The ABC-Stroke Risk Score and Effects of Atrial Fibrillation Screening on Stroke Prevention: Results From the Randomized LOOP Study.

BACKGROUND: The ABC-stroke score is a risk scheme for prediction of stroke or systemic embolism (SE) in atrial fibrillation (AF). This study sought to examine whether the score could be useful in predicting stroke in AF-naïve individuals and risk stratifying for AF screening. METHODS AND RESULTS: The LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals) study randomized 6004 AF-naïve individuals aged 70 to 90 years with stroke risk factors to either screening with an implantable loop recorder and anticoagulation upon detection of new-onset AF episodes ≥6 minutes, or usual care. A total of 5781 participants had available ABC-stroke score at baseline and were included in this secondary analysis: 4170 (72.1%) with an estimated stroke/SE risk ≤1%/year versus 1611 (27.9%) with an estimated stroke/SE risk >1%/year. Having an annual ABC-stroke risk >1% was associated with stroke/SE, stroke/SE/cardiovascular death, and all-cause death (hazard ratio, 1.82 [95% CI, 1.44-2.21], 2.17 [95% CI, 1.80-2.62], and 2.19 [95% CI, 1.87-2.56], respectively). For screening with implantable loop recorder versus usual care, no significant reduction in these study outcomes was obtained in any ABC-stroke risk groups (P>0.0500 for all), with no signal toward interaction (Pinteraction>0.2500 for all). Similar findings were yielded when assessing the ABC-stroke score as a continuous variable. CONCLUSIONS: In an elderly, AF-naïve population with additional stroke risk factors, a higher ABC-stroke score could identify individuals with increased stroke risk. However, this risk score may not be useful in pinpointing those more likely to benefit from AF screening and subsequent preventive treatment. These findings should be considered as hypothesis generating and warrant further study. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT02036450.

Anticoagulation-Associated Bleeding in Patients Screened for Atrial Fibrillation versus Usual Care-A Post Hoc Analysis from the LOOP Study.

Background Atrial fibrillation (AF) prevalence is rising; however, data on the bleeding risks associated with the detection of subclinical AF are needed. Objective Our objective was to determine the bleeding increment associated with implantable loop recorder (ILR) screening for subclinical AF and subsequent anticoagulation initiation compared with usual care. Methods This post hoc study utilized LOOP trial data from 6,004 elderly patients with stroke risks randomized to either ILR ( n = 1,503) or usual care ( n = 4,503). The mean follow-up time was 64.5 months, and none were lost to follow-up. The primary exposure was the initiation of oral anticoagulation, and the main outcome was the risk of major bleeding events following initiation of oral anticoagulants (OACs), determined by time-dependent cox regression. Second, we investigated antithrombotic prescription patterns and major bleeding events after antiplatelet treatment and in subgroups. Results OAC was initiated in 1,019 participants with a mean age (years) of 78.8 (± 4.67) in control versus 77.0 (± 4.84) in ILR, p < 0.0001. Altogether did 202 participants end or pause OAC treatment. Among AF patients (n = 910) had 40 (28%) completely ended OAC and 105 (72%) temporarily paused OAC during follow-up. Major bleeding events totaled 221 (3.7%). Forty-seven major bleeding events followed an OAC initiation in 1,019 participants (4.6%); 26 versus 21 events in the control and ILR groups, respectively. The hazard ratio (HR) for major bleeding after OAC initiation compared with before initiation was 2.08 (1.50-2.90) p < 0.0001 overall, 2.81 (1.82-4.34) p < 0.0001 for control and 1.32 (0.78-2.23) p = 0.31 for the ILR group ( p = 0.07 for interaction). Antiplatelet treatment resulted in an overall adjusted HR of 1.3 (0.96-1.75) p = 0.09. For OAC users aged ≥75 years in the ILR group, the rate of major bleeding was 1.73 (0.92-2.96) compared with 0.84 (0.36-1.66) for an age <75 years, and the rate of the corresponding control subgroup aged ≥75 years was 2.20 (1.23-3.63) compared with 1.64 (0.82-2.93) for an age <75 years. Conclusion The individual risk of major bleeding increased twofold after initiation of oral anticoagulation for all patients in this study. However, the patients screened for subclinical AF did not have a higher bleeding risk after initiation of anticoagulation compared with those in usual care. Trial Registration: The LOOP study is registered at ClinicalTrials.gov, identifier: NCT020364 50.

Epicardial adipose tissue and subclinical incident atrial fibrillation as detected by continuous monitoring: a cardiac magnetic resonance imaging study.

Epicardial adipose tissue (EAT) has endocrine and paracrine functions and has been associated with metabolic and cardiovascular disease. This study aimed to investigate the association between EAT, determined by cardiac magnetic resonance imaging (CMR), and incident atrial fibrillation (AF) following long-term continuous heart rhythm monitoring by implantable loop recorder (ILR). This study is a sub-study of the LOOP study. In total, 203 participants without a history of AF received an ILR and underwent advanced CMR. All participants were at least 70 years of age at inclusion and had at least one of the following conditions: hypertension, diabetes, previous stroke, or heart failure. Volumetric measurements of atrial- and ventricular EAT were derived from CMR and the time to incident AF was subsequently determined. A total of 78 participants (38%) were diagnosed with subclinical AF during a median of 40 (37-42) months of continuous monitoring. In multivariable Cox regression analyses adjusted for age, sex, and various comorbidities, we found EAT indexed to body surface area to be independently associated with the time to AF with hazard ratios (95% confidence intervals) up to 2.93 (1.36-6.34); p = 0.01 when analyzing the risk of new-onset AF episodes lasting ≥ 24 h. Atrial EAT assessed by volumetric measurements on CMR images was significantly associated with the incident AF episodes as detected by ILR.

Electrocardiographic Morphology-Voltage-P-Wave-Duration (MVP) Score to Select Patients for Continuous Atrial Fibrillation Screening to Prevent Stroke.

Morphology-voltage-P-wave-duration (MVP) score combining P-wave duration (PWD), P-wave voltage in lead I (PWVI), and interatrial block (IAB) has been demonstrated to predict atrial fibrillation (AF). Therefore, this study aimed to examine MVP score and its P-wave components as potential predictors of AF screening effects on stroke prevention. This was a secondary analysis of the LOOP Study (Atrial Fibrillation detected by Continuous ECG Monitoring using Implantable Loop Recorder to prevent Stroke in High-risk Individuals) which randomized older persons (aged 70 to 90 years) with additional stroke risk factors to either continuous monitoring with implantable loop recorder and anticoagulation upon detection of AF episodes ≥6 minutes (the intervention group), or usual care. A total of 5,759 participants were included in the present analysis, where PWD, PWVI, and IAB were determined through a computerized analysis of 12-lead electrocardiogram and further employed to calculate baseline MVP score (0 to 6) for each participant. In total, 305 (5.3%) had stroke or systemic embolism during follow-up, with a higher risk in the group with MVP score 5 to 6 than those having score 0 to 2 (hazard ratio (HR) 1.54 [95% confidence interval (CI) 1.01 to 2.35]). This risk increase was mainly upheld by participants with IAB (HR 1.62 [95% CI 1.11 to 2.36] for IAB vs no IAB) and with longer PWD (HR 1.37 [95% CI 1.07 to 1.75] for >110 vs ≤110 ms). Compared with usual care, implantable loop recorder screening did not significantly reduce the risk of stroke or systemic embolism in any MVP risk categories (HR 0.80 [95% CI 0.60 to 1.08] for MVP score 0 to 2, 0.54 [95% CI 0.16 to 1.85] for MVP score 3 to 4, and 0.89 [95% CI 0.35 to 2.25] for MVP score 5 to 6; pinteraction = 0.78). In conclusion, a higher MVP score was associated with an increased stroke risk, but it did not demonstrate an association with effects of AF screening on stroke prevention. These findings should be considered hypothesis-generating and warrant further study.

Electrocardiographic markers of subclinical atrial fibrillation detected by implantable loop recorder: insights from the LOOP Study.

AIMS: Insights into subclinical atrial fibrillation (AF) development are warranted to inform the strategies of screening and subsequent clinical management upon AF detection. Hence, this study sought to characterize the onset and progression of subclinical AF with respect to 12-lead electrocardiogram (ECG) parameters. METHODS AND RESULTS: We included AF-naïve individuals aged 70-90 years with additional stroke risk factors who underwent implantable loop recorder (ILR) monitoring in the LOOP Study. Using data from daily ILR recordings and the computerized analysis of baseline ECG, we studied empirically selected ECG parameters for AF detection (≥6 min), cumulative AF burden, long-lasting AF (≥24 h), and AF progression. Of 1370 individuals included, 419 (30.6%) developed AF during follow-up, with a mean cumulative AF burden of 1.5% [95% CI: 1.2-1.8]. Several P-wave-related and ventricular ECG parameters were associated with new-onset AF and with cumulative AF burden in AF patients. P-wave duration (PWD), P-wave terminal force in Lead V1, and interatrial block (IAB) further demonstrated significant associations with long-lasting AF. Among AF patients, we observed an overall reduction in cumulative AF burden over time (IRR 0.70 [95% CI: 0.51-0.96]), whereas IAB was related to an increased risk of progression to AF ≥24 h (HR 1.86 [95% CI: 1.02-3.39]). Further spline analysis also revealed longer PWD to be associated with this progression in AF duration. CONCLUSION: We identified several ECG parameters associated with new-onset subclinical AF detected by ILR. Especially PWD and IAB were robustly related to the onset and the burden of AF as well as progression over time.

Effects of Atrial Fibrillation Screening According to N-Terminal Pro-B-Type Natriuretic Peptide: A Secondary Analysis of the Randomized LOOP Study.

BACKGROUND: Research suggests NT-proBNP (N-terminal pro-B-type natriuretic peptide) to be a strong predictor of incident atrial fibrillation (AF) and stroke. However, its utility in AF screening remains unknown. The aim of this study was to investigate NT-proBNP as a potential marker for screening efficacy with respect to AF yield and stroke prevention. METHODS: In the LOOP Study (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals), 6004 AF-naïve individuals at least 70 years old and with additional stroke risk factors were randomized 1:3 to either screening with an implantable loop recorder (ILR) and initiation of anticoagulation upon detection of AF episodes lasting ≥6 minutes or usual care (control). This post hoc analysis included study participants with available NT-proBNP measurement at baseline. RESULTS: A total of 5819 participants (96.9% of the trial population) were included. The mean age was 74.7 years (SD, 4.1 years) and 47.5% were female. The median NT-proBNP level was 15 pmol/L (interquartile range, 9-28 pmol/L) corresponding to 125 pg/mL (interquartile range, 76-233 pg/mL). NT-proBNP above median was associated with an increased risk of AF diagnosis both in the ILR group (hazard ratio, 1.84 [95% CI, 1.51-2.25]) and the control group (hazard ratio, 2.79 [95% CI, 2.30-3.40]). Participants with NT-proBNP above the median were also at higher risk of clinical events compared with those having lower levels (hazard ratio, 1.21 [95% CI, 0.96-1.54] for stroke or systemic embolism [SE], 1.60 [95% CI, 1.32-1.95] for stroke/SE/cardiovascular death, and 1.91 [95% CI, 1.61-2.26] for all-cause death). Compared with usual care, ILR screening was associated with significant reductions in stroke/SE and stroke/SE/cardiovascular death among participants with NT-proBNP above median (hazard ratio, 0.60 [95% CI, 0.40-0.90] and 0.70 [95% CI, 0.53-0.94], respectively) but not among those with lower levels (Pinteraction=0.029 for stroke/SE and 0.045 for stroke/SE/cardiovascular death). No risk reduction in all-cause death was observed in either NT-proBNP subgroup for ILR versus control (Pinteraction=0.68). Analyzing NT-proBNP as a continuous variable yielded similar findings. CONCLUSIONS: In an older population with additional stroke risk factors, ILR screening for AF was associated with a significant reduction in stroke risk among individuals with higher NT-proBNP levels but not among those with lower levels. These findings should be considered hypothesis generating and warrant further study before clinical implementation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02036450.

Prevalence and Prognostic Significance of Bradyarrhythmias in Patients Screened for Atrial Fibrillation vs Usual Care: Post Hoc Analysis of the LOOP Randomized Clinical Trial.

Importance: There is increasing interest in heart rhythm monitoring and technologies to detect subclinical atrial fibrillation (AF), which may lead to incidental diagnosis of bradyarrhythmias. Objective: To assess bradyarrhythmia prevalence and prognostic significance in persons screened for AF using implantable loop recorder (ILR) compared with unscreened persons. Design, Setting, and Participants: This was a post hoc analysis of the Implantable Loop Recorder Detection of Atrial Fibrillation to Prevent Stroke (LOOP) randomized clinical trial, which took place in 4 sites in Denmark. Participants were 70 years or older without known AF but diagnosed with at least 1 of the following: hypertension, diabetes, heart failure, or prior stroke. Participants were recruited by letter invitation between January 31, 2014, and May 17, 2016. The median (IQR) follow-up period was 65 (59-70) months. Analysis took place between February and June 2022. Interventions: ILR screening for AF with treatment of any bradyarrhythmia left to the discretion of the treating physician (ILR group) vs usual care (control group). Main Outcomes and Measures: Adjudicated bradyarrhythmia episodes, pacemaker implantation, syncope, and sudden cardiovascular death. Results: A total of 6004 participants were randomized (mean [SD] age, 75 [4.1] years; 2837 [47.3%] female; 5444 [90.7%] with hypertension; 1224 [20.4%] with prior syncope), 4503 to control and 1501 to ILR. Bradyarrhythmia was diagnosed in 172 participants (3.8%) in the control group vs 312 participants (20.8%) in the ILR group (hazard ratio [HR], 6.21 [95% CI, 5.15-7.48]; P < .001), and these were asymptomatic in 41 participants (23.8%) vs 249 participants (79.8%), respectively. The most common bradyarrhythmia was sinus node dysfunction followed by high-grade atrioventricular block. Risk factors for bradyarrhythmia included higher age, male sex, and prior syncope. A pacemaker was implanted in 132 participants (2.9%) vs 67 (4.5%) (HR, 1.53 [95% CI, 1.14-2.06]; P < .001), syncope occurred in 120 (2.7%) vs 33 (2.2%) (HR, 0.83 [95% CI, 0.56-1.22]; P = .34), and sudden cardiovascular death occurred in 49 (1.1%) vs 18 (1.2%) (HR, 1.11 [95% CI, 0.64-1.90]; P = .71) in the control and ILR groups, respectively. Bradyarrhythmias were associated with subsequent syncope, cardiovascular death, and all-cause death, with no interaction between bradyarrhythmia and randomization group. Conclusions and Relevance: More than 1 in 5 persons older than 70 years with cardiovascular risk factors can be diagnosed with bradyarrhythmias when long-term continous monitoring for AF is applied. In this study, ILR screening led to a 6-fold increase in bradyarrhythmia diagnoses and a significant increase in pacemaker implantations compared with usual care but no change in the risk of syncope or sudden death.

Screening for atrial fibrillation to prevent stroke in elderly individuals with or without preexisting cardiovascular disease: A post hoc analysis of the randomized LOOP Study.

BACKGROUND: An evidence-based approach for risk stratification of subclinical atrial fibrillation (AF) and hereby AF screening is lacking. This study aimed to investigate whether established cardiovascular diseases (CVD) could help to identify the population more likely to benefit from AF screening. METHODS: The LOOP Study randomized AF-naïve individuals aged ≥70 years and with additional stroke risk factors to either screening with implantable loop recorder (ILR) and subsequent anticoagulation upon detection of new-onset AF episodes ≥6 min, or usual care. In this sub-study, all participants were divided into two risk groups according to the presence/absence of CVD (defined as ischemic heart disease, heart failure, previous stroke, valvular heart disease, or peripheral artery disease). RESULTS: A total of 1997 (33.3%) had CVD at baseline and experienced higher incidences of stroke or systemic arterial embolism (SAE), ischemic stroke, stroke/SAE/cardiovascular death, and all-cause death (adjusted HR 1.34 [1.06-1.69], 1.31 [1.02-1.69], 1.49 [1.23-1.79], and 1.59 [1.36-1.85], respectively) than those without. For ILR screening versus usual care, there was no decrease in stroke/SAE, ischemic stroke, or stroke/SAE/cardiovascular death among participants with CVD (adjusted p-values >0.05), whereas significant reductions in these outcomes were obtained by screening among those without CVD (adjusted HR 0.64 [0.44-0.93], 0.54 [0.35-0.82], 0.64 [0.46-0.87], respectively); adjusted p-values for interaction ≤0.05. CONCLUSIONS: In an elderly, at-risk population, ILR screening did not prevent stroke significantly in individuals with CVD, whereas screening was associated with approximately 40% stroke risk reduction among those without CVD. However, these findings should be considered as hypothesis-generating and warrant further study.

Severity and Etiology of Incident Stroke in Patients Screened for Atrial Fibrillation vs Usual Care and the Impact of Prior Stroke: A Post Hoc Analysis of the LOOP Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) screening trials have failed to demonstrate a significant reduction in stroke risk. The impact on stroke severity and the importance of prior strokes are unknown. Objective: To assess stroke characteristics in patients undergoing implantable loop recorder (ILR) screening for AF vs usual care and assess the importance of prior stroke. Design, Setting, and Participants: This was a post hoc analysis of the Atrial Fibrillation Detected by Continuous Electrocardiogram Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-Risk Individuals (LOOP) randomized clinical trial. Persons 70 years or older without known AF but diagnosed with 1 or more of the following, hypertension, diabetes, heart failure, or prior stroke, were screened for inclusion. Four sites in Denmark recruited participants by letter between January 31, 2014, and May 17, 2016. The median (IQR) follow-up period was 65 (59-70) months. Data were analyzed from April 1 to May 31, 2022. Interventions: ILR screening for AF and anticoagulation initiation if AF duration of 6 minutes or longer was detected (ILR group) vs usual care (control group). Main Outcomes and Measures: Adjudicated stroke, classified according to the modified Rankin Scale (mRS) using a score of 3 or more as a cutoff for severe (disabling or lethal) stroke, and according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification for ischemic strokes. Results: A total of 6205 individuals were screened for inclusion, and 6004 were randomized and included in the analysis; 4503 participants (75%; mean [SD] age, 74.7 [4.1] years; 2375 male [52.7%]) were assigned to the control group and 1501 participants (25%; mean [SD] age, 74.7 [4.1] years; 792 male [52.8%]) were assigned to the ILR group. A total of 794 of 4503 participants (17.6%) in the control group had a history of prior stroke compared with 262 of 1501 participants (17.5%) in the ILR group. During follow-up, AF was diagnosed in 1027 participants (control group, 550 [12%] vs ILR group, 477 [32%]), and anticoagulation was initiated in 89% of these (910). A total of 315 participants (5.2%) had a stroke (control group, 249 [5.5%] vs ILR group, 66 [4.4%]), and the median (IQR) mRS score was 2 (1-3) with no difference across the groups. A total of 272 participants (4.5%) had ischemic stroke (control group, 217 [4.8%] vs ILR group, 55 [3.7%]), and 123 (2.0%) had severe stroke (control group, 100 [2.2%] vs ILR group, 23 [1.5%]), and the hazard ratios comparing the control and ILR groups were 0.76 (95% CI, 0.57-1.03; P = .07) and 0.69 (95% CI, 0.44-1.09; P = .11), respectively. For participants without prior stroke, the hazard ratios were 0.68 (95% CI, 0.48-0.97; P = .04) and 0.54 (95% CI, 0.30-0.97; P = .04), respectively. Conclusions and Relevance: This post hoc analysis of the LOOP randomized clinical trial found that ILR screening for AF did not result in a significant decrease in ischemic or severe strokes compared with usual care. Exploratory subgroup analyses indicated a possible reduction of these outcomes among participants without prior stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02036450.

Systolic Blood Pressure and Effects of Screening for Atrial Fibrillation With Long-Term Continuous Monitoring (a LOOP Substudy).

BACKGROUND: Hypertension is a well-known risk factor for atrial fibrillation (AF) and stoke, but data on the interaction between systolic blood pressure (SBP) and effects of AF screening are lacking. METHODS: The LOOP Study randomized AF-naïve individuals aged 70 to 90 years with additional stroke risk factors to either screening with implantable loop recorder (ILR) and anticoagulation initiation upon detection of AF episodes ≥6 minutes, or usual care. In total, 5997 participants with available baseline SBP measurements were included in this substudy. Outcomes were analyzed according to the time-to-first-event principle using cause-specific Cox models. RESULTS: The hazard ratio of stroke or systemic arterial embolism for ILR versus control decreased with increasing SBP. ILR screening yielded a 44% risk reduction of stroke or systemic arterial embolism among participants with SBP ≥150 mm Hg (adjusted hazard ratio, 0.56 [0.37-0.83]). Within the ILR group, SBP≥150 mm Hg was associated with a higher incidence of AF episodes ≥24 hours than lower SBP (adjusted hazard ratio, 1.70 [1.08-2.69]) but not with the overall occurrence of AF (adjusted P>0.05). CONCLUSIONS: The impact of AF screening on thromboembolic events increased with increasing blood pressure. SBP≥150 mm Hg was associated with a >1.5-fold increased risk of AF episodes ≥24 hours, along with an almost 50% risk reduction of stroke or systemic arterial embolism by ILR screening compared to lower blood pressure. These findings should be considered hypothesis-generating and warrant further study. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique Identifier: NCT02036450.

Left Atrial Remodeling and Cerebrovascular Disease Assessed by Magnetic Resonance Imaging in Continuously Monitored Patients.

BACKGROUND: Atrial remodeling is associated with future atrial fibrillation (AF) and stroke. AF has been associated with cognitive impairment and cerebral white matter lesions. We wished to investigate the possible direct association between atrial remodeling and cerebrovascular disease in patients with and without AF documented by implantable loop recorder (ILR). METHODS: Cardiac and cerebral magnetic resonance imaging were acquired in a cross-sectional study, including participants ≥70 years of age with stroke risk factors without known AF. Cerebrovascular disease was visually rated using the Fazekas scale and number of lacunar strokes. Left atrial (LA) and ventricular volumes and function were analyzed. Associations between atrial remodeling and cerebrovascular disease were assessed with logistic regression models. The analyses were stratified according to sinus rhythm or any AF during 3 months of continuous ILR monitoring to account for subclinical AF. RESULTS: Of 200 participants investigated, 87% had a Fazekas score ≥1 and 45% had ≥1 lacunar infarct. Within 3 months of ILR monitoring, AF was detected in 28 (14%) participants. For participants with sinus rhythm (n = 172), lower LA passive emptying fraction was associated with Fazekas score after multivariable adjustment (OR [95% CI]: 0.51 [0.27; 0.86] p = 0.02), and increased LA maximum (OR [95% CI]: 1.38 [1.07; 1.82] p = 0.01) and minimum volumes (OR [95% CI]: 1.48 [1.03; 2.17] p = 0.04) were associated with lacunar infarcts. There were no significant associations in patients with AF. CONCLUSION: In AF-free patients, as documented by ILR monitoring, we found an independent association between LA passive emptying fraction and Fazekas score and between atrial volumes and lacunar infarcts.

Day-to-day measurement of physical activity and risk of atrial fibrillation.

AIMS: The aim of this study was to investigate the association between within-individual changes in physical activity and onset of atrial fibrillation (AF). METHODS AND RESULTS: A total of 1410 participants from the general population (46.2% women, mean age 74.7 ± 4.1 years) with risk factors but with no prior AF diagnosis underwent continuous monitoring for AF episodes along with daily accelerometric assessment of physical activity using an implantable loop recorder during ≈3.5 years. The combined duration of monitoring was ≈1.6 million days, where 10 851 AF episodes lasting ≥60 min were detected in 361 participants (25.6%) with a median of 5 episodes (2, 25) each. The median daily physical activity was 112 (66, 168) min/day. A dynamic parameter describing within-individual changes in daily physical activity, i.e. average daily activity in the last week compared to the previous 100 days, was computed and used to model the onset of AF. A 1-h decrease in average daily physical activity was associated with AF onset the next day [odds ratio 1.24 (1.18-1.31)]. This effect was modified by overall level of activity (P < 0.001 for interaction), and the signal was strongest in the tertile of participants with lowest activity overall [low: 1.62 (1.41-1.86), mid: 1.27 (1.16-1.39), and high: 1.10 (1.01-1.19)]. CONCLUSIONS: Within-individual changes in physical activity are associated with the onset of AF episodes as detected by continuous monitoring in a high-risk population. For each person, a 1-h decrease in daily physical activity during the last week increased the odds of AF onset the next day by ≈25%, while the strongest association was seen in the group with the lowest activity overall. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02036450.

Atrial fibrillation burden and cognitive decline in elderly patients undergoing continuous monitoring.

AIMS: To study the relationship between subclinical atrial fibrillation (AF) and changes in cognitive function in a large cohort of individuals with stroke risk factors. METHODS: Individuals with no prior AF diagnosis but with risk factors for stroke were recruited to undergo annual cognitive assessment with the Montreal Cognitive Assessment (MoCA) along with implantable loop recorder (ILR) monitoring for AF for 3 years. If AF episodes lasting ≥6 minutes were detected, oral anticoagulation (OAC) treatment was initiated. RESULTS: A total of 1194 participants (55.2 % men, mean age 74.5 (±3.9)) had a combined duration of heart rhythm monitoring of ≈1.3 million days. Among these, 339 participants (28.3%) had adjudicated AF, with a median AF burden of 0.072% (0.02, 0.39), and 324 (96%) initiated OAC. When stratifying the participants into AF burden groups (No AF, AFlow (AF burden <0.25%), and AFhigh, (AF burden >0.25%)), only participants in the AFlow group had a decrease in MoCA score over time (P = .03), although this was not significant after adjustment for stroke risk factors. A subgroup analysis of 175 participants (14.6%) with a MoCA <26 at 3 years found no association to AF diagnosis or burden. CONCLUSIONS: In a high-risk population, subclinical AF detected by continuous monitoring and subsequently treated with OAC was not associated with a significant change in MoCA score over a 3-year period.

Comparison of the three-level and the five-level versions of the EQ-5D.

EQ-5D is a generic instrument to measure health-related quality of life. In 2009, a new version, EQ-5D-5L, was introduced as an attempt to reduce ceiling effects and improve sensitivity to small changes over time. The objective of this study was to assess the measurement properties of the EQ-5D-5L instrument compared to the EQ-5D-3L instrument in an elderly general population with a moderate to a high degree of comorbidity. A subgroup of participants in a large clinical trial completed the EQ-5D-3L and the EQ-5D-5L questionnaires. Based on the collected data, we tested for feasibility and ceiling and floor effects. Furthermore, we assessed the redistribution properties of the responses and examined the level of inconsistency, informativity, and convergent validity. A total of 1002 persons diagnosed with hypertension, diabetes, heart failure, and/or previous stroke completed both the EQ-5D-3L and the EQ-5D-5L questionnaires. The overall ceiling effect decreased from 46% with the EQ-5D-3L to 30% with the EQ-5D-5L and absolute and relative informativity were higher for EQ-5D-5L, and there was a stronger correlation between EQ-5D-5L and EQ VAS. The EQ-5D-5L seemed to perform better than the EQ-5D-3L in terms of feasibility, ceiling effect, discriminatory power, and convergent validity. The overall ceiling effect was higher than that found in patient samples in previous studies but lower than the one found in population studies.

Left Atrial Late Gadolinium Enhancement is Associated With Incident Atrial Fibrillation as Detected by Continuous Monitoring With Implantable Loop Recorders.

OBJECTIVES: The authors hypothesized that left atrial (LA) fibrosis was associated with incident atrial fibrillation (AF) as detected by continuous long-term monitoring in an at-risk population. BACKGROUND: LA late gadolinium enhancement (LGE) measured with cardiac magnetic resonance is emerging as a marker of atrial fibrosis and has been associated with worse outcomes in AF ablation procedures; however, the prognostic value of LA LGE for incident AF remains unknown. METHODS: Cardiac magnetic resonance, including measurement of left ventricular and LA volumes and function, as well as left ventricular extracellular volume fraction and LA LGE, was acquired in 68 patients aged at least 70 years with risk factors for stroke. All included patients received an implantable loop recorder and were continuously monitored for previously unknown AF. Incident AF was adjudicated by senior cardiologists. RESULTS: Patients were monitored for AF with an implantable loop recorder during a median of 41 (interquartile range: 7) months. AF episodes lasting ≥6 min were detected in 32 patients (47%), and 16 patients (24%) experienced AF episodes lasting ≥5.5 h. In Cox regression analyses adjusted for sex, age, and comorbidities, we found that LA volumes and function and LA LGE were independently associated with incident AF. For LA LGE, the hazard ratios for time to AF episodes lasting ≥6 min and ≥5.5 h were 1.40 (95% CI: 1.03 to 1.89) per 10 cm2 increase (p = 0.03) and 1.63 (95% CI: 1.11 to 2.40) per 10 cm2 increase (p = 0.01), respectively. LA LGE was significantly associated with high burden of AF. The addition of LA LGE to a multivariable risk prediction model for incident AF significantly increased the predictive value. CONCLUSIONS: Extent of LA fibrosis measured by LA LGE was significantly associated with incident AF detected by implantable loop recorder. (Atrial Fibrillation Detected by Continuous ECG Monitoring [LOOP]; NCT02036450).

Comprehensive Evaluation of Rhythm Monitoring Strategies in Screening for Atrial Fibrillation: Insights From Patients at Risk Monitored Long Term With an Implantable Loop Recorder.

BACKGROUND: Stroke is an increasing health problem worldwide. Atrial fibrillation (AF) is a major risk factor for stroke, and the attention given to AF screening is rising, as new monitoring technologies emerge. We aimed to evaluate the performance of a large panel of screening strategies and to assess population characteristics associated with diagnostic yield. METHODS: Individuals with stroke risk factors but without AF were recruited from the general population to undergo screening with an implantable loop recorder. New-onset AF lasting ≥6 minutes was adjudicated by senior cardiologists. After continuous monitoring for >3 years, complete day-to-day heart rhythm data sets were reconstructed for every participant, including exact time of onset and termination of all AF episodes. Random sampling was applied to assess the sensitivity and negative predictive value of screening with various simulated screening strategies compared with the implantable loop recorder. The diagnostic yield across strategies and population subgroups was compared by use of nonparametric tests. RESULTS: The rhythm data sets comprised 590 participants enduring a total of 659 758 days of continuous monitoring and 20 110 AF episodes. In these data, a single 10-second ECG yielded a sensitivity (and negative predictive value) of 1.5% (66%) for AF detection, increasing to 8.3% (67%) for twice-daily 30-second ECGs during 14 days and to 11% (68%), 13% (68%), 15% (69%), 21% (70%), and 34% (74%) for a single 24-hour, 48-hour, 72-hour, 7-day, or 30-day continuous monitoring, respectively. AF detection further improved when subsequent screenings were performed or when the same monitoring duration was spread over several periods compared with a single period (eg, three 24-hour monitorings versus one 72-hour monitoring; P<0.0001 for all comparisons). The sensitivity was consistently higher among participants with age ≥75 years, male sex, CHADS2 score >2, or NT-proBNP (N-terminal pro-B-type natriuretic peptide) ≥40 pmol/L and among participants with underlying ≥24-hour AF episodes compared with shorter AF (P<0.0001 for all screening strategies). CONCLUSIONS: In screening for AF among participants with stroke risk factors, the diagnostic yield increased with duration, dispersion, and number of screenings, although all strategies had low yield compared with the implantable loop recorder. The sensitivity was higher among participants who were older, were male, or had higher NT-proBNP. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02036450.

Left atrial volume and function assessed by cardiac magnetic resonance imaging are markers of subclinical atrial fibrillation as detected by continuous monitoring.

AIMS: We aimed to investigate whether left atrial (LA) markers from cardiovascular magnetic resonance (CMR) were able to predict atrial fibrillation (AF) in elderly patients with risk factors for stroke. METHODS AND RESULTS: At baseline, 203 participants with stroke risk factors but without history of AF underwent advanced CMR and received an implantable loop recorder. During a median of 40 (37-42) months of continuous monitoring, incident AF was detected in 79 patients (39%). With regards to CMR markers, a steep increase in incidence rate of AF was seen with LA maximum volume (LAmax) above 55 mL/m2, LA minimum volume (LAmin) above 30 mL/m2, LA total emptying fraction (LA TEF) below 45%, LA active emptying fraction (LA AEF) below 37%, LA strain S below 25%, LA strain A below 17%, and LA strain rate A above -1.7 s-1. After multivariate adjustment, the above-mentioned CMR markers remained associated with AF incidence: hazard ratio (95% confidence interval) 1.25 (1.06-1.48) and 1.51 (1.22-1.87) per 10 mL/m2 increase of LAmax and LAmin, respectively, 1.49 (1.26-1.76) and 1.46 CI (1.25-1.71) per 5% decrease in LA TEF and LA AEF, respectively, 1.23 (1.05-1.44) and 1.56 (1.18-2.06) per 5% decrease in LA strain S and A, respectively, and 2.06 (1.31-3.23) per s-1 increase in LA strain rate A. In prediction analyses, LA functional indices increased area under the receiver operating characteristic curve significantly. CONCLUSION: The risk of AF, including asymptomatic AF, increases significantly with increasing LA volumes and worsening LA function.

Incidence and predictors of atrial fibrillation episodes as detected by implantable loop recorder in patients at risk: From the LOOP study.

BACKGROUND: Recent studies have suggested a high prevalence of subclinical atrial fibrillation (AF) in various patient populations, and interest in AF screening has increased. However, knowledge about episode duration is scarce, and risk factors for short or long subclinical AF episodes have yet to be recognized. The aim of the study was to assess AF by long-term continuous screening and to investigate predictors of episodes lasting ≥6 minutes, ≥5.5 hours, or ≥24 hours, respectively. METHODS: A total of 597 patients aged ≥70 years and diagnosed with ≥1 of hypertension, diabetes, previous stroke, or heart failure were recruited from the general population to receive implantable loop recorder with remote monitoring. Exclusion criteria included history of AF or cardiac implantable electronic device. AF episodes were adjudicated by senior cardiologists. RESULTS: During 40 (37; 42) months of continuous monitoring, AF was detected in 209 (35%) of the patients. The cumulative incidences at 3 years were 33.8% (30.2%-37.8%), 16.1% (13.4%-19.4%), and 5.7% (4.1%-7.9%) for AF episodes lasting ≥6 minutes, ≥5.5 hours, and ≥24 hours, respectively. Slower resting sinus rate and higher body mass index, N-terminal prohormone of brain natriuretic peptide, and troponin T at baseline were independently associated with AF detection. Addition of these markers to a model of sex, age, and comorbidities improved prediction of AF episodes ≥24 hours (time-dependent area under the receiver operating characteristic curve 79% vs 65%, P = .037). CONCLUSIONS: A considerable burden of previously unknown AF was detected when long-term monitoring was applied in at-risk patients. Biomarkers were associated with AF incidence and improved prediction of long AF episodes.

Natural History of Subclinical Atrial Fibrillation Detected by Implanted Loop Recorders.

BACKGROUND: As new heart rhythm monitoring technologies emerge, subclinical atrial fibrillation (AF) signifies a future challenge to health care systems. The pathological characteristics of this condition are largely unknown. OBJECTIVES: This study sought to characterize the natural history of subclinical AF in at-risk patients from the general population. METHODS: The authors studied 590 individuals ≥70 years of age with ≥1 of hypertension, diabetes, previous stroke, or heart failure, without history of AF, undergoing long-term implantable loop recorder monitoring as part of the LOOP (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals) study. Baseline assessments included N-terminal pro-B-type natriuretic peptide (NT-proBNP). All day-to-day heart rhythm and symptom data were extracted from the device. Endpoints included AF burden, AF progression, symptom reports, and heart rate during AF. RESULTS: A total of 685,445 monitoring days were available for analysis. Adjudicated AF episodes lasting ≥6 min were detected in 205 participants (35%). The AF burden was median 0.13% (interquartile range: 0.03% to 1.05%) of the monitoring time and changed by a factor of 1.31 (95% CI: 1.02 to 1.68) per doubling of NT-proBNP. AF episodes were present 2.7% (interquartile range: 1.0% to 15.7%) of monitoring days after debut. Progression to 24-h episodes was seen in 33 of the AF patients (16%), whereas 46 (22%) had no AF episodes in the last 6 months of monitoring or longer. Symptoms were absent in 185 (90%) at debut, and 178 (87%) never reported AF-related symptoms during follow-up. The averaged heart rate during AF was 96 (interquartile range: 83 to 114) beats/min, 24 (interquartile range: 9 to 41) beats/min faster than daytime sinus rates. CONCLUSIONS: Although previously unknown AF was highly prevalent, the burden was low, and progression was limited. In addition, symptoms were scarce, and the heart rate was only modestly elevated. (Atrial Fibrillation Detected by Continuous ECG Monitoring Using Implantable Loop Recorder to Prevent Stroke in High-risk Individuals [LOOP]; NCT02036450).