whether warfarin was prescribed. The outcomes of interest were ischaemic stroke, haemorrhagic stroke and death from any cause. Rate ratio and cox proportional hazard regression model were compare the differences in outcome between the two cohorts. The Kaplan-Meier method was used to analyse survival. RESULTS Three ischaemic strokes and four haemorrhagic strokes occurred in the unexposed group of 166 patients over 484.44 patient-years follow-up. One ischaemic stroke and no cases of haemorrhagic stroke occurred in the exposed warfarin group of 16 patients over 39.32 patient-years of follow-up. 87% of patients in both groups were indigenous. More than 90% of each cohort was had CHA2DS2VaSc score ≥2. 101 deaths occurred in the follow-up period, ninety in the unexposed group and eleven in the warfarin group. A non-statistically significant trend towards increasing mortality was observed in the warfarin group (Hazard ratio =1.63, p=0.13). CONCLUSION This retrospective study of prevalent haemodialysis patients with co-existing history of non-valvular AF failed to demonstrate sufficient evidence for the routine use of warfarin for prophylaxis of thromboembolic stroke. This article is protected by copyright. All rights reserved.

Among patients with atrial fibrillation (AF) who have high risk of bleeding secondary to haematologic disorders, left atrial appendage (LAA) occlusion therapy has been shown to be an excellent alternative to long-term use of oral anticoagulation for thromboembolic stroke prevention. However, there remains a major concern of device-associated thrombosis post-procedure, that can lead to life-threatening embolic events. To this date, there is no systematic guideline for the selection and management of patients with haematological disorders with LAA occlusion therapy, especially in those with platelet disorders such as immune thrombocytopenia (ITP). Patients with platelet disorders are at a higher risk for bleeding; however, that does not prevent such patients from thromboembolic events secondary to AF. We present a case of ITP with permanent AF, where an LAA device was complicated by thrombus formation due to challenges faced with anticoagulation therapy.

Here is a case of a Pulmonary AVM in a female presenting with sudden onset of dizziness and vomiting most likely secondary to a paradoxical emboli causing an ischemic stroke of the cerebellum.

Aims Secondary bleeding and further hematoma expansion (HE) aggravate brain injury after intracerebral hemorrhage (ICH). The majority of HE results from hypertensive ICH. Previous study reported higher iron content in the brains of hypertensive patients. Iron overload exacerbates the risk of hemorrhagic transformation in thromboembolic stroke mice. Whether iron overload during the process of hypertension participates in secondary bleeding of hypertensive ICH remains unclear. Methods Hypertension was induced by continuous infusion of angiotensin II (Ang II) with an osmotic pump into C57BL/6 mice. ICH was simulated by intrastriatal injection of the liquid polymer Onyx‐18. Iron chelation and iron overload was achieved by deferoxamine mesylate or iron dextran injection. Secondary bleeding was quantified by measuring the hemoglobin content in the ipsilateral brain hemisphere. Results Ang II‐induced hypertensive mice showed increased iron accumulation in the brain and expanded secondary hemorrhage after ICH modeling. Moreover, iron chelation suppressed while iron overload aggravated secondary bleeding. Mechanistically, iron exacerbated the loss of contractile cerebral vascular smooth muscle cells (VSMCs), aggravated blood–brain barrier (BBB) leakage in Ang II‐induced hypertensive mice, and increased glial and MMP9 accumulation after ICH. Conclusion Iron overload plays a key role in secondary bleeding after ICH in Ang II‐induced hypertensive mice. Iron chelation during the process of Ang II‐induced hypertension suppresses secondary bleeding after ICH., Iron accumulation in the brain tissues of Ang II‐induced hypertensive mice might exacerbate the loss of contractile VSMCs, enhance perivascular inflammation and BBB leakage. These factors might lead to increased vascular fragility and increased vulnerability to rupture, ultimately causing more secondary bleeding and subsequent HE after ICH.

Acute ischemic thromboembolic stroke is one of the most feared complications of atrial fibrillation (AF), and the risk increases with higher CHA2DS2-VASc scores. Postoperative atrial fibrillation (POAF) is common after noncardiac surgery, particularly after thoracic surgery, and can result in significant morbidity and mortality. We report the case of an 85-year-old female with a history of untreated hypertension (HTN) and no prior history of AF, who presented 5 days after an elective repair of a paraesophageal hernia with recurrence of a large type III paraesophageal hiatal hernia, AF, and subsequent acute thromboembolic ischemic stroke. Patient’s AF resolved shortly after treatment with calcium channel blocker. The risk of stroke is high in patients who develop AF and a period of 48 h after onset of AF is usually considered safe as the risk of stroke is low in this time period. However, this may not be the case during the perioperative period and preventive measures such as preoperative calcium channel blocker could be considered. Our case highlights that acute ischemic thromboembolic stroke might develop earlier tha 48 h after onset of POAF in patients undergoing paraesophageal hernia repair. Initiation of a calcium channel blocker should be considered during preoperative evaluation for patients undergoing paraesophageal hernia repairs, especially in those with untreated HTN.

Background Coronary sinus (CS) ostial atresia/abnormalities prevent access to the CS from the right atrium (RA) for left ventricular (LV) lead implantation. Some patients with CS ostial abnormalities also have a small persistent left superior vena cava (sPLSVC). Objective The purpose of this study was to describe CS ostial abnormalities and sPLSVC as an opportunity for LV lead implantation and unrecognized source of stroke. Methods Twenty patients with CS ostial abnormalities and sPLSVC were identified. Clinical information, imaging methods, LV lead implantation techniques, and complications were summarized. Results Forty percent had at least 1 previously unsuccessful LV lead placement. In 70%, sPLSVC was identified by catheter manipulation and contrast injection in the left brachiocephalic vein, and in 30% by levophase CS venography. In 30%, sPLSVC was associated with drainage from the CS into the left atrium (LA). When associated with CS ostial abnormalities, the sPLSVC diameter averaged 5.6 ± 3 mm. sPLSVC was used for successful LV lead implantation in 90% of cases. In 80%, the LV lead was implanted down sPLSVC, and in 20%, sPLSVC was used to access the CS from the RA. Presumably because of unrecognized drainage from the CS to the LA, 1 patient had a stroke during implantation via sPLSVC. Conclusion When CS ostial abnormalities prevent access to the CS from the RA, sPLSVC can be used to successfully implant LV leads. In some, the CS partially drains into the LA and stroke can occur spontaneously or during lead intervention. It is important to distinguish sPLSVC associated with CS ostial abnormalities from isolated PLSVC.

Valvular heart disease affects more that 100 million people worldwide. Valvular replacement remains the only definite treatment for most of the patients with severe disease. Careful medical management and periodic follow-up of valve function is mandatory in order to prevent or diagnose prosthesis-related complications. We present a case of extensive mitral and aortic valve thrombosis and possible recurrent endocarditis in a 44-year-old woman non-adherent to anticoagulation therapy, presented with stroke. She also had a history of two mitral and aortic valvular heart replacement surgeries. Comprehensive and repeated imaging was used to evaluate and monitor the patient progression and outcome. Failure of adequate anticoagulation therapy to improve prosthesis function during hospitalization required third re-do surgery for mitral and aortic valve replacement with mechanical prosthesis.

Antithrombotic agents are widely used on the globe for prevention of thrombotic events such as atherothrombotic events and thromboembolic stroke in atrial fibrillation or for prevention and treatment of venous thromboembolism. However, the net clinical benefit of antithrombotic intervention may differ substantially in various sub-population of patients. Here, the authors attempt to address the risk of serious bleeding in East Asian as compared to the other regions of the world. The community-based epidemiological data suggest numerically higher risk of hemorrhage stroke in East Asian as compared to the globe. Importantly, the life-time risk of ischemic stroke in East Asia is higher than that of the globe. Regarding the serious bleeding risk in East Asians with the use of antithrombotic agents, various clinical trials and international registries provided conflicting information. It is hard to draw generalized conclusion, but there are some specific sub-population in East Asian with higher risk of specific serious bleeding events with the use of specific antithrombotic agents such as the risk of intra-cranial bleeding (ICH) with Vitamin K antagonists. Specific characteristics in East Asian such as higher prevalence of lacunar stroke may contribute higher risk of ICH in East Asian, but the detailed mechanism is still to be elucidated. In conclusion, further investigations are necessary to clarify the specific conditions where the risk of serious bleeding events in East Asian patients differ substantially compared to the global. In addition, further understanding of the mechanisms causing the different bleeding response in specific conditions in East Asian is awaited.

Introduction Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis (e.g. dilated cardiomyopathy), resulting in increased risk of thromboembolic complications. Historically, observational studies support the general safety and efficacy of warfarin for this indication. To date, limited data exists regarding the use of the direct oral anticoagulants (DOACs) for LV thrombus. Methods A retrospective cohort study utilizing electronic medical records was conducted from September 2012 - October 2018 at the University of Colorado Hospital System. Patients were included if they had any diagnosis of LV thrombus and received either a DOAC or warfarin within 90 days of diagnosis. The primary outcome was to determine the incidence of thromboembolic stroke in patients receiving a DOAC compared to warfarin. Secondary outcomes consisted of the composite incidence of thromboembolic events (stroke and systemic embolism), bleeding rates defined by the The Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria, and blood product administration. Chi square test was used to analyze categorical variables and the student's t-test and Wilcoxon Rank Sum test for continuous data. All statistical analyses were conducted using SAS. Results A total of 949 patients met inclusion, of whom 180 (19%) received a DOAC and 769 (81%) warfarin. Of the DOAC cohort, 77 (41.6%) received rivaroxaban, 79 (42.7%) apixaban, and 29 (15.7%) dabigatran. For baseline demographic information, see table 1. For the primary endpoint of new onset thromboembolic stroke on or within 90 days of LV thrombus diagnosis, no difference existed between treatment groups (DOAC: 7.8% vs warfarin: 11.7%, p=0.524). When compared to warfarin, no difference existed in the composite of thromboembolic events (33.1% vs 30.6%, P=0.524, respectively) or in GUSTO bleeding (11.1% vs 7.8%, p=0.397, for DOAC vs. warfarin, respectively). However, more patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p Conclusions Compared to warfarin, DOACs may be safe and efficacious for the treatment of LV thrombus, however further studies are warranted.

Background: Atrial fibrillation (AF) is associated with a 5-fold increased risk of thromboembolic stroke. Extracellular vesicles (EVs) convey pathophysiological information and are possible biomarkers for risk of stroke. Methods: EVs were measured in 836 patients with AF (of which 280 were stroke cases) selected from the ARISTOTLE trial and in a cohort of unselected 70 year old individuals (n = 1007, reference material). EVs from platelets, leukocytes, erythrocytes and inflammatory endothelial cells were measured using flow cytometry and a solid-phase proximity ligation assay. Results: Concentrations of EVs were higher in the ARISTOTLE patients than in the PIVUS cohort for all the EV groups except EVs from endothelial cells (p < 0.0001). The distributions of the concentrations of the EVs were similar among the control group and the stroke cases for all of the sources of EVs in the ARISTOTLE study. EVs were modestly correlated with the levels of NT-ProBNP, Cystatin C, GDF-15 and D-dimer. Stronger correlations were found for platelet EVs as well as phosphatidyl serine positive EVs that were correlated with CD40 ligand in the ARISTOTLE study. Leukocyte EVs were correlated with IL-6 in both the ARISTOTLE and the PIVUS study, implicating them in different physiological processes. Conclusions: Higher levels of EVs were found in anticoagulated patients with AF and a higher risk of stroke than in a general population of similar age, possibly due to the high disease burden in AF patients. Our data with EVs representing a broad repertoire of activated blood cells in AF patients suggest that EVs are likely not a key mediator of occurrence of stroke in this population.

BACKGROUND AND PURPOSE: Intravenous thrombolysis (IVT) after stroke enhances C3a generation, which may abrogate the benefits of reperfusion. The C3aR antagonist SB290157 is neuroprotective following transient but not permanent middle cerebral artery occlusion (MCAo). SB290157 remains untested in thromboembolic (TE) models, which better approximate human stroke and also facilitate testing in combination with IVT. We hypothesized SB290157 would confer neuroprotection in TE stroke with and without “late” IVT. EXPERIMENTAL APPROACH: We used two different models of TE stroke to examine the efficacy of SB290157 alone and in combination with late IVT. We evaluated the benefit of SB290157 in attenuating post‐ischaemic behavioural deficits, infarction, brain oedema and haemorrhage. KEY RESULTS: Plasma C3a was elevated 6 hr after TE stroke alongside increased cerebrovascular C3aR expression, which was sustained to 4 weeks. Increased C3aR expression also was visualized in human ischaemic brain. In a photothrombotic (PT) stroke model, which exhibits rapid spontaneous reperfusion, SB290157 given at 1 hr post‐PT significantly improved neurofunction and reduced infarction at 48 hr. In an embolic (eMCAo) model, SB290157 administered at 2 hr improved histological and functional outcomes. Conversely, late IVT administered 4.5 hr post‐eMCAo was ineffective likely due to increased haemorrhage and brain oedema. However, SB290157 administered prior to late IVT ameliorated haemorrhage and oedema and improved outcomes. CONCLUSIONS AND IMPLICATIONS: We conclude that SB290157 is safe and effective with and without late IVT following TE stroke. Therefore, C3a receptor antagonist therapy represents a promising candidate for clinical translation in stroke, particularly as an adjuvant to IVT.

OBJECTIVE: The authors aimed to study the association between postoperative atrial fibrillation (POAF) and thromboembolic stroke and to determine risk factors for thromboembolic stroke after cardiac surgery.DESIGN: The authors performed a secondary analysis from a randomized controlled trial (GRIP-COMPASS). The patients with thromboembolic stroke were compared with those without thromboembolic stroke, and the difference in the incidence of POAF between these groups was assessed. Odds ratios (OR) were calculated using logistic regression analyses. Brain imaging was studied for the occurrence of thromboembolic stroke during hospital admission, and POAF was monitored for seven days. To assess which characteristics were associated with occurrence of thromboembolic stroke, stepwise backward regression analysis was performed.PARTICIPANTS: All adult consecutive cardiac surgery patients admitted postoperatively to the intensive care unit.SETTING: Academic tertiary care medical center.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Of the 910 patients included in this study, 26 patients (2.9%) had a thromboembolic stroke during hospital admission. The incidence of POAF during the first seven days after cardiac surgery in those with thromboembolic stroke was 65%, compared with 39% in those without thromboembolic stroke: adjusted OR 3.01 (95% confidence interval, 1.13-8.00). POAF, a history of peripheral vascular disease, a higher EuroSCORE, and a longer duration of surgery were associated with thromboembolic stroke.CONCLUSIONS: POAF within seven days after cardiac surgery was associated with a three-fold increased risk for a thromboembolic stroke during hospital admission. Expeditious treatment of POAF may, therefore, reduce early stroke risk after cardiac surgery.

COVID-19 pneumonia has several complications, such as acute respiratory distress syndrome, septic shock, myocarditis, pulmonary embolism, and thromboembolic stroke. We present a case of a 71-year-old woman who was diagnosed with COVID-19 pneumonia and was found to have a pneumothorax, spontaneous pneumomediastinum (SPM), and subcutaneous emphysema without a history of lung disease. The pathophysiology of SPM and subcutaneous emphysema is likely caused by rupture of the alveolar membrane due to direct damage by COVID-19 infection and frequent cough-induced barotrauma.

Prompt recognition and treatment for thrombotic thrombocytopenic purpura (TTP) are critical to prevent the irreversible manifestations of this rare and quickly fatal hematologic disorder. Untreated TTP is typically a rapid‐onset disease with mortality exceeding 90% within days in the absence of appropriate treatment. In the current report, we describe a case of immune‐mediated TTP (iTTP) in a 62‐year‐old man manifesting as longstanding thrombocytopenia, recurrent cardioembolic strokes, and valvular thrombogenesis over a period of 3 years. We provide correlative evidence to support the potential contribution of adalimumab, a TNFα inhibitor, to the development of iTTP. We offer several educational insights regarding the identification of atypical presentations of iTTP owing to the longstanding disease course and numerous clinical comorbidities seen in this patient., We report an atypical manifestation of immune‐mediated thrombotic thrombocytopenic purpura (TTP) that we hypothesize represents a longstanding, or “smoldering,” process. As typified by this case, the prompt recognition and treatment for immune‐mediated TTP are often confounded by clinical comorbidities. Thus, TTP should be considered in cases of unremitting thrombocytopenia of unknown origin in patients with stroke or other thrombosis.

The ventricular non-compaction or spongy myocardium is a rare congenital cardiomyopathy which is caused by defective morphogenesis of myocardium during embryonic life. It is characterised by excessive, coarse trabeculations within ventricular myocardium beyond papillary muscle insertion which communicates freely with the ventricular cavity. This carries high risk for development of serious arrhythmia, thromboembolic stroke, pump failure etc. Isolated LV involvement is the most common presentation (68%) and biventricular involvement is the next most common presentation (22-38%). Isolated non-compaction of RV myocardium is a rare anomaly. We are hereby presenting such a case.

Heart valve replacements are commonly performed these days in India with mitral valve replacement being most common of all. Thromboemboli are a major source of morbidity in patients with prosthetic heart valves. The incidence of clinically recognizable events ranges from 0.6% to 2.3% per patient-year. Mechanical valve thrombosis is another common complication, incidence of which is estimated at 0.3% to 1.3% per patient-year in developed countries, but as high as 6% per patient-year in developing countries. Management of either complication in these patients requires adequate knowledge and clinical experience. We here describe a rare case of a patient who came to us with both complication of stuck mitral valve prosthesis and embolic stroke simultaneously. We here discuss the approach, monitoring and management of these patients, the clinical difficulties we faced in our case, immediate and short term prognosis of our patient.

Objective To assess different bridging anticoagulation therapies early after mechanical heart valve replacement (MHVR) in Chinese patients. Methods We performed a prospective, single-center, observational cohort study of 305 patients who underwent elective MHVR with different bridging anticoagulation regimens. Patients enrolled in the study were divided into three bridging therapy groups: the unfractionated heparin (UFH) group (n = 109), the low-molecular-weight heparin (LMWH) group (n = 97), and the UFH with sequential LMWH (UFH-LMWH) group (n = 99). All patients were followed for 4 weeks. Results Two patients experienced thromboembolic stroke events in the UFH group. The LMWH group was associated with an increase in the incidence of bleeding events compared with the UFH group (10.3% VS 2.8%; P = 0.03). With a comparison of LMWH and UFH group in secondary endpoints, the statistical test for significance indicated a trend of reduced ICU length of stay (P = 0.08), postoperative length of stay (P = 0.08) and time of achieving target INR (P = 0.06). The creatinine level (odds ratio = 1.03; 95% confidence interval = 1.01 to 1.05; P = 0.02) and hypertension (odds ratio = 3.72; 95% confidence interval = 1.35 to 10.28; P = 0.01) were risk factors for bleeding events. Conclusion For Chinese patients, the LMWH bridging anticoagulation presents the increased the incidence of bleeding events, but enables patients to benefit from achieving an early anticoagulation effect. Close follow-up and personalized management are required in patients with thromboembolic and bleeding risk factors. Trial registration Chinese Clinical Trial Registry ChiCTR1800019841. Registered 2 December 2018 retrospectively.

Physical exercise is known to reduce cardiovascular risk but its role in ischemic stroke is not clear. It was previously shown that an acute single bout of exercise reduced increased eNOS activation in the heart and reduced myocardial infarction. However, the impact of a single bout or short-term exercise on eNOS-induced neuroprotection after stroke was not previously studied. Accordingly, this study was designed to test the hypothesis that short-term acute exercise can provide “immediate neuroprotection” and improve stroke outcomes through induced eNOS activation. Male Wistar rats (300 g) were subjected to HIIT treadmill exercise for 4 days (25 min/day), break for 2 days, and then one acute bout for 30 min. Exercised animals were subjected to thromboembolic stroke 1 h, 6 h, 24 h, or 72 h after the last exercise session. At 24 h after stroke, control (sedentary) and exercised rats were tested for neurological outcomes, infarct size, and edema. The expression of active eNOS (p-S1177-eNOS) and active AMPK (p-T172-AMPK) was measured in the brain, cerebral vessels, and aorta. In an additional cohort, animals were treated with the eNOS inhibitor, L-NIO (I.P, 20 mg/kg), and stroked 1 h after exercise and compared with non-exercise animals. Acute exercise significantly reduced infarct size, edema, and improved functional outcomes, and significantly increased the expression of peNOS and pAMPK in the brain, cerebral vessels, and aorta. eNOS inhibition abolished the exercise-induced improvement in outcomes. Short-term acute preconditioning exercise reduced the neurovascular injury and improved functional outcomes after stroke through eNOS activation.

Internal carotid artery (ICA) stenosis, usually caused by atherosclerosis plaque, restricts the blood supply to the brain and causes cerebral ischemia. The plaque can be stable and asymptomatic, or it can cause embolization. An emboli can break from the plaque and travel to the blood vessels in the brain, causing a transient ischemic attack (TIA) or thromboembolic stroke. To reduce the risk of a stroke, estimation of the blood flow and stress distribution at the ICA stenosis is important. Common diagnostic methods, such as computed tomography (CT) and magnetic resonance imaging (MRI) are only able to provide a stenotic configuration. In addition, conventional image-based computational fluid dynamics (CFD) assumes the blood is a single-phase fluid, ignoring the circulating blood cell particles. This may result in an unreliable estimation of the blood flow and stress distribution at the ICA stenosis. Therefore, a multiphase particle-in-cell (MP-PIC) model was introduced to calculate the plasma flow and blood cell motion separately. The MP-PIC simulation showed a reverse flow, flow stagnation, and flow swigging at the stenosis that was not demonstrated by the single-phase model simulation. Thus, the blood cell motion caused significant temporal and spatial flow oscillation variations at the stenosis and must be considered in a hemodynamic simulation.

Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis-generating post hoc analysis of the LeukoCAPE-1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart disease patients for association with MACCE (composite of cardiac death, myocardial infarction, myocardial ischemia, myocardial injury after noncardiac surgery, thromboembolic stroke) within 30 d after surgery. Regulatory T cells (Tregs) were the only leukocyte subgroup associated with MACCE. We found reduced Tregs in patients experiencing MACCE versus no-MACCE (0.02 [0.01; 0.03] vs. 0.04 [0.03; 0.05] Tregs nl−1, P = 0.002). Using Youden index, we derived the optimal threshold value for association with MACCE to be 0.027 Tregs nl−1. Subsequently, we recruited 233 coronary heart disease patients for the prospective, observational LeukoCAPE-2 study and independently validated this Treg cutoff for prediction of MACCE within 30 d after noncardiac surgery. After multivariate logistic regression, Tregs < 0.027 cells nl−1 remained an independent predictor for MACCE (OR = 2.54 [1.22; 5.23], P = 0.012). Tregs improved risk discrimination of the revised cardiac risk index based on ΔAUC (area under the curve; ΔAUC = 0.09, P = 0.02), NRI (0.26), and IDI (0.06). Preoperative Treg levels below 0.027 cells nl−1 predicted perioperative MACCE and can be measured to increase accuracy of established preoperative cardiac risk stratification in coronary heart disease patients undergoing noncardiac surgery.

The poor clinical relevance of experimental models of stroke contributes to the translational failure between preclinical and clinical studies testing anti-inflammatory molecules for ischemic stroke. Here, we (i) describe the time course of inflammatory responses triggered by a thromboembolic model of ischemic stroke and (ii) we examine the efficacy of two clinically tested anti-inflammatory drugs: Minocycline or anti-CD49d antibodies (tested in stroke patients as Natalizumab) administered early (1 h) or late (48 h) after stroke onset. Radiological (lesion volume) and neurological (grip test) outcomes were evaluated at 24 h and 5 days after stroke. Immune cell responses peaked 48 h after stroke onset. Myeloid cells (microglia/macrophages, dendritic cells, and neutrophils) were already increased 24 h after stroke onset, peaked at 48 h, and remained increased—although to a lesser extent—5 days after stroke onset. CD8+ and CD4+ T-lymphocytes infiltrated the ipsilateral hemisphere later on (only from 48 h). These responses occurred together with a progressive blood-brain barrier leakage at the lesion site, starting 24 h after stroke onset. Lesion volume was maximal 24–48 h after stroke onset. Minocycline reduced both lesion volume and neurological deficit only when administered early after stroke onset. The blockade of leukocyte infiltration by anti-CD49d had no impact on lesion volume or long-term neurological deficit, independently of the timing of treatment. Our data are in accordance with the results of previous clinical reports on the use of Minocycline and Natalizumab on ischemic stroke. We thus propose the use of this clinically relevant model of thromboembolic stroke with recanalization for future testing of anti-inflammatory strategies for stroke.

Venomous snakes are found in every state and territory in Australia and are amongst the most dangerous in the world. Of Australia's snakes the Eastern Brown snake (Pseudonaja textilis) is responsible for the majority of the cases of envenomation and death. We describe a case of thromboembolic stroke associated with Eastern Brown snake envenomation in a 2-year-old boy. Following the incident, the boy has made a good recovery. Keywords: Snake bite, Stroke

Takotsubo syndrome (TTS) is a poorly understood phenomenon that manifests as reversible myocardial damage. Despite the overall benign course of TTS, acute complications and significant mortality and morbidity are frequently encountered. However, the risk factors for developing such complications are not well determined. We present a case of reversible TTS within 48 hours after correction of cola-induced hypokalemia complicated by thromboembolic stroke. We present the patient's clinical presentation with imaging studies and discuss the case in light of related literature. A 62-year-old woman with a longstanding history of inadequate oral intake and excessively sweetened cola soft drinks consumption. Presented with progressive symmetrical quadriparesis and found to have severe hypokalemia with rhabdomyolysis, elevated troponin, and acute left ventricular dysfunction. The patient was diagnosed with TTS and hypokalemic paralysis. Her hospital course was complicated with an acute thromboembolic stroke of bilateral occipital lobes and left cerebellum. Takotsubo cardiomyopathy was reversible 48 hours after correction of severe hypokalemia. Cardiac ischemic workup was negative for any evidence of myocardial ischemia. In this presented case, TTS was revisable within 48 hours after the correction of cola-induced hypokalemia. However, patients with similar presentations might have a higher risk for in-hospital thromboembolic complications of TTS.

An ideal thromboembolic stroke model requires certain properties, including relatively simple surgical procedures with low mortality, a consistent infarction size and location, precipitation of platelet:fibrin intermixed blood clots similar to those in patients, and an adequate sensitivity to fibrinolytic treatment. The rose bengal (RB) dye-based photothrombotic stroke model meets the first two requirements but is highly refractory to tPA-mediated lytic treatment, presumably due to its platelet-rich, but fibrin-poor clot composition. We reason that combination of RB dye (50 mg/kg) and a sub-thrombotic dose of thrombin (80 U/kg) for photoactivation aimed at the proximal branch of middle cerebral artery (MCA) may produce fibrin-enriched and tPA-sensitive clots. Indeed, the thrombin and RB (T+RB)-combined photothrombosis model triggered mixed platelet:fibrin blood clots, as shown by immunostaining and immunoblots, and maintained consistent infarct sizes and locations plus low mortality. Moreover, intravenous injection of tPA (Alteplase, 10 mg/kg) within 2 h post-photoactivation significantly decreased the infarct size in T+RB photothrombosis. Thus, the thrombin-enhanced photothrombotic stroke model may be a useful experimental model to test novel thrombolytic therapies.

Thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) is currently the only FDA-approved drug for acute ischemic stroke. However, its administration is still limited due to the associated increased risk of hemorrhagic transformation (HT). rt-PA may exacerbate blood-brain barrier (BBB) injury by several mechanisms that have not been fully elucidated. Caveolin-1 (Cav-1), a major structural protein of caveolae, has been linked to the endothelial barrier function. The effects of rt-PA on Cav-1 expression remain largely unknown. Here, Cav-1 protein expression after ischemic conditions, with or without rt-PA administration, was analyzed in a murine thromboembolic middle cerebral artery occlusion (MCAO) and in brain microvascular endothelial bEnd.3 cells subjected to oxygen/glucose deprivation (OGD). Our results show that Cav-1 is overexpressed in endothelial cells of infarcted area and in bEnd.3 cell line after ischemia but there is disagreement regarding rt-PA effects on Cav-1 expression between both experimental models. Delayed rt-PA administration significantly reduced Cav-1 total levels from 24 to 72 h after reoxygenation and increased pCav-1/Cav-1 at 72 h in the bEnd.3 cells while it did not modify Cav-1 immunoreactivity in the infarcted area at 24 h post-MCAO. Importantly, tissue Cav-1 positively correlated with Cav-1 serum levels at 24 h post-MCAO and negatively correlated with the volume of hemorrhage after infarction, the latter supporting a protective role of Cav-1 in cerebral ischemia. In addition, the negative association between baseline serum Cav-1 levels and hemorrhagic volume points to a potential usefulness of baseline serum Cav-1 levels to predict hemorrhagic volume, independently of rt-PA administration. This work was supported by grants from Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund “A Way to Achieve Europe” Health Strategic Action Program PI13/02258 and PI17/02123 (MC), PI20/00535 (IL), and Spanish Stroke Research Network RETICS RD12/0014/0010 (MC), and RD16/0019/0003 (JS), RD16/0019/0004 (MC), and RD16/0019/0009 (IL); from Regional Madrid Government B2017/BMD- 3688 (IL); from Spanish Ministry of Science and Innovation PID2019-106581RBI00 (MAM); from Leducq Foundation for Cardiovascular Research TNE-19CVD01 (MAM); and from Fundación La Caixa HR17_00527 (MAM). P. Comajoan was a recipient of a predoctoral fellowship from the University of Girona (IF-UdG 2015). Sí

Sinus P-wave abnormalities have been associated stroke in people with atrial fibrillation (AF). The majority of AF-related strokes occur from left atrial appendage (LAA) thromboembolism. Dysfunction of the left atrium (LA) and left atrial appendage (LAA) can increase rates of thromboembolic stroke. We studied whether abnormal P wave terminal force in V1 (aPTFV1) is associated with decreased LAA ejection velocity (LAAV) on transesophageal echocardiography (TEE).We conducted a retrospective cross-sectional study reviewing patients at a tertiary care medical center who underwent TEE in sinus rhythm and had an interpretable sinus ECG within 12 months of TEE. Participants were excluded for complex congenital heart disease, age18, cardiac transplantation, and chronic atrial pacing. Logistic regression analysis was used to estimate the odds ratios of LAAV40 cm/s for aPTFV1.In our final cohort of 169 patients (28% of which had LAAV40), the multivariate odds ratio of aPTFV1 for LAAV40 cm/s after adjustment for CHAAbnromal P-wave terminal force in lead V1 is associated with low LAAV after adjustment for potential confounders. Future research is needed for validation of our findings and determination of clinical utility.

Background Left ventricular thrombus (LVT) may develop in systolic heart failure or after acute myocardial infarction. The current recommendations support the use of vitamin K antagonists (VKAs) for the treatment of LVT. Limited data exist regarding the use of direct oral anticoagulants (DOACs) in patients with LVT. This meta-analysis aims to investigate the efficacy and safety of DOACs versus VKAs for LVT. Methods We performed a comprehensive literature search using PubMed, Embase, and Cochrane Library databases through November 2020 for all studies that evaluated the efficacy and safety of DOACs versus VKAs in patients with LVT. The primary outcomes were LVT resolution, overall thromboembolic events, and thromboembolic stroke. The secondary outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence intervals (CIs) were obtained by the Mantel-Haenszel method within a random-effects model. Heterogeneity was assessed by I2 statistic. Results A total of 11 studies including 2153 patients with LVT on anticoagulation (570 on DOACs vs. 1583 on VKAs) were included. LVT resolution was significantly higher in DOACs compared with VKAs [RR: 1.18 (95% CI: 1.04-1.35); P = 0.01, I2 = 25%]. However, no significant difference existed between DOACs and VKAs regarding overall thromboembolic events [RR: 1.10 (95% CI: 0.75-1.62); P = 0.61, I2 = 0%] and thromboembolic stroke [RR: 0.63 (95% CI: 0.39-1.02); P = 0.06, I2 = 0%]. Major bleeding [RR: 1.00 (95% CI: 0.66-1.51); P = 0.99, I2 = 4%] and all-cause mortality [RR: 0.84 (95% CI: 0.50-1.43); P = 0.53, I2 = 0%] were similar between the 2 groups. Conclusions DOACs seem to be more efficacious in achieving LVT resolution compared with VKAs. However, there was no significant difference between the 2 groups in thromboembolic events, major bleeding, and all-cause mortality. Randomized controlled trials are needed to confirm our findings.

Atrial fibrillation (AF) is the most common sustained arrhythmia, with an estimated prevalence in the U.S.of 6.1 million. AF increases the risk of a thromboembolic stroke in five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function in AF remains unknown. We have recently identified protein phosphatase 1 subunit 12c (PPP1R12C) as a key molecule targeting myosin light-chain phosphorylation in AF. Objective: We hypothesize that the overexpression of PPP1R12C causes hypophosphorylation of atrial myosin light-chain 2 (MLC2a), thereby decreasing atrial contractility in AF. Methods and Results: Left and right atrial appendage tissues were isolated from AF patients versus sinus rhythm (SR). To evaluate the role of the PP1c-PPP1R12C interaction in MLC2a de-phosphorylation, we utilized Western blots, co-immunoprecipitation, and phosphorylation assays. In patients with AF, PPP1R12C expression was increased 3.5-fold versus SR controls with an 88% reduction in MLC2a phosphorylation. PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF. In vitro studies of either pharmacologic (BDP5290) or genetic (T560A), PPP1R12C activation demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Additionally, to evaluate the role of PPP1R12C expression in cardiac function, mice with lentiviral cardiac-specific overexpression of PPP1R12C (Lenti-12C) were evaluated for atrial contractility using echocardiography, versus wild-type and Lenti-controls. Lenti-12C mice demonstrated a 150% increase in left atrium size versus controls, with reduced atrial strain and atrial ejection fraction. Also, programmed electrical stimulation was performed to evaluate AF inducibility in vivo. Pacing-induced AF in Lenti-12C mice was significantly higher than controls. Conclusion: The overexpression of PPP1R12C increases PP1c targeting to MLC2a and provokes dephosphorylation, associated with a reduction in atrial contractility and an increase in AF inducibility. All these discoveries suggest that PP1 regulation of sarcomere function at MLC2a is a main regulator of atrial contractility in AF.

Atrial fibrillation (AF) is the most common cardiac arrythmia and a major cause of stroke, heart failure, sudden death, and cardiovascular morbidity. AF increases risk of thromboembolic stroke via stasis in the left atrium and subsequent embolization to the brain. In patients with acute ischemic stroke, it is essential that clinicians undertake careful investigation to search for AF. In these patients, up to 23.7% eventually are found to have underlying AF. Oral anticoagulation is effective in prevention of strokes secondary to AF, reducing overall stroke numbers by approximately 64%. Left atrial appendage occlusion is promising for prevention of stroke in AF.

Objectives We demonstrate the feasibility and safety of robotics-assisted left atrial appendage clip exclusion in clinical practice. Methods Analysis of a single center robotics-assisted left atrial appendage clip exclusion experience using an epicardial linear clip device in patients with atrial fibrillation with high-risk of thromboembolic stroke and intolerance to oral anticoagulants. Results During the period from December 2017 to September 2020, we performed 42 robotics-assisted left atrial appendage clip exclusions in response to increased risk of bleeding in patients with atrial fibrillation and intolerance to oral anticoagulants. The average congestive heart failure, hypertension, age, diabetes, stroke, and vascular disease score was 5.2 ± 1.6 and hypertension, abnormal liver or kidney function, stroke, bleeding, labile international normalized ratio, elderly, drugs (aspirin, other antiplatelets, or anticoagulants) score was 4.5 ± 0.9. No patients died intraoperatively or within 30 days, or due to conversion to thoracotomy, intraoperative complications, or failure to apply the clip satisfactorily. The procedure was successfully completed despite pericardial adhesions in 2 patients with prior coronary bypass grafts and 3 with postpericarditis scars. Intraoperative transesophageal echocardiography was performed in 38 out of 42 patients; satisfactory exclusion with left atrial appendage stump

Multiple randomized controlled trials and many real-world evidence studies have consistently shown that non-vitamin K antagonist oral anticoagulants (NOACs) are preferable to vitamin K antagonists for thromboembolic stroke prevention in the majority of patients with atrial fibrillation (AF). However, their role in the management of patients with AF and comorbidities, as well as in other patient populations with a high risk of stroke, such as patients with prior embolic stroke of undetermined source (ESUS) and those with atherosclerosis, is less clear. There is now increasing evidence suggesting that NOACs have a beneficial effect in the prevention of stroke in patients with AF and comorbidities, such as renal impairment and diabetes. In addition, while studies investigating the efficacy and safety of NOACs for the prevention of secondary stroke in patients with a history of ESUS demonstrated neutral results, subanalyses suggested potential benefits in certain subgroups of patients with ESUS. One NOAC, rivaroxaban, has also recently been found to be effective in reducing the risk of stroke in patients with chronic cardiovascular disease including coronary artery disease and peripheral artery disease, further broadening the patient groups that may benefit from NOACs. In this article, we will review recent evidence for the use of NOACs across the stroke spectrum in detail, and discuss the progress and future prospects in the different stroke areas.

The aim of this study was to compare outcomes of the full maze procedure with left atrial appendage closure (LAAc) as concomitant procedures for atrial fibrillation (AF) in patients undergoing cardiovascular surgery. A total of 151 patients (88 men, 62 women) underwent elective AF surgery concomitantly with cardiovascular surgery from April 2005 to December 2019. The mean age at time of operation was 70 years and the mean follow-up period was 5.2 ± 3.8 years. Patients were divided into two groups according to the procedure performed: the maze group (n = 87) and the LAAc group (n = 63). Patients in the LAAc group were significantly older and had more comorbidities than those in the maze group. The operative mortality rate was significantly higher in the LAAc group. There was no difference in the rate of freedom from cardiac-related death between the groups (p = 0.86). Furthermore, there was no difference in the 5-year rate of freedom from thromboembolic stroke between the maze group and the LAAc group (p = 0.17). However, the 5-year rate of freedom from heart failure was significantly higher in the maze group compared with the LAAc group (100% vs. 86% ± 6%, respectively; p = 0.006). Patients undergoing the maze procedure had good operative and long-term results, suggesting that this procedure should be performed if indicated. Concomitant LAAc may be effective for preventing thromboembolic stroke in patients with AF if they have no indication for the maze procedure.

The recent clinical trial (DAWN) suggests that recanalization treatment may be beneficial up to 24 h after stroke onset, thus re-opening avenues for development of new therapeutic strategies. Unfortunately, there is a continuous failure of drugs in clinical trials and one of the major reasons proposed for this translational roadblock is the animal models. Therefore, the purpose of this study was to validate a new thromboembolic stroke rat model that mimics the human pathology, and that can be used for evaluating new strategies to save the brain in conditions compatible with recanalization. Stroke was induced by injection of thrombin into the middle cerebral artery. Recombinant tissue-type plasminogen activator (rt-PA) or saline was administrated at 1 h/4 h after stroke onset, and outcome was evaluated after 24 h. Induced ischemia resulted in reproducible cortical brain injuries causing a decrease in neurological function 24 h after stroke onset. Early rt-PA treatment resulted in recanalization, reduced infarct size and improved neurological functions, while late rt-PA treatment showed no beneficial effects and caused hemorrhagic transformation in 25% of the rats. This validated and established model’s resemblance to human ischemic stroke and high translational potential, makes it an important tool in the development of new therapeutic strategies for stroke.

Recent studies reported that the new coronavirus disease (COVID-19) invades the central or peripheral nervous system by various mechanisms including angiotensin converting enzyme-2 receptors, blood-brain barrier injury, and immune injury. The possibility that COVID-19 can occur due to the mechanism of thromboembolic stroke, as a result central nervous system, was confirmed by brain images and laboratory test. What we need to note is that COVID-19 can also appear as a focal neurological defect. In addition, if the COVID-19 patient has a high D-dimer and an inflammatory maker, clinicians must be aware of multiple thromboembolic strokes as well as the occurrence of ischemic stroke caused by large vessel stroke.

Background Elderly patients with atrial septal defect (ASD) often present with chronic atrial fibrillation and large left to right shunt. This study reports the experience of left atrial appendage (LAA) and ASD closure in patients with significant ASD and chronic atrial fibrillation. Methods We report six consecutive elderly patients with chronic atrial fibrillation and significant ASD who underwent LAA and fenestrated ASD closure from January 1, 2014 until December 31, 2019. All periprocedural and long-term (>1 year) outcomes were reported. Results Six patients (male: 33.3%; mean age: 66.8 ± 3.3 years) were included. Mean CHADS2 , CHA2 DS2 -VASc , and HAS-BLED scores were 2.33 ± 0.82, 3.83 ± 0.75, and 1.83 ± 0.75. Four patients underwent simultaneous procedure, while two patients underwent a staged procedure. Procedural success was achieved in all patients. Total occlusion was achieved during LAA occlusion without device embolization prior to ASD closure. Patients who underwent simultaneous procedure had a shorter total hospital stay and lower total hospital stay. During a follow-up period of 32.8 ± 19.4 months, both the devices were well seated. No device-related thrombosis or erosion reported. All patients remained in atrial fibrillation. No patients experienced any thromboembolic stroke or transient ischemic attack. Conclusions LAA and ASD closure is feasible and can be safely performed in the same seating in elderly patients with a significant ASD.

Background Arterial thoracic outlet syndrome is a rare condition characterized by a subclavian artery pathology associated with a bone abnormality. It is rarely associated with thromboembolic stroke. The mechanism of cerebral embolism associated with thoracic outlet syndrome have rarely been demonstrated. We present here a fully studied case with a high probability of reverse flow embolism. Case presentation A 24-year-old man with a known arterial thoracic outlet syndrome presented with a right cerebral posterior artery brain infarction. An ultrasound examination depicted the compression of the right subclavian artery in the scalene defile with a post stenotic aneurysm and the presence of a floating thrombus in this aneurysm. There was a reverse flow during diastole in this aneurysm. Anticoagulation was carried out with the disappearance of the floating thrombus with no new clinical or brain MRI event. Corrective surgery of this thoracic outlet syndrome was performed one month after stroke. Conclusion Very few cases of stroke in arterial thoracic outlet syndrome have been described with thorough dynamic vascular imaging. To our knowledge, this is the fourth reported case that advocates for a reverse flow embolism mechanism in stroke associated with thoracic outlet syndrome, and the first to realize an extensive ultrasound and doppler workup.

The most common causes of ischaemic stroke are represented by carotid artery atherosclerotic disease (CAAD) and atrial fibrillation. While oral anticoagulants substantially reduce the incidence of thromboembolic stroke (< 1%/year), the rate of ischaemic stroke and other cardiovascular disease events in patients with CAAD remains high, ranging from 8.4 to 18.1 events per 100 patient-years. Similar to any other atherosclerotic disease, anti-thrombotic therapies are proposed for CAAD to reduce stroke and other cardiovascular events. The 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines recommend for patients with asymptomatic CAAD ≥60% the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily at the exception of patient at very high bleeding risk. For patients with symptomatic CAAD ≥50%, the use of aspirin 75 to 100 mg once daily or clopidogrel 75 mg once daily is recommended. New perspectives for anti-thrombotic therapy for the treatment of patients with CAAD come from the novel dual pathway strategy combining a low-dose anticoagulant (i.e. rivaroxaban) and aspirin that may help reduce long-term ischaemic complications in patients with CAAD. This review summarizes current evidence and recommendations for the anti-thrombotic management of patients with symptomatic or asymptomatic CAAD or those undergoing carotid revascularization.

Author(s): Ford, James S.; Holmes, James F.; Jones, Russell F. | Abstract: Introduction: There is a growing body of literature detailing coronavirus 2019 (COVID-19) cardiovascular complications and hypercoagulability, although little has been published on venous or arterial thrombosis risk.Case Report: In this report, we present a single case of cardioembolic stroke in the setting of COVID-19 related myocarditis, diagnosed via cardiac magnetic resonance imaging and echocardiography. COVID-19 infection was confirmed via a ribonucleic acid polymerase chain reaction assay.Conclusion: Further research is needed to evaluate the hypercoagulable state of patients with COVID-19 to determine whether prophylactic anticoagulation may be warranted to prevent intracardiac thrombi and cardioembolic disease in patients with COVID-19 related myocarditis.

A patient undergoes intracranial stent insertion for stent-assisted coiling of a basilar tip aneurysm and left middle cerebral artery aneurysm. A flow diverting stent is also placed across an anterior communicating artery aneurysm. Prior to the procedure, the patient takes dual antiplatelet medications, being aspirin and clopidogrel. Because of the concern regarding in-stent thrombus and thromboembolic complications related to intracranial stenting and the high rate of clopidogrel resistance, preoperative platelet function testing (PFT) was undertaken to ensure platelet inhibition. In this case, PFT was performed on a platelet function analyser which demonstrated platelet inhibition. Ten days following the procedure, the patient represented with thromboembolic stroke. Repeat PFT performed with whole blood impedance aggregometry and despite full medication compliance demonstrated clopidogrel resistance. Clopidogrel was then ceased and prasugrel commenced. This case demonstrates the importance of appropriate platelet inhibition in patients with intracranial stents and the controversy surrounding PFT.

Background and importance Anticoagulants are one of the therapeutic groups most frequently involved in drug related problems in the emergency services. However, the therapeutic management and the impact of assistance for those anticoagulated patients who suffer a stroke episode are not known. Aim and objectives To describe the therapeutic management and healthcare impact of patients with atrial fibrillation treated with oral anticoagulants (OAT) admitted in an emergency services due to a thromboembolic stroke. Material and methods This was a retrospective observational study. Adult patients (>18 years old) with atrial fibrillation receiving treatment with OAT admitted for cardioembolic stroke were included (January 2017–June 2019). Anticoagulant dosing prior to the stroke episode was evaluated. The modified Rankin Scale (mRS) score and National Institutes of Health Stroke Scale (NIHSS) score at admission and discharge, anticoagulant treatment prescribed after the episode and number of consultations to the emergency department in the year after hospital discharge were recorded. Results Thirty-two patients were included (mean Age 75.2 (11.8) years): 22 (68.7%) were treated with vitamin K antagonists (VKA) and 10 (31.2%) with direct oral anticoagulants (DOACs). Eleven (34.4%) patients had a mRS score of 0 prior to the episode, 6 (18.8%) had a score of 1, 13 (40.6%) a score of 2 and 2 (6.2%) a score >2. The median score on the NIHSS scale at admission was 14 points (IQR 10–20) and 1 (0–7) point at discharge. Five (15.6%) patients died during hospitalisation. Among patients receiving VKA treatment, 13 (59.1%) had an international normalised ratio of Conclusion and relevance A significant percentage of patients treated with DOACs suffering from stroke were under dosed. Consultations after discharge were frequent in this group of patients. Our results open the door to the design of multicentre studies that will allow us to verify the best anticoagulation strategies in this group of patients. References and/or acknowledgements No conflict of interest.

Emerging evidence indicates combination therapy with anticoagulants and antiplatelet agents for atrial fibrillation (AF) will be increasingly required. Numerous studies compare the efficacy and cost-effectiveness of anticoagulation alone in AF, i. e., non-vitamin K oral anticoagulants (NOACs) vs. warfarin. However, the addition of antiplatelet agents with their potential for decreasing thromboembolic stroke counter-balanced by an increased bleeding risk has received less attention. Thus, we evaluated the cost–utility of this combination therapy. We obtained event estimates from our recent meta-analysis of four randomized clinical trials designed to compare NOACs with warfarin in patients with AF. We examined patient subgroups within each trial that received antiplatelet therapy in addition to anticoagulation. Utilities were derived from the literature and cost estimates from the German health-care system. A decision tree was constructed and populated with these parameters. We used a 1-year time horizon because combination therapy is not recommended beyond this time. We calculated the incremental cost–effectiveness ratio (ICER) per quality-adjusted life-year (QALY). The derived ICER was 13,168.50 € per QALY. NOAC prices exerted considerable influence on the calculation. Nevertheless, there is potential for ICER shifts in favor of warfarin, e.g., if warfarin-mediated anticoagulation control is improved and thereby adverse events decrease. Conversely, if NOAC adherence decreases, adverse events could increase. The derived ICER was 13,168.50 € per QALY, consistent with NOACs being cost-effective vs. warfarin when anticoagulation is used with antiplatelet agents. Nevertheless, country-, practice-, and patient-related factors influence the ICER. Our cost–utility calculation should be used a starting point for decision-making.

Background and purpose The recent literature suggests that a cardiac origin in ischaemic stroke is more frequent than previously assumed. However, it is not always clear which patients benefit from additional cardiac investigations if obvious cardiac pathology is absent.Methods A single-center retrospective observational study was performed with 7454 consecutive patients admitted to the intensive care unit after cardiac surgery in the period 2006-2015 and who had postoperative brain imaging. Cerebral imaging was studied for the occurrence of stroke including subtype and involved vascular territory. It was assumed that all perioperative thromboembolic strokes are of cardiac origin. Data obtained from a hospital cohort of consecutive patients who received a diagnosis of ischaemic stroke were used for comparison. Results Thromboembolic stroke occurred in 135 cardiac surgery patients in 56 (41%) of whom the posterior cerebral circulation was involved. In the control group, 100 out of 503 strokes (20%) were located in the posterior cerebral circulation. The relative risk for a posterior location for stroke after cardiac surgery compared to patients with ischaemic stroke without prior cardiac surgery was 2.09; 95% confidence interval 1.60-2.72.Conclusions Thromboembolic stroke after cardiac surgery occurs twice as often in the posterior cerebral circulation compared to ischaemic strokes in the general population. If confirmed in general stroke cohorts, the consequence of this finding may be that in patients with an ischaemic stroke that involves the posterior cerebral circulation the chance of a cardiac origin is increased and therefore might trigger additional cardiac investigations such as long-term heart rhythm monitoring or echocardiography.

The recent success of endovascular stroke treatment has heralded a new era in the management of acute ischemic stroke (AIS) with significantly improved outcome for patients. A large number of patients may be amenable to this new treatment and as the evidence expands the number of patients eligible for mechanical thrombectomy continues to increase. Recent evidence suggests that the time window for treatment can be extended up to 24 h after symptom onset for patients with anterior circulation strokes; however, many clinicians and medical professionals may not be aware of these recent changes and it is important that they are kept up-to-date with this rapidly evolving treatment. This review provides an overview of the recent successful trials and highlights important steps that should be instituted in order to achieve rapid reperfusion and optimize the outcome for ischemic stroke patients. It also looks at the remaining controversies facing the field of thrombectomy. A short summary of each of these contentious areas is provided and the current state of the art.

The novel direct oral anticoagulants (NOACs) represent a major advance in oral anticoagulant therapy and are replacing vitamin K antagonists as the preferred options for many indications. Given in fixed doses without routine laboratory monitoring, they have been shown to be at least as effective in reducing thromboembolic stroke as dose-adjusted warfarin in phase 3 randomized trials and less likely to cause hemorrhagic stroke. Pharmacokinetic and/or pharmacodynamic subanalyses of the major NOAC trials in patients with atrial fibrillation have established relationships between clinical characteristics, and drug levels and/or pharmacodynamic responses with both efficacy and safety. Based on these analyses, pharmaceutical manufacturers and regulatory authorities have provided contraindications and dosing recommendations based on clinical characteristics that are associated with drug levels and/or pharmacodynamic responses, stroke reduction, and bleeding risk to optimize the risk-benefit profile of the NOACs in the real world. The current fixed-dosing strategy of NOACs has triggered discussions about the potential value of laboratory monitoring and dose adjustment in customizing drug exposure to further improve the safety and efficacy of the NOACs in patients with atrial fibrillation. As there is neither high-quality evidence nor consensus about the potential role of laboratory monitoring and dose adjustment for the NOACs, a Cardiac Research Safety Consortium "Think Tank" meeting was held at the American College of Cardiology Heart House in December 2015 to discussions these issues. This manuscript reports on the deliberations and the conclusions reached at that meeting.

Aim and objective: Atrial fibrillation (AF), a major cause of thromboembolic stroke, is under-detected. Our aim was to compare the established pathway of AF detection, reporting to point-of-treatment decision, with a pilot pathway coordinated by the clinical nurse specialists (CNS) for stroke in Qatar. Methods: The established system uses traditional holter monitors, attached by a technician. The report is sent to cardio-electrophysiology physicians, and then uploaded onto electronic records. The piloted stroke system used a cardiac monitoring device capable of prolonged recording. The device is calibrated, downloaded, reviewed and uploaded onto electronic records by the CNS. Results: 319 holters were requested during the 6-month pilot period, 217 via the stroke cardiac monitor service (SCMS) and 102 via the hospital holter monitor service (HHMS). Sixty-two percent of the SCMS reports were attached within 24 hours of admission compared to 31% of the HHMS reports. The reports were available within 48 hours in 2% of patients in the HHMS as compared to 76% with SCMS. The time from detachment to the consultant's decision was 2.6 days in SCMS versus 18.4 days in the HHMS. Conclusion: Utilising the skills of the CNS team for the application, interpretation and reporting provided a more efficient service with improved initiation of anticoagulation treatment for patients.

Resection of the left atrial appendage (LAA) to prevent recurrent arterial emboli in patients with atrial fibrillation was first suggested more than 60 years ago. Longer-term follow-up from randomized studies of the safety and efficacy of transcatheter LAA occlusion has recently been completed; data from large, observational cohorts are being reported. These recent data provide further insights into procedural safety with current techniques and the ability of LAA closure to reduce thromboembolic stroke compared with warfarin anticoagulation. This review summarizes the latest data regarding transcatheter LAA occlusion, focusing on larger prospective studies and further analyses of seminal clinical trials.