Direct oral anticoagulants in embolic stroke of undetermined source: an updated meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

The Usefulness of Outpatient Cardiac Telemetry in Patients with Cryptogenic Stroke.

Introduction: Atrial fibrillation (AF), apart from non-stenotic supracardiac atherosclerosis and neoplastic disease, is the leading cause of cryptogenic stroke, including embolic stroke of un-determined source (ESUS). The aim of our study was to determine the prevalence of AF in ESUS patients based on 30-day telemetric heart rate monitoring initiated within three months after stroke onset. Another aim was to identify factors that increase the likelihood of detecting subsequent AF among ESUS patients. Material and Methods: patients with first-ever stroke classified as per the ESUS definition were eligible for this study. All patients underwent outpatient 30-day telemetric heart rate monitoring. Results: In the period between 2020 and 2022, 145 patients were included. The mean age of all qualified patients was 54; 40% of eligible patients were female. Six patients (4.14%), mostly male patients (4 vs. 2), were diagnosed with AF within the study period. In each case, the diagnosis related to a patient whose stroke occurred in the course of large vessel occlusion. Episodes of AF were detected between day 1 and 25 after starting ECG monitoring. Out of the analyzed parameters that increase the probability of, A.F.; only supraventricular extrasystoles proved to be an independent factor regarding an increased risk of AF [OR 1.046, CI 95% 1.016-1.071, p-value < 0.01]. Conclusions: The use of telemetry heart rhythm monitoring in an outpatient setting can detect AF in 4% of ESUS patients who have undergone prior diagnostic procedures for cardiogenic embolism. Supraventricular extrasystoles significantly increases the likelihood of AF detection in patients with ESUS within three months following stroke. Comorbid coronary artery disease, diabetes and hypertension, rather than a single-factor clinical burden, increase the likelihood of AF detection in older ESUS patients. ESUS in the course of large vessel occlusion is probably associated with an increased likelihood of cardiogenic embolism.

Tumor Embolic Stroke: The Importance of Pathological Assessment of Clots after Thrombectomy.

While tumor emboli are a rare cause of stroke in cancer patients, they highlight the importance of gross observations and pathological assessments in the evaluation of clots. In this case report, a 70-year-old male with type 2 diabetes mellitus and coronary artery disease presented with acute left-sided weakness. He was clinically diagnosed with stroke and given alteplase at 1.5 h from last known normal. He then underwent CT angiography that showed right internal carotid artery occlusion and immediate thrombectomy. The recovered clot was white and lipid-like; due to its atypical appearance, it was sent for pathological assessment, where it was shown to bear features of malignancy. Subsequent imaging identified masses indicating malignancy in the left gluteus, right pleural hilum, and spine. Tumor embolic stroke is a rare pathology. Embolic diseases such as strokes and pulmonary embolisms are common in patients with cancer. Embolic stroke of undetermined source (ESUS) represents a significant portion of cancer strokes. Tumor emboli, though rare, may be an underappreciated source of ESUS in cancer patients. We intend for this case to demonstrate the value of pathological assessment for atypical thrombi as well as highlight the etiology of tumor embolic strokes.

Bleeding Risk Prediction in Patients Treated with Antithrombotic Drugs According to the Anatomic Site of Bleeding, Indication for Treatment, and Time Since Treatment Initiation.

Background Reasons for the relatively poor performance of bleeding prediction models are not well understood but may relate to differences in predictors for various anatomical sites of bleeding. Methods We pooled individual participant data from four randomized controlled trials of antithrombotic therapy in patients with coronary and peripheral artery diseases, embolic stroke of undetermined source (ESUS), or atrial fibrillation. We examined discrimination and calibration of models for any major bleeding, major gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH), according to the time since initiation of antithrombotic therapy, and indication for antithrombotic therapy. Results Of 57,813 patients included, 1,948 (3.37%) experienced major bleeding, including 717 (1.24%) major GI bleeding and 274 (0.47%) ICH. The model derived to predict major bleeding at 1 year from any site (c-index, 0.69, 95% confidence interval [CI], 0.68-0.71) performed similarly when applied to predict major GI bleeding (0.71, 0.69-0.74), but less well to predict ICH (0.64, 0.61-0.69). Models derived to predict GI bleeding (0.75, 0.74-0.78) and ICH (0.72, 0.70-0.79) performed better than the general major bleeding model. Discrimination declined over time since the initiation of antithrombotic treatment, stabilizing at approximately 2 years for any major bleeding and major GI bleeding and 1 year for ICH. Discrimination was best for the model predicting ICH in the ESUS population (0.82, 0.78-0.92) and worst for the model predicting any major bleeding in the coronary and peripheral artery disease population (0.66, 0.65-0.69). Conclusion Performance of risk prediction models for major bleeding is affected by site of bleeding, time since initiation of antithrombotic therapy, and indication for antithrombotic therapy.

Comparison of echocardiographic and clinical characteristics in embolic stroke and migraine patients with patent foramen ovale.

BACKGROUND: This single-center observational study aimed to compare the echocardiographic and clinical features in patients diagnosed with migraine and embolic stroke of undetermined source (ESUS) who presented with a known patent foramen ovale (PFO). METHODS: Two-dimensional and color Doppler images were obtained using various transthoracic echocardiography views for both migraine and ESUS patients. Suspected PFO cases underwent further assessment through contrast echocardiography and transesophageal echocardiography (TEE). High-risk PFO characteristics were evaluated using TEE, and the Risk of Paradoxical Embolism (RoPe) score was calculated. RESULTS: The study included 310 participants (age range: 18-60, 73.2% female), with 43.5% diagnosed with migraine and 56.5% with ESUS. Common comorbidities included diabetes (26.1%). High-velocity shunting through the interatrial septum was observed in 35.5% of patients. ESUS patients were older, with higher rates of diabetes and hypertension, while active smoking was more prevalent among migraine patients. Basic echocardiographic parameters were mostly similar, except for elevated pulmonary artery systolic pressure in ESUS. ESUS patients exhibited a greater occurrence of large microbubble passage through the interatrial septum and longer PFO lengths compared to migraine patients. However, the RoPe and High-risk PFO scores were similar between the groups. CONCLUSIONS: ESUS patients, characterized by older age and higher rates of diabetes and hypertension, demonstrated increased pulmonary artery pressure, more significant microbubble crossings, and longer PFO lengths. Conversely, migraine patients had a higher prevalence of active smoking. Despite differing clinical profiles, the risk scores for PFO-related embolic events were comparable between the groups. These findings underscore potential distinctions between ESUS and migraine patients with PFO and their implications for management strategies.

Left atrial strain, embolic stroke of undetermined source, and atrial fibrillation detection.

BACKGROUND: Atrial cardiopathy is a proposed mechanism of embolic stroke of undetermined source (ESUS). Left atrial (LA) strain may identify early atrial cardiopathy prior to structural changes. We aim to study the associations between LA strain, ESUS, and atrial fibrillation (AF) detection in ESUS. METHODS: The study population included patients with ESUS and noncardioembolic (NCE) stroke presenting to the Rhode Island Hospital Stroke Center between January 2016 and June 2017 who underwent transthoracic echocardiography. Speckle tracking echocardiography (STE) was used to measure the three phases of LA strain (reservoir, conduit, and contractile). Binary logistic regression analysis was performed to determine the associations between LA strain and stroke subtype (ESUS vs. NCE) as well as follow-up detection of AF in ESUS patients. RESULTS: We identified 656 patients, 307 with ESUS and 349 with NCE. In binary logistic regression, the lowest tertiles of LA reservoir (adjusted OR 1.944, 95% CI 1.266-2.986, p = .002), contractile (aOR 1.568, 95% CI 1.035-2.374, p = .034), and conduit strain (aOR 2.288, 95% CI 1.448-3.613, p = .001) were more likely to be significantly associated with ESUS compared to NCE stroke. Among all ESUS patients, the lowest tertiles of LA reservoir strain (OR 2.534, 95% CI 1.029-6.236, p = .043), contractile strain (OR 2.828, 95% CI 1.158-6.903, p = .022), and conduit strain (OR 2.614, 95% CI 1.003-6.815, p = .049) were significantly associated with subsequent detection of AF. CONCLUSION: Reduced LA strain is associated with ESUS occurrence and AF detection in ESUS patients. Therefore, quantification of LA strain in ESUS patients may improve risk stratification and guide secondary prevention strategies.

Cardiac Blood-Based Biomarkers of Myocardial Stress as Predictors of Atrial Fibrillation Development in Patients With Embolic Stroke of Undetermined Source/Cryptogenic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Undiagnosed atrial fibrillation (AF) is a major risk factor for stroke that can go unnoticed in individuals with embolic stroke of undetermined source (ESUS) or cryptogenic stroke (CS). Early detection is critical for stroke prognosis and secondary prevention. This study aimed to determine if blood biomarkers of myocardial stress can accurately predict AF in patients with ESUS/CS, which would allow the identification of those who would benefit from closer monitoring. METHODS: In February 2023 we performed a systematic date-unrestricted search of three databases for studies on patients with ESUS/CS who were subsequently diagnosed with AF. We examined the relationships between AF and serum myocardial stress markers such as brain natriuretic peptide (BNP), N-terminal-pro-BNP (NT-proBNP), midregional proatrial natriuretic peptide, and troponin. RESULTS: Among the 1,527 studies reviewed, 23 eligible studies involving 6,212 participants, including 864 with AF, were analyzed. A meta-analysis of 9 studies indicated that they demonstrated a clear association between higher NT-proBNP levels and an increased risk of AF, with adjusted and raw data indicating 3.06- and 9.03-fold higher AF risks, respectively. Lower NT-proBNP levels had a pooled negative predictive value of 91.7%, indicating the potential to rule out AF with an 8% false-negative rate. CONCLUSIONS: Further research is required to fully determine the potential of biomarkers for AF detection after stroke, as results from previous studies lack homogeneity. However, lower NT-proBNP levels have potential in ruling out AF in patients with ESUS/CS. Combining them with other relevant biomarkers may enhance the precision of identifying patients who will not benefit from extended monitoring, which would optimize resource allocation and patient care.

Chronic ischemic lesions and presence of patent foramen ovale in young adults with embolic stroke of undetermined source: Results of the young ESUS patient registry.

BACKGROUND: Chronic ischemic lesions (CILs) are frequent findings in patients with acute ischemic stroke, but their phenotypes and relevance in young adults with embolic stroke of undetermined source (Y-ESUS) remains uncertain. We aimed to compare Y-ESUS patients with CIL to those without CIL and assessed the association of CIL and its phenotypes with the presence of patent foramen ovale (PFO). METHODS: This prospective longitudinal, multicenter cohort study enrolled consecutive patients 50 years and younger with ESUS from October 2017 to October 2019 in 41 stroke research centers in 13 countries. Local investigators adjudicated presence and phenotypes of CIL on routine brain imaging (either magnetic resonance imaging (MRI) or computed tomography (CT)). RESULTS: Overall, 535 patients were enrolled (mean age = 40.4 (standard deviation (SD) = 7.3) years, 238 (44%) female). CILs were present in 76/534 (14.2%) patients with a median count CIL count of 1.0 (interquartile range (IQR) = 1-2), 42/76 (55%) had at least one cortical phenotype and 38/76 (50%) at least one non-cortical phenotype. Y-ESUS with CIL were less often female (32% vs 47% in non-CIL Y-ESUS), were older (mean 43 vs 40 years), had more often hypertension (42% vs 19%), diabetes (17% vs 7%), and hyperlipidemia (34% vs 18%). CIL Y-ESUS were independently associated with lower stroke recurrence (relative risk (RR) = 0.17 (0.05-0.61)). In Y-ESUS with PFO, CILs were less frequent in probable pathogenic PFO than with probable non-pathogenic PFO (6.1% vs 30% p< 0.001). CONCLUSION: One in seven Y-ESUS patients has additional CIL. CILs were associated with several vascular risk factors, lower probability of a pathogenic PFO, and lower stroke recurrence.

Effectiveness of statins on outcomes of patients with Embolic Stroke of Undetermined Source (ESUS).

BACKGROUND: Statins are highly recommended as a secondary prevention strategy after a stroke. Embolic Stroke of Undetermined Source (ESUS) accounts for up to one fifth of cases of ischemic stroke. There is a lack of studies investigating the effectiveness of statins in this subgroup of patients. METHODS: We designed a longitudinal cohort study involving patients properly diagnosed with ESUS. Data about statin therapy included information about the time of initiation of the treatment, pre-stroke statin use, statin withdrawal, and the type and dosage of the statin prescribed. Patients were followed for 48 months after the index stroke. The primary endpoints included stroke recurrence, major cardiovascular events, and death from all causes. The secondary endpoint was the functional outcome, assessed in a standardized and systematic way using the modified Rankin Scale (mRS). RESULTS: Patients who were not taking any statin after ESUS have significantly increased odds of stroke recurrence (OR = 3.29, 95% CI 1.27 - 8.55) or presenting the composite outcome of stroke recurrence, major cardiovascular events, and death (OR = 3.70, 95% CI 1.44 - 9.50) in the multivariate analysis. No statin therapy was directly associated with the functional outcome as well (OR = 3.32, 95% CI = 1.58 - 6.96). The early initiation of the statin therapy was estimated to reduce the risk of a second stroke and the composite outcome by 89% and 87%. CONCLUSIONS: Our pioneering study provides evidence that patients with ESUS may benefit from statin therapy, especially if prescribed early and at higher dosages.

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.

Independent external validation of a stroke recurrence score in patients with embolic stroke of undetermined source.

BACKGROUND: Embolic stroke of undetermined source (ESUS) accounts for a substantial proportion of ischaemic strokes. A stroke recurrence score has been shown to predict the risk of recurrent stroke in patients with ESUS based on a combination of clinical and imaging features. This study aimed to externally validate the performance of the ESUS recurrence score using data from a randomized controlled trial. METHODS: The validation dataset consisted of eligible stroke patients with available magnetic resonance imaging (MRI) data enrolled in the PreDAFIS sub-study of the MonDAFIS study. The score was calculated using three variables: age (1 point per decade after 35 years), presence of white matter hyperintensities (2 points), and multiterritorial ischaemic stroke (3 points). Patients were assigned to risk groups as described in the original publication. The model was evaluated using standard discrimination and calibration methods. RESULTS: Of the 1054 patients, 241 (22.9%) were classified as ESUS. Owing to insufficient MRI quality, three patients were excluded, leaving 238 patients (median age 65.5 years [IQR 20.75], 39% female) for analysis. Of these, 30 (13%) patients experienced recurrent ischaemic stroke or transient ischemic attack (TIA) during a follow-up period of 383 patient-years, corresponding to an incidence rate of 7.8 per 100 patient-years (95% CI 5.3-11.2). Patients with an ESUS recurrence score value of ≥ 7 had a 2.46 (hazard ratio (HR), 95% CI 1.02-5.93) times higher risk of stroke recurrence than patients with a score of 0-4. The cumulative probability of stroke recurrence in the low-(0-4), intermediate-(5-6), and high-risk group (≥ 7) was 9%, 13%, and 23%, respectively (log-rank test, χ2 = 4.2, p = 0.1). CONCLUSIONS: This external validation of a published scoring system supports a threshold of ≥ 7 for identifying ESUS patients at high-risk of stroke recurrence. However, further adjustments may be required to improve the model's performance in independent cohorts. The use of risk scores may be helpful in guiding extended diagnostics and further trials on secondary prevention in patients with ESUS. TRIAL REGISTRATION: Clinical Trials, NCT02204267. Registered 30 July 2014, https://clinicaltrials.gov/ct2/show/NCT02204267 .

Predictors of Atrial Fibrillation in Patients with Embolic Stroke of Unknown Etiology and Implantable Loop Recorders-Further Insights of the TRACK AF Study on the Role of ECG and Echocardiography.

Aims-Electrocardiography (ECG) and echocardiographic left atrial (LA) parameters may be helpful to assess the risk of atrial fibrillation (AF) in embolic stroke of unknown etiology (ESUS) and could therefore guide intensity of ECG monitoring. Methods-1153 consecutive patients with ischemic stroke or transient ischemic attack (TIA) were analyzed. An internal loop recorder (ILR) was implanted in 104 consecutive patients with ESUS. Multiple morphologic P-wave parameters in baseline 12-channel ECG and echocardiographic LA parameters were measured and analyzed in patients with and without ILR-detected AF. Using logistic regression, we evaluated the predictive value of several ECG parameters and LA dimensions on the occurrence of AF. Results-In 20 of 104 (19%) patients, AF was diagnosed by ILR during a mean monitoring time of 575 (IQR 470-580) days. Patients with AF were significantly older (72 (67-75) vs. 60 (52-72) years; p = 0.001) and premature atrial contractions (PAC) were more frequently observed (40% vs. 2%; p < 0.001) during baseline ECG. All morphologic P-wave parameters did not show a significant difference between groups. There was a non-significant trend towards a larger LA volume index (31 (24-36) vs. 29 (25-37) mL/m2; p = 0.09) in AF patients. Conclusions-Age and PAC are independently associated with incident AF in ESUS and could be used as markers for selecting patients that may benefit from more extensive rhythm monitoring or ILR implantation. In our consecutive cohort of patients with ESUS, neither morphological P-wave parameters nor LA size were predictive of AF.

Prevalence of high-risk aortic arch atherosclerosis features on computed tomography angiography in embolic stroke of undetermined source.

INTRODUCTION: Embolic stroke of undetermined source (ESUS) comprises a heterogenous group. There is a need to further identify etiologies within this group to guide management strategies. We examined the prevalence of aortic arch atherosclerosis (AAA) on CT angiography (CTA) in patients with embolic stroke of undetermined source (ESUS) to characterize high-risk plaque features. METHODS: All patients from two prospective multicenter acute ischemic stroke studies (INTERRSeCT and PRove-IT) were included if the CTA adequately imaged the proximal aortic arch and the stroke etiology was recorded. Three readers blinded to stroke etiology analyzed the following AAA plaque features on baseline CTA at the time of stroke: 1) thickness in millimetres (mm); 2) morphology (none, smooth, ulcerated, or protruding); 3) location within the aortic arch (proximal, transverse, or distal); and 4) calcification (none, single small, multiple small, single large, or diffuse extensive). RESULTS: We included 1063 patients, of which 293 (27.6%) had ESUS (mean age 67.5 years; 46.4% men; median NIHSS 12; 80.6% large vessel occlusion). Mean AAA thickness was significantly larger in ESUS patients (3.8 mm) compared to non-ESUS patients (3.0 mm; p<0.0001) and to a subgroup of patients with large artery atherosclerosis (2.9 mm; p=0.003). ESUS patients had a significantly higher proportion of ulcerated or protruding plaques (17.4% vs 10.3%; risk ratio 1.7, 95% C.I. 1.2-2.4, p=0.002). The location of AAA in the ESUS group was the ascending aorta in 37.9%, transverse arch in 42.3%, and descending aorta in 84.6%. Although AAA was mostly located in the distal aortic arch, ulcerated or protruding plaques were least common in the distal arch (p=0.002). There was no difference between ESUS and non-ESUS patients in plaque location (p=0.23) or calcification grade (p=0.092). CONCLUSION: ESUS patients in our study had thicker AAA and a higher prevalence of ulcerated or protruding plaques located more proximally within the aortic arch. High-risk plaque features may suggest a causal role of AAA in the ESUS population with visible intracranial occlusions.

Risk Stratification Tools to Guide a Personalized Approach for Cardiac Monitoring in Embolic Stroke of Undetermined Source.

Current recommendations support a personalized sequential approach for cardiac rhythm monitoring to detect atrial fibrillation after embolic stroke of undetermined source. Several risk stratification scores have been proposed to predict the likelihood of atrial fibrillation after embolic stroke of undetermined source. This systematic review aimed to provide a comprehensive overview of the field by identifying risk scores proposed for this purpose, assessing their characteristics and the cohorts in which they were developed and validated, and scrutinizing their predictive performance. We identified 11 risk scores, of which 4 were externally validated. The most frequent variables included were echocardiographic markers and demographics. The areas under the curve ranged between 0.70 and 0.94. The 3 scores with the highest area under the curve were the Decryptoring (0.94 [95% CI, 0.88-1.00]), newly diagnosed atrial fibrillation (0.87 [95% CI, 0.79-0.94]), and AF-ESUS (Atrial Fibrillation in Embolic Stroke of Undetermined Source) (0.85 [95% CI, 0.80-0.87]), of which only the latter was externally validated. Risk stratification scores can guide a personalized approach for cardiac rhythm monitoring after embolic stroke of undetermined source.

Predicting risk of AF in ischaemic stroke using sinus rhythm ECG abnormalities: A meta-analysis.

OBJECTIVE: To identify ECG changes in sinus rhythm that may be used to predict subsequent development of new AF. METHOD: We identified prospective and retrospective cohort or case control studies evaluating ECG patterns from a 12-lead ECG in sinus rhythm taken in hospital or community predicting subsequent development of new AF. For each identified ECG predictor, we then identify absolute event rates and pooled risk ratios (RR) using an aggregate level random effects meta-analysis. RESULTS: We identified 609,496 patients from 22 studies. ECG patterns included P wave terminal force V1 (PTFV1), interatrial block (IAB) and advanced interatrial block (aIAB), abnormal P wave axis (aPWA), PR prolongation and atrial premature complexes (APCs). Pooled risk ratios reached significance for each of these; PTFV1 RR 1.48 (95% CI 1.04-2.10), IAB 2.54 (95% CI 1.64-3.93), aIAB 4.05 (95% CI 2.64-6.22), aPWA 1.89 (95% CI 1.25-2.85), PR prolongation 2.22 (95% CI 1.27-3.87) and APCs 3.71 (95% CI 2.23-6.16). Diabetes reduced the predictive value of PR prolongation. CONCLUSION: APC and aIAB were most predictive of AF, while IAB, PR prolongation, PTFV1 and aPWA were also significantly associated with development of AF. These support their use in a screening tool to identify at risk cohorts who may benefit from further investigation, or following stroke, with empirical anticoagulation.