Background: Atrial fibrillation (AF) is common and highly morbid. AF screening may detect AF earlier and facilitate preventive measures (e.g., anticoagulation to prevent stroke). However, current AF screening approaches using a guideline age-based threshold of 65 years have shown limited yield. AF screening informed by AF risk models, including emerging artificial intelligence (AI)-based methods, may improve AF screening efficiency. Research Question: In a large AF screening trial, we sought to assess whether the effect of AF screening was higher among individuals with elevated AF risk. Methods: VITAL-AF was a cluster-randomized trial of patients aged 65 years treated at one of 16 primary care practices affiliated with Massachusetts General Hospital. Patients randomized to a screening practice underwent screening with single-lead ECG. Among individuals in VITAL-AF with 1 12-lead ECG within 3 years prior to enrollment, we estimated AF risk using three validated models derived independent of VITAL-AF: a) the Cohorts of Heart and Aging Research in Genomic Epidemiology-AF (CHARGE-AF) clinical score, b) an AI-based model utilizing 12-lead ECG alone (ECG-AI), and c) a model combining ECG-AI and CHARGE-AF (CH-AI). Discrimination of 2-year incident AF was quantified using the area under the receiver operating characteristic curve (AUROC) and average precision (AP). AF screening effect was defined as the difference in 2-year incident AF diagnosis (%) in screening versus control in the screened population across deciles of AF risk. Results: Of 30,630 VITAL-AF participants without prevalent AF, we analyzed 16,937 with available pre-trial ECG and clinical data. Each score discriminated 2-year AF risk (AUROC CHARGE-AF 0.700 [95%CI 0.654-0.739]; ECG-AI 0.780 [0.747-0.810]; CH-AI 0.781 [0.740-0.814]) (AP 0.0935 [0.0818-0.109]; 0.129 [0.111-0.154]; 0.131 [0.115-0.153]) ( Figure 1 ). An AF screening effect was observed in the top decile of CH-AI (2-year AF diagnosis rate 15.6% [13.1-19.4] in screening vs 11.9% [9.9-15.6] in control; difference 3.7% [0.3-7.1]) ( Figure 2 ). The AF screening effect was largest in the top decile of all three scores, but was numerically highest with CH-AI ( Figure 3 ). Conclusions: In VITAL-AF, the yield of AF screening appeared larger among individuals at high AF risk, particularly using a model combining clinical factors and AI-based ECG analysis. Future trials should assess whether risk-informed AF screening improves outcomes.

Importance People living with HIV and atrial fibrillation (AF) often receive anticoagulation that may interact with their antiretroviral therapy (ART). No studies exist comparing the safety of oral anticoagulants in this population. Objective To compare the bleeding risks among warfarin, rivaroxaban, and apixaban users in a national US cohort with AF and HIV. Design, Setting, and Participants A new-user, active-comparator, propensity score overlap-weighted cohort study using the target trial emulation framework including Medicare claims database data (January 1, 2013, to December 31, 2020) was carried out. The analysis was conducted from July 2023 to April 2024. Exposure New initiators of warfarin vs apixaban, rivaroxaban vs apixaban, and rivaroxaban vs warfarin aged 50 years or older with nonvalvular AF and HIV. Main Outcomes and Measures The primary outcome was hospitalization for major bleeding. Secondary outcomes included hospitalization for gastrointestinal bleeding, ischemic stroke, and all-cause mortality. Results Overall, 2683 individuals (mean [SD] age, 66.22 [8.97] years; 580 female individuals [21.6%]) in the warfarin vs apixaban cohort, 2176 (mean [SD] age, 66.61 [8.87] years; 455 female individuals [20.9%]) in the rivaroxaban vs apixaban cohort, and 1787 (mean age, 65.47 years; 377 female individuals [21.1%]) in the rivaroxaban vs warfarin cohort. After propensity score overlap weighting, warfarin initiation was associated with a higher rate of major bleeding than initiation of apixaban (hazard ratio [HR], 2.60; 95% CI, 1.51-4.49), including major gastrointestinal bleeding (HR, 2.99; 95% CI, 1.52-5.90). This association was intensified in the 71% of patients taking concurrent ART (major bleeding, HR, 6.68; 95% CI, 2.78-16.02; gastrointestinal bleeding, HR, 5.28; 95% CI, 2.08-13.42). Rivaroxaban vs apixaban was also associated with a higher rate of major bleeding (HR, 2.15; 95% CI, 1.18-3.94) and gastrointestinal bleeding (HR, 3.38; 95% CI, 1.57-7.25), with a stronger association in those using ART (major bleeding, HR, 4.83; 95% CI, 2.11-11.08; gastrointestinal bleeding, HR, 4.76; 95% CI, 1.78-12.70). Estimates were similar when comparing rivaroxaban with warfarin. No significant difference was observed in the rate of ischemic stroke or mortality among the 3 oral anticoagulants. Conclusions and Relevance This study found that in patients with HIV and AF, especially those treated with ART, warfarin and rivaroxaban were associated with higher rates of major bleeding compared with apixaban, suggesting a superior safety profile for apixaban in this high-risk population.

ABSTRACTBackgroundOne-time atrial fibrillation (AF) screening trials have produced mixed results; however, it is unclear if there is a subset for whom screening is effective. Identifying such a subgroup would support targeted screening.MethodsWe conducted a secondary analysis of VITAL-AF, a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup where screening is effective. First, we developed an effect-based model using a T-learner. Specifically, we separately predicted the likelihood of AF diagnosis under screening and usual care conditions; the difference in probabilities was the predicted screening effect. Second, we used a validated AF risk model to test for a heterogeneous screening effect. We used interaction testing to determine if observed AF diagnosis rates in the screening and usual care groups differed when stratified by decile of the predicted screening effect and predicted AF risk.ResultsBaseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). In the effect-based analysis, in the highest decile of predicted screening effectiveness (n=3026), AF diagnosis rates were higher in the screening group (6.50 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28). In this group, the mean age was 84 years and 68% were female. The risk-based analysis did not identify a subgroup where screening was more effective. Predicted screening effectiveness and predicted baseline AF risk were poorly correlated (Spearman coefficient 0.13).ConclusionsIn a secondary analysis of the VITAL-AF trial, we identified a small subgroup where one-time screening was associated with increased AF diagnoses using an effect-based approach. In this study, predicted AF risk was a poor proxy for predicted screening effectiveness. These data caution against the assumption that high AF risk is necessarily correlated with high screening effectiveness.

Background Incident atrial fibrillation (AF) is common among adults with kidney failure treated with maintenance dialysis and is associated with poor clinical outcomes. Limited data exist informing treatment of AF among patients on dialysis. We aimed to describe the use of rate‐control and antiarrhythmic medications for AF among patients on dialysis and associations of these medication use strategies with stroke and all‐cause death. Methods We evaluated patients on dialysis with incident AF between 2010 and 2017 in the Kaiser Permanente Northern and Southern California integrated health care delivery systems. We characterized time‐updated incident receipt of rate‐control (β blockers, calcium channel blockers, and digoxin) and antiarrhythmic medications from pharmacy databases. We evaluated associations of these therapies with the composite outcome of ischemic stroke and all‐cause death using Cox regression, adjusting for potential confounders. Results Of 2100 patients, 44.0% were newly prescribed rate‐control medications, 4.6% were prescribed antiarrhythmic medications, 8.9% were prescribed both, and 42.9% were prescribed neither within 12 months of newly diagnosed AF. During a median 1.66 (interquartile range, 0.45–3.39) years, we observed 1406 composite events (stroke and death). Time‐updated use of antiarrhythmics alone (adjusted hazard ratio [HR], 0.74 [95% CI, 0.57–0.96]) or with rate‐control (adjusted HR, 0.72 [95% CI, 0.58–0.90]) was associated with lower stroke or death risk versus neither medication. Use of rate‐control medications alone was not significantly associated with the composite outcome. Conclusions Among patients on dialysis with incident AF, use of antiarrhythmic medications may be associated with lower risk of stroke and death. Future randomized trials are needed to determine the efficacy and safety of antiarrhythmic medications in this high‐risk population.

Left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OAC) for stroke prevention in nonvalvular atrial fibrillation (NVAF); however, real-world data on adherence to its postprocedural treatment protocol remain limited. We evaluated post-LAAO antithrombotic treatment patterns in a cohort of 16304 NVAF patients (mean [SD] age = 78 [6]; 47% female; CHA2DS2-VASc score = 5.0 [1.5]) undergoing first-time LAAO using Optum claims data 2015-2024. OAC discontinuation was defined as a ≥ 60-day gap in supply, and prolonged OAC use was operationally defined as either (1) an OAC refill following a TEE performed 30–90 days post-implantation or (2) OAC refill beyond 90 days post-implantation, regardless of TEE completion. Among LAAO recipients, 9844 (60%) received concomitant OAC and 3499 (10%) received P2Y12 inhibitor at implantation. Transesophageal echocardiography (TEE) was performed in 11237 (69%) patients at 45 (±15) days. Among OAC users (n = 9844), 30% and 85% discontinued OAC by 45 days and 6 months post-implantation, respectively; only 23% patients followed the standard postprocedural protocol. Common deviation from the protocol included no TEE at 45 (±15) days (30%), early OAC discontinued (22%), continued OAC use post-TEE (10%), and P2Y12 inhibitor initiated early or not initiated (10%). Prolonged OAC use was observed in 1970 patients. Factors associated with a higher likelihood of prolonged OAC use included older age, Black race, cardio ablation, and a longer duration of prior OAC use. These findings suggest moderate to low adherence to the LAAO postprocedural protocol, warranting further evaluation of the clinical impact of these adherence patterns.

BACKGROUND:The benefits of switching from warfarin to direct oral anticoagulants in atrial fibrillation remain unclear. METHODS:This retrospective study used the Medicare fee-for-service (2013-2020) and Optum Deidentified Clinformatics Data Mart databases (2013-2023). Among patients with atrial fibrillation who received warfarin for at least 180 days, we created 2 cohorts: (1) patients switching to apixaban versus continuing warfarin (the apixaban cohort) and (2) patients switching to rivaroxaban versus continuing warfarin (the rivaroxaban cohort). The index date was the switch date for switchers and a matched date based on warfarin duration for warfarin continuers. After 1:1 propensity score matching, we estimated the rate ratios (RR) for a composite of ischemic stroke, major bleeding, and death in each database and pooled the results using meta-analysis. Subgroup analyses by claims-based frailty and by follow-up time (first 60 days versus beyond 60 days) were performed. RESULTS:In the apixaban cohort (n=164 480; mean age, 80.5 years; 55.5% female; median follow-up, 354 days), switching to apixaban was associated with a lower rate of composite outcome (97.1 versus 104.9 per 1000 person-years; rate ratio, 0.92 [95% CI, 0.89-0.95]) compared with continuing warfarin. In the rivaroxaban cohort (n=96 030, mean age 79.7 years, 54.8% female, median follow-up 365 days), switching to rivaroxaban was associated with an increased rate of composite outcome (105.8 versus 99.3 per 1000 person-years; rate ratio, 1.08 [95% CI, 1.04-1.13]). No heterogeneity by frailty levels was observed. However, switching was associated with an initial risk increase within the first 60 days, followed by risk attenuation beyond 60 days, for both apixaban and rivaroxaban. CONCLUSIONS:In patients with atrial fibrillation on warfarin therapy, switching to apixaban may reduce the risk of ischemic stroke, major bleeding, and death, whereas switching to rivaroxaban may increase the risk. For both apixaban and rivaroxaban, switching may temporarily increase risk during the first 60 days.

Real-world evidence comparing left atrial appendage occlusion (LAAO) devices to oral anticoagulants (OAC) in nonvalvular atrial fibrillation (NVAF) remain limited. We emulated a target trial and evaluated the effectiveness and safety of LAAO device versus OAC in 35326 NVAF patients (aged ≥65 years, CHA2DS2-VASc score ≥2 [males] or ≥ 3 [females]) using Medicare 2016-2020 and Optum 2016-2024 data. LAAO recipients on OAC (warfarin, apixaban, rivaroxaban, or dabigatran) at implantation (index date) were 1:1 matched to patients who received these medications alone via propensity score matching based on 75 pre-treatment covariates. Outcomes included hospitalization for major bleeding events, ischemic stroke, and all-cause mortality. Follow-up was censored at 2 years or upon treatment deviation (OAC discontinuation or LAAO implantation in OAC users and OAC continuation beyond 90 days in LAAO users). Database-specific rate ratios (RR) were estimated via Poisson regression with inverse probability of censoring weighting and pooled using fixed-effect meta-analysis. Compared to OAC users, LAAO users had a higher bleeding rate over 2 years (RR 1.29; 95% CI 1.11-2.49); however, beyond 6 months post-implantation, LAAO users had a 36% reduction in bleeding rate (0.64; 0.51-0.80). LAAO was also associated with a higher rate of ischemic stroke over 2 years (1.43; 1.10-1.85), though the effect size diminished over time and was no longer statistically significant beyond 6 months (1.16; 0.84-1.62). We found no evidence of association with mortality. These findings suggest that LAAO may reduce long-term bleeding risk but may carry an early increased risk of bleeding and ischemic stroke compared to OAC.

Background:It is uncertain if anticoagulants provide a net benefit in subclinical AF (SCAF). The ARTESIA trial showed apixaban reduced the relative hazard of stroke/systemic embolism (SSE) in SCAF, but did not report absolute risk reduction (ARR). The reported Kaplan-Meier analysis did not account for the competing risk of death or 24-hour AF events. We reanalyzed ARTESIA accounting for competing risks to determine the ARR of apixaban vs. aspirin. Methods:Individual time-to-event and time-to-censoring data were extracted from the published Kaplan-Meier curve. ARTESIA classified deaths and 24-hour AF events as censoring events. We probabilistically reclassified them to competing events to estimate the ARR. We used the Aalen-Johansen estimator to estimate the cumulative risk of stroke/systemic embolism at 3.5 years, accounting for competing events. We compared these results to the Kaplan-Meier estimator. Result:After reclassification of deaths and 24-hour AF to competing events, there were 1111 censoring and 852 competing events in the apixaban arm, and 1100 censoring and 816 competing events in the aspirin arm. Compared to the Aalen-Johansen estimator, the Kaplan-Meier estimator overestimated the cumulative SSE risk at 3.5 years with apixaban (2.64% vs. 2.20%, difference in estimates 0.43 percentage points; 95% CI 0.27 to 0.62) and with aspirin (4.58% vs. 3.82%, difference in estimates 0.76 percentage points; 95% CI 0.56 to 1.01). Compared to the Aalen-Johansen estimator, the Kaplan-Meier estimator overestimated the ARR of SSE risk at 3.5 years with apixaban compared to aspirin (1.94% vs. 1.61%, difference in estimates 0.33 percentage points; 95% CI, 0.06 to 0.64). Conclusion:In SCAF, apixaban reduced the 3.5-year risk of SSE by 1.61%, which would be overestimated by 20% if death and >24-hour AF events are treated as censoring rather than competing events.

BACKGROUND:Wrist-worn wearables can detect irregular heart rhythms using photoplethysmography, but ECGs are required to confirm atrial fibrillation (AF). We sought to determine the frequency of a recurrent irregular heart rhythm detection (IHRD; ≥30 minutes of an irregular rhythm), estimate the potential diagnostic yield of different electrocardiographic monitoring strategies for confirming AF, and identify predictors of recurrent IHRDs. METHODS:The Fitbit Heart Study enrolled wrist-worn photoplethysmography device users without diagnosed AF. Of 455 699 participants, 1057 who wore and returned a 1-week ECG patch monitor after receiving an IHRD were analyzed. Baseline clinical data, device-derived metrics, IHRDs during follow-up, and electrocardiographic patch data were used for analysis. RESULTS:A total of 570 (53.9%) participants were aged 40 to 64 years, 422 (39.9%) were aged ≥65 years, and 510 (48.2%) were women. Median follow-up after ECG patch initiation was 80 days (interquartile range, 45-122 days). The frequency of another IHRD was 57.2% (95% CI, 53.1%-60.9%) at 3 months. After an initial IHRD, the estimated diagnostic yield for AF with a 10-second ECG was 7.6% (95% CI, 6.2%-9.0%), twice-daily 30-second ECGs over 1 week 19.0% (95% CI, 16.7%-21.2%), 24-hour monitor 17.4% (95% CI, 15.5%-19.3%), 1-week monitor 32.2% (95% CI, 29.4%-35.0%), 2-week monitor 46.8% (95% CI, 42.7%-50.8%), and 4-week monitor 60.8% (95% CI, 56.5%-65.1%). The risk of a recurrent IHRD was greater with older age (P<0.001), male sex (P=0.001), vascular disease (P=0.03), longer initial runs of consecutive IHRDs at detection (P=0.02), and less nightly sleep (P=0.03). CONCLUSIONS:Irregular heart rhythms are common after initial detection using a wrist-worn wearable device. Longer electrocardiographic monitoring periods increase the likelihood of confirming AF. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04380415.

BACKGROUND:Detection of undiagnosed atrial fibrillation (AF) after ischemic stroke through extended cardiac monitoring is important for preventing recurrent stroke. We evaluated whether a tool that displays clinically predicted AF risk to clinicians caring for stroke patients was associated with the use of extended cardiac monitoring. METHODS:We prospectively included hospitalized ischemic stroke patients without known AF in a preintervention (October 2018 - June 2019) and intervention period (March 11, 2021 - March 10, 2022). The intervention consisted of an electronic health record (EHR)-based best-practice advisory (BPA) alert which calculated and displayed 5-year risk of AF. We used a multivariable Fine and Gray model to test for an interaction between predicted AF risk and period (preintervention vs intervention) with regards to incidence of extended cardiac monitoring. We compared the incidence of extended cardiac monitoring within 6-months of discharge between periods, stratified by BPA completion. RESULTS:We included 805 patients: 493 in the preintervention cohort and 312 in the intervention cohort. In the intervention cohort, the BPA was completed for 180 (58%) patients. The association between predicted clinical risk of AF and incidence of 6-month extended cardiac monitoring was not different by time period (interaction HR = 1.00 [95% Confidence Interval (CI) 0.98; 1.02]). The intervention period was associated with an increased cumulative incidence of cardiac monitoring (adjusted HR = 1.32 [95% CI 1.03-1.69]). CONCLUSIONS:An embedded EHR tool displaying predicted AF risk in a poststroke setting had limited clinician engagement and predicted risk was not associated with the use of extended cardiac monitoring. CLINICAL TRIAL REGISTRATION:NCT04637087.

Introduction: Triggered atrial fibrillation (AF), defined as new-onset AF in the setting of a reversible physiological stressor, is common. However, risk factors, outcomes, and management remain poorly understood. Methods: We analyzed data from VITAL-AF, a pragmatic, cluster-randomized AF screening trial (2018-2019) of adults aged 65 and greater across 16 primary care practices affiliated with Massachusetts General Hospital, with 2 years of follow-up and adjudicated incident AF type (triggered vs. primary AF) and clinical outcomes. We compared associations between clinical AF risk factors and incident AF type (i.e, triggered vs non-triggered/primary) using Fine-Gray models. We quantified rates of OAC initiation following AF diagnosis. We then fit Cox proportional hazards models to measure the association between AF type and a composite endpoint of major bleeding, stroke, and all-cause mortality (pre-specified adjudicated VITAL-AF outcomes), with adjustment for CHA 2 DS 2 -VASc (stroke) and ATRIA (bleeding) scores and time-varying OAC exposure. Results: The study included 30,215 patients (59% female, 83% White, mean age 74). Of 998 incident AF events, 290 (29%) were triggered AF. Clinical risk factors including age, hypertension, and heart failure showed similar associations with both primary and triggered AF (Fig. 1). OAC initiation within 90 days of diagnosis was lower for triggered AF than primary AF, notably in medium (63% vs. 79%) and high (54% vs. 74%) CHA 2 DS 2 -VASc risk groups (p<0.05 for both) (Fig. 2). The incidence of the composite endpoint (per 100 person years) was 1.32 (95% CI 1.22-1.43), 8.06 (6.03-10.54), and 7.45 (4.42-11.78), for no AF, primary AF, and triggered AF, respectively (Fig. 3). In adjusted models, both primary (HR 2.23; 95% CI, 1.45-3.43) and triggered AF (HR 2.39; 95% CI, 1.36-4.22) were associated with similarly higher risk of the composite endpoint compared to no AF. Conclusions: Among over 30,000 primary care patients with manually adjudicated events, nearly one-third of incident AF cases were triggered. Despite similar risk factor profiles and similarly higher risk of AF-related adverse outcomes, OAC use appears lower when AF is triggered. Future work is needed to raise awareness of the substantial morbidity and mortality associated with triggered atrial fibrillation and to develop standardized approaches to risk stratification and anticoagulation in this population.

Background:High risk of intracranial hemorrhage (ICH) is a leading reason for withholding anticoagulation in patients with atrial fibrillation (AF). We aimed to develop a claims-based ICH risk prediction model in older adults with AF initiating oral anticoagulation (OAC).Methods:We used US Medicare claims data to identify new users of OAC aged ≥65 years with AF in 2010-2017. We used regularized Cox regression to select predictors of ICH. We compared our AF ICH risk score with the HAS-BLED bleed risk and Homer fall risk scores by area under the receiver operating characteristic curve (AUC) and assessed net reclassification improvement (NRI) when predicting 1-year risk of ICH.Results:Our study cohort comprised 840,020 patients (mean [SD] age 77.5 [7.4] years and female 52.2%) split geographically into training (3963 ICH events [0.6%] in 629,804 patients) and validation (1397 ICH events [0.7%] in 210,216 patients) sets. Our AF ICH risk score, including 50 predictors, had superior AUCs of 0.653 and 0.650 in the training and validation sets than the HAS-BLED score of 0.580 and 0.567 (p<0.001) and the Homer score of 0.624 and 0.623 (p<0.001). In the validation set, our AF ICH risk score reclassified 57.8%, 42.5%, and 43.9% of low, intermediate, and high-risk patients, respectively, by HAS-BLED score (NRI: 15.3%, p<0.001). Similarly, it reclassified 0.0, 44.1, and 19.4% of low, intermediate, and high-risk patients, respectively, by the Homer score (NRI: 21.9%, p<0.001).Conclusion:Our novel claims-based ICH risk prediction model outperformed the standard HAS-BLED score and can inform OAC prescribing decisions.

Background Atrial fibrillation (AF) often remains undiagnosed, and it independently raises the risk of ischemic stroke, which is largely reversible by oral anticoagulation. Although randomized trials using longer term screening approaches increase identification of AF, no studies have established that AF screening lowers stroke rates. Objectives To address this knowledge gap, the GUARD-AF (Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals) trial screened participants in primary care practices using a 14-day continuous electrocardiographic monitor to determine whether screening for AF coupled with physician/patient decision-making to use oral anticoagulation reduces stroke and provides a net clinical benefit compared with usual care. Methods GUARD-AF was a prospective, parallel-group, randomized controlled trial designed to test whether screening for AF in people aged ≥70 years using a 14-day single-lead continuous electrocardiographic patch monitor could identify patients with undiagnosed AF and reduce stroke. Participants were randomized 1:1 to screening or usual care. The primary efficacy and safety outcomes were hospitalization due to all-cause stroke and bleeding, respectively. Analyses used the intention-to-treat population. Results Enrollment began on December 17, 2019, and involved 149 primary care sites across the United States. The COVID-19 pandemic led to premature termination of enrollment, with 11,905 participants in the intention-to-treat population. Median follow-up was 15.3 months (Q1-Q3: 13.8-17.6 months). Median age was 75 years (Q1-Q3: 72-79 years), and 56.6% were female. The risk of stroke in the screening group was 0.7% vs 0.6% in the usual care group (HR: 1.10; 95% CI: 0.69-1.75). The risk of bleeding was 1.0% in the screening group vs 1.1% in the usual care group (HR: 0.87; 95% CI: 0.60-1.26). Diagnosis of AF was 5% in the screening group and 3.3% in the usual care group, and initiation of oral anticoagulation after randomization was 4.2% and 2.8%, respectively. Conclusions In this trial, there was no evidence that screening for AF using a 14-day continuous electrocardiographic monitor in people ≥70 years of age seen in primary care practice reduces stroke hospitalizations. Event rates were low, however, and the trial did not enroll the planned sample size.(Reducing Stroke by Screening for Undiagnosed Atrial Fibrillation in Elderly Individuals [GUARD-AF]; NCT04126486).

BACKGROUND:The "burden" of atrial fibrillation (AF) detected by screening likely influences stroke risk, but the distribution of burden is not well described. OBJECTIVES:This study aims to determine the frequency of AF and the distribution of AF burden found when screening individuals ≥70 years of age with a 14-day electrocardiograph monitor. METHODS:This is a cohort study of the screening arm of a randomized AF screening trial among those ≥70 years of age without a prior AF diagnosis (between 2019 and 2021). Screening was performed with a 14-day continuous electrocardiogram patch monitor. RESULTS:Analyzable patches were returned by 5,684 (95%) of screening arm participants; the median age was 75 years (Q1-Q3: 72-78 years), 57% were female, and the median CHA2DS2-VASc score was 3 (Q1-Q3: 2-4). AF was detected in 252 participants (4.4%); 29 (0.5%) patients had continuous AF and 223 (3.9%) had paroxysmal AF. Among those with paroxysmal AF, the average indices of AF burden were of low magnitude with right-skewed distributions. The median percent time in AF was 0.46% (Q1-Q3: 0.02%-2.48%), or 75 (Q1-Q3: 3-454) minutes, and the median longest episode was 38 (Q1-Q3: 2-245) minutes. The upper quartile threshold of 2.48% time in AF corresponded to 7.6 hours. Age >80 years was associated with screen-detected AF in our multivariable model (OR: 1.46; 95% CI: 1.06-2.02). CONCLUSIONS:Most AF detected in these older patients was very low burden. However, one-quarter of those with AF had multiple hours of AF, raising concern about stroke risk. These findings have implications for targeting populations for AF screening trials and for responding to heart rhythm alerts from mobile devices (GUARD-AF [A Study to Determine if Identification of Undiagnosed Atrial Fibrillation in People at least 70 Years of Age Reduces the Risk of Stroke]; NCT04126486).

ABSTRACT Importance Secondary prevention interventions to reduce post-stroke cognitive impairment (PSCI) can be aided by the early identification of high-risk individuals who would benefit from risk factor modification. Objective To develop and evaluate a predictive model to identify patients at increased risk of PSCI over 5 years using data easily accessible from electronic health records. Design Cohort study with patients enrolled between 2003-2016 with follow-up through 2022. Setting Primary care practices affiliated with two academic medical centers. Participants Individuals 45 years or older, without prior stroke or prevalent cognitive impairment, with primary care visits and an incident ischemic stroke between 2003-2016 (development/internal validation cohort) or 2010-2022 (external validation cohort). Exposures Predictors of PSCI were ascertained from the electronic health record. Main Outcome The outcome was incident dementia/cognitive impairment within 5 years and beginning 3 months following stroke, ascertained using ICD-9/10 codes. For model variable selection, we considered potential predictors of PSCI and constructed 400 bootstrap samples with two-thirds of the model derivation sample. We ran 10-fold cross-validated Cox proportional hazards models using a least absolute shrinkage and selection operator (LASSO) penalty. Variables selected in >25% of samples were included. Results The analysis included 332 incident diagnoses of PSCI in the development cohort (n=3,741), and 161 and 128 incident diagnoses in the internal (n=1,925) and external (n=2,237) validation cohorts. The c-statistic for predicting PSCI was 0.731 (95% CI: 0.694-0.768) in the internal validation cohort, and 0.724 (95% CI: 0.681-0.766) in the external validation cohort. A risk score based on the beta coefficients of predictors from the development cohort stratified patients into low (0-7 points), intermediate (8-11 points), and high (12-35 points) risk groups. The hazard ratios for incident PSCI were significantly different by risk categories in internal (High, HR: 6.2, 95% CI 4.1-9.3; Intermediate, HR 2.7, 95% CI: 1.8-4.1) and external (High, HR: 6.1, 95% CI: 3.9-9.6; Intermediate, HR 2.8, 95% CI: 1.9-4.3) validation cohorts. Conclusions and Relevance Five-year risk of PSCI can be accurately predicted using routinely collected data. Model output can be used to risk stratify and identify individuals at increased risk for PSCI for preventive efforts.

BackgroundSingle-lead electrocardiograms (1L ECG) are increasingly used for atrial fibrillation (AF) detection. Automated 1L ECG interpretation may possess prognostic value for future AF among cases where screening does not result in a short-term AF diagnosis.ObjectiveInvestigate the association between automated 1L ECG interpretation and incident AF.MethodsVITAL-AF was a randomized controlled trial investigating the effectiveness of screening for AF using 1L ECGs. For the present study, participants were divided into four groups based on automated classification of 1L ECGs. Patients with prevalent AF were excluded. Associations between groups and incident AF were assessed using Cox proportional hazards models adjusted for risk factors. The start of follow-up was defined as 60 days after the latest 1L ECG (as some individuals had numerous screening 1L ECGs).ResultsThe study sample included: Never screened (n=16,306), Normal (n=10,914), Other (n=2,675), Possible AF (n=561). Possible AF had the highest AF incidence (5.91 per 100 person-years, 95% Confidence Interval [CI] 4.24-8.23). Possible AF was associated with greater hazard of incident AF compared to Normal (adjusted Hazard Ratio (2.48, 95% CI 1.66-3.71). Other was associated with greater hazard of incident AF when compared to Normal (1.41, 95% CI 1.04-1.90).ConclusionsIn patients undergoing AF screening with 1L ECGs without prevalent AF or AF within 60 days of screening, presumptive positive and indeterminate 1L ECG interpretations were associated with future AF. Abnormal 1L ECGs may identify individuals at higher risk for future AF.

Background Days alive out of hospital (DAOH) is an objective and patient‐centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. Methods and Results ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double‐blind, double‐dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator‐reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin ( P =0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P =0.88). Conclusions DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

BACKGROUND: Transcatheter left atrial appendage occlusion (LAAO) is an alternative to oral anticoagulants (OACs) for stroke prevention in patients with atrial fibrillation, but the predictors of LAAO use in routine care are unclear. We aimed to assess the utilization trends of LAAO and compare the change in characteristics of LAAO users versus OACs since its marketing. METHODS: Using the US Medicare claims database (March 15, 2015, to December 31, 2020), we identified patients with atrial fibrillation, >= 65 years, and CHA(2)DS(2)-VASc score >= 2 (men) or >= 3 (women), with either first implantation of an LAAO device or initiation of OACs, including apixaban, dabigatran, rivaroxaban, edoxaban, or warfarin. Patient characteristics, measured 365 days before the first LAAO or OAC use date, were compared using logistic regression. RESULTS: There were 30 058 LAAO recipients (mean age, 77.74 years; female, 42.1%) and 792 600 OAC initiators (mean age, 78.48; female, 53.3%). In 2020, patients had higher odds of initiating LAAO use than in 2015 (0.52 versus 9.32%; adjusted odds ratio [aOR], 13.64 [95% CI, 12.56-14.81]). Old age (ie, >85 versus 65-75 years; aOR, 0.84 [95% CI, 0.80-0.88]), female sex (aOR, 0.74 [95% CI, 0.71-0.76]), Black race (aOR, 0.63 [95% CI, 0.58-0.68]) versus White race, and Medicaid eligibility (aOR, 0.61 [95% CI, 0.58-0.64]) were associated with lower odds of receiving LAAO. Among clinical characteristics, frailty, cancer, fractures, and venous thromboembolism were associated with lower odds of LAAO use, while history of intracranial and extracranial bleeding, coagulopathy, and falls were associated with higher odds of receiving LAAO. CONCLUSIONS: Among patients with atrial fibrillation receiving stroke-preventive therapy, LAAO use increased rapidly from 2015 to 2020 and was positively associated with the risk factors for OAC complications but negatively associated with old age, advanced frailty, and cancer. Black race and female sex were associated with a lower likelihood of receiving LAAO.

Aims This study aimed to develop and apply natural language processing (NLP) algorithms to identify recurrent atrial fibrillation (AF) episodes following rhythm control therapy initiation using electronic health records (EHRs). Methods and results We included adults with new-onset AF who initiated rhythm control therapies (ablation, cardioversion, or antiarrhythmic medication) within two US integrated healthcare delivery systems. A code-based algorithm identified potential AF recurrence using diagnosis and procedure codes. An automated NLP algorithm was developed and validated to capture AF recurrence from electrocardiograms, cardiac monitor reports, and clinical notes. Compared with the reference standard cases confirmed by physicians’ adjudication, the F-scores, sensitivity, and specificity were all above 0.90 for the NLP algorithms at both sites. We applied the NLP and code-based algorithms to patients with incident AF (n = 22 970) during the 12 months after initiating rhythm control therapy. Applying the NLP algorithms, the percentages of patients with AF recurrence for sites 1 and 2 were 60.7% and 69.9% (ablation), 64.5% and 73.7% (cardioversion), and 49.6% and 55.5% (antiarrhythmic medication), respectively. In comparison, the percentages of patients with code-identified AF recurrence for sites 1 and 2 were 20.2% and 23.7% for ablation, 25.6% and 28.4% for cardioversion, and 20.0% and 27.5% for antiarrhythmic medication, respectively. Conclusion When compared with a code-based approach alone, this study's high-performing automated NLP method identified significantly more patients with recurrent AF. The NLP algorithms could enable efficient evaluation of treatment effectiveness of AF therapies in large populations and help develop tailored interventions.