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Importance: Understanding the temporal association between atrial fibrillation (AF) and ischemic stroke informs our understanding of the AF-stroke mechanism and treatment of paroxysmal AF., Objective: To define the temporal association between episodes of AF and stroke in patients with cardiac implantable electronic devices (CIEDs)., Design, Setting, and Participants: In this case-crossover study, data from a large national electronic health record database were linked with a single-vendor database of heart rhythm records of patients with CIEDs capable of continuous heart rhythm monitoring. Patients with CIEDs who sustained an ischemic stroke who also had 120 days of continuous remote rhythm monitoring prestroke were included. Data were collected from January 2007 to March 2017, and data were analyzed from November 2019 to June 2020., Exposure: AF for 5.5 hours or more on any given day during days 1 to 30 vs days 91 to 120 prestroke., Main Outcomes and Measures: Odds ratio for stroke comparing AF during days 1 to 30 vs 91 to 120 prestroke. This analysis was planned prior to the study., Results: From 466 635 patients included in both the Optum electronic health record and CareLink databases, 891 patients with CIEDs and ischemic stroke with continuous monitoring in the 120 days prestroke were identified. Of 891 included patients, 575 (64.5%) were male, and the median (interquartile range) age was 76 (67-82) years. The vast majority of patients with stroke had either no AF meeting the threshold duration of 5.5 hours or more in both the case and control periods (682 of 891 [76.5%]) or AF of 5.5 hours or more in both periods (143 of 891 [16.0%]). For those not meeting the 5.5-hour AF threshold in either period, there was no or very little AF throughout the 120 days prestroke. A total of 66 patients had informative, discordant arrhythmic states, with 52 having AF of 5.5 hours or more in the case period vs 14 in the control period (odds ratio [OR], 3.71; 95% CI, 2.06-6.70). Stroke risk was increased most in days 1 to 5 following an AF episode (OR, 5.00; 95% CI, 2.62-9.55). AF greater than 23 hours on a given day was associated with the clearest increase in stroke risk (OR, 5.00; 95% CI, 2.08-12.01)., Conclusions and Relevance: In this large cohort of patients with CIEDs and continuous rhythm monitoring prior to ischemic stroke, excess stroke risk above baseline was highest within 5 days of an episode of AF of 5.5 hours or more in duration and diminished rapidly thereafter. Our findings are consistent with the traditional view that AF is directly and transiently associated with ischemic stroke. These results provide support for trials of time-delimited anticoagulation for patients with infrequent multihour episodes of AF and rigorous, continuous rhythm monitoring.

Objective: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies., Methods: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective., Results: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years)., Conclusions: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.

Background Guideline recommendations for oral anticoagulation (OAC) in patients with atrial fibrillation (AF) are based on CHA 2 DS 2 -VASc score alone. Patients with cardiac implantable electronic devices provide an opportunity to assess how the interaction between AF duration and CHA 2 DS 2 -VASc score influences OAC prescription rates. Methods and Results Data from the Optum de-identified Electronic Health Record data set were linked to the Medtronic CareLink database of cardiac implantable electronic devices. An index date was assigned as the later of 6 months after device implant or 1 year after Electronic Health Record data availability. Maximum daily AF duration (no AF, 6 minutes-23.5 hours, and >23.5 hours) was assessed for 6 months before index date. OAC prescription rates were computed as a function of both AF duration and CHA 2 DS 2 -VASc score. A total of 35 779 patients with CHA 2 DS 2 -VASc scores ≥1 were identified, including 27 198 not prescribed OAC. Overall OAC prescription rate among the 12 938 patients with device-detected AF >6 minutes was 36.7% and significantly higher in those with a maximum daily AF duration >23.5 hours (45.4%) compared with those with 6 minutes to 23.5 hours (28.7%). OAC prescription rates increased monotonically with both increasing AF duration and CHA 2 DS 2 -VASc score, reaching a maximum of 67.2% for patients with AF >23.5 hours and a CHA 2 DS 2 -VASc score ≥5. Conclusions Real-world prescription of OAC increased with both increasing duration of AF and CHA 2 DS 2 -VASc score. This highlights the need for further research into the role of AF duration, stroke risk, and the need for anticoagulation in patients with devices capable of long-term AF monitoring.

Background: Device-detected atrial fibrillation (AF) is associated with increased risk of stroke; however, there are no clearly defined thresholds of AF burden at which to initiate oral anticoagulation (OAC). We sought to describe OAC prescription practice variation in response to new device-detected AF and the association with outcomes., Methods: We performed a retrospective cohort study using data from the Veterans Health Administration linked to remote monitoring data that included day-level AF burden. We included patients with cardiac implantable electronic devices and remote monitoring from 2011 to 2014, CHA 2 DS 2 -VASc score ≥2, and no prior stroke or OAC receipt in the preceding 2 years. We determined the proportion of patients prescribed OAC within 90 days after new device-detected AF across a range of AF thresholds (≥6 minutes to >24 hours) and examined site variation in OAC prescription. We used multivariable Cox proportional hazards regressions to determine the association of OAC prescription with stroke by device-detected AF burden., Results: Among 10 212 patients with cardiac implantable electronic devices, 4570 (45%), 3969 (39%), 3263 (32%), and 2469 (24%) had device-detected AF >6 minutes, >1 hour, >6 hours, and >24 hours, respectively. For device-detected AF >1 hour, 1712 patients met inclusion criteria (72±10 years; 1.5% female; CHA 2 DS 2 -VASc score 4.0±1.4; HAS-BLED score 2.6±1.1). The proportion receiving OAC varied based on device-detected AF burden (≥6 minutes: 272/2101 [13%]; >1 hour: 273/1712 [16%]; >6 hours: 263/1279 [21%]; >24 hours: 224/818 [27%]). Across 52 sites (N=1329 patients), there was substantial site-level variation in OAC prescription after device-detected AF >1 hour (median, 16%; range, 3%-67%; median odds ratio, 1.56 [95% credible interval, 1.49-1.71]). In adjusted models, OAC prescription after device-detected AF >24 hours was associated with reduced stroke risk (hazard ratio, 0.28; 95% CI, 0.10-0.81; P=0.02), although the propensity-adjusted model was significant when AF lasted at least 6 minutes., Conclusions: Among veterans with cardiac implantable electronic devices, device-detected AF is common. There is large practice variation in 90-day OAC initiation after new device-detected AF, with low rates of treatment overall, even for episodes that last >24 hours. The strongest association of OAC with reduction in stroke was observed after device-detected AF >24 hours. Randomized trials are needed to confirm these observational findings.

Background: Many patients with non-valvular atrial fibrillation (NVAF) with high risk for thromboembolic stroke and bleeding may not wish to continue long-term oral anticoagulants (OACs) to avoid bleeding complications. We aimed to investigate whether AF burden assessment by cardiovascular implantable electronic devices (CIEDs) would allow an individualised disease-guided approach for safe withdrawal of long-term OAC in high-risk patients., Methods and Results: We studied 145 patients (age 77.6 ± 10.6 years; 49.7% females) with NVAF, CHA 2 DS 2 -VASc score ≥2, HAS-BLED score ≥3, in whom CIEDs were implanted. These patients wished to stay off long-term OAC based on their previous adverse bleeding event/s or due to similar events witnessed in the family or friend circle. These patients were grouped into 'low AF burden' [n = 121 (83%)], or 'high AF burden' [n = 24 (17%)] defined as <24 hours or >24 hours cumulatively in 30 consecutive days respectively, and followed for 51.2 ± 29.8 months. All patients with 'low AF burden' were allowed to discontinue OAC, but OAC was resumed in 1 patient who experienced TIA. Bleeding events developed in 9 out of 24 (37.5%) patients with 'high AF burden' who were maintained on OAC, as compared to 3 out of 121 (2.47%) patients with 'low AF burden' who were off OAC (p <.05). There were 9 (6.2%) deaths unrelated to AF treatment approach., Conclusions: In NVAF patients, AF burden assessment by CIEDs allows an individualised disease-guided approach to safe withdrawal of long-term OAC in patients with high bleeding risk who do not wish to continue long-term anticoagulation.

Background: Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial., Study Design: STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years., Outcomes: The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms., Conclusion: This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aims: We aimed to ascertain whether an insertable cardiac monitor (ICM)-guided rhythm-control strategy and assessment of atrial fibrillation (AF) burden may allow safe withdrawal and obviate long-term use of oral anticoagulants (OACs) in AF patients at high bleeding risk., Methods and Results: We implanted ICMs in 70 patients with AF with high risk of stroke (CHADS2 ≥2, CHA2DS2-VASc score ≥2) and bleeding (HAS-BLED score ≥3) after restoration of normal sinus rhythm (NSR) for continuous rhythm monitoring and optimization of antiarrhythmic drugs (AADs) when necessary. Patients were categorized into: (i) Group A (NSR/low AF burden, <1%), (ii) Group B (moderate/variable AF burden), and (iii) Group C (high AF burden, always AF). At patients' insistence, OACs were discontinued after proper counselling only if they maintained NSR/low AF burden for ≥3 consecutive months. All patients (age 73.3 ± 11.7 years; 53% male) were followed clinically and with ICM monitoring for 23.5 ± 10.5 months for outcomes including stroke, bleeding, death, device malfunction or infection, and AADs' adverse effects. Patients in Group A (n = 43), Group B (n = 20), and Group C (n = 7) had similar CHADS2 (2.09 ± 0.65, 2.05 ± 0.51, and 2.14 ± 0.38, respectively), CHA2DS2-VASc (3.05 ± 1.05, 2.85 ± 0.99, and 2.42 ± 0.53, respectively), and HAS-BLED (3.02 ± 1.01, 3.40 ± 0.68, and 3.00 ± 0.58, respectively) scores (P > 0.05). In 53 (76%) patients (Group A = 41 and Group B = 12) who maintained NSR/low AF burden, OACs were discontinued without adverse events. Severe bleeding occurred in 4 of 17 (24%) patients who remained on OACs., Conclusion: In AF patients with high bleeding risk, ICM-guided rhythm control with AADs and assessment of AF burden may allow safe discontinuation of OACs., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

The term "silent" atrial fibrillation (AF) has recently re-emerged to describe atrial arrhythmias that are detected by implanted cardiac devices but would generally go undetected in the clinical setting. The precise role that silent AF plays in increasing the risk of ischemic stroke is not fully understood. The purpose of this article is to: (1) review the current evidence demonstrating that silent AF is associated with thromboembolic events; (2) describe the temporal proximity of silent AF episodes to thromboembolic events; (3) present data on the incidence of newly detected silent AF in patients without a previous history of AF; and (4) provide an overview of ongoing and new clinical studies on this important topic. The current evidence suggests that the prevalence of silent AF is considerable among patients with implanted devices, and that the presence of silent AF increases the risk of thromboembolism. The AF burden threshold which confers this increased thromboembolism risk is not precisely defined, but might be as brief as several minutes to several hours. The advent of novel oral anticoagulation medications, which offer the promise of improved efficacy along with superior safety profiles, might warrant more aggressive identification of patients who might benefit from these therapies. However, to find high risk patients who have brief episodes of silent AF will likely require new methods of monitoring to permit the detection of this elusive but potentially dangerous arrhythmia., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: In patients with cardiac implanted electronic devices, detection of new atrial fibrillation (AF) is associated with an increased risk of stroke.Objective: To characterize daily AF burden at first detection and the rate of temporal transition to higher device-detected AF burden.Methods: A pooled analysis of data from 3 prospective projects was analyzed, and 6580 patients (mean age 68 ± 12 years, 72% male) with no history of AF and no use of anticoagulants at baseline were identified. Various thresholds of daily AF burden (5 minutes and 1, 6, 12, and 23 hours) were analyzed.Results: Among the study population of 6580 patients, a new AF, with an AF burden of ≥5 minutes, was detected in 2244 patients (34%) during a follow-up period of 2.4 ± 1.7 years. Among these patients, 1091 (49.8%) transitioned to a higher AF-burden threshold during follow-up. A higher duration of daily AF burden manifest at first detection and CHADS2 score ≥2 were associated with faster transition to a subsequent higher burden. Approximately 24% of patients transitioned from a lower threshold to a daily AF burden of ≥23 hours during follow-up.Conclusion: More than one-third of patients with no history of AF developed device-detected AF, with attainment of different thresholds of daily AF burden over time. Continuous long-term monitoring, especially when the initial detection corresponds to a higher daily AF burden and the CHADS2 score is ≥2, could support timely clinical decisions on anticoagulation by capturing transitions to higher AF-burden thresholds. [ABSTRACT FROM AUTHOR]

Background: The risk of recurrence after an initial ischemic stroke or transient ischemic attack (TIA) may be impacted by undiagnosed atrial fibrillation (AF). We therefore assessed the impact of AF diagnosis and timing on stroke/TIA recurrence rates in a large real-world sample of patients.Methods and Results: Using commercial claims data (Truven Health Analytics MarketScan), we performed a retrospective cohort study of patients with an index stroke or TIA event recorded in years 2008 through 2011. Patients were characterized by baseline oral anticoagulation, CHADS2 and CHA2DS2-VASc scores, AF diagnosis and timing with respect to the index stroke, and presence or absence of post-index ambulatory cardiac monitoring. The primary outcome was the recurrence of an ischemic stroke or TIA. Of 179 160 patients (age 67±16.2 years; 53.7% female), the Kaplan-Meier estimate for stroke/TIA recurrence within 1 year was 10.6%. Not having oral anticoagulation prescribed at baseline and having AF first diagnosed >7 days post-stroke (late AF) was highly associated with recurrent stroke/TIA (hazard ratio, 2.0; 95% confidence interval, 1.9-2.1). Among patients with at least 1 year of follow-up, only 2.6% and 9.7% had ambulatory ECG monitoring in the 7 days and 12 months post-stroke, respectively.Conclusions: AF diagnosed after stroke is an important hallmark of recurrent stroke risk. Increasing the low utilization of cardiac monitoring after stroke could identify undiagnosed AF earlier, leading to appropriate oral anticoagulation treatment and a reduction in stroke/TIA recurrence. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) can be a cause of previously diagnosed cryptogenic stroke. However, AF can be paroxysmal and asymptomatic, thereby making detection with routine ECG methods difficult. Oral anticoagulation is highly effective in reducing recurrent stroke in patients with AF, but its initiation is dependent on the detection of AF. Cryptogenic Stroke and Underlying Atrial Fibrillation (CRYSTAL AF) is the first randomized study to report the detection of AF in cryptogenic stroke patients using continuous long-term monitoring via insertable cardiac monitors (ICM).Methods and Results: Patients with prior cryptogenic stroke were randomized to control (n=220) or ICM (n=221) and followed for ≤36 months. Cumulative AF detection rates in the ICM arm increased progressively during this period (3.7%, 8.9%, 12.4%, and 30.0% at 1, 6, 12, and 36 months, respectively), but remained low in the control arm (3.0% at 36 months). This resulted in oral anticoagulation prescription in 94.7% of ICM patients with AF detected at 6 months, 96.6% at 12 months, and 90.5% at 36 months. Among ICM patients with AF detected, the median time to AF detection was 8.4 months, 81.0% of first AF episodes were asymptomatic, and 94.9% had at least 1 day with >6 minutes of AF.Conclusions: Three-year monitoring by ICM in cryptogenic stroke patients demonstrated a significantly higher AF detection rate compared with routine care. Given the frequency of asymptomatic first episodes and the long median time to detection, these findings highlight the limitations of using traditional AF detection methods. The majority of patients with AF were prescribed oral anticoagulation therapy.Clinical Trial Registration: Clinicaltrials.gov; Unique identifier: NCT00924638. [ABSTRACT FROM AUTHOR]