Natriuretic Peptides to Classify Risk of Atrial Fibrillation Detection After Stroke: Analysis of the BIOSIGNAL and PRECISE Cohort Studies.

BACKGROUND AND OBJECTIVES: Prolonged cardiac monitoring (PCM) increases atrial fibrillation (AF) detection after ischemic stroke, but access is limited, and it is burdensome for patients. Our objective was to assess whether midregional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) could classify people who are unlikely to have AF after ischemic stroke and allow better targeting of PCM. METHODS: We analyzed people from the Biomarker Signature of Stroke Aetiology (BIOSIGNAL) study with ischemic stroke, no known AF, and ≥3 days cardiac monitoring. External validation was performed in the Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) study of 28 days of cardiac monitoring in people with ischemic stroke or transient ischemic attack and no known AF. The main outcome is no AF detection. We assessed the discriminatory value of MR-proANP and NT-proBNP combined with clinical variables to identify people with no AF. A decision curve analysis was performed with combined data to determine the net reduction in people who would undergo PCM using the models based on a 15% threshold probability for AF detection. RESULTS: We included 621 people from the BIOSIGNAL study. The clinical multivariable prediction model included age, NIH Stroke Scale score, lipid-lowering therapy, creatinine, and smoking status. The area under the receiver-operating characteristic curve (AUROC) for clinical variables was 0.68 (95% CI 0.62-0.74), which improved with the addition of log10MR-proANP (0.72, 0.66-0.78; p = 0.001) or log10NT-proBNP (0.71, 0.65-0.77; p = 0.009). Performance was similar for the models with log10MR-proANP vs log10NT-proBNP (p = 0.28). In 239 people from the PRECISE study, the AUROC for clinical variables was 0.68 (0.59-0.76), which improved with the addition of log10NT-proBNP (0.73, 0.65-0.82; p < 0.001) or log10MR-proANP (0.79, 0.72-0.86; p < 0.001). Performance was better for the model with log10MR-proANP vs log10NT-proBNP (p = 0.03). The models could reduce the number of people who would undergo PCM by 30% (clinical and log10MR-proANP), 27% (clinical and log10NT-proBNP), or 20% (clinical only). DISCUSSION: MR-proANP and NT-proBNP help classify people who are unlikely to have AF after ischemic stroke. Measuring MR-proANP or NT-proBNP could reduce the number of people who need PCM by 30%, without reducing the amount of AF detected. TRIAL REGISTRATION INFORMATION: NCT02274727; clinicaltrials.gov/study/NCT02274727.

Stroke-heart syndrome: Incidence and clinical outcomes of cardiac complications following intracerebral haemorrhage.

INTRODUCTION: Newly diagnosed cardiovascular complications following an ischaemic stroke, termed stroke-heart syndrome, are common and associated with worse outcomes. Little is known regarding stroke-heart syndrome in relation to intracerebral haemorrhage (ICH). This study aimed to investigate the incidence and 5-year major adverse cardiovascular events (MACE; acute myocardial infarction, ischaemic stroke, all-cause mortality and recurrent ICH) of newly diagnosed cardiovascular complications following incident ICH, using a global federated database. PATIENTS AND METHODS: A retrospective cohort study was conducted using anonymised electronic medical records. Patients aged ⩾ 18 years with non-traumatic ICH and 5-year follow-up were included. Patients with newly diagnosed cardiovascular complications within 4-weeks following the initial ICH were 1:1 propensity score-matched with patients without new-onset cardiovascular complications. Each cardiovascular complications were investigated as a composite stroke-heart syndrome cohort and separately for associated MACE. Cox hazard regression models were used to determine 5-year incidence of MACE. RESULTS: Before propensity score matching, 171,489 patients with non-traumatic ICH, 15% (n = 26,449) experienced ⩾1 newly diagnosed cardiovascular complication within 4 weeks. After matching, patients with ICH and cardiovascular complications were associated with a significantly higher risk of 5-year MACE (HR 1.35 [95% CI 1.32-1.38]), and in each composite compared to matched controls. There was no significant risk of rehospitalisation over 5-year follow-up [HR 0.90 [0.73-1.13]). The risk of MACE was significantly higher in patients with newly diagnosed cardiovascular complications. DISCUSSION AND CONCLUSIONS: Newly diagnosed cardiovascular complications following ICH (i.e. stroke-heart syndrome) were common and associated with a significantly worsened 5-year prognosis.

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.

European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Neurostimulation for treatment of post-stroke impairments.

Neurostimulation, the use of electrical stimulation to modulate the activity of the nervous system, is now commonly used for the treatment of chronic pain, movement disorders and epilepsy. Many neurostimulation techniques have now shown promise for the treatment of physical impairments in people with stroke. In 2021, vagus nerve stimulation was approved by the FDA as an adjunct to intensive rehabilitation therapy for the treatment of chronic upper extremity deficits after ischaemic stroke. In 2024, pharyngeal electrical stimulation was conditionally approved by the UK National Institute for Health and Care Excellence for neurogenic dysphagia in people with stroke who have a tracheostomy. Many other approaches have also been tested in pivotal device trials and a number of approaches are in early-phase study. Typically, neurostimulation techniques aim to increase neuroplasticity in response to training and rehabilitation, although the putative mechanisms of action differ and are not fully understood. Neurostimulation techniques offer a number of practical advantages for use after stroke, such as precise dosing and timing, but can be invasive and costly to implement. This Review focuses on neurostimulation techniques that are now in clinical use or that have reached the stage of pivotal trials and show considerable promise for the treatment of post-stroke impairments.

Albumin Levels and Risk of Early Cardiovascular Complications After Ischemic Stroke: A Propensity-Matched Analysis of a Global Federated Health Network.

BACKGROUND: No studies have investigated the association between albumin levels and the risk of early cardiovascular complications in patients with ischemic stroke. METHODS: Retrospective analysis with a federated research network (TriNetX) based on electronic medical records (International Classification of Diseases-Tenth Revision-Clinical Modification and logical observation identifiers names and codes) mainly reported between 2000 and 2023, from 80 health care organizations in the United States. Based on albumin levels measured at admission to the hospital, patients with ischemic stroke were categorized into 2 groups: (1) reduced (≤3.4 g/dL) and (2) normal (≥3.5 g/dL) albumin levels. The primary outcome was a composite of all-cause death, heart failure, atrial fibrillation, ventricular arrhythmias, myocardial infarction, and Takotsubo cardiomyopathy 30 days from the stroke. Secondary outcomes were the risk for each component of the primary outcome. Cox regression analyses were used to calculate hazard ratios (HRs) and 95% CIs following propensity score matching. RESULTS: Overall, 320 111 patients with stroke had normal albumin levels (70.9±14.7 years; 48.9% females) and 183 729 (57.4%) had reduced albumin levels (72.9±14.3 years; 50.3% females). After propensity score matching, the primary outcomes occurred in 36.0% of patients with reduced and 26.1% with normal albumin levels (HR, 1.48 [95% CI, 1.46-1.50]). The higher risk in patients with reduced albumin levels was consistent also for all-cause death (HR, 2.77 [95% CI, 2.70-2.84]), heart failure (HR, 1.31 [95% CI, 1.29-1.34]), atrial fibrillation (HR, 1.11 [95% CI, 1.09-1.13]), ventricular arrhythmias (HR, 1.38 [95% CI, 1.30-1.46]), myocardial infarction (HR, 1.60 [95% CI, 1.54-1.65]), and Takotsubo cardiomyopathy (HR, 1.51 [95% CI, 1.26-1.82]). The association between albumin levels and the risk of cardiovascular events was independent of advanced age, sex, multimorbidity, and other causes of hypoalbuminemia. A progressively increased risk of adverse events was found in patients with mild and severe reduced compared to normal albumin levels. CONCLUSIONS: Albumin levels are associated with the risk of early cardiovascular events and death in patients with ischemic stroke. The potential pathophysiological or therapeutic roles of albumin in patients with stroke warrant further investigation.

Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulants in the Prevention of Ischaemic Stroke in Patients with Atrial Fibrillation.

Introduction Existing randomised controlled trials assessing the safety and efficacy of left atrial appendage occlusion (LAAO) in atrial fibrillation (AF) were of relatively small sample size, or included patients who could receive oral anticoagulant treatment after device implantation. We compared the outcomes of patients with newly diagnosed AF who received percutaneous LAAO or direct oral anticoagulants (DOAC) treatment, in a large population from a global federated health network (TriNetX). Methods Patients with AF treated with percutaneous LAAO were matched with those treated with DOAC between 1st December 2010 and 1st October 2018. Outcomes were all-cause mortality, ischaemic stroke and intracranial haemorrhage (ICH) at 5 years. Results We included 200 patients with AF, who received either LAAO or DOAC. The risk of all-cause mortality, ischaemic stroke and ICH at 5 years was not significantly different between the two groups (Risk Ratio [RR] for all-cause mortality: 1.52, 95% confidence interval (CI): 0.97- 2.38, RR for ischaemic stroke: 1.09, 95% CI: 0.51- 2.36, and RR for ICH: 1.0, 95% CI: 0.44- 2.30). Conclusion Patients newly diagnosed with AF, eligible for DOAC, showed similar 5-year risk of death, ischemic stroke, and ICH when comparing those who underwent percutaneous LAAO to those receiving DOAC. Future randomised controlled trials are needed to confirm the findings and advise changes in guidelines.

Atrial fibrillation and stroke: State-of-the-art and future directions.

Atrial fibrillation (AF) and stroke remain a major cause of morbidity and mortality. The two conditions shared common co-morbidities and risk factors. AF-related strokes are associated with worse clinical outcomes and higher mortality compared to non-AF-related. Early detection of AF is vital for prevention. While various scores have been developed to predict AF in such a high-risk group, they are yet to incorporated into clinical guidelines. Novel markers and predictors of AF including coronary and intracranial arterial calcification have also been studied. There are also ongoing debates on the management of acute stroke in patients with AF, and those who experienced breakthrough stroke while on oral anticoagulants. We provided an overview of the complex interplay between AF and stroke, as well as the treatment and secondary prevention of stroke in AF. We also comprehensively discussed the current evidence and the ongoing conundrums, and highlighted the future directions on the topic.

Social determinants of health and clinical outcomes among patients with atrial fibrillation. Evidence from a global federated health research network.

BACKGROUND: Few studies have investigated the role of SDoH in patients with atrial fibrillation (AF). AIM: To investigate the relationship between SDoH and adverse events in a large multinational AF cohort. DESIGN: Retrospective study utilizing a global federated health research network (TriNetX). METHODS: Patients with AF were categorized as socially deprived defined according to ICD codes based on three SDoHs: i) extreme poverty; ii) unemployment; iii) and/or problems related with living alone. The outcomes were the five-year risk of a composite outcomes of all-cause death, hospitalization, ischemic heart disease, stroke, heart failure, or severe ventricular arrhythmias. Cox-regression was used to compute hazard rate ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). RESULTS: The study included 24,631 socially deprived (68.8 ± 16.0 years; females 51.8%) and 2,462,092 non-deprived AF patients (75.5 ± 13.1 years; females 43.8%). Before PSM, socially deprived patients had a higher risk of the composite outcome (HR 1.9, 95%CI 1.87-1.93), all-cause death (HR 1.34, 95%CI 1.28-1.39), hospitalization (HR 2.01, 95%CI 1.98-2.04), ischemic heart disease (HR 1.67, 95%CI 1.64-1.70), stroke (HR 2.60, 95%CI 2.51-2.64), heart failure (HR 1.91, 95%CI 1.86-1.96) and severe ventricular arrhythmias (HR 1.83, 95%CI 1.76-1.90) compared to non-deprived AF patients. The PSM based hazard ratios for the primary composite outcome were 1.54 (95%CI 1.49-1.60) for the unemployed AF patients; 1.39 (95%CI 1.31-1.47) for patients with extreme poverty or with low income; and 1.42 (95%CI 1.37-1.47) for those with problems related with living alone. CONCLUSIONS: In patients with AF, social deprivation is associated with an increased risk of death and adverse cardiac events. The presence of possible unmeasured bias associated with the retrospective design requires confirmation in future prospective studies.

Epilepsy-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications in patients with Epilepsy.

The risks of cardiovascular events (CVEs) in people with epilepsy (PWE) are not well understood. To establish the short- and long-term burden of CVEs in PWE. Electronic health records from a global federated health research network (TriNetX) were used to establish a cohort of PWE. Primary outcomes were: (1) the proportion of people experiencing a composite outcome of cardiac arrest, acute heart failure (HF), acute coronary syndrome (ACS), atrial fibrillation (AF), severe ventricular arrhythmia or all-cause death within 30 days of a seizure; and (2) the 5-year risk for a composite outcome of ischemic heart diseases, stroke, hospitalization, or all-cause death in the PWE experiencing early CVEs. Cox-regression analyses with propensity score matching was used to produce hazard ratios (HRs) and 95% confidence intervals (CI). In 271,172 PWE (mean age 50 ± 20 years; 52% females), the 30-day risk of CVEs following seizure was: 8.7% for the composite outcome, 0.9% for cardiac arrest, 0.8% for HF, 1.2% for ACS, 4.1% for AF, 0.7% for severe ventricular arrhythmias, and 1.6% for all-cause death. For the 15,120 PWE experiencing CVEs within 30 days of seizure, the 5-year adjusted risks for all composite outcomes measured were significantly increased (overall HR: 2.44, 95% CI 2.37-2.51), ischemic heart diseases HR 3.23 (95% CI 3.10-3.36), stroke HR 1.56 (95% CI 1.48-1.64), hospitalization HR 2.03 (95% CI 1.97-2.10), and all-cause death HR 2.75 (95% CI 2.61-2.89). The large proportions of PWE with active disease that experience CVEs and the poor long-term outcome associated suggest the existence of an "epilepsy-heart syndrome."

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.

Preventing Recurrent Cardioembolic Stroke: Right Approach, Right Patient (PRECISE) Study Protocol.

Cardiac rhythm monitoring is performed to search for atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA). Prolonged cardiac rhythm monitoring increases AF detection but is challenging to implement in many healthcare settings and is not needed for all people after ischaemic stroke/TIA. We aimed to develop and validate a model that includes clinical, electrocardiogram (ECG), blood-based, and genetic biomarkers to identify people with a low probability of AF detection after ischaemic stroke or TIA. We will recruit 675 consenting participants who are aged over 18 years, who were admitted with ischaemic stroke or TIA in the 5 days prior, who are not known to have AF, and who would be suitable for anticoagulation if AF is found. We will collect baseline demographic and clinical data, a 12-lead ECG, and a venous blood sample for blood biomarkers (including midregional pro-atrial natriuretic peptide, MRproANP) and genetic data. We will perform up to 28 days of cardiac rhythm monitoring using an R-test or patch device to search for AF in all participants. The sample size of 675 participants is based on true sensitivity of 92.5%, null hypothesis sensitivity of 80%, 80% power, and 5% significance. The primary outcome is AF detection ≥30 s duration during 28 days of cardiac rhythm monitoring. Secondary outcomes are AF detection at 1-year, recurrent cardiovascular events, and mortality and will be identified by electronic linkage and telephone follow-up. The results will guide the development of a more personalized care pathway to search for AF after ischaemic stroke or TIA. This could help to reduce cardiac rhythm monitoring for people with a low probability of AF detection and allow more intensive cardiac monitoring to be focused on people who are more likely to have AF and benefit. Participants will be consented for their data to be used in future research studies, providing a rich resource for stroke and cardiovascular research communities.

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.

Improving detection and management of atrial fibrillation after ischaemic stroke in Glasgow (IMPROVE-AF): A quality improvement project.

BACKGROUND: The use of cardiac monitoring to detect atrial fibrillation (AF) is routine after ischaemic stroke but is often delayed leaving patients at risk from undetected AF. We sought to improve the detection of AF by delivering early prolonged 'in-house' cardiac monitoring. METHODS: We collected 3-months of data of people with stroke/transient ischaemic attack (TIA), but without AF, who underwent cardiac monitoring (Phase 1, pre-quality improvement project (QIP)). We then implemented an 'in-house' 7-day cardiac monitoring service for 12 months (Phase 2, during QIP). RESULTS: We included 244 people in Phase 1 and 172 in Phase 2. In Phase 1, 232 (95%) people completed cardiac monitoring. Of these, new AF was detected in 10 (4%). Median time from stroke/TIA onset to availability of the monitoring report in Phase 1 was 50 (interquartile range (IQR): 24-123) days. In Phase 2, 166 (97%) of people completed 7-day cardiac monitoring, with new AF detected in 17 (10%). Median time from onset to availability of the report in Phase 2 was 12 (IQR: 9-15) days. In people with AF detected, 'in-house' monitoring reduced the time of stroke/TIA onset to anticoagulant commencement from 41 (Phase 1) to 14 (Phase 2) days. DISCUSSION: The QIP has improved AF detection, reduced delays associated with conventional cardiac monitoring and prompted early initiation of oral anticoagulation.

Predicting stroke in heart failure and reduced ejection fraction without atrial fibrillation.

AIMS: Patients with heart failure with reduced ejection fraction (HFrEF) are at significant risk of stroke. Anticoagulation reduces this risk in patients with and without atrial fibrillation (AF), but the risk-to-benefit balance in the latter group, overall, is not favourable. Identification of patients with HFrEF, without AF, at the highest risk of stroke may allow targeted and safer use of prophylactic anticoagulant therapy. METHODS AND RESULTS: In a pooled patient-level cohort of the PARADIGM-HF, ATMOSPHERE, and DAPA-HF trials, a previously derived simple risk model for stroke, consisting of three variables (history of prior stroke, insulin-treated diabetes, and plasma N-terminal pro-B-type natriuretic peptide level), was validated. Of the 20 159 patients included, 12 751 patients did not have AF at baseline. Among patients without AF, 346 (2.7%) experienced a stroke over a median follow up of 2.0 years (rate 11.7 per 1000 patient-years). The risk for stroke increased with increasing risk score: fourth quintile hazard ratio (HR) 2.35 [95% confidence interval (CI) 1.60-3.45]; fifth quintile HR 3.73 (95% CI 2.58-5.38), with the first quintile as reference. For patients in the top quintile, the rate of stroke was 21.2 per 1000 patient-years, similar to participants with AF not receiving anticoagulation (20.1 per 1000 patient-years). Model discrimination was good with a C-index of 0.84 (0.75-0.91). CONCLUSION: It is possible to identify a subset of HFrEF patients without AF with a stroke-risk equivalent to that of patients with AF who are not anticoagulated. In these patients, the risk-to-benefit balance might justify the use of prophylactic anticoagulation, but this hypothesis needs to be tested prospectively.

Paired vagus nerve stimulation for treatment of upper extremity impairment after stroke.

The use of a paired vagus nerve stimulation (VNS) system for the treatment of moderate-to-severe upper extremity motor deficits associated with chronic ischemic stroke has recently been approved by the US Food and Drug Administration. This treatment aims to increase the task-specific neuroplasticity through the activation of cholinergic and noradrenergic networks during rehabilitation therapy. A recent pivotal Phase III trial showed that VNS paired with rehabilitation led to improvements in upper extremity impairment and function in people with moderate-to-severe arm weakness for an average of 3 years after ischemic stroke. The between-group difference following 6 weeks of in-clinic therapy and 90 days of home exercise therapy was three points on the upper extremity Fugl-Meyer score. A clinically meaningful response defined as a greater than or equal to six-point improvement was seen in approximately half of the people treated with VNS compared to approximately a quarter of people treated with rehabilitation alone. Further post-marketing research should aim to establish whether the treatment is also of use for people with intracerebral hemorrhage, in people with more severe arm weakness, and for other post-stroke impairments. In addition, high-quality randomized studies of non-invasive VNS are required.