Prevalence and factors associated with carotid stenosis in acute ischemic stroke patients with atrial fibrillation.

INTRODUCTION: Among stroke patients with atrial fibrillation (AF) it is not uncommon to identify carotid atherosclerosis. This study aimed to estimate the prevalence of, and factors associated with, carotid atherosclerosis among patients with AF and acute ischemic stroke. PATIENTS AND METHODS: Prospectively collected data from consecutive patients with anterior ischemic stroke and AF who underwent carotid imaging from 10 stroke registries were categorized retrospectively according to the degree of stenosis in: no atherosclerosis, stenosis <50%, stenosis ≥50%, and occlusion. Logistic regression analysis was used to identify factors associated with ipsilateral carotid atherosclerosis. RESULTS: Among 2,955 patients with ischemic stroke and AF, carotid atherosclerosis was evident in 1022 (34.6%) patients, while carotid stenosis ≥50% and occlusion were identified in 204 (6.9%) and 168 (5.7%) patients respectively. Ipsilateral carotid stenosis ≥50% or occlusion was associated with higher age (OR:1.15,95%CI:1.01-1.32, per decade), previous ischemic stroke or transient ischaemic attack (OR:1.70,95%CI:1.29-2.25), peripheral artery disease (OR:1.85, 95%CI:1.23-2.78), coronary artery disease (OR:1.53,95%CI:1.16-2.04) and statin treatment on admission (OR:1.30,95%CI:1.01-1.67). Patients with lacunar stroke had a lower likelihood of stenosis ≥50% or occlusion (OR:0.29,95%CI:0.13-0.68). Compared to the absence of atherosclerotic disease, atherosclerosis in one and two arterial beds was associated with the identification of ipsilateral carotid stenosis (OR:1.49,95%CI:1.22-2.98 and OR: 3.18,95%CI: 1.85-5.49, respectively). CONCLUSION: Among acute ischemic stroke patients with AF, 1 out of 3 had ipsilateral carotid atherosclerosis, and 1 out of 8 had ipsilateral carotid stenosis ≥50% or occlusion. Atherosclerosis in two arterial beds was the most important predictor for the identification of ipsilateral carotid stenosis. Among ischemic stroke patients with AF, carotid atherosclerosis is common while carotid imaging should not be overlooked, especially in those with coronary or/and peripheral artery disease.

Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Sodium-glucose cotransporter-2 inhibitors in heart failure patients across the range of body mass index: a systematic review and meta-analysis of randomized controlled trials.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors improve outcomes in patients with heart failure, with or without diabetes. We sought to assess whether there is an interaction of these effects with body mass index (BMI). A systematic review of the MEDLINE and Scopus databases (last search: November 15th, 2022) was performed according to the PRISMA statement. Studies eligible for this review were randomized control trials (RCTs) with patients with chronic heart failure with either preserved or reduced ejection fraction randomly assigned to SGLT2 inhibitors or placebo. Data were extracted independently by two reviewers. BMI was classified according to the WHO classification into under/normal weight (BMI: < 25 kg/m2), overweight (BMI: 25-29.9 kg/m2), obesity class I (BMI: 30-34.9 kg/m2), and obesity classes II/III (BMI: ≥ 35 kg/m2). All analyses were performed using RevMan 5.4. Among 1461 studies identified in the literature search, 3 were eligible and included in the meta-analysis. Among 14,737 patients (32.2% were women), 7,367 were randomized to an SGLT2 inhibitor (dapagliflozin or empagliflozin) and 7,370 to placebo. There were significantly fewer hospitalizations for HF (OR: 0.70, 95%CI: 0.64-0.76), cardiovascular deaths (OR:0.86, 95%CI: 0.77-0.97) and all-cause deaths (OR:0.90, 95%CI: 0.82-0.98) in the SGLT2 inhibitors group compared to the placebo group, without any interaction with BMI group (test for subgroup differences: x2 = 1.79, p = 0.62; x2 = 0.27, p = 0.97; x2 = 0.39, p = 0.94, respectively). There is no interaction between the efficacy of SGLT2 inhibitors and BMI in patients with HF with either preserved or reduced ejection fraction. SGLT2 inhibitors are associated with improved outcomes regardless of the BMI.Trial registration: PROSPERO ID: CRD42022383643.

Magnetic resonance imaging for diagnostic workup of embolic stroke of undetermined source: A systematic review.

BACKGROUND: Embolic stroke of undetermined source (ESUS) refers to ischemic stroke where the underlying cause of thromboembolism cannot be found despite the recommended diagnostic workup. Unidentified source of emboli hinders clinical decision-making and patient management with detrimental consequences on long-term prognosis. The rapid development and versatility of magnetic resonance imaging (MRI) make it an appealing addition to the diagnostic routine of patients with ESUS for the assessment of potential vascular and cardiac embolic sources. AIMS: To review the use of MRI in the identification of cardiac and vascular embolic sources in ESUS and to assess the reclassification value of MRI examinations added to the conventional workup of ESUS. SUMMARY OF REVIEW: We reviewed the use of cardiac and vascular MRI for the identification of a variety of embolic sources associated with ESUS, including atrial cardiomyopathy, left ventricular pathologies, and supracervical atherosclerosis in carotid and intracranial arteries and in distal thoracic aorta. The additional reclassification after MRI examinations added to the workup of patients with ESUS ranged from 6.1% to 82.3% and varied depending on the combination of imaging modalities. CONCLUSION: MRI techniques allow us to identify additional cardiac and vascular embolic sources and may further decrease the prevalence of patients with the diagnosis of ESUS.

Calprotectin serum levels on admission and during follow-up predict severity and outcome of patients with COVID-19: A prospective study.

BACKGROUND & AIMS: Calprotectin reflects neutrophil activation and is increased in various inflammatory conditions including severe COVID-19. However, serial serum calprotectin measurements in COVID-19 patients are limited. We assessed prospectively, calprotectin levels as biomarker of severity/outcome of the disease and a COVID-19 monitoring parameter in a large cohort of consecutive COVID-19 patients. METHODS: Calprotectin serum levels were measured in 736 patients (58.2 % males; median age 63-years; moderate disease, n = 292; severe, n = 444, intubated and/or died, n = 50). Patients were treated with combined immunotherapies according to our published local algorithm. The endpoint was the composite event of intubation due to severe respiratory failure (SRF)/COVID-19-related mortality. RESULTS: Median (interquartile range) calprotectin levels were significantly higher in patients with severe disease [7(8.2) vs. 6.1(8.1)µg/mL, p = 0.015]. Calprotectin on admission was the only independent risk factor for intubation/death (HR=1.473, 95 %CI=1.003-2.165, p = 0.048) even after adjustment for age, sex, body mass index, comorbidities, neutrophils, lymphocytes, neutrophil to lymphocytes ratio, ferritin, and CRP. The area under the curve (AUC, 95 %CI) of calprotectin for prediction of intubation/death was 0.619 (0.531-0.708), with an optimal cut-off at 13 µg/mL (sensitivity: 44 %, specificity: 79 %, positive and negative predictive values: 13 % and 95 %, respectively). For intubated/died patients, paired comparisons from baseline to middle of hospitalization and subsequently to intubation/death showed significant increase of calprotectin (p = 0.009 and p < 0.001, respectively). Calprotectin alteration had the higher predictive ability for intubation/death [AUC (95 %CI):0.803 (0.664-0.943), p < 0.001]. CONCLUSIONS: Calprotectin levels on admission and their subsequent dynamic alterations could serve as indicator of COVID-19 severity and predict the occurrence of SRF and mortality.

Beyond antithrombotics: recent advances in pharmacological risk factor management for secondary stroke prevention.

Patients with ischaemic stroke represent a diverse group with several cardiovascular risk factors and comorbidities, which classify them as patients at very high risk of stroke recurrence, cardiovascular adverse events or death. In addition to antithrombotic therapy, which is important for secondary stroke prevention in most patients with stroke, cardiovascular risk factor assessment and treatment also contribute significantly to the reduction of mortality and morbidity. Dyslipidaemia, diabetes mellitus and hypertension represent common and important modifiable cardiovascular risk factors among patients with stroke, while early recognition and treatment may have a significant impact on patients' future risk of major cardiovascular events. In recent years, there have been numerous advancements in pharmacological agents aimed at secondary cardiovascular prevention. These innovations, combined with enhanced awareness and interventions targeting adherence and persistence to treatment, as well as lifestyle modifications, have the potential to substantially alleviate the burden of cardiovascular disease, particularly in patients who have experienced ischaemic strokes. This review summarises the evidence on the contemporary advances on pharmacological treatment and future perspectives of secondary stroke prevention beyond antithrombotic treatment.

Direct oral anticoagulants are associated with lower risk of dementia in patients with atrial fibrillation.

BACKGROUND AND AIM: Atrial fibrillation (AF) is associated with increased risk of dementia. Whether direct oral anticoagulation (DOAC) reduce this risk compared to vitamin-K antagonist (VKA) is unclear. The aim of this study was to assess the risk of new all-cause dementia and vascular dementia in AF patients, treated with either DOAC or VKAs. METHODS: Anonymized electronic medical records from the TriNetX federated research network were used. AF patients treated with DOACs within 1 month of AF diagnosis, were 1:1 propensity score-matched with those treated with a VKA. The analysis included patients who completed 5 and 10 years of follow-up and were assessed for all-cause dementia and vascular dementia. Cox proportional hazard models were used to hazard ratios (HR), respectively with 95% confidence intervals (CIs). RESULTS: Among patients who completed 5 years of follow-up, after propensity score matching the final cohort consisted of 215,404 well-matched AF patients. All-cause dementia was diagnosed in 4,153 (3.9%) patients among those treated with DOACs and 4,150 (3.9%) among the VKA-treated patients (HR: 1.01, 95%CI: 0.96-1.05). Among patients 65-74 years old who were followed, DOAC treatment was associated with lower risk of dementia compared to VKAs (HR: 0.72; 95%CI: 0.59-0.86). Among patients who completed 10 years of follow-up, after propensity score matching the final cohort consisted of 19,208 well-matched AF patients. All-cause dementia was diagnosed in 314 (3.3%) patients among those treated with DOACs and 451 (4.7%) among the VKA-treated patients. DOAC treatment was associated with significantly lower risk of all-cause dementia during a follow-up period of 10 years compared to VKA treatment (HR: 0.72, 95%CI: 0.62-0.83), which remained consistent in patiens ≥65 years old. CONCLUSION: This propensity-score matched analysis showed that among AF patients, treatment with a DOACs for a period of 10 years was associated with lower risk of all-cause dementia and vascular dementia compared to VKA treatment, an effect which was not apparent in those treated for shorter duration. This finding requires confirmation in ongoing randomised controlled trials.

Adherence to an integrated care pathway for stroke is associated with lower risk of major cardiovascular events: A report from the Athens Stroke Registry.

BACKGROUND: A recent European Society of Cardiology (ESC) Council on Stroke position paper proposed a holistic integrated care management approach for stroke patients, to improve cardiovascular outcomes. The impact of implementing the ABCstroke pathway 'concept' on clinical outcomes has never been estimated before. In order to investigate the potential effect of ABCstroke pathway adherence to cardiovascular outcomes post stroke, we performed a post-hoc analysis from the Athens Stroke Registry. METHODS AND RESULTS: This analysis was performed in the Athens Stroke Registry, which includes all consecutive patients with acute first-ever ischemic stroke. The Kaplan-Meier product limit was used to estimate the cumulative hazard of each outcome according to adherence with the ABCstroke pathway. We studied 2513 patients [median (IQR) age 71 (62-78) years; 37.7 % female] with ischemic stroke with median follow-up period of 30 (6-75) months. Full adherence to the ABC pathway was identified in 156 (6.2 %) of the patients, while 192 (7.6 %) did not adhere to any of the therapeutic pillars of ABCstroke. Full adherence to ABC treatment pathway was associated with significant reduction of stroke recurrence, compared to patients with no or partial adherence (aHR: 0.61; 95 %CI: 0.37-0.99), as well as a lower risk of MACE (HR: 0.59; 0.39-0.88) and death (aHR: 0.22; 95 %CI: 0.12-0.41). CONCLUSION: Full adherence to the ABCstroke pathway based on the current guidelines was evident in only 6.2 % of our ischaemic stroke cohort but was independently associated with lower risks of stroke recurrence, major cardiovascular events and mortality. This highlights a potential opportunity to improve clinical outcomes post-stroke with a holistic or integrated care management approach.

Management of ischaemic stroke survivors in primary care setting: the road to holistic care.

The management of ischaemic stroke survivors is multidisciplinary, necessitating the collaboration of numerous medical professionals and rehabilitation specialists. However, due to the lack of comprehensive and holistic follow-up, their post-discharge management may be suboptimal. Achieving this holistic, patient-centred follow-up requires coordination and interaction of subspecialties, which general practitioners can provide as the first point of contact in healthcare systems. This approach can improve the management of stroke survivors by preventing recurrent stroke through an integrated post-stroke care, including appropriate Antithrombotic therapy, assisting them to have a Better functional and physiological status, early recognition and intervention of Comorbidities, and lifestyles. For such work to succeed, close interdisciplinary collaboration between primary care physicians and other medical specialists is required in a holistic or integrated way.

A Coherent Assessment of the Compressive Strain Rate Response of PC, PETG, PMMA, and TPU Thermoplastics in MEX Additive Manufacturing.

In this study, we successfully address a significant research and engineering gap by quantitatively assessing the impact of varying compressive loading rates on the mechanical behavior of four popular thermoplastic polymers in material-extrusion-based (MEX) 3D printing. Raw powders of polycarbonate (PC), polyethylene terephthalate glycol (PETG), polymethyl methacrylate (PMMA), and thermoplastic polyurethane (TPU) were processed through melt extrusion, and the filaments were used to 3D-print the test samples. For completeness, thermogravimetric analysis and a compressive test following the ASTM-D695 standard were conducted. Ultimately, the compressive strength and yield stress, the compressive modulus of elasticity and toughness, and the maximum compressive sensitivity index were thoroughly documented. Specimens were tested in strain rates from 1.3 mm/min to 200 mm/min. The compressive strength (40% for the PMMA) and stiffness (29% for the TPU) increased with the increase in the strain rate in all polymers tested. PC had the highest strain rate sensitivity. Significant variations in deformation and fracture modes were observed and thoroughly documented throughout this study. Our findings can be useful in industrial engineering as valued design optimization input parameters in various applications involving the above-mentioned polymeric materials.

Mitral valve geometrical echocardiographic analysis and 3D computational modeling of a normal mitral valve.

Aim: This research aims to develop a consistent computational model of a normal mitral valve (MV) and describe mitral regurgitation (MR) geometry based on Carpentier's classification. Materials & methods: MV geometry was assessed by 2D transthoracic echocardiogram in 100 individuals. A 3D parametric geometric model of the MV was developed. A computational model of a normal MV was performed. Results: The simulation of the valve function was successfully accomplished and its kinematics was analyzed. Differences in geometry were revealed between normal and type III MR. Conclusion: 3D computational models of the normal MV can be constructed relying on standard measurements performed by 2D echocardiography. Certain geometrical differences exist among the normal and the most severe type of MR.

Stroke Patients' Management During COVID-19 Pandemic: Results from the Sun4Patients Web-Based Registry.

Covid-19 pandemic has influenced stroke care in different ways. Recent reports demonstrated a sharp decline in acute stroke admissions worldwide. Even for patients presented to dedicated healthcare services, management at the acute phase may be sub-optimal. On the other hand, Greece has been praised for the early initiation of restriction measures which were associated with a 'milder' surge of SARS-CoV-2 infection. Methods Data derived from a prospective cohort multicenter registry. The study population consisted of first-ever acute stroke patients, hemorrhagic or ischemic, admitted within 48 hours of symptom onset in seven national healthcare system (NHS) and University hospitals in Greece. Two different time periods have been considered, defined as "before Covid-19" (15/12/2019-15/02/2020) and "during Covid-19" (16/02/2020-15/04-2020) era. Statistical comparisons on acute stroke admission characteristics between the two different time periods have been performed. Results This exploratory analysis of 112 consecutive patients showed a reduction of acute stroke admissions by 40during Covid-19 period. No significant differences were observed regarding stroke severity, risk factor profile and baseline characteristics for patients admitted before and during Covid-19 pandemic period. There is a significant delay between symptom onset to CT scan during Covid-19 era compared to the period before pandemic reached Greece (p=0.03). Conclusions The rate of acute stroke admissions has been reduced by 40% during Covid-19 pandemic. Further research is needed to clarify whether the reduction in stroke volume is actual or not and identifying the reasons underlying the paradox.

Risk of myocardial infarction and ischemic stroke in individuals with first-diagnosed paroxysmal vs. non-paroxysmal atrial fibrillation under anticoagulation.

AIMS: There is conflicting evidence on whether the type of atrial fibrillation (AF) is associated with risk of cardiovascular events, including acute myocardial infarction (MI) and ischemic stroke. The aim of the present study was to investigate whether the risk of MI and ischemic stroke differs between individuals with first-diagnosed paroxysmal vs. non-paroxysmal AF treated with anticoagulants. METHODS AND RESULTS: De-identified electronic medical records from the TriNetX federated research network were used. Individuals with a new diagnosis of paroxysmal AF who had no evidence of other types of AF in their records were 1:1 propensity score-matched with individuals with non-paroxysmal AF, defined as persistent or chronic AF, who had no evidence of other types of AF in their records. All patients were followed for three years for the outcomes of MI and ischemic stroke. Cox proportional hazard models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). In the propensity-matched cohort, among 24 848 well-matched AF individuals [mean age 74.4 ± 10.4; 10 101 (40.6%) female], 410 (1.7%) were diagnosed with acute MI and 875 (3.5%) with ischemic stroke during the three-year follow-up. Individuals with paroxysmal AF had significantly higher risk of acute MI (HR: 1.65, 95%CI: 1.35-2.01) compared to those with non-paroxysmal AF. First diagnosed paroxysmal AF was associated with higher risk of non-ST elevation MI (nSTEMI) (HR: 1.89, 95%CI: 1.44-2.46). No significant association was observed between the type of AF and risk of ischemic stroke (HR: 1.09, 95%CI: 0.95-1.25). CONCLUSION: Patients with first-diagnosed paroxysmal AF had higher risk of acute MI compared to individuals with non-paroxysmal AF, attributed to the higher risk of nSTEMI among patients with first-diagnosed paroxysmal AF. There was no significant association between type of AF and risk of ischemic stroke.

C-reactive protein levels are associated with early cardiac complications or death in patients with acute ischemic stroke: a propensity-matched analysis of a global federated health from the TriNetX network.

The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1-3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1-3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1-3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05-1.52; HR 1.51, 95%CI 1.45-1.58), death (HR 1.43, 95%CI 1.24-1.64; HR 3.50, 95%CI 3.01-3.96), HF (HR 1.08, 95%CI 1.01-1.16; HR 1.51, 95%CI 1.41-1.61), AF (HR 1.10, 95% CI:1.02-1.18; HR 1.42, 95%CI 1.33-1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02-1.52; HR 1.67, 95% CI 1.38-2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26-1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death.

Mobile health-technology integrated care in secondary prevention atrial fibrillation patients: a post-hoc analysis from the mAFA-II randomized clinical trial.

AF patients with history of thromboembolic events are at higher risk of thromboembolic recurrences, despite appropriate antithrombotic treatment. We aimed to evaluate the effect of mobile health (mHealth) technology-implemented 'Atrial fibrillation Better Care' (ABC) pathway approach (mAFA intervention) in secondary prevention AF patients. The Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) cluster randomized trial enrolled adult AF patients across 40 centers in China. The main outcome was the composite outcome of stroke or thromboembolism, all-cause death, and rehospitalization. Using Inverse Probability of Treatment Weighting (IPTW), we evaluated the effect of the mAFA intervention in patients with and without prior history of thromboembolic events (i.e., ischemic stroke or thromboembolism). Among the 3324 patients enrolled in the trial, 496 (14.9%, mean age: 75.1 ± 11.4 years, 35.9% females) had a previous episode of thromboembolic event. No significant interaction was observed for the effect of mAFA intervention in patients with vs. without history of thromboembolic events [Hazard ratio, (HR): 0.38, 95% confidence interval (CI):0.18-0.80 vs. HR 0.55, 95% CI 0.17-1.76, p for interaction = 0.587); however, a trend towards lower efficacy of mAFA intervention among AF patients in secondary prevention was observed for secondary outcomes, with significant interaction for bleeding events (p = 0.034) and the composite of cardiovascular events (p = 0.015). A mHealth-technology-implemented ABC pathway provided generally consistent reduction of the risk of primary outcome in both primary and secondary prevention AF patients. Secondary prevention patients may require further specific approaches to improve clinical outcomes such as bleeding and cardiovascular events.Trial registration: WHO International Clinical Trials Registry Platform (ICTRP) Registration number ChiCTR-OOC-17014138.

Stroke in Atrial Fibrillation and Other Atrial Dysrhythmias.

PURPOSE OF REVIEW: Atrial fibrillation (AF) is a major risk factor for systemic embolism and ischaemic stroke. Furthermore, AF-related strokes are associated with higher mortality, greater disability, longer hospital stays and lower rates of hospital discharge than strokes caused by other reasons. The aim of this review to summarise the existing evidence on the association of AF with ischemic stroke and provide insights on the pathophysiological mechanisms and the clinical management of patients with AF in order to reduce the burden of ischemic stroke. RECENT FINDINGS: Beyond Virchow's triad, several pathophysiological mechanisms associated with structural changes in the left atrium, which may precede the identification of AF, may contribute to the increased risk of arterial embolism in AF patients. Individualised thromboembolic risk stratification based on CHA2DS2-VASc score and clinically relevant biomarkers provides essential tool towards a personalised holistic approach in thromboembolism prevention. Anticoagulation remains the cornerstone of stroke prevention moving from vitamin K antagonists (VKA) to safer non-vitamin K direct oral anticoagulants in the majority of AF patients. Despite the efficacy and safety of oral anticoagulation, still the equilibrium between thrombosis and haemostasis in AF patients remains suboptimal and future directions in anticoagulation and cardiac intervention may provide novel treatment options in stroke prevention. This review summarises the pathophysiologic mechanisms of thromboembolism, aiming the current and potential future perspectives in stroke prevention in AF patients.

Atrial fibrillation and stroke.

INTRODUCTION: Stroke is one of the leading causes of mortality and morbidity globally. Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is set to reach epidemic proportions. AF is associated with a five-fold increase in risk of stroke. Strokes caused by AF more often are fatal or result in severe disability. Even though the incidence of stroke has been significantly reduced by oral anticoagulation, AF is thought to account for a significant proportion of cryptogenic strokes where no etiology is identified. AREAS COVERED: This article reviews the literature related to AF and stroke, pathophysiological insights, diagnosis of AF in stroke patients, and its management (Graphical Abstract). EXPERT OPINION: The pathophysiology of thrombogenesis that links AF and stroke is not well understood and is an area of active research to identify new therapeutic targets to prevent AF and stroke. As the nature of AF and stroke is multifaceted, an integrated care approach to managing AF and stroke is increasingly essential.

Endovascular treatment for ischemic stroke patients with and without atrial fibrillation, and the effects of adjunctive pharmacotherapy: a narrative review.

INTRODUCTION: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in patients with ischemic stroke, but the impact of EVT on clinical outcomes in patients with ischemic stroke with and without atrial fibrillation (AF), and the effect of adjunctive pharmacological therapies with EVT, remains unclear. AREAS COVERED: The goal of this narrative review is to provide an overview of studies which have examined: 1) associations between EVT and outcomes for patients following ischemic stroke, 2) associations between EVT and outcomes for patients following ischemic stroke with and without AF , including function, reperfusion, hemorrhage, and mortality, 3) the effect of adjunctive pharmacological therapies peri- and post-thrombectomy, and 4) integration of prehospital care on endovascular treatment outcomes. EXPERT OPINION: There is little evidence from randomized controlled trials on the effect of AF on stroke outcomes following EVT and the safety and efficacy of AF treatment in the peri-EVT such as tirofiban or Intravenous thrombolysis with Non-vitamin K Antagonist Oral Anticoagulant. The available evidence from observational studies on AF and EVT outcomes is inconsistent, but factors such as procedural EVT devices, the center volume, clinician experience, stroke recognition, and inclusion criteria of studies have all been associated with poorer clinical outcomes. Enhancing the clinical network among prehospital and hospitals will facilitate direct transfer to EVT centers, reducing stroke onset to EVT time and optimizing stroke outcomes.

Sinus rhythm restoration and improved outcomes in patients with acute ischemic stroke and in-hospital paroxysmal atrial fibrillation.

Aims: It is unclear whether early cardiac rhythm control is beneficial in patients with acute ischemic stroke and paroxysmal atrial fibrillation (PAF). We sought to investigate whether PAF self-termination and in-hospital sinus rhythm (SR) restoration is associated with improved outcome in ischemic stroke patients with PAF, compared to those with sustained atrial fibrillation (AF). Methods: Consecutive patients with first-ever acute stroke and confirmed PAF during hospitalization were followed for up to 10 years after the index stroke or until death. We investigated the association of in-hospital self-terminated PAF and PAF conversion to SR compared to sustained AF with 10-year all-cause mortality, stroke recurrence, and major adverse cardiovascular events (MACE). Cox regression analysis was performed to identify independent predictors of each outcome. Results: Among 297 ischemic stroke patients with in-hospital PAF detection, PAF was self-terminated in 87 (29.3%) patients, while 143 (48.1%) patients received antiarrhythmic medication in order to achieve PAF conversion to SR. During a median (Interquartile range, IQR) period of 28 (4-68) months, among patients with self-terminated PAF there were 13.5 deaths, 3.6 stroke recurrences, and 5.3 MACE per 100 patient-year while in patients who underwent medical PAF conversion there were 11.7 deaths, 4.6 stroke recurrences, and 5.8 MACE per 100 patient-year. Patients with sustained AF experienced 23.8 deaths, 8.7 stroke recurrences, and 13.9 MACE per 100 patient-years. In multivariable analysis, compared to patients with sustained AF, PAF self-termination was associated with significantly lower 10 years-risk of death (adjusted hazards ratio (adjHR): HR: 0.63, 95% Confidence interval: 0.40-0.96), stroke recurrence (adjHR: HR: 0.41, 95% CI: 0.19-0.91), and MACE (adjHR: 0.43, 95% CI: 0.23-0.81), while PAF medical conversion to SR was associated with lower 10 years-risk of death (adjHR: 0.65, 95% CI: 0.44-0.97) and MACE (adjHR: 0.56, 95% CI: 0.33-0.95). Discussion: This study showed that in-hospital PAF self-termination was associated with lower risk of 10-year mortality, stroke recurrence, and MACE, potentially attributed to the lower burden of AF, whereas in-hospital PAF conversion to SR was associated with lower risk of 10-year mortality and MACE. Conclusion: Early restoration of sinus rhythm is associated with improved survival and MACE in patients with acute ischemic stroke and PAF.