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BACKGROUND AND PURPOSE Hierarchical clustering, a common 'unsupervised' machine-learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data-driven machine-learning method, and explored variation in stroke recurrence between clusters. METHODS We used a hierarchical k-means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum-variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. RESULTS Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64-4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43-3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. CONCLUSIONS This data-driven machine-learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease.

Introduction The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39–2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16–1.80). Discussion our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

Background and aims Only a minority of patients with Embolic Stroke of Undetermined Source (ESUS) receive prolonged cardiac monitoring despite current recommendations. The identification of ESUS patients who have low probability of new diagnosis of atrial fibrillation (AF) could potentially support a strategy of more individualized allocation of available resources and hence, increase their diagnostic yield. We aimed to develop a tool that can identify ESUS patients who have low probability of new incident AF. Methods We performed multivariate stepwise regression in a pooled dataset of consecutive ESUS patients from three prospective stroke registries to identify predictors of new incident AF. The coefficient of each independent covariate of the fitted multivariable model was used to generate an integer-based point scoring system. Results Among 839 patients (43.1% women, median age 67.0 years) followed-up for a median of 24.3 months (2999 patient-years), 125 (14.9%) had new incident AF. The proposed score assigns 3 points for age ≥ 60 years; 2 points for hypertension; −1 point for left ventricular hypertrophy reported at echocardiography; 2 points for left atrial diameter >40 mm; −3 points for left ventricular ejection fraction 0 (relative risk: 13.7, 95%CI: 5.9--31.5). The area under the curve of the score was 84.8% (95%CI: 79.9--86.9%). The sensitivity and negative predictive value of a score of ≤0 for new incident AF during follow-up were 94.9% (95%CI: 89.3--98.1%) and 98.0% (95%CI: 95.8--99.3%), respectively. Conclusions The proposed AF-ESUS score has high sensitivity and high negative predictive value to identify ESUS patients who have low probability of new incident AF. Patients with a score of 1 or more may be better candidates for prolonged automated cardiac monitoring. Clinical trial registration URL: https://www.clinicaltrials.gov / Unique identifier: NCT02766205.

Background and aims Patients with embolic strokes of undetermined source (ESUS) usually present with mild symptoms. We aimed to compare the baseline characteristics between mild and severe ESUS, identify predictors for severe ESUS, and assess outcomes of patients with severe ESUS. Methods In the AF-ESUS (AF-ESUS) dataset, we stratified ESUS severity using the median National Institutes of Health Stroke Scale (NIHSS) score on admission as cut-off. We performed multivariable stepwise regression analyses to identify independent predictors of severe ESUS and to assess the association between ESUS severity and stroke recurrence, death, and new incident atrial fibrillation (AF) on follow-up. The 10-year cumulative probabilities of outcome incidence were estimated by the Kaplan–Meier product limit method. Results In 772 patients (median NIHSS: 6 (interquartile range: 3–12)), 414 (53.6%) patients had severe ESUS (i.e. NIHSS ≥6). Female sex was the only independent predictor for severe ESUS (odds ratio: 1.72 (1.27–2.33)). The rates of recurrence (3.3%/year vs. 3.4%/year, adjusted-hazard ratio: 1.09 (0.73–1.62)) and new incident AF (13.5% vs. 17.0%, adjusted odds ratio: 0.67 (0.44–1.03)) were similar between severe and mild ESUS, but mortality was higher (5.4%/year vs. 3.7%/year, adjusted-hazard ratio: 1.51 (1.05–2.16)) in severe ESUS. The 10-year cumulative probability for stroke recurrence was similar between severe and mild ESUS (38.1% (29.2–48.6) vs. 36.6% (27.8–47.0), log-rank test: 0.01, p = 0.920). The 10-year cumulative probability of death was higher in patients with severe ESUS compared with mild ESUS (40.5% (32.5–50.0) vs. 34.0% (26.0–43.6) respectively; log-rank test: 4.54, p = 0.033). Conclusions Women have more severe ESUS compared with men. Patients with severe ESUS have similar rates of stroke recurrence and new incident AF, but higher mortality compared with mild ESUS.

Background and Purpose— The HAVOC score (hypertension, age, valvular heart disease, peripheral vascular disease, obesity, congestive heart failure, coronary artery disease) was proposed for the prediction of atrial fibrillation (AF) after cryptogenic stroke. It showed good model discrimination (area under the curve, 0.77). Only 2.5% of patients with a low-risk HAVOC score (ie, 0–4) were diagnosed with new incident AF. We aimed to assess its performance in an external cohort of patients with embolic stroke of undetermined source. Methods— In the AF-embolic stroke of undetermined source dataset, we assessed the discriminatory power, calibration, specificity, negative predictive value, and accuracy of the HAVOC score to predict new incident AF. Patients with a HAVOC score of 0 to 4 were considered as low-risk, as proposed in its original publication. Results— In 658 embolic stroke of undetermined source patients (median age, 67 years; 44% women), the median HAVOC score was 2 (interquartile range, 3). There were 540 (82%) patients with a HAVOC score of 0 to 4 and 118 (18%) with a score of ≥5. New incident AF was diagnosed in 95 (14.4%) patients (28.8% among patients with HAVOC score ≥5 and 11.3% among patients with HAVOC score 0–4 [age- and sex-adjusted odds ratio, 2.29 (95% CI, 1.37–3.82)]). The specificity of low-risk HAVOC score to identify patients without new incident AF was 88.7%. The negative predictive value of low-risk HAVOC score was 85.1%. The accuracy was 78.0%, and the area under the curve was 68.7% (95% CI, 62.1%–73.3%). Conclusions— The previously reported low rate of AF among embolic stroke of undetermined source patients with low-risk HAVOC score was not confirmed in our cohort. Further assessment of the HAVOC score is warranted before it is routinely implemented in clinical practice.

Background and Purpose— Despite treatment with oral anticoagulants, patients with nonvalvular atrial fibrillation (AF) may experience ischemic cerebrovascular events. The aims of this case-control study in patients with AF were to identify the pathogenesis of and the risk factors for cerebrovascular ischemic events occurring during non–vitamin K antagonist oral anticoagulants (NOACs) therapy for stroke prevention. Methods— Cases were consecutive patients with AF who had acute cerebrovascular ischemic events during NOAC treatment. Controls were consecutive patients with AF who did not have cerebrovascular events during NOACs treatment. Results— Overall, 713 cases (641 ischemic strokes and 72 transient ischemic attacks; median age, 80.0 years; interquartile range, 12; median National Institutes of Health Stroke Scale on admission, 6.0; interquartile range, 10) and 700 controls (median age, 72.0 years; interquartile range, 8) were included in the study. Recurrent stroke was classified as cardioembolic in 455 cases (63.9%) according to the A-S-C-O-D (A, atherosclerosis; S, small vessel disease; C, cardiac pathology; O, other causes; D, dissection) classification. On multivariable analysis, off-label low dose of NOACs (odds ratio [OR], 3.18; 95% CI, 1.95–5.85), atrial enlargement (OR, 6.64; 95% CI, 4.63–9.52), hyperlipidemia (OR, 2.40; 95% CI, 1.83–3.16), and CHA 2 DS 2 -VASc score (OR, 1.72 for each point increase; 95% CI, 1.58–1.88) were associated with ischemic events. Among the CHA 2 DS 2 -VASc components, age was older and presence of diabetes mellitus, congestive heart failure, and history of stroke or transient ischemic attack more common in patients who had acute cerebrovascular ischemic events. Paroxysmal AF was inversely associated with ischemic events (OR, 0.45; 95% CI, 0.33–0.61). Conclusions— In patients with AF treated with NOACs who had a cerebrovascular event, mostly but not exclusively of cardioembolic pathogenesis, off-label low dose, atrial enlargement, hyperlipidemia, and high CHA 2 DS 2 -VASc score were associated with increased risk of cerebrovascular events.

Background and Purpose— Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods— We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results— Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients ( P =0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4–3.7; P P =0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2–4.9; P =0.01) end points separately. Conclusions— Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.

ObjectiveTo investigate the association between the presence of ipsilateral nonstenotic carotid plaques and the rate of detection of atrial fibrillation (AF) during follow-up in patients with embolic strokes of undetermined source (ESUS).MethodsWe pooled data of all consecutive ESUS patients from 3 prospective stroke registries. Multivariate stepwise regression assessed the association between the presence of nonstenotic carotid plaques and AF detection. The 10-year cumulative probabilities of AF detection were estimated by the Kaplan-Meier product limit method.ResultsAmong 777 patients followed for 2,642 patient-years, 341 (38.6%) patients had an ipsilateral nonstenotic carotid plaque. AF was detected in 112 (14.4%) patients in the overall population during follow-up. The overall rate of AF detection was 8.5% in patients with nonstenotic carotid plaques (2.9% per 100 patient-years) and 19.0% in patients without (5.0% per 100 patient-years) (unadjusted hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.37–0.84). The presence of ipsilateral nonstenotic carotid plaques was associated with lower probability for AF detection (adjusted HR 0.57, 95% CI 0.34–0.96, p = 0.03). The 10-year cumulative probability of AF detection was lower in patients with ipsilateral nonstenotic carotid plaques compared to those without (34.5%, 95% CI 21.8–47.2 vs 49.0%, 95% CI 40.4–57.6 respectively, log-rank-test: 11.8, p = 0.001).ConclusionsAF is less frequently detected in ESUS patients with nonstenotic carotid plaques compared to those without.Clinicaltrials.gov identifierNCT02766205.

Background Stratification of cardiovascular risk in patients with ischemic stroke is important as it may inform management strategies. We aimed to develop a machine-learning-derived prognostic model for the prediction of cardiovascular risk in ischemic stroke patients. Materials and Methods Two prospective stroke registries with consecutive acute ischemic stroke patients were used as training/validation and test datasets. The outcome assessed was major adverse cardiovascular event, defined as non-fatal stroke, non-fatal myocardial infarction, and cardiovascular death during 2-year follow-up. The variables selection was performed with the LASSO technique. The algorithms XGBoost (Extreme Gradient Boosting), Random Forest and Support Vector Machines were selected according to their performance. The evaluation of the classifier was performed by bootstrapping the dataset 1000 times and performing cross-validation by splitting in 60% for the training samples and 40% for the validation samples. Results The model included age, gender, atrial fibrillation, heart failure, peripheral artery disease, arterial hypertension, statin treatment before stroke onset, prior anticoagulant treatment (in case of atrial fibrillation), creatinine, cervical artery stenosis, anticoagulant treatment at discharge (in case of atrial fibrillation), and statin treatment at discharge. The best accuracy was measured by the XGBoost classifier. In the validation dataset, the area under the curve was 0.648 (95%CI:0.619–0.675) and the balanced accuracy was 0.58 ± 0.14. In the test dataset, the corresponding values were 0.59 and 0.576. Conclusions We propose an externally validated machine-learning-derived model which includes readily available parameters and can be used for the estimation of cardiovascular risk in ischemic stroke patients.

Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50–1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53–2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation–related acute ischemic stroke, who started on oral anticoagulant.

Background and Purpose— We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods— We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results— In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99–1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87–1.73) or categorical covariate (likelihood-ratio test 2.59, P =0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60–89, 21.7% for eGFR 45–59, 19.2% for eGFR 30–44, and 24.9% for eGFR P =0.63). The results were similar for the outcome of death. Conclusions— The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

We analyzed consecutive patients with embolic stroke of undetermined source (ESUS) from three prospective stroke registries to compare the prognostic performance of different LAD thresholds for the prediction of new incident AF.We calculated the sensitivity, specificity, positive prognostic value (PPV), negative prognostic value (NPV) and Youden's J-statistic of different LAD thresholds to predict new incident AF. We performed multivariate stepwise regression with forward selection of covariates to assess the association between the LAD threshold with the highest Youden's J-statistic and AF detection.Among 675 patients followed for 2437 patient-years, the mean LAD was 38.5 ± 6.8 mm. New incident AF was diagnosed in 115 (17.0%) patients. The LAD threshold of 40mm yielded the highest Youden's J-statistic of 0.35 with sensitivity 0.69, specificity 0.66, PPV 0.27 and NPV 0.92. The likelihood of new incident AF was nearly twice in patients with LAD 40 mm compared to LAD ≤ 40 mm (HR:1.92, 95%CI:1.24-2.97, p = 0.004). The 10-year cumulative probability of new incident AF was higher in patients with LAD40 mm compared to LAD ≤ 40 mm (53.5% and 22.4% respectively, log-rank-test: 28.2, p 0.001). The annualized rate of stroke recurrence of 4.0% in the overall population did not differ significantly in patient above vs. below this LAD threshold (HR:0.96, 95%CI:0.62-1.48, p = 0.85).The LAD threshold of 40 mm has the best prognostic performance among other LAD values to predict new incident AF after ESUS. The diagnostic yield of prolonged cardiac rhythm monitoring in patients with LAD ≤ 40 mm seems low; therefore, such patients may have lower priority for prolonged cardiac monitoring.

Background: The diagnosis of covert atrial fibrillation (AF) remains a major challenge to guide secondary prevention of patients with embolic stroke of undetermined source (ESUS). Aims: We analyzed consecutive ESUS patients from 3 prospective stroke registries to assess whether the presence of supraventricular extrasystoles (SVE) on standard 12-lead electrocardiogram (ECG) is associated with the detection of AF (primary outcome), stroke recurrence and death (secondary outcomes) during follow-up. Methods: We measured the number of SVEs in all available ECGs of patients hospitalized for ESUS. Multivariate stepwise regression with forward selection of covariates assessed the association between SVE (classified in 4 groups according to their number per 10 seconds of ECG: no SVE, >0-1SVEs, >1-2SVEs, and >2SVEs) and outcomes during follow-up. The Kaplan–Meier product limit method estimated the 10-year cumulative probabilities of outcomes in each SVE group. We calculated the negative prognostic value (NPV) of the presence of any SVE to predict new AF, defined as the probability that AF will not be detected during follow-up if there is no SVE. Results: Among 853 ESUS patients followed for 2857 patient-years (median age: 67 years, 43.0% women), 226 (26.5%) patients had at least 1 SVE at the standard 12-lead ECGs performed during hospitalization. AF was detected in 125 (14.7%) of patients in the overall population during follow-up: 8.9%, 22.5%, 28.1%, and 48.3% in patients with no SVE, greater than 0-1SVE, greater than 1-2SVE and greater than 2SVE respectively. In multivariate regression analysis, compared to patients with no SVEs, the corresponding hazard-ratios were 1.80 [95% confidence intervals (95%CI):1.06-3.05], 2.26 (95%CI:1.28-4.01) and 3.19 (95%CI:1.93-5.27). The NPV of the presence of any SVE for the prediction of new AF was 91.4%. There was no statistically significant association of SVE with the risk of ischemic stroke recurrence and death. Conclusions: In ESUS patients without SVEs during hospitalization, the probability that AF will not be detected during a follow-up of 3.4 years is more than 91%.

Objective:\ud It is not known whether patients with atrial fibrillation (AF) with ischemic stroke despite oral anticoagulant therapy are at increased risk for further recurrent strokes or how ongoing secondary prevention should be managed.\ud \ud Methods:\ud We conducted an individual patient data pooled analysis of 7 prospective cohort studies that recruited patients with AF and recent cerebral ischemia. We compared patients taking oral anticoagulants (vitamin K antagonists [VKA] or direct oral anticoagulants [DOAC]) prior to index event (OACprior ) with those without prior oral anticoagulation (OACnaive ). We further compared those who changed the type (ie, from VKA or DOAC, vice versa, or DOAC to DOAC) of anticoagulation (OACchanged ) with those who continued the same anticoagulation as secondary prevention (OACunchanged ). Time to recurrent acute ischemic stroke (AIS) was analyzed using multivariate competing risk Fine-Gray models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs).\ud \ud Results:\ud We included 5,413 patients (median age = 78 years [interquartile range (IQR) = 71-84 years]; 5,136 [96.7%] had ischemic stroke as the index event, median National Institutes of Health Stroke Scale on admission = 6 [IQR = 2-12]). The median CHA2 DS2 -Vasc score (congestive heart failure, hypertension, age≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65-74 years, sex category) was 5 (IQR = 4-6) and was similar for OACprior (n = 1,195) and OACnaive (n = 4,119, p = 0.103). During 6,128 patient-years of follow-up, 289 patients had AIS (4.7% per year, 95% CI = 4.2-5.3%). OACprior was associated with an increased risk of AIS (HR = 1.6, 95% CI = 1.2-2.3, p = 0.005). OACchanged (n = 307) was not associated with decreased risk of AIS (HR = 1.2, 95% CI = 0.7-2.1, p = 0.415) compared with OACunchanged (n = 585).\ud \ud Interpretation:\ud Patients with AF who have an ischemic stroke despite previous oral anticoagulation are at a higher risk for recurrent ischemic stroke despite a CHA2 DS2 -Vasc score similar to those without prior oral anticoagulation. Better prevention strategies are needed for this high-risk patient group.

Background The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. Purpose In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. Methods In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. Results A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24–2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74–2.04)). Conclusions After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.

Background and Purposes— This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods— The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00–1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08–2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P =0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30–1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632–0.763; P =0.0001) for ischemic outcome events and 0.585 (0.493–0.678; P =0.10) for major bleedings. Results— The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529–0.763; P =0.009) for ischemic outcome events and 0.407 (0.275–0.540; P =0.14) for hemorrhagic outcome events. Conclusions— In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.