The Danish Atrial Fibrillation Registry: A Multidisciplinary National Pragmatic Initiative for Monitoring and Supporting Quality of Care Based on Data Retrieved from Administrative Registries.

Aim: The Danish Atrial Fibrillation (AF) Registry monitors and supports improvement of quality of care for all AF patients in Denmark. This report describes the registry's administrative and organizational structure, data sources, data flow, data analyses, annual reporting, and feedback between the registry, clinicians, and the administrative system. We also report the selection process of the quality indicators and the temporal trends in results from 2017-2021. Methods and Results: The Danish AF Registry aims for complete registration and monitoring of care for all patients diagnosed with AF in Denmark. Administrative registries provide data on contacts to general practice, contacts to private cardiology practice, hospital contacts, medication prescriptions, updated vital status information, and biochemical test results. The Danish Stroke Registry provides information on stroke events. From 2017 to 2021, the proportion with a reported echocardiography among incident AF patients increased from 39.9% (95% CI: 39.3-40.6) to 82.6% (95% CI: 82.1-83.1). The initiation of oral anticoagulant therapy among patients with incident AF and a CHA2DS2-VASc score of ≥1 in men and ≥2 in women increased from 85.3% (95% CI: 84.6-85.9) to 90.4% (95% CI: 89.9-91.0). The 1-year and 2-year persistence increased from 85.2% (95% CI: 84.5-85.9) to 88.7% (95% CI: 88.0-89.3), and from 85.4% (95% CI: 84.7-86.2) to 88.2% (95% CI: 87.5-88.8), respectively. The 1-year risk of ischemic stroke among prevalent patients with AF decreased from 0.88% (95% CI: 0.83-0.93) to 0.71% (95% CI: 0.66-0.75). Variation in clinical performance between the five administrative Danish regions was reduced. Conclusion: Continuous nationwide monitoring of quality indicators for AF originating from administrative registries is feasible and supportive of improvements of quality of care.

Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P=0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes (P=0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes (P=0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03542188.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

Management and Prognosis of Acute Stroke in Atrial Fibrillation.

Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases the risk of systemic bleeding, including intracerebral hemorrhage (ICH). AF-related strokes are associated with greater disability and mortality compared to non-AF strokes. The management of patients with AF-related strokes is challenging, and it involves weighing individual risks and benefits in the acute treatment and preventive strategies of these patients. This review summarizes the current knowledge of the acute management of ischemic and hemorrhagic stroke in patients with AF, and the prognosis and potential implications for management both in the acute and long-term setting.

Stressed systems: Stroke unit bed occupancy and impact on reperfusion therapy in acute ischemic stroke.

Objectives: We observed a decrease in the number of patients who were offered reperfusion therapy. We aimed to investigate if whether hospital system pressure measured as the percentage of stroke bed occupancy influenced decisions on treatment and disposition. Design: Data from a regional quality of stroke care database were obtained and linked to the organizational data monitoring of the hourly inpatient stroke bed occupancy rate. Logistic regression was used to analyze the relationship. Results: A total of 15,025 admissions were included from 1 January 2019 to 24 August 2022. Of these, 5,659 (38%) had an acute ischemic stroke. The rates of reperfusion therapy treatment were the highest in 2019 (36.2%) and 2020 (34.1%) and declined afterward (30.0% in 2021). In the logistic regression analysis, an occupancy rate of ≥85% in the hour of the first admission was associated with reduced odds of admission at the stroke unit within 3 h from the symptom onset [adjusted odds ratio: 0.80, 95% confidence interval: (0.71-0.90), p < 0.001] and a reduced odds of receiving reperfusion therapy (adjusted odds ratio: 0.83 (0.73-0.95), p = 0.007). Conclusion: An increased bed occupancy level in the hour of the first hospital admission for stroke patients was strongly associated with decreased odds of receiving reperfusion therapy.

Quality in stroke care during the early phases of the COVID-19 pandemic: A nationwide study.

Introduction: Evidence-based early stroke care as reflected by fulfillment of process performance measures, is strongly related to better patient outcomes after stroke and transient ischemic attack (TIA). Detailed data on the resilience of stroke care services during the COVID-19 pandemic are limited. We aimed to examine the quality of early stroke care at Danish hospitals during the early phases of the COVID-19 pandemic. Materials and methods: We extracted data from Danish national health registries in five time periods (11 March, 2020-27 January, 2021) and compared these to a baseline pre-pandemic period (13 March, 2019-10 March, 2020). Quality of early stroke care was assessed as fulfilment of individual process performance measures and as a composite measure (opportunity-based score). Results: A total of 23,054 patients were admitted with stroke and 8153 with a TIA diagnosis in the entire period. On a national level, the opportunity-based score (95% confidence interval [CI]) at baseline for ischemic patients was 81.1% (80.8-81.4), for intracerebral hemorrhage (ICH) 85.5% (84.3-86.6), and for TIA 96.0% (95.3-96.1). An increase of 1.1% (0.1-2.2) and 1.5% (0.3-2.7) in the opportunity-based score was observed during the first national lockdown period for AIS and TIA followed by a decline of -1.3% (-2.2 to -0.4) in the gradual reopening phase for AIS indicators. We found a significant negative association between regional incidence rates and quality-of-care in ischemic stroke patients implying that quality decreases when admission rates increase. Conclusion: The quality of acute stroke/TIA care in Denmark remained high during the early phases of the pandemic and only minor fluctuations occurred.

Is the socioeconomic inequality in stroke prognosis changing over time and does quality of care play a role?

Introduction: In a publicly financed healthcare system we aimed to study the development in socioeconomic disparity in ischemic stroke outcomes over time. In addition, we study whether the healthcare system affects these outcomes through the quality of early stroke care when adjustments are made for various patient characteristics incl. comorbidity and stroke severity. Patients and methods: Using nationwide, detailed individual-level register-data we analysed how income-related and education-related inequality in 30-day mortality and 30-day readmission risk developed between 2003 and 2018. In addition, focusing on income-related inequality, we applied mediation analyses to estimate the mediating role of quality of acute stroke care on 30-day mortality and 30-day readmission. Results: A total of 97,779 individual ischemic stroke patients were registered in Denmark with a first ever stroke in the study period. Three-point-seven percent died within 30 days of their index-admission and 11.5% were readmitted within 30 days of discharge. The income-related inequality in mortality remained virtually unchanged over time from an RR of 0.53 (95% CI: 0.38; 0.74) in 2003-06 to RR 0.69 (95% CI: 0.53; 0.89)) in 2015-18 when high income was compared to low income (Family income-time interaction: RR 1.00 (95% CI: 0.98-1.03)). A similar but less uniform trend was found for the education-related inequality in mortality (Education-time interaction: RR 1.00 (95% CI: 0.97-1.04)). The income-related disparity in 30-day readmission was smaller than in 30-day mortality and it diminished over time from 0.70 (95% CI: 0.58; 0.83) to 0.97 (95% CI: 0.87; 1.10). The mediation analysis showed no systematic mediating effect of quality of care on neither mortality nor readmission. However, it cannot be ruled out that residual confounding may have washed out some mediating effects. Discussion and Conclusion: The socioeconomic inequality in stroke mortality and re-admission risk has yet to be eliminated. Additional studies from different settings are warranted in order to clarify the impact of socioeconomic inequality of quality of acute stroke care.

Clinical outcomes of left atrial appendage occlusion versus direct oral anticoagulation in patients with atrial fibrillation and prior ischemic stroke: A propensity-score matched study.

BACKGROUND: This propensity-score matched study investigated clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulation (DOAC) in patients with AF and prior ischemic stroke. METHODS: AF patients enrolled in the Amulet Observational Study with a history of ischemic stroke and successful LAAO (n = 299) were compared with a propensity-score matched cohort of incident AF patients with prior ischemic stroke and treated by DOAC (n = 301). The control cohort was identified through the Danish National Patient Registries. Propensity score matching was based on covariates of the CHA2DS2-VASc and HAS-BLED scores, with a 1:2 ratio and using Greedy 5:1 digit matching with replacement. The analysis included 2-years follow-up, with a primary composite outcome of ischemic stroke, major bleeding (BARC ≥ 3) or all-cause mortality. RESULTS: Mean (SD) CHA2DS2-VASc scores were 5.26 (1.42) and 5.40 (1.31) and HAS-BLED scores were 3.95 (0.91) and 4.03 (0.96), for the LAAO and DOAC group, respectively. Total number of primary composite outcome events were 61 (12.4 events/100 patient-years) and 117 (26.9 events/100 patient-years) in the LAAO and DOAC group, respectively. Risk of the primary composite outcome was significantly lower in the LAAO group, hazard rate ratio [HR] 0.48 (95% CI: 0.35-0.65). Ischemic stroke risk was comparable, HR 0.71 (95% CI: 0.34-1.45), while risk of major bleeding, HR 0.41 (95% CI: 0.25-0.67), and all-cause mortality, HR 0.48 (95% CI: 0.32-0.71), were significantly lower with LAAO. Cardiovascular mortality did not differ statistically between the LAAO and DOAC group, HR 0.75 (95% CI: 0.39-1.42). Results were consistent across sensitivity analyses. CONCLUSION: This study indicated significantly lower risk of the composite outcome of stroke, major bleeding and all-cause mortality with LAAO therapy compared to DOAC, in patients with AF and prior stroke. The stroke prevention effectiveness appeared similar, with a significantly lower risk of major bleeding events with LAAO. The suggested clinical benefit of LAAO over DOAC require confirmation in the ongoing randomized OCCLUSION-AF trial.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial.

BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. OBJECTIVE: The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). METHODS AND ANALYSIS: Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. CONCLUSIONS: The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.

Frequency and Patterns of Brain Infarction in Patients With Embolic Stroke of Undetermined Source: NAVIGATE ESUS Trial.

BACKGROUND AND PURPOSE: The spectrum of brain infarction in patients with embolic stroke of undetermined source (ESUS) has not been well characterized. Our objective was to define the frequency and pattern of brain infarcts detected by magnetic resonance imaging (MRI) among patients with recent ESUS participating in a clinical trial. METHODS: In the NAVIGATE ESUS trial (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source), an MRI substudy was carried out at 87 sites in 15 countries. Participants underwent an MRI using a specified protocol near randomization. Images were interpreted centrally by those unaware of clinical characteristics. RESULTS: Among the 918 substudy cohort participants, the mean age was 67 years and 60% were men with a median (interquartile range) of 64 (26-115) days between the qualifying ischemic stroke and MRI. On MRI, 855 (93%) had recent or chronic brain infarcts that were multiple in 646 (70%) and involved multiple arterial territories in 62% (401/646). Multiple brain infarcts were present in 68% (510/755) of those without a history of stroke or transient ischemic attack before the qualifying ESUS. Prior stroke/transient ischemic attack (P<0.001), modified Rankin Scale score >0 (P<0.001), and current tobacco use (P=0.01) were associated with multiple infarcts. Topographically, large and/or cortical infarcts were present in 89% (757/855) of patients with infarcts, while in 11% (98/855) infarcts were exclusively small and subcortical. Among those with multiple large and/or cortical infarcts, 57% (251/437) had one or more involving a different vascular territory from the qualifying ESUS. CONCLUSIONS: Most patients with ESUS, including those without prior clinical stroke or transient ischemic attack, had multiple large and/or cortical brain infarcts detected by MRI, reflecting a substantial burden of clinical stroke and covert brain infarction. Infarcts most frequently involved multiple vascular territories. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02313909.

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy.

BACKGROUND: Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. AIMS: To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. METHODS: At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. RESULTS: Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52-1.7). CONCLUSIONS: Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide.Registration: https://www.clinicaltrials.gov. Unique identifier: NCT02313909.

Assessment of patients with a suspected cardioembolic ischemic stroke. A national consensus statement.

OBJECTIVES: Several cardiovascular, structural, and functional abnormalities have been considered as potential causes of cardioembolic ischemic strokes. Beyond atrial fibrillation, other sources of embolism clearly exist and may warrant urgent action, but they are only a minor part of the many stroke mechanisms and strokes that seem to be of embolic origin remain without a determined source. The associations between stroke and findings like atrial fibrillation, valve calcification, or heart failure are confounded by co-existing risk factors for atherosclerosis and vascular disease. In addition, a patent foramen ovale which is a common abnormality in the general population is mostly an innocent bystander in patients with ischemic stroke. For these reasons, experts from the national Danish societies of cardiology, neurology, stroke, and neuroradiology sought to develop a consensus document to provide national recommendations on how to manage patients with a suspected cardioembolic stroke. Design: Comprehensive literature search and analyses were done by a panel of experts and presented at a consensus meeting. Evidence supporting each subject was vetted by open discussion and statements were adjusted thereafter. Results: The most common sources of embolic stroke were identified, and the statement provides advise on how neurologist can identify cases that need referral, and what is expected by the cardiologist. Conclusions: A primary neurological and neuroradiological assessment is mandatory and neurovascular specialists should manage the initiation of secondary prophylactic treatment. If a cardioembolic stroke is suspected, a dedicated cardiologist experienced in the management of cardioembolism should provide a tailored clinical and echocardiographic assessment.

Clinical Outcomes Associated With Left Atrial Appendage Occlusion Versus Direct Oral Anticoagulation in Atrial Fibrillation.

OBJECTIVES: This study sought to investigate clinical outcomes associated with left atrial appendage occlusion (LAAO) versus direct oral anticoagulants (DOACs) in patients with high-risk atrial fibrillation (AF). BACKGROUND: LAAO has been shown to be noninferior to warfarin for stroke prevention in AF. However, anticoagulation with DOACs is now preferred over warfarin as thromboprophylaxis in AF. METHODS: Patients with AF enrolled in the Amulet Observational Registry (n = 1,088) who had successful LAAO with the Amplatzer Amulet device (n = 1,078) were compared with a propensity score-matched control cohort of incident AF patients (n = 1,184) treated by DOACs identified from Danish national patient registries. Propensity score matching was based on the covariates of the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65-74 years, sex category) and HAS-BLED (hypertension, abnormal renal or liver function, stroke, bleeding, labile international normalized ratio, elderly, drugs or alcohol) scores for predicting stroke and bleeding. The primary outcome was a composite of ischemic stroke, major bleeding (Bleeding Academic Research Consortium ≥3), or all-cause mortality, and follow-up was 2 years. RESULTS: AF patients treated with LAAO had a significantly lower risk of the primary composite outcome as compared with patients treated with DOACs (hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.49 to 0.67). Total events and event rates per 100 patient-years were (LAAO vs. DOACs) 256 vs. 461 and 14.5 vs. 25.7, respectively. The risk of ischemic stroke was comparable between groups (HR: 1.11; 95% CI: 0.71 to 1.75), while risk of major bleeding (HR: 0.62; 95% CI: 0.49 to 0.79) and all-cause mortality (HR: 0.53; 95% CI: 0.43 to 0.64) were significantly lower in patients treated with LAAO. CONCLUSIONS: Among high-risk AF patients, LAAO in comparison with DOACs may have similar stroke prevention efficacy but lower risk of major bleeding and mortality.

Burden of Premature Atrial Complexes and Risk of Recurrent Stroke and Death in Patients with Mild to Moderate Ischemic Stroke.

BACKGROUND: Premature atrial complexes (PACs) meet increased attention as a potential intermediary between sinus rhythm and atrial fibrillation (AF). Patients with even high numbers of PACs do not fulfill current guidelines for oral anticoagulation treatment though an associated stroke risk is suspected. OBJECTIVE: We aimed to determine whether a high number of PACs or runs of AF less than 30 seconds in 2-day continuous electrocardiogram (ECG) recording was associated with risk of recurrent ischemic stroke/transient ischemic attack (TIA) or death in a large cohort of patients with acute ischemic stroke or TIA and no prior AF. METHODS: We performed 48 hours continuous ECG recording within 1 week after ischemic stroke/TIA. PACs were reported as mean number of PACs per hour. Patients were followed in Danish Stroke Registry, Danish Civil Registration System, and Danish National Patient Registry. Cox Regression analysis was used to calculate hazard ratios. RESULTS: We included 1507 patients with TIA (40%) or ischemic stroke (60%), of which 98.7% had mild to moderate strokes. Mean age was 72.9 (7.8) years, 43.4% were females. Follow-up was 2.3 (1.3) years. Hazard ratio for recurrent stroke/TIA or death did not differ between quartiles of PAC burden, nor did any of the 2 components of this composite endpoint. Nonsustained AF less than 30 seconds was not associated with higher risk of recurrent stroke/TIA or death. CONCLUSIONS: In a large cohort of patients with recent ischemic stroke or TIA, burden of PACs or nonsustained AF less than 30 seconds were not associated to higher risk of recurrent stroke/TIA or death.

Trends in preadmission oral anticoagulant use and clinical outcome in atrial fibrillation patients admitted with acute stroke in Denmark.

AIMS: Use of oral anticoagulation (OAC) therapy has increased in recent years among patients with atrial fibrillation (AF). However, it remains uncertain whether this translates into improved clinical outcomes. We aimed to examine time trends in preadmission OAC use and clinical outcomes among AF patients admitted with stroke. METHODS AND RESULTS: We used nationwide registries to perform a follow-up study of 14 999 patients with AF who were admitted with acute stroke to a Danish hospital between 2008 and 2016. The proportion of AF-related stroke was 16.1% in 2008 and 17.6% in 2016. Among patients with AF-related stroke, the overall proportion of preadmission OAC users increased from 22.6% in 2008 to 41.5% in 2016. Between 2008 and 2016, the proportion of patients with AF admitted with severe stroke declined from 32.4% to 27.4% [adjusted odds ratio (OR) = 0.78, 95% confidence interval (CI): 0.75-0.81], the median length of hospital stay (LOS) decreased from 12 to 8 days (adjusted hazard ratio of discharge = 1.32, 95% CI: 1.30-1.34) and 30-day mortality decreased from 19.2% to 13.7% (adjusted OR = 0.72, 95% CI: 0.68-0.75). CONCLUSION: The incidence of AF-related strokes remains high although preadmission use of OAC has increased substantially in recent years. Despite the proportion of OAC users almost doubled from 2008 to 2016, a sizeable proportion of AF patients is still without OAC when admitted with stroke. The increased use of OAC has been accompanied by a lower proportion of patients with severe stroke, shorter LOS, and lower mortality.

External continuous ECG versus loop recording for atrial fibrillation detection in patients who had a stroke.

BACKGROUND: Detection of atrial fibrillation (AF) in patients who had ischaemic stroke and transient ischaemic attack (IS/TIA) is recommended. We aimed to compare external loop recording (ELR) against simultaneous continuous ECG recording for AF detection in patients who had acute IS/TIA and determine sensitivity, specificity and positive predictive value of AF detection using ELR. We hypothesised ELR to detect 15% fewer patients with AF than continuous ECG recording. METHODS: In this prospective cohort study, we included 1412 patients who had acute IS/TIA without prior AF. Monitoring was 48 hours. Primary outcome was AF >30 s. Cardiologist verified AF in continuous ECG was gold standard. RESULTS: In continuous ECG, 38 (2.7%) patients had AF. ELR automatically categorised 219/1412 patients (15.5%) with AF, including 32/38 (85%) patients with AF in continuous ECG. After cardiologist adjudication of ELR recordings, AF was diagnosed in 57/219 patients, of which 32 (56%) had AF in continuous ECG. For adjudicated AF detection by ELR, sensitivity was 84%, 95% CI (69% to 94%), specificity was 98%, 95% CI (97% to 99%) and positive predictive value was 56%, 95% CI (42% to 69%). CONCLUSION: Automatic AF detection with ELR results in an AF diagnosis in more than five patients without AF for each patient with AF as verified in continuous ECG. For adjudicated AF detection by ELR, sensitivity was confirmed to 84% and specificity 98%. Automatic ELR as investigated in this study may be considered to rule out AF, but it is not suitable as a single monitoring device for AF screening in patients early after stroke. TRIAL REGISTRATION NUMBER: NCT02155907.

Effects of centralizing acute stroke services: A prospective cohort study.

OBJECTIVE: To investigate the effects of centralizing the acute stroke services in the Central Denmark Region (CDR). METHODS: The CDR (1.3 million inhabitants) centralized acute stroke care from 6 to 2 designated acute stroke units with 7-day outpatient clinics. We performed a prospective "before-and-after" cohort study comparing all strokes from the CDR with strokes in the rest of Denmark to discover underlying general trends, adopting a difference-in-differences approach. The population comprised 22,141 stroke cases hospitalized from May 2011 to April 2012 and May 2013 to April 2014. RESULTS: Centralization was associated with a significant reduction in length of acute hospital stay from a median of 5 to 2 days with a length-of-stay ratio of 0.53 (95% confidence interval 0.38-0.75, data adjusted) with no corresponding change seen in the rest of Denmark. Similarly, centralization led to a significant increase in strokes with same-day admission (mainly outpatients), whereas this remained unchanged in the rest of Denmark. We observed a significant improvement in quality of care captured in 11 process performance measures in both the CDR and the rest of Denmark. Centralization was associated with a nonsignificant increase in thrombolysis rate. We observed a slight increase in readmissions at day 30, but this was not significantly different from the general trend. Mortality at days 30 and 365 remained unchanged, as in the rest of Denmark. CONCLUSIONS: Centralizing acute stroke care in the CDR significantly reduced the length of acute hospital stay without compromising quality. Readmissions and mortality stayed comparable to the rest of Denmark.

Left atrial appendage occlusion versus standard medical care in patients with atrial fibrillation and intracerebral haemorrhage: a propensity score-matched follow-up study.

AIMS: The aim of this study was to investigate the prognosis in patients with atrial fibrillation (AF) and intracerebral haemorrhage (ICH) having a left atrial appendage occlusion (LAAO) versus patients receiving standard medical therapy. METHODS AND RESULTS: A total of 151 patients from the Nordic countries with AF and previous ICH who underwent LAAO using the AMPLATZER Cardiac Plug or the AMPLATZER AMULET were compared to a propensity score-matched group of 151 patients receiving standard medical therapy. The two groups were matched so that their risks for stroke and bleeding were similar (CHA2DS2-VASc and HAS-BLED scores). The standard care patients were identified from the Danish Stroke Registry among 787 patients with AF and ICH. The primary endpoint was a composite of all-cause mortality, ischaemic stroke and major bleeding. Patients with AF and a prior ICH treated with LAAO had a lower risk of the composite outcome as compared to patients treated with standard medical care (events/1,000 years [95% confidence interval]: 53.3 [44.3-64.1] vs. 366.7 [298.2-450.9]; hazard ratio 0.16 [0.07-0.37]). CONCLUSIONS: LAAO is suggested to be of major clinical benefit in AF patients having sustained an ICH. These results have to be confirmed in a randomised clinical trial.

Atrial fibrillation detected by external loop recording for seven days or two-day simultaneous Holter recording: A comparison in patients with ischemic stroke or transient ischemic attack.

Atrial fibrillation (AF) is the most common cardiac cause of ischemic stroke and transient ischemic attack (IS/TIA). AIM: To compare the diagnostic value of seven-day external loop recording (ELR) and two-day Holter recording for detecting AF after IS/TIA. METHODS: 191 IS/TIA patients without AF history. Endpoint was AF >30s. We started two-day Holter recording and seven-day ELR simultaneously. RESULTS: Seven-day ELR and two-day Holter recording detected the same three AF patients. ELR detected another six patients with AF adjudicated by cardiologists, four detections after Holter (3 vs. 7, p=0.125) and two false-positive detections during Holter. Seven-day ELR automatically classified 50/191 patients (26%) with AF, but only 7/50 (14%) were confirmed as AF by cardiologists. CONCLUSION: Seven-day ELR did not detect significantly more patients with AF than two-day Holter recording. 86% of patients with ELR-classified AF were false positives, indicating a poor performance of the automatic AF detection algorithm used.

Use of Antithrombotic Therapy and Long-Term Clinical Outcome Among Patients Surviving Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT among patients hospitalized with first-time intracerebral hemorrhage and examined the impact of subsequent AT use on the long-term clinical outcome. METHODS: We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were identified and followed up. We estimated the hazard ratio of all-cause death, thromboembolic events, or major bleeding according to use of AT. RESULTS: We identified 6369 patients between 2005 and 2013. Among these patients, 2978 (47%) had indication for AT, and during the follow-up, (median: 2.3 year) 1281 (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence interval, 0.43-0.82) and thromboembolic events (adjusted hazard ratio 0.58; 95% confidence interval, 0.35-0.97) and no increased risk of major bleeding (adjusted hazard ratio 0.65; 95% confidence interval, 0.41-1.02). In contrast, use of platelet inhibitors among patients with indication for platelet inhibitors was not related to statistically significantly improved clinical outcome. CONCLUSIONS: Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality and thromboembolic events and no increased risk of major bleeding.