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Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA₂DS₂-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension ( p = 0.045) and dyslipidaemia ( p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): NOR-FIB is an investigator driven academic study. 100 of 259 devices are supported by Medtronic. BRT and ATL are recipients of a PhD grants from the South-Eastern Norway Regional Health Authority. The study is supported by the research infrastructure of the European Cerebrovascular Research Infrastructure (ECRI). Background Cardioembolism due to occult atrial fibrillation (AF) is one of the common causes often identified by additional investigations in patients with cryptogenic stroke (CS). A large proportion of recurrent cerebral infarctions caused by AF can probably be prevented if more patients receive optimal cardiac monitoring after CS and TIA. Purpose The aim of the prospective observational multi-center NOR-FIB study was to detect and quantify AF in patients with cryptogenic stroke or TIA under continuous 12 months cardiac rhythm monitoring with an implantable cardiac monitor (ICM) and to possibly identify biomarkers predicting incident AF. Methods Patients with cryptogenic stroke and TIA diagnosed after state-of-the-art work-up had their ICM implanted by a stroke physician within 14 days after symptom onset. All patients were followed clinically and by rhythm monitoring for 12 months. AF was defined by detected atrial arrhythmia episodes ≥ 2 min, and these patients were considered for a change of their secondary prevention from antiplatelet drugs to oral anticoagulants (OAC). Results A total of 259 patients with cryptogenic stroke or TIA from 18 hospitals in Norway, Sweden and Denmark were included. After 12 months follow-up 74 (28.6 %) patients were diagnosed with paroxysmal AF, of which 91.9% were asymptomatic. Patients with AF had significantly higher mean age (72.6 vs 62.2, p&lt;0.001), more severe stroke (median National Institute Stroke Scale Score on admission 2 vs 1, p 0.002) and higher pre-stroke median CHA2DS2-VASc score (3 vs 2, p&lt;0.001) than patients without AF. Both hypertension and hyperlipidemia was more common in patients with AF. In 64 (86.5%) cases AF was detected early after index stroke, i.e., within the first two months of monitoring (mean 47.7 days + 52,1). Recurrent AF episodes were detected in 68 (91.9%) cases. Of the 74 AF patients, 72 (97.3%) were switched to OAC. Recurrent strokes during follow-up occurred in 2 AF patients (2.7 %) and in 9 non-AF patients (4.9 %). Conclusion AF was detected in 29% of all cryptogenic stroke/TIA patients. Most of the patients were asymptomatic for their arrhythmia, and would have gone undiagnosed without a continuous monitoring approach. Since most of the patients with detected AF were switched to OAC, the 12 months risk of recurrent stroke in this group was low. Prolonged cardiac rhythm monitoring with ICMs is an effective tool for diagnosing underlying asymptomatic AF in a patient population typically confined to a stroke unit.

Background Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study. Method The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. Results In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7. Conclusion Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units.

Background Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. Methods Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. Results After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). Conclusion Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. Trial registration ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Background and purpose There are currently no biomarkers to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF. Methods Eligible CS and cryptogenic transient ischaemic attack patients underwent 12‐month monitoring with ICMs, clinical follow‐up and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n = 74) during monitoring and those without AF (n = 185). Receiver operating characteristic curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut‐off values and were used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models. Results B‐type natriuretic peptide (BNP), N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), creatine kinase, D‐dimer and high‐sensitivity cardiac troponin I and T were significantly higher in the AF than non‐AF group. BNP and NT‐proBNP reached the predefined area under the curve level, 0.755 and 0.725 respectively. Optimal cut‐off values were 33.5 ng/l for BNP and 87 ng/l for NT‐proBNP. Regression analysis showed that NT‐proBNP was a predictor of AF in both unadjusted (odds ratio 7.72, 95% confidence interval 3.16–18.87) and age‐ and sex‐adjusted models (odds ratio 4.82, 95% confidence interval 1.79–12.96). Conclusion Several clinically established biomarkers were associated with AF. NT‐proBNP performed best as AF predictor and could be used for selecting patients for long‐term monitoring with ICMs.

Purpose Fraction of exhaled nitric oxide (FeNO) and soluble advanced glycation end-product receptor (sRAGE) are proposed as biomarkers of asthma, therefore we sought to assess their use in asthmatic children of Jordan. Patients and Methods We conducted a case-control study at The University of Jordan Hospital. A total of 141 asthmatic children followed by respiratory pediatricians and 118 healthy children aged 4–18 years were recruited. FeNO was measured by NObreath device and serum sRAGE by ELISA that detect endogenously soluble isoform (esRAGE) and total soluble RAGE (sRAGE). Results sRAGE in asthmatic was half of the control (p <0.001). In addition, ratio of esRAGE/sRAGE was two-fold higher in asthmatic (p = <0.001). Neither FeNO nor esRAGE levels were significantly different between groups. FeNO and asthma control test (ACT) score were negatively correlated corrected for age and body mass index (BMI), (r = −0.180, p= 0.034). For the uncontrolled asthma group, esRAGE/sRAGE negatively correlated with ACT score (r = −.329, p = 0.038). Receiver operating curve (ROC) analysis revealed significant predictive value (PV) for sRAGE and esRAGE/sRAGE in asthma detection with area under the curve (AUC) of (0.751 ± 0.031) and (0.711±.033), consequently. However, no biomarker had a significant PV for lack of control. Conclusion The current study supports utilizing sRAGE as a marker for asthma and present a potential therapeutic target. However, our results indicate that both FeNO and sRAGE have a limited role in the management of asthmatic children or assessment of asthma control.