Some of the patients' and carers' perspectives have not been previously reported in the stroke literature, including a desire for individualized treatment, the consideration of wider, non-physical needs and the carers' sense of burden. In addition, the study revealed how staff, carers and patients viewed each other and the service and demonstrated the concordance of their perceptions. However, staff showed little insight into the users' need for information and negative experiences of care. In contrast with previous research, lack of emotional care, poor continuity of care and lack of staff knowledge and skills were not identified as problems.

Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous longterm ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors

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 and Purpose: Cardioembolic stroke due to paroxysmal atrial fibrillation (AF) may account for 1 out of 4 cryptogenic strokes (CS) and transient ischemic attacks (TIAs). The purpose of this pilot study was to search for biomarkers potentially predicting incident AF in patients with ischemic stroke or TIA. Methods: Plasma samples were collected from patients aged 18 years and older with ischemic stroke or TIA due to AF (n = 9) and large artery atherosclerosis (LAA) with ipsilateral carotid stenosis (n = 8) and age-and sex-matched controls (n = 10). Analyses were performed with the Olink technology simultaneously measuring 184 biomarkers of cardiovascular disease. For bioinformatics, acquired data were analyzed using gene set enrichment analysis (GSEA). Selected proteins were validated using ELISA. Individual receiver operating characteristic (ROC) curves and odds ratios from logistic regression were calculated. A randomForest (RF) model with out-of-bag estimate was applied for predictive modeling. Results: GSEA indicated enrichment of proteins related to inflammatory response in the AF group. Interleukin (IL)-6, growth differentiation factor (GDF)-15, and pentraxin-related protein PTX3 were the top biomarkers on the ranked list for the AF group compared to the LAA group and the control group. ELISA validated increased expression of all tested proteins (GDF-15, PTX3, and urokinase plasminogen activator surface receptor [U-PAR]), except for IL-6. 19 proteins had the area under the ROC curve (AUC) over 0.85 including all of the proteins with significant evolution in the logistic regression. AUCs were very discriminant in distinguishing patients with and without AF (LAA and control group together). GDF-15 alone reached AUC of 0.95. Based on RF model, all selected participants in the tested group were classified correctly, and the most important protein in the model was GDF-15. Conclusions: Our results demonstrate an association between inflammation and AF and that multiple proteins alone and in combination may potentially be used as indicators of AF in CS and TIA patients. However, further studies including larger samples sizes are needed to support these findings. In the ongoing NOR-FIB study, we plan further biomarker assessments in patients with CS and TIA undergoing long-term cardiac rhythm monitoring with insertable cardiac monitors.

The etiology of approximately one third of ischemic strokes remains undetermined, resulting in their classification as cryptogenic. 1 One sixth meet the definition of embolic stroke of undetermined source (ESUS). 2 The category cryptogenic is heterogeneous and includes cases with unknown etiology, where two or more competing causes are possible, or where the investigation is incomplete. ESUS occurs in the absence of lacunar infarcts, significant stenosis in pre-and cerebral arteries, or cardiac conditions with high risk of embolism, such as atrial fibrillation. Treatment is challenging: it is unknown whether standard secondary prevention provides sufficient protection against recurrence in all cases, while an empiric strategy of routinely administered anticoagulation appears to be both harmful

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.