Clonal haematopoiesis of indeterminate potential and atrial fibrillation: an east Asian cohort study.

BACKGROUND AND AIMS: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. METHODS: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. RESULTS: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). CONCLUSIONS: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.

Reduction of Upper Gastrointestinal Bleeding Risk With Proton Pump Inhibitor Therapy in Asian Patients With Atrial Fibrillation Receiving Direct Oral Anticoagulant: A Nationwide Population-based Cohort Study.

BACKGROUND & AIMS: In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users. METHODS: We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model. RESULTS: A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHA2DS2-VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001). CONCLUSIONS: In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients.

Effect of physical activity on incident atrial fibrillation in individuals with varying duration of diabetes: a nationwide population study.

BACKGROUND: Diabetes mellitus (DM) duration affects incident atrial fibrillation (AF) risk; the effect of physical activity on mitigating AF risk related to varying DM duration remains unknown. We assessed the effect of physical activity on incident AF in patients with DM with respect to known DM duration. METHODS: Patients with type 2 DM who underwent the Korean National Health Insurance Service health examination in 2015-2016 were grouped by DM duration: new onset and < 5, 5-9, and ≥ 10 years. Physical activity was classified into four levels: 0, < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (MET)-min/week, with the primary outcome being new-onset AF. RESULTS: The study enrolled 2,392,486 patients (aged 59.3 ± 12.0 years, 39.8% female) with an average follow-up of 3.9 ± 0.8 years and mean DM duration of 5.3 ± 5.1 years. Greater physical activity was associated with a lower AF risk. Lowering of incident AF risk varied with different amounts of physical activity in relation to known DM duration. Among patients with new-onset DM, DM duration < 5 years and 5-9 years and 1,000-1,499 MET-min/week exhibited the lowest AF risk. Physical activity ≥ 1,500 MET-min/week was associated with the lowest incident AF risk in patients with DM duration ≥ 10 years (by 15%), followed DM duration of 5-9 years (12%) and < 5 years (9%) (p-for-interaction = 0.002). CONCLUSIONS: Longer DM duration was associated with a high risk of incident AF, while increased physical activity generally reduced AF risk. Engaging in > 1,500 MET-min/week was associated with the greatest AF risk reduction in patients with longer DM duration, highlighting the potential benefits of higher activity levels for AF prevention.

Plasma apixaban concentrations and thrombin generation assay parameters in response to dose reduction for atrial fibrillation.

AIMS: To investigate plasma apixaban concentrations and thrombin generation assay (TGA) parameters across different apixaban doses in atrial fibrillation patients who had dose-reduction criteria for apixaban. METHODS: This observational study included 374 patients (mean age 75.6 ± 7.7 years, 54.8% female) with dose-reduction criteria for apixaban. The patients were divided into 3 groups: (i) on-label standard dose (5 mg twice daily, n = 166); (ii) on-label reduced dose (2.5 mg twice daily, n = 55); and (iii) off-label underdose (2.5 mg twice daily, n = 153). Apixaban concentrations determined via the anti-Xa assay and TGA parameters were compared at trough levels. RESULTS: The off-label underdose group exhibited significantly lower apixaban trough concentrations than the on-label reduced-dose and standard-dose groups (56.7 ± 42.9 vs. 83.7 ± 70.4 vs. 129.9 ± 101.8 ng/mL, all P < .001). Less than 70% of all patients fell within the expected range of apixaban concentrations. Proportions exceeding the upper limit of the expected range were significantly lower in the off-label underdose group (1.3%) than in the on-label reduced-dose (9.1%, P = .005) and standard-dose (12.7%, P < .001) groups. The TGA parameters showed the on-label standard-dose group displaying the lowest thrombogenic profiles. Lower creatinine clearance was the most significant predictor of higher apixaban concentrations. CONCLUSION: Off-label underdosed apixaban resulted in lower apixaban concentrations than both on-label standard and reduced-dose regimens. A considerable proportion of the patients exhibited apixaban concentrations outside the expected range, suggesting the potential benefits of plasma concentration monitoring. Further studies are needed to compare dosages directly, investigate the impact of plasma apixaban concentration monitoring and validate the current dose-reduction criteria.

Association between antithrombotic therapy after stroke in patients with atrial fibrillation and the risk of net clinical outcome: an observational cohort study.

AIMS: Data on the optimal use of antithrombotic drugs and associated clinical outcomes in patients with atrial fibrillation (AF) and acute ischaemic stroke (IS) are limited. We investigated the prescription patterns of antithrombotics in community practice and long-term clinical prognosis according to early post-stroke antithrombotic therapy in patients with AF and acute IS. METHODS AND RESULTS: Patients with AF who were admitted for acute IS at a single tertiary hospital in 2010-2020 were retrospectively reviewed. Clinical profiles including the aetiology of stroke and prescription patterns of antithrombotics were identified. The net clinical outcome (NCO)-the composite of recurrent stroke, any bleeding, hospitalization or emergency department visits for cardiovascular (CV) events, and death-was compared according to the antithrombotic therapy at the first outpatient clinic visit [oral anticoagulation (OAC) alone vs. antiplatelet (APT) alone vs. OAC/APT(s)] following discharge. A total of 918 patients with AF and acute IS (mean age, 72.6 years; male, 59.3%; mean CHA2DS2-VASc score 3.3) were analysed. One-third (33.9%, n = 310) of patients were simultaneously diagnosed with AF and IS. The most common aetiology of IS was cardioembolism (71.2%), followed by undetermined aetiology (19.8%) and large artery atherosclerosis (6.0%). OAC, APT(s), and concomitant OAC and APT(s) were prescribed in 33.4%, 11.1%, and 53.4% of patients during admission that changed to 67.0%, 9.1%, and 21.7% at the first outpatient clinic, and were mostly continued up to one year after IS. Non-prescription of OAC was observed in 11.3% of post-stroke patients with AF. During a median follow-up of 2.1 years, the overall incidence rate of NCO per 100 patient-year (PY) was 20.14. APT(s) monotherapy presented the highest cumulative risk of NCO (adjusted hazard ratio 1.47, 95% confidence interval 1.08-2.00, P = 0.015; with reference to OAC monotherapy) mainly driven by the highest rates of recurrent stroke and any bleeding. OAC/APT(s) combination therapy was associated with a 1.62-fold significantly higher risk of recurrent stroke (P = 0.040) and marginally higher risk of any bleeding than OAC monotherapy. CONCLUSION: Approximately one-third of acute IS in AF have a distinctive mechanism from cardioembolism. Although APT was frequently prescribed in post-stroke patients with AF, no additive clinical benefit was observed. Adherence to OAC treatment is essential to prevent further CV adverse events in patients with AF and IS.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Accelerometer-derived physical activity and the risk of death, heart failure, and stroke in patients with atrial fibrillation: a prospective study from UK Biobank.

OBJECTIVE: Data on cardiovascular outcomes according to objectively measured physical activity (PA) in patients with atrial fibrillation (AF) are scarce. This study explored the associations between PA derived from wrist-worn accelerometers and the risk of death, incident heart failure (HF), and incident stroke in patients with AF. METHODS: From 37 990 patients with AF in UK Biobank, 2324 patients with accelerometer data were included. Weekly moderate-to-vigorous PA (MVPA) duration was computed from accelerometer data. The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular mortality, incident HF, and incident stroke. Restricted cubic splines estimated the dose-response associations between MVPA duration and the outcomes. The adjusted HRs (aHRs) of the outcomes according to adherence to PA standard guidelines (performing MVPA≥150 min/week) were also evaluated. RESULTS: The mean age was 66.9±6.2 years and 64.9% were male. During a median follow-up of 6.7 years, there were 181 all-cause deaths, 62 cardiovascular deaths, 225 cases of incident HF, and 91 cases of incident stroke; the overall incidence rate per 1000 patient-years was 11.76, 4.03, 15.16 and 5.99, respectively. There was a linear inverse dose-response relationship between MVPA (≥108 min/week) and all-cause mortality. Performing MVPA for 105-590 min/week was associated with a lower risk of HF than those with no measurable MVPA. The risk of stroke and cardiovascular mortality was not associated with MVPA. Performing guideline-adherent MVPA was related to a 30% lower risk of all-cause mortality (aHR: 0.70 (0.50-0.98), p=0.04) and 33% lower risk of HF (aHR 0.67 (0.49-0.93), p=0.02). CONCLUSION: In patients with AF, accelerometer-derived PA data supports lower risks of all-cause mortality and HF according to a greater level of MVPA and adherence to PA guidelines. Regular MVPA should be encouraged in patients with AF as a part of integrated management.

Three-Day Monitoring of Adhesive Single-Lead Electrocardiogram Patch for Premature Ventricular Complex: Prospective Study for Diagnosis Validation and Evaluation of Burden Fluctuation.

BACKGROUND: Wearable electrocardiogram (ECG) monitoring devices are used worldwide. However, data on the diagnostic yield of an adhesive single-lead ECG patch (SEP) to detect premature ventricular complex (PVC) and the optimal duration of wearing an SEP for PVC burden assessment are limited. OBJECTIVE: We aimed to validate the diagnostic yield of an SEP (mobiCARE MC-100, Seers Technology) for PVC detection and evaluate the PVC burden variation recorded by the SEP over a 3-day monitoring period. METHODS: This is a prospective study of patients with documented PVC on a 12-lead ECG. Patients underwent simultaneous ECG monitoring with the 24-hour Holter monitor and SEP on the first day. On the subsequent second and third days, ECG monitoring was continued using only SEP, and a 3-day extended monitoring was completed. The diagnostic yield of SEP for PVC detection was evaluated by comparison with the results obtained on the first day of Holter monitoring. The PVC burden monitored by SEP for 3 days was used to assess the daily and 6-hour PVC burden variations. The number of patients additionally identified to reach PVC thresholds of 10%, 15%, and 20% during the 3-day extended monitoring by SEP and the clinical factors associated with the higher PVC burden variations were explored. RESULTS: The recruited data of 134 monitored patients (mean age, 54.6 years; males, 45/134, 33.6%) were analyzed. The median daily PVC burden of these patients was 2.4% (IQR 0.2%-10.9%), as measured by the Holter monitor, and 3.3% (IQR 0.3%-11.7%), as measured in the 3-day monitoring by SEP. The daily PVC burden detected on the first day of SEP was in agreement with that of the Holter monitor: the mean difference was -0.07%, with 95% limits of agreement of -1.44% to 1.30%. A higher PVC burden on the first day was correlated with a higher daily (R2=0.34) and 6-hour burden variation (R2=0.48). Three-day monitoring by SEP identified 29% (12/42), 18% (10/56), and 7% (4/60) more patients reaching 10%, 15%, and 20% of daily PVC burden, respectively. Younger age was additionally associated with the identification of clinically significant PVC burden during the extended monitoring period (P=.02). CONCLUSIONS: We found that the mobiCARE MC-100 SEP accurately detects PVC with comparable diagnostic yield to the 24-hour Holter monitor. Performing 3-day PVC monitoring with SEP, especially among younger patients, may offer a pragmatic alternative for identifying more individuals exceeding the clinically significant PVC burden threshold.

Correction: Three-Day Monitoring of Adhesive Single-Lead Electrocardiogram Patch for Premature Ventricular Complex: Prospective Study for Diagnosis Validation and Evaluation of Burden Fluctuation.

[This corrects the article DOI: 10.2196/46098.].

Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

BACKGROUND: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION: This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Risk of newly developed atrial fibrillation by alcohol consumption differs according to genetic predisposition to alcohol metabolism: a large-scale cohort study with UK Biobank.

BACKGROUND: The predictive relationship between mild-to-moderate alcohol consumption and the risk of incident atrial fibrillation (AF) remains controversial. OBJECTIVE: We investigated whether the relationship between alcohol consumption and the risk of incident AF could be associated with the genetic predisposition to alcohol metabolism. METHODS: A total of 399,329 subjects with genetic data from the UK Biobank database, enrolled between 2006 and 2010, were identified and followed for incident AF until 2021. Genetic predisposition to alcohol metabolism was stratified according to the polygenic risk score (PRS) tertiles. Alcohol consumption was categorized as non-drinkers, mild-to-moderate drinkers (< 30 g/day), and heavy drinkers (≥ 30 g/day). RESULTS: During the follow-up (median 12.2 years), 19,237 cases of AF occurred. When stratified by PRS tertiles, there was a significant relationship between genetic predisposition to alcohol metabolism and actual alcohol consumption habits (P < 0.001). Mild-to-moderate drinkers showed a decreased risk of AF (HR 0.96, 95% CI 0.92-0.99), and heavy drinkers showed an increased risk of AF (HR 1.06, 95% CI 1.02-1.10) compared to non-drinkers. When stratified according to PRS tertiles for genetic predisposition to alcohol metabolism, mild-to-moderate drinkers had equivalent AF risks, and heavy drinkers showed increased AF risk in the low PRS tertile group. However, mild-to-moderate drinkers had decreased AF risks and heavy drinkers showed similar risks of AF in the middle/high PRS tertile groups. CONCLUSIONS: Differential associations between alcohol consumption habits and incident AF across genetic predisposition to alcohol metabolism were observed; individuals with genetic predisposition to low alcohol metabolism were more susceptible to AF.

Atrial fibrillation: comorbidities, lifestyle, and patient factors.

Modern anticoagulation therapy has dramatically reduced the risk of stroke and systemic thromboembolism in people with atrial fibrillation (AF). However, AF still impairs quality of life, increases the risk of stroke and heart failure, and is linked to cognitive impairment. There is also a recognition of the residual risk of thromboembolic complications despite anticoagulation. Hence, AF management is evolving towards a more comprehensive understanding of risk factors predisposing to the development of this arrhythmia, its' complications and interventions to mitigate the risk. This review summarises the recent advances in understanding of risk factors for incident AF and managing these risk factors. It includes a discussion of lifestyle, somatic, psychological, and socioeconomic risk factors. The available data call for a practice shift towards a more individualised approach considering an increasingly broader range of health and patient factors contributing to AF-related health burden. The review highlights the needs of people living with co-morbidities (especially with multimorbidity), polypharmacy and the role of the changing population demographics affecting the European region and globally.

Comparison of Novel Telemonitoring System Using the Single-lead Electrocardiogram Patch With Conventional Telemetry System.

BACKGROUND AND OBJECTIVES: Although a single-lead electrocardiogram (ECG) patch may provide advantages for detecting arrhythmias in outpatient settings owing to user convenience, its comparative effectiveness for real-time telemonitoring in inpatient settings remains unclear. We aimed to compare a novel telemonitoring system using a single-lead ECG patch with a conventional telemonitoring system in an inpatient setting. METHODS: This was a single-center, prospective cohort study. Patients admitted to the cardiology unit for arrhythmia treatment who required a wireless ECG telemonitoring system were enrolled. A single-lead ECG patch and conventional telemetry were applied simultaneously in hospitalized patients for over 24 hours for real-time telemonitoring. The basic ECG parameters, arrhythmia episodes, and signal loss or noise were compared between the 2 systems. RESULTS: Eighty participants (mean age 62±10 years, 76.3% male) were enrolled. The three most common indications for ECG telemonitoring were atrial fibrillation (66.3%), sick sinus syndrome (12.5%), and atrioventricular block (10.0%). The intra-class correlation coefficients for detecting the number of total beats, atrial and ventricular premature complexes, maximal, average, and minimal heart rates, and pauses were all over 0.9 with p values for reliability <0.001. Compared to a conventional system, a novel system demonstrated significantly lower signal noise (median 0.3% [0.1-1.6%] vs. 2.4% [1.4-3.7%], p<0.001) and fewer episodes of signal loss (median 22 [2-53] vs. 64 [22-112] episodes, p=0.002). CONCLUSIONS: The novel telemonitoring system using a single-lead ECG patch offers performance comparable to that of a conventional system while significantly reducing signal loss and noise. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0008176.

Combination of early rhythm control and healthy lifestyle on the risk of stroke in elderly patients with new-onset atrial fibrillation: a nationwide population-based cohort study.

Background: The impact of early rhythm control (ERC) combined with healthy lifestyle (HLS) on the risk of ischemic stroke in elderly patients with atrial fibrillation (AF) remains unaddressed. Objective: To evaluate the impact of combined ERC and HLS on the risk of stroke in elderly patients with new-onset AF. Methods: Using the Korean National Health Insurance Service database, we included patients aged ≥75 years with new-onset AF from January 2009 to December 2016 (n = 41,315). Patients who received rhythm control therapy within 2 years of AF diagnosis were defined as the ERC group. Non-smoking, non-to-mild alcohol consumption (<105 g/week), and regular exercise were defined as HLS. Subjects were categorized into four groups: group 1 (without ERC and HLS, n = 25,093), 2 (HLS alone, n = 8,351), 3 (ERC alone, n = 5,565), and 4 (both ERC and HLS, n = 2,306). We assessed the incidence of ischemic stroke as the primary outcome, along with admissions for heart failure, all-cause death, and the composite of ischemic stroke, admission for heart failure, and all-cause death. Results: Median follow-up duration of the study cohort was 3.4 years. After adjusting for multiple variables, groups 2 and 3 were associated with a lower stroke risk (adjusted hazard ratio [aHR]: 95% confidence interval [CI]: 0.867, 0.794-0.948 and 0.713, 0.637-0.798, respectively) than that of group 1. Compared to Group 1, group 4 showed the lowest stroke risk (aHR: 0.694, 95% CI: 0.586-0.822) among all groups, followed by group 3 (0.713, 0.637-0.798) and group 2 (0.857, 0.794-0.948), respectively. Group 4 was associated with the lowest risk of all-cause death (aHR: 0.680, 95% CI: 0.613-0.754) and the composite outcome (aHR: 0.708, 95% CI: 0.649-0.772). Conclusion: ERC and HLS were associated with a lower risk of ischemic stroke in elderly patients with new-onset AF. Concurrently implementing ERC and maintaining HLS was associated with the lowest risk of death and the composite outcome, with a modest synergistic effect on stroke prevention.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

Background: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Trial Registration: Clinicaltrials.gov: NCT05801068.

Early Rhythm Control and Incident Dementia in Patients With Atrial Fibrillation and Prior Stroke.

BACKGROUND: Although early rhythm control (ERC) in patients with atrial fibrillation (AF) reduces the risk of stroke, there is no evidence thus far on whether ERC reduces the risk of developing dementia in patients with AF and prior stroke. OBJECTIVES: This study sought to evaluate whether ERC reduces the risk of developing dementia in patients with new-onset AF and prior stroke. METHODS: Using the Korean nationwide claims database, we identified patients with new-onset AF and prior stroke between 2010 and 2016. Patients who received rhythm control therapy within 1 year after AF onset were defined as the ERC group, otherwise patients were categorized as the usual care group. A propensity score weighting method was used to balance the 2 groups. Incident dementia defined by relevant diagnostic codes was evaluated. RESULTS: A total of 41,370 patients were included (mean age 70 ± 11 years; mean CHA2DS2-VASc score 5.3 ± 1.6): 10,213 in the ERC group and 31,157 in the usual care group. Compared with usual care, ERC was associated with lower risks of all dementia, Alzheimer's dementia, and vascular dementia (weighted HR: 0.825 [95% CI: 0.776-0.876], 0.831 [95% CI: 0.774-0.893], and 0.800 [95% CI: 0.702-0.913], respectively, all P < 0.001). The benefit of ERC was slightly accentuated in the younger age group (<65 years). The beneficial effect of ERC in reducing the risk of dementia was consistent regardless of the characteristics of prior stroke. CONCLUSIONS: ERC might be beneficial in the prevention of dementia in patients with AF and prior stroke. To prevent the progression of cognitive dysfunction, ERC should be considered in this population.

Performance and Physician Experience of INGEVITY+ Active Fixation Leads: Prospective INGEVITY+ Lead Clinical Study in Korea.

Background: Boston Scientific INGEVITY+ pacing lead (Boston Scientific, Marlborough, MA, USA) has been upgraded to INGEVITY. The performance of the INGEVITY+ pacing lead has not yet been reported. This study aimed to evaluate the short- and long-term safety, effectiveness, and handling experience of INGEVITY+ leads. Methods: Consecutive patients were included from 9 institutions in Korea, where 400 leads (200 right ventricular active fixation leads and 200 right atrial active fixation leads) were implanted or attempted in 200 subjects. Results: During the implantation, only one patient required a lead change because of lead screw failure. The handling questionnaires of the lead received very positive feedback with 88% of operators agreeing that it is easy for leads to pass through small vessels or vessels with multiple leads. At the 3-month follow-up, 95.7% of RA leads and 99.5% of RV leads had pacing thresholds less than 1.5 V. A total of 92.4% of atrial leads had amplitudes greater than 1.5 mV, and 96.5% of ventricular leads had sensing amplitudes greater than 5 mV at 3 months. A total of 99.8% had impedances between 300 and 1,300 ohms. The lead-related complication-free rate for all leads during follow-up was 100%, and the overall rates of lead dislodgment, perforation, and pericardial effusion were all 0.0%. Conclusions: The INGEVITY+ pacing lead exhibited exceptional clinical performance, with a high complication-free rate throughout the 3-month follow-up period. In addition, the lead displayed excellent electrical characteristics, and the lead-handling experience was reported to be very good.

Neuroticism and the Risk of Atrial Fibrillation: An Observational Epidemiologic and Mendelian Randomization Study.

Background: The association between neuroticism and atrial fibrillation (AF) remains unknown. Objectives: This study aimed to assess the epidemiological and causal relationships between neuroticism and AF. Methods: Individuals without AF history were selected From the UK Biobank nationwide prospective cohort study. Participants were divided into 2 groups (high and low) based on the median summary score from a self-questionnaire of 12 neurotic behavior domains. The 10-year AF risk was compared between the neuroticism score groups using inverse probability of treatment weighting. The causal relationship between neuroticism and AF was evaluated using a 2-sample summary-level Mendelian randomization with the inverse variance-weighted method. Results: Of 394,834 participants (mean age 56.3 ± 8.1 years, 45.9% male), AF occurred in 23,509 (6.0%) during a 10-year follow-up. The risk of incident AF significantly increased in the high neuroticism score group (score ≥4) (inverse probability of treatment weighting-adjusted HR: 1.05; 95% CI: 1.02-1.09; P = 0.005) compared with the low neuroticism group. In the subgroup analysis, younger age, lower body mass index, or nonsmoker/ex-smoker participants were particularly susceptible to increased AF risk due to high neuroticism scores. A Mendelian randomization analysis showed a significant causal relationship between an increase in neuroticism score and increased risk of AF (OR by inverse variance-weighted method 1.06; 95% CI: 1.02-1.11; P = 0.007) without evidence of reverse causality. Conclusions: There was a significant longitudinal and causal relationship between neuroticism and AF. An integrated care including active mental health screening and management may benefit in high-risk populations.

Clinical Impact of Early Rhythm Control and Healthy Lifestyles in Patients With Atrial Fibrillation.

BACKGROUND: There are limited data regarding the combined effect of early rhythm control (ERC) and healthy lifestyle (HLS) behaviors on the risk of ischemic stroke in patients with atrial fibrillation (AF). OBJECTIVES: This study sought to evaluate how the combination of ERC and HLS behaviors affects the risk of ischemic stroke in patients with AF. METHODS: Using the Korean National Health Insurance database, we included patients with new-onset AF between 2009 and 2016 (n = 208,662). Patients who received rhythm control therapy within 2 years after AF diagnosis were defined as the ERC group. Patients with ≥2 HLS behaviors were defined as the HLS group. Patients were categorized into 4 groups: group 1, without ERC and without HLS (n = 46,972); group 2, with HLS alone (n = 110,479); group 3, with ERC alone (n = 15,133); and group 4, with both ERC and HLS (n = 36,078). The primary outcome was ischemic stroke. RESULTS: Compared to group 1, group 2 and group 3 were associated with a lower risk of stroke (HR: 0.769 [95% CI: 0.728-0.881] and HR: 0.774 [95% CI: 0.703-0.852], respectively). Group 4 showed the lowest risk of stroke (HR: 0.575; 95% CI: 0.536-0.617). After propensity score weighting, the incorporation of additional ERC alongside HLS was associated with a relative risk reduction of 22% for stroke, and additional HLS alongside ERC were associated with a relative risk reduction of 27% for stroke. CONCLUSIONS: Each of ERC and HLS might reduce the risk of ischemic stroke in patients with new-onset AF. The presence of both ERC and HLS is associated with an enhanced benefit for stroke prevention in this population.

RandomizEd comparison of PRogrESsion of atherosclerotic plaquEs aNd calcificaTion of coronary artery in Atrial Fibrillation patients treated with edoxaban versus warfarin (The REPRESENT-AF trial).

BACKGROUND: Although the adverse effects of long-term use of vitamin K oral anticoagulant (OAC), warfarin, on the coronary vasculature are well established, it remains unknown whether non-vitamin K oral anticoagulants play a role in the attenuation of plaque progression and coronary calcification. This study aimed to compare changes in atherosclerotic plaques and calcification of the coronary arteries in patients with atrial fibrillation (AF) treated with edoxaban and warfarin. METHODS: A total of 150 OAC-naïve patients with AF and atherosclerotic lesions on coronary computed tomography angiography (CCTA) were enrolled and randomly assigned to the edoxaban or warfarin treatment groups. All enrolled patients received rosuvastatin 10mg and 119 patients completed the entire study protocol. Twelve months after the assigned OAC treatment, follow-up CCTA was performed, and changes in plaque and calcium volumes of the coronary arteries were analyzed. RESULTS: Baseline characteristics of the two groups were well-balanced. The percentage of time in therapeutic range in the warfarin group was 61.1%. Compared with the baseline CCTA, there was a significant reduction in plaque volume after 12 months of OAC and rosuvastatin administration in both groups, and the extent of regression did not differ significantly between the two groups. The increase in calcium volume was greater in the warfarin group than in the edoxaban group, but the difference was not significant. CONCLUSION: In OAC-naïve, moderate-intensity statin treated patients with AF and atherosclerotic coronary lesions, edoxaban use did not have a positive effect on atherosclerotic plaques and coronary calcification compared with warfarin use over a 12-month follow-up period.