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Background: Genetic variation and modifiable risk factors play a significant role in the pathogenesis of atrial fibrillation (AF). The influence of epigenetic modification on AF remains to be elucidated. We investigated the role of DNA methylation in the etiology of AF. Epigenetic evaluation was performed in 115 AF patients who underwent radiofrequency catheter ablation in a single institution. We measured methylation at approximately 850,000 bp cytosine-phosphate-guanine (CpG) sites in the 115 samples. The degree of methylation was compared across seven classification criteria: type of AF, late recurrence, impaired left atrium (LA) function, late gadolinium enhancement, LA diameter, LA volume, and flow velocity of the LA appendage., Results: The four most significantly methylated genes were DEFB104B, C3, TANC1, and TMEM9B. The DEFB104B gene (cg20223677 in the transcription start site), which encodes β-defensin 104B, was hypomethylated in three groups: AF patients with late recurrence, impaired LA function, and impaired LAA flow velocity. Enriched functional annotation of the differentially methylated datasets revealed that five out of the seven AF groups in this cohort were associated with genes involved in the cell movement of endothelial cell lines, sprouting angiogenesis by endothelial cell lines, or migration of endothelial cell lines., Conclusions: Epigenetic profiling revealed that epigenetic modification might affect important characteristics of AF. Our results suggest that the pathogenesis of AF might be affected by not only genetic variation or modifiable factors but also by epigenetic modulation., Competing Interests: Declarations. Conflict of interests: The authors have no conflicts of interest and no relationships with industry. Ethical approval and consent to participate: The Institutional Review Board of the Korea University Medicine Anam Hospital approved this study. The requirement for written informed consent was waived by the Institutional Review Board of Korea University Medicine Anam Hospital because of the retrospective nature of the study. Consent for publication: Not applicable., (© 2024. The Author(s).)

Aims: Evidence of an association between atrial fibrillation (AF) and sudden cardiac arrest (SCA) in young adults is limited. In this study, we aim to evaluate this association in a general population aged between 20 and 39 years., Methods and Results: Young adults who underwent health check-ups between 2009 and 2012 were screened from a nationwide healthcare database in South Korea. A history of AF diagnosis before the health check-ups was identified based on the relevant International Classification of Diseases, 10th edition codes reported in the database. Associations between an established diagnosis of AF and the risk of SCA during follow-up were examined. A total of 6 345 162 young people were analysed with a mean follow-up duration of 9.4 years. The mean age was 30.9 ± 5.0 years, and 5875 (0.09%) individuals were diagnosed with AF. During follow-up, SCA occurred in 5352 (0.08%) individuals, and the crude incidence was 0.56 and 0.09 events per 1000 person-years for participants with and without AF, respectively. Individuals with AF had a 3.0-fold higher risk in a multivariate model adjusted for age, sex, lifestyle, anthropometric data, and medical comorbidities (adjusted hazard ratio 2.96, 95% confidence interval 1.99-4.41, P < 0.001). Both incident and prevalent AFs were associated with an increased risk of SCA, with no significant differences between the two groups., Conclusion: Atrial fibrillation was associated with a significantly higher risk of SCA developing in healthy young adults. Whether the rate or rhythm control influences the risk of SCA in young patients with AF remains to be examined., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Early rhythm control therapy mainly with antiarrhythmic drugs (AADs) for new-onset atrial fibrillation (AF) reduces major adverse cardiovascular events. However, negative dromotropic effects of AADs via ion channel blocking may cause bradyarrhythmias., Objectives: This study aimed to evaluate the association between AAD use and the risk of pacemaker implantation or syncope in patients with new-onset AF receiving early rhythm control therapy with AADs., Methods: This study was based on data from the Korean National Health Insurance Service system. We screened all new-onset AF diagnoses that occurred from 2013 to 2019 and identified patients who were prescribed AADs within 1 year of AF diagnosis. The risk of pacemaker implantation or syncope was compared between AAD users and nonusers., Results: A total of 770,977 new-onset AF cases were identified and 142,141 patients were prescribed AADs. After multivariate adjustment, use of AADs was associated with 3.5-, 2.0-, and 5.0-fold increased risk of pacemaker implantation or syncope, syncope, and pacemaker implantation, respectively. Propensity score-matched analysis revealed similar results, demonstrating a significant association between AAD use and the risk of pacemaker implantation or syncope. This association was consistent across various subgroups. Women were more susceptible to adverse effects of AADs than men., Conclusions: This study showed an association between AADs and risk of pacemaker implantation or syncope, a consistent finding across various subgroups. Precise evaluation of such risk should be undertaken before prescription of AADs., Competing Interests: Funding Support and Author Disclosures This work was supported by a Korea University grant (Dr Jong-Il Choi), a grant from Korea University Anam Hospital, Seoul, Republic of Korea (Dr Jong-Il Choi), and in part by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT, Ministry of Science and ICT) (No. 2021R1A2C2011325 to Dr Jong-Il Choi). The funders had no role in data collection, analysis, or interpretation; trial design; patient recruitment; or any other aspect pertinent to the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The risk of having atrial fibrillation (AF) is associated with alcohol intake. However, it is not clear whether sudden cardiac arrest (SCA) and ventricular arrhythmia (VA) including ventricular tachycardia, flutter, or fibrillation have similar associations with alcohol. We aimed to evaluate the association of alcohol intake with all-cause death, new-onset AF, VA, and SCA using single cohort with a sufficient sample size. A total of 3,990,373 people without a prior history of AF, VAs, or SCA was enrolled in this study based on nationwide health check-up in 2009. We classified the participants into four groups according to weekly alcohol consumption, and evaluated the association of alcohol consumption with each outcome. We observed a significant association between mild (hazard ratio [HR] = 0.826; 95% confidence interval [CI] = 0.815-0.838) to moderate (HR = 0.930; 95% CI = 0.912-0.947) drinking with decreased risk of all-cause mortality. However heavy drinking (HR = 1.108; 95% CI = 1.087-1.129) was associated with increased all-cause death. The risk of new-onset AF was significantly associated with moderate (HR = 1.129; 95% CI = 1.097-1.161) and heavy (HR = 1.298; 95% CI = 1.261-1.337) drinking. However, the risk of SCA showed negative association with all degrees of alcohol intake: 20% (HR = 0.803; 95% CI = 0.769-0.839), 15% (HR = 0.853; 95% CI = 0.806-0.902), and 8% (HR = 0.918; 95% CI = 0.866-0.974) lower risk for mild, moderate, and heavy drinkers, respectively. Mild drinking was associated with reduced risk of VA with moderate and heavy drinking having no associations. In conclusion, the association between alcohol and various outcomes in this study were heterogeneous. Alcohol might have different influences on various cardiac disorders., (© 2024. The Author(s).)

Background: Impaired atrial functional reserve during exercise may represent an early stage of atrial cardiomyopathy. To test this hypothesis, the authors evaluated left atrial (LA) and left ventricular (LV) function reserve during exercise in patients with paroxysmal atrial fibrillation (PAF)., Methods: Sixty-one patients with PAF undergoing radiofrequency catheter ablation and 38 healthy control subjects were prospectively enrolled. LV global longitudinal strain and LA reservoir strain (RS) were measured at rest and during supine bicycle exercise. To identify the early stage of atrial cardiomyopathy without LA structural remodeling, patients with PAF were divided into two groups according to LA volume index (LAVI): atrial fibrillation (AF) group 1 (LAVI ≥ 34 mL/m 2 ) and AF group 2 (LAVI < 34 mL/m 2 )., Results: LV ejection fraction and global longitudinal strain did not differ between patients with AF and control subjects. LAVI and LA RS did not differ between AF group 2 and control subjects. During exercise, LV global longitudinal strain improved in all groups. Increases in LA RS were attenuated in both AF groups, which also exhibited lower LA functional reserve index than the control subjects. Although resting LA RS was similar between AF group 2 and control subjects, LA functional reserve index was significantly lower in AF group 2. LA functional reserve index was associated with risk for AF recurrence (hazard ratio, 0.852; 95% CI, 0.736-0.988)., Conclusions: Atrial cardiomyopathy can be anticipated by impaired LA functional reserve during exercise in patients with AF, even in those with normal-sized left atria. Atrial cardiomyopathy occurs independently of changes in LV function and is associated with the recurrence of AF in patients with PAF after radiofrequency catheter ablation., (Copyright © 2022 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Aims: An epicardial approach is an effective means to detect and eliminate residual potentials in non-transmural lesions created during prior endocardial ablation. We sought to determine the impact of a combined epicardial and endocardial approach compared with a conventional endocardial approach, on recurrence-free survival after redo ablation., Methods and Results: Participants with recurred persistent atrial fibrillation after prior endocardial ablation were randomized (1:1) to undergo treatment with the combined approach (epicardial followed by endocardial ablation) for the treatment group or conventional approach (endocardial ablation only) for the control group. The primary outcome was the time to recurrence of atrial fibrillation or atrial tachycardia following a 90-day blanking period within 12 months after the procedure. The secondary safety outcome was the occurrence of procedure-related complications within 24 h after the procedure. Of 100 randomized participants {median age, 59.0 [(interquartile range (IQR): 53.8-64.3] years, including 16% women, with one prior ablation (IQR: 1-1)}, 93 (93%) completed the trial. Events relevant to the primary outcome occurred in 16 patients in the treatment group and in 21 patients in the control group {Kaplan-Meier estimator percentages, 32 vs. 42%; hazard ratio, 0.71 [95% confidence interval (CI): 0.37-1.37]}. The periprocedural complication rate was lower in the treatment group [2 vs. 16%; odds ratio, 0.11 (95% CI: 0.00-0.87)] with similar achievement of the procedural endpoint in the two groups., Conclusion: In the redo procedure for persistent atrial fibrillation, the combined approach had no significant difference of recurrence-free survival and a lower procedural complication rate compared with the conventional approach., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Atrial fibrosis can present as an arrhythmogenic substrate that is correlated with higher recurrence after catheter ablation for atrial fibrillation. Galectin-3, a beta-galactoside-binding lectin, is highly expressed and secreted from macrophages and is important in inflammation and fibrosis. We assessed the clinical implications of serum galectin-3 in patients with atrial fibrillation. This was a prospective cohort study of consecutive patients who underwent radiofrequency catheter ablation in a tertiary referral center from February 2017 to September 2017. Intracardiac blood sampling, echocardiographic measurements, magnetic resonance imaging with late gadolinium enhancement, electrophysiologic testing, and endocardial voltage mapping were consistently implemented in 75 patients before the ablation. Serum galectin-3 level was higher in patients with diabetes mellitus and was correlated with values that indicated the left atrial size. During a median 14 months of follow-up, atrial tachyarrhythmia recurred in 27% of patients. In multivariable Cox regression analysis, non-paroxysmal atrial fibrillation (hazard ratio 6.8; 95% confidence interval 1.6-28.9) and higher galectin-3 levels (hazard ratio 1.3; 95% confidence interval 1.0-1.7) were associated with increased risk of recurrence. Serum galectin-3 may be a prognostic biomarker for risk stratification in patients with atrial fibrillation planned catheter ablation., (© 2022. The Author(s).)

Importance: The risk of atrial fibrillation (AF) in people with depression is not fully known. Depression is associated with sympathetic activation and emotional stress, which might increase the risk of new-onset AF., Objective: To assess the incidence of new-onset AF in those with and without depression using data from a nationwide health care database., Design, Setting, and Participants: This cohort study obtained data from the Korean National Health Insurance Service database and enrolled people who underwent a nationwide health checkup in 2009. People younger than 20 years and those with a history of heart valve surgery, previous diagnosis of mitral stenosis, or who were diagnosed with AF between January 1, 2002 and December 31, 2008 were excluded. The risk of new-onset AF (occurring between 2009 and 2018) was compared in people who were and were not diagnosed with depression within a year before the 2009 nationwide health checkup. Data were analyzed between August 1, 2020 and October 31, 2020., Exposure: Previous diagnosis of depression., Main Outcomes and Measures: Cumulative incidence and risk of new-onset AF between 2009 and 2018 in participants with and without depression. Kaplan-Meier analysis was conducted to assess incidence of AF, and Cox proportional hazards regression was used to calculate adjusted and unadjusted hazard ratios (HRs) and 95% CIs., Results: A total of 5 031 222 individuals with a mean (SD) age of 46.99 (14.06) years (2 771 785 men [55.1%]) were included in the analysis; of these individuals, 148 882 (3.0%) had a diagnosis of depression in the year before the 2009 health checkup and 4 882 340 (97%) did not. People with depression vs those without depression were older (aged 56.7 vs 46.7 years) and more likely to be women (96 472 [64.8%] vs 2 162 965 [44.3%]). Prevalence of hypertension, diabetes, dyslipidemia, and heart failure was higher in the depression group. The cumulative incidence of new-onset AF was significantly higher in people with depression vs without depression in the Kaplan-Meier analysis and showed steady divergence throughout 10 years of follow-up (cumulative incidence, 4.44% vs 1.92%; log-rank P < .001). After adjusting for covariates, depression was associated with a 25.1% increased risk of new-onset AF (HR, 1.25; 95% CI, 1.22-1.29; P < .001). People with recurrent episodes of depression showed even higher risk of new-onset AF (HR, 1.32; 95% CI, 1.27-1.37; P < .001). Young age and female sex had significant interactions with depression, which suggests that young people and women with depression may have an increased risk of new-onset AF., Conclusions and Relevance: This study found that depression was associated with a significantly increased cumulative incidence and risk of new-onset AF. Recurrent episodes of depression were associated with even higher risk. These findings suggest the need for adequate screening for AF in people with depression, particularly in younger people and women.

Atrial fibrillation (AF) is associated with various major adverse cardiac events such as ischemic stroke, heart failure, and increased overall mortality. However, its association with lethal ventricular arrhythmias such as ventricular tachycardia (VT), ventricular flutter (VFL), and ventricular fibrillation (VF) is controversial. We conducted this study to determine whether AF can increase the risk of VT, VFL, and VF. We utilized the Korean National Health Insurance Service database for this nationwide population-based study. This study enrolled people who underwent a nationwide health screen in 2009 for whom clinical follow-up data were available until December 2018. Primary outcome endpoint was the occurrence of VT, VFL, or VF in people who were and were not diagnosed with new-onset AF in 2009. We analyzed a total of 9,751,705 people. In 2009, 12,689 people were diagnosed with new-onset AF (AF group). The incidence (events per 1000 person-years of follow-up) of VT, VFL, and VF was 2.472 and 0.282 in the AF and non-AF groups, respectively. After adjustment for covariates, new-onset AF was associated with 4.6-fold increased risk (p < 0.001) of VT, VFL, and VF over 10 years of follow-up. The risk of VT, VFL, and VF was even higher if identification of AF was based on intensified criteria (≥ 2 outpatient records or ≥ 1 inpatient record; hazard ratio = 5.221; p < 0.001). In conclusion, the incidence of VT, VFL, and VF was significantly increased in people with new-onset AF. The potential risk of suffering lethal ventricular arrhythmia in people with AF should be considered in clinical practice., (© 2021. The Author(s).)

Larger left atrial appendage (LAA) volume is associated with a higher risk of late recurrence (LR) in patients undergoing radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). However, it is unclear whether LAA volume predicts LR, independent of established risk factors. We sought to evaluate the value of LAA volume in predicting LR after RFCA for AF and to develop a score prediction model including LAA volume for these patients. We retrospectively studied 992 patients who underwent RFCA for AF and cardiac computed tomography before RFCA at a single center. At 3 years after RFCA, 362 patients (36.5 %) experienced recurrence. The multivariate Cox regression model showed that age ≥ 75 years (10 points), non-paroxysmal AF (9 points), diabetes mellitus (4 points), left atrial volume index (1 point per 10 ml/m 2 rounded to the nearest integer), and the second (4.7 to < 7 ml/m 2 ; 4 points) and third (≥ 7 ml/m 2 ; 5 points) tertiles of the LAA volume index were independent risk factors LR. The above-mentioned risk factors were included in the integrated score model, and the C-index of the proposed score model was 0.715 (95 % confidence interval [CI] 0.679-0.752). LAA volume is an independent predictor of LR and the predictive model including LAA volume showed good discrimination power. These findings provide evidence for the inclusion of LAA volume in the risk stratification for AF recurrence in patients undergoing RFCA for AF.

Aims: There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups., Methods and Results: A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed., Conclusions: Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

[Figure: see text].

Background/aims: Vascular disease is an established risk factor for stroke in patients with atrial fibrillation (AF), which is included in CHA2DS2-VASc score. However, the role of carotid atherosclerosis remains to be determined., Methods: Three hundred-ten patients with AF who underwent carotid sonography were enrolled., Results: During a median follow-up of 31 months, 18 events (5.8%) of stroke were identified. Patients with stroke had higher carotid intima-media thickness (CIMT) (1.16 ± 0.33 mm vs. 0.98 ± 0.25 mm, p = 0.017). CIMT was significantly increased according to the CHA2DS2-VASc score (p < 0.001) and it was correlated with left ventricular mass index and early diastolic mitral annular velocity (e'), a ratio of early transmitral flow velocity to e' (E/e') and pulmonary artery systolic pressure (all p < 0.05). Cox regression using multivariate models showed that carotid plaque was associated with the risk of stroke (hazard ratio, 3.748; 95% confidence interval [CI], 1.107 to 12.688; p = 0.034). C-statistics increased from 0.648 (95% CI, 0.538 to 0.757) to 0.716 (95% CI, 0.628 to 0.804) in the CHA2DS2-VASc score model after the addition of CIMT and carotid plaque as a vascular component (p = 0.013)., Conclusion: Increased CIMT and presence of carotid plaque are associated with a high risk of ischemic stroke, and CIMT is related to myocardial remodeling and diastolic dysfunction, suggesting that carotid atherosclerosis can improve risk prediction of stroke in patients with AF, when included under vascular disease in the CHA2DS2-VASc scoring system.

Introduction: Hemodynamics of left atrial appendage (LAA) is an important factor for future risk of ischemic stroke in atrial fibrillation (AF) patients. Velocity encoded cardiac magnetic resonance imaging (VENC-MRI) can evaluate blood flow volume of LAA without any invasive procedures. We aimed to evaluate the association between radiofrequency catheter ablation (RFCA) and LAA hemodynamics measured by MRI., Methods and Results: Consecutive RFCA cases in a single arrhythmia center were retrospectively analyzed. A total of 3120 AF patients who underwent first RFCA were analyzed. Among these patients 360 patients had both pre- and post-RFCA VENC-MRI evaluation. Atrial fibrillation was non-paroxysmal in 174 (48.3%) patients. Mean VENC-MRI (ml/sec) was significantly improved after RFCA with 49.93 ± 32.92 and 72.00 ± 34.82 for pre- and post-RFCA, respectively. Patients with non-paroxysmal AF (∆VENC-MRI = 14.63 ± 40.67 vs. 30.03 ± 35.37; p < .001) and low pre-RFCA VENC-MRI (∆VENC-MRI = 17.19 ± 38.35 vs. 50.35 ± 29.12; p < .001) had significantly higher improvement in VENC-MRI. Those who experienced late recurrence before post-RFCA MRI had significantly less improvement in LAA flow volume (∆VENC-MRI = 15.55 ± 41.41 vs. 26.18 ± 36.77; p = .011). Late recurrence and pre-RFCA VENC-MRI were significantly associated with ∆VENC-MRI after adjusting covariates. Patients who were AF before RFCA but maintained sinus rhythm after RFCA showed greatest improvement in VENC-MRI., Conclusion: Effective rhythm control through RFCA can be associated with significant improvement in LAA hemodynamics. Low pre-RFCA VENC-MRI and absence of late recurrence were associated with greater improvement in LAA hemodynamics., (© 2021 Wiley Periodicals LLC.)

Objectives: This study aimed to compare the risk of late recurrence in patients with and without early recurrence., Background: Early recurrence of atrial fibrillation (AF) or atrial tachycardia (AT) after radiofrequency catheter ablation (RFCA) in AF patients is known to be a transient phenomenon. The theoretical basis of the blanking period is based on such observations. However, the clinical implications of early recurrence need further validation., Methods: Consecutive RFCA cases in a tertiary hospital were analyzed. Early recurrence was defined as any AT or AF event occurring within 90-days post-RFCA. Early recurrence as AT and AF were also analyzed separately., Results: A total of 3,120 patients underwent RFCA. Early recurrence occurred in 751 patients (24.1%). Patients who experienced early recurrence had a larger left atrium, worse hemodynamics in the left atrial appendage, and a higher prevalence of nonparoxysmal AF and heart failure. Among patients who experienced early recurrence, 69.6% of patients eventually had late recurrence. Early recurrence was associated with a 4.3- and 3.6-fold increase in the risk of late recurrence after single and multiple procedures, respectively. After multivariate adjustment, early recurrence was an independent risk factor for late recurrence with 3.6- and 2.8-fold increase in the risk of late recurrence after single and multiple procedures, respectively. Early recurrence AT had a lower risk of late recurrence compared with early recurrence AF., Conclusions: Early recurrence was a reliable predictor for late recurrence. The clinical significance of the blanking period in the current guidelines may need to be revisited., Competing Interests: FUNDING SUPPORT AND AUTHOR DISCLOSURES This work was supported by a Korea University Grant (to Dr. J.I. Choi), a grant from Korea University Anam Hospital, Seoul, Republic of Korea (grant No. K1922851), and in part, by grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education (NRF-2015R1D1A1A02061859 to Dr. J.I. Choi), and the Ministry of Science, ICT, and Future Planning (NRF-2012R1A1A1013260 to Dr. J. I. Choi). The funders had no role in data collection, analysis, or interpretation; trial design; patient recruitment; or any aspect pertinent to the study. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Premature ventricular contraction (PVC) and atrial fibrillation (AF) are common arrhythmias affecting 1-2% of the general population. During PVC, retrograde ventriculo-atrial activation can occur and act like an atrial ectopy. However, the clinical significance of this phenomenon is not fully understood. We aimed to elucidate whether the clinical diagnosis of PVC can increase the risk of new-onset AF. We performed a nationwide population-based analysis using the Korean National Health Insurance Service database. A total of 9,537,713 people without prior history of PVC and AF were identified. Among these people, 4135 developed PVC in 2009, and people with and without PVC were followed until 2018. People who had PVC showed an increased risk of new-onset AF as compared with people without PVC (hazard ratio [HR] = 2.705; 95% confidence interval [CI] = 2.428-3.013; p < 0.001). The risk of ischemic stroke was also significantly increased in people with PVC (HR 1.160; 95% CI 1.048-1.284; p = 0.0041). New-onset AF developed in 72 people (19.3%) among 374 people with PVC who had ischemic stroke during their follow-up. A significant interaction was observed between PVC and age with people < 65 years at greater risk of new-onset AF for having PVC. In this observational analysis, the risk of new-onset AF and ischemic stroke was increased in people with PVC. Additional evaluation to identify AF in people with PVC can be helpful.

Open irrigation ablation catheters are now the standard in radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). Among various irrigation catheters, laser-cut slit-based irrigation system (Cool Flex and FlexAbility) has a unique design to cool the catheter tip more efficiently. We aimed to assess the safety of slit-based irrigation catheters regarding prevention of procedure-related ischemic complication in AF patients undergoing RFCA. The analysis was performed with Korea University Medicine Anam Hospital RFCA registry. Procedure-related ischemic complication was defined as ischemic stroke or transient ischemic attack (TIA) occurring within 30 days after RFCA. Patients were divided into 3 groups: non-irrigation, hole-based irrigation, and slit-based irrigation catheter groups. A total of 3,120 AF patients underwent first RFCA. Non-irrigation, non-slit-based irrigation, and slit-based irrigation catheters were used in 290, 1,539, and 1,291 patients, respectively. As compared with non-irrigation and non-slit-based irrigation catheter groups, slit-based irrigation catheter group had significantly older age, higher prevalence of non-paroxysmal AF, large left atrial size, and decreased left atrial appendage flow velocity. The CHA2DS2-VASc score was not different among the 3 groups. Procedure-related ischemic complication occurred in 17 patients (0.54%) with 16 ischemic strokes and 1 TIA event: 5/290 (1.72%), 11/1,539 (0.71%), and 1/1,291 (0.08%) events in non-irrigation, non-slit-based irrigation, and slit-based irrigation catheter groups, respectively (p = 0.001). Slit-based irrigation catheter was superior in direct comparison with non-slit-based irrigation catheter (0.71% vs. 0.08%; p = 0.009). Slit-based irrigation catheters were highly effective in preventing procedure-related ischemic complications., Competing Interests: The authors have declared that no competing interests exist.

Atrio-esophageal fistula (AEF) is one of the most devastating complication of radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) and surgical repair is strongly recommended. However, optimal surgical approach remains to be elucidated. We retrospectively reviewed AEF cases that occurred after RFCA in a single center and evaluated the clinical results of different surgical approach. Surgical or endoscopic repair was attempted in five AF patients who underwent RFCA. Atrio-esophageal fistula and mediastinal infection was not controlled in the patient who underwent endoscopic repair eventually died. Lethal cerebral air embolism occurred two days after surgery in a patient who underwent esophageal repair only. Primary surgical repair of both the left atrium (LA) and esophagus was performed in the remaining three patients. Among these three patients, two underwent external LA repair and the remaining had internal LA repair via open-heart surgery. External repair of the LA was unsuccessful and one patient dies and another had to undergo second operation with internal repair of the LA. The patient who underwent internal LA repair during the first operation survived without additional surgery. Furthermore, we applied veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with artificial induction of ventricular fibrillation in this patient to prevent air and septic embolism and she had no neurologic sequelae. In summary, surgical correction can be considered preferentially to correct AEF. Open-heart surgical repair of LA from the internal side seems to be an acceptable surgical method. Application of VA-ECMO with artificial induction of ventricular fibrillation might be effective to prevent air and septic embolism.

Non-vitamin K antagonist anticoagulants (NOACs) have been used to prevent thromboembolism in patients with atrial fibrillation (AF) and shown favorable clinical outcomes compared with warfarin. However, off-label use of NOACs is frequent in practice, and its clinical results are inconsistent. Furthermore, the quality of anticoagulation available with warfarin is often suboptimal and even inaccurate in real-world data. We have therefore compared the effectiveness and safety of off-label use of NOACs with those of warfarin whose anticoagulant intensity was accurately estimated. We retrospectively analyzed data from 2,659 and 3,733 AF patients at a tertiary referral center who were prescribed warfarin and NOACs, respectively, between 2013 and 2018. NOACs were used at off-label doses in 27% of the NOAC patients. After adjusting for significant covariates, underdosed NOAC (off-label use of the reduced dose) was associated with a 2.5-times increased risk of thromboembolism compared with warfarin, and overdosed NOAC (off-label use of the standard dose) showed no significant difference in either thromboembolism or major bleeding compared with warfarin. Well-controlled warfarin (TTR ≥ 60%) reduced both thromboembolism and bleeding events. In conclusion, the effectiveness of NOACs was decreased by off-label use of the reduced dose.

Aims: Heavy consumption of alcohol is a known risk factor for new-onset atrial fibrillation (AF). We aimed to evaluate the relative importance of frequent drinking vs. binge drinking., Methods and Results: A total of 9 776 956 patients without AF who participated in a national health check-up programme were included in the analysis. The influence of drinking frequency (day per week), alcohol consumption per drinking session (grams per session), and alcohol consumption per week were studied. Compared with patients who drink twice per week (reference group), patients who drink once per week showed the lowest risk [hazard ratio (HR) 0.933, 95% confidence interval (CI) 0.916-0.950] and those who drink everyday had the highest risk for new-onset AF (HR 1.412, 95% CI 1.373-1.453), respectively. However, the amount of alcohol intake per drinking session did not present any clear association with new-onset AF. Regardless of whether weekly alcohol intake exceeded 210 g, the frequency of drinking was significantly associated with the risk of new-onset AF. In contrast, when patients were stratified by weekly alcohol intake (210 g per week), those who drink large amounts of alcohol per drinking session showed a lower risk of new-onset AF., Conclusion: Frequent drinking and amount of alcohol consumption per week were significant risk factors for new-onset AF, whereas the amount of alcohol consumed per each drinking session was not an independent risk factor. Avoiding the habit of consuming a low but frequent amount of alcohol might therefore be important to prevent AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Age is a well-established risk factor for thromboembolic events in patients with atrial fibrillation (AF). However, the mechanism underlying the association between age and thromboembolic events in AF remains unknown., Methods: The prognostic value of age as a risk factor for thromboembolic events was analyzed using data from the Korean National Health Insurance Service (NHIS). In a large-scale single-center registry, cardiac hemodynamic parameters were examined to elucidate the cause of increased risk of thromboembolic events in older patients., Results: NHIS sample cohort data including 5896 patients with AF revealed that the risk of thromboembolic complication differed significantly according to age despite equal CHA 2 DS 2 -VASc score. In the registry of 2801 patients, age showed significant correlations with left atrium (LA) diameter, LA volume, E/e', pulmonary artery pressure, and LA appendage flow velocity. Older patients had a significantly higher prevalence of spontaneous echocontrast (odds ratio [OR] = 1.030; P < .001). Age (OR = 1.031; P < .001), E/e' (OR = 1.065; P = .004), and LA appendage flow velocity (OR = .988; P = .009) were significant predictors for thromboembolic events in multivariate analyses. In data from the NHIS, CHA 2 DS 2 -VASc score did not outperform age to predict thromboembolic events., Conclusions: Age is a significant risk factor for thromboembolic events in patients with AF, and old age is associated with adverse cardiac hemodynamics. This study suggests that older patients with AF are at high risk of thromboembolic events regardless of CHA 2 DS 2 -VASc score., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Aims: The impact of persistent left superior vena cava (PLSVC) in atrial fibrillation (AF) patients undergoing radiofrequency catheter ablation (RFCA) is not well known. We performed this analysis to evaluate the electrophysiological characteristics of PLSVC and its role in triggering and maintaining AF., Methods and Results: Patients with AF referred to two tertiary hospitals were screened and patients with PLSVC in pre-RFCA imaging studies were enrolled. Among 3967 patients, PLSVC was present in 36 patients (0.9%). There were four morphological types of PLSVC: type 1, atresia of the right superior vena cava (SVC) (n = 2); type 2A, dual SVCs with an anastomosis between right and left SVCs (n = 15); type 2B, dual SVCs without an anastomosis (n = 16); type 3, PLSVC draining into the left atrium (LA; n = 2); and unclassified in one patient. Thirty-two patients underwent RFCA and electrophysiology study focusing on PLSVC: PLSVC was the trigger of AF in 48.4% of patients and the driver of AF in 46.9% of patients. Cumulatively, PLSVC was a trigger or driver of AF in 22 patients (68.8%). Whether to ablate PLSVC was determined by the results of electrophysiology study, and no significant difference in the late recurrence rate was observed between patients who did and did not have either trigger or driver from PLSVC., Conclusion: Pre-RFCA cardiac imaging revealed PLSVC in 0.9% of AF patients. This study demonstrated that PLSVC has an important role in initiating and maintaining AF in substantial proportion of patients. Electrophysiology study focusing on PLSVC can help to decide whether to ablate PLSVC., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Hypertension and obesity are known risk factors for atrial fibrillation (AF). However, it is unclear whether uncontrolled, long-standing hypertension has a particularly profound effect on AF. Because they have a similar underlying pathophysiology, hypertension and obesity could act synergistically in the context of AF. We evaluated how various stages of hypertension and body weight status affect new-onset AF. We analyzed a total of 9 797 418 participants who underwent a national health checkup. Hypertension was classified into 5 stages: nonhypertension, prehypertension, hypertension without medication, hypertension with medication <5 years, and hypertension with medication ≥5 years. The participants were also stratified based on body mass index and waist circumference. During the 80 130 161 person×years follow-up, a total of 196 136 new-onset AF cases occurred. The incidence of new-onset AF gradually increased among the 5 stages of hypertension: the adjusted hazard ratio for each group was 1 (reference), 1.145, 1.390, 1.853, and 2.344 for each stage of hypertension. A graded escalation in the risk of new-onset AF was also observed in response to increased systolic and diastolic blood pressure. The incidence of new-onset AF correlated with body mass index and waist circumference, with obese people having a higher risk than others. Hypertension and obesity acted synergistically: obese people with hypertension on medication ≥5 years had the highest risk of AF. In conclusion, the degree and duration of hypertension, as well as the presence of hypertension, were important factors for new-onset AF. Body weight status was significantly associated with new-onset AF and acted synergistically with hypertension.

Background: Being obese or underweight, and having diabetes are important risk factors for new-onset atrial fibrillation (AF). However, it is unclear whether there is any interaction between body weight and diabetes in regard to development of new-onset AF. We aimed to evaluate the role of body weight status and various stage of diabetes on new-onset AF., Methods: This was a nationwide population based study using National Health Insurance Service (NHIS) data. A total of 9,797,418 patients who underwent national health check-ups were analyzed. Patients were classified as underweight [body mass index (BMI) < 18.5], normal reference group (18.5 ≤ BMI < 23.0), upper normal (23.0 ≤ BMI < 25.0), overweight (25.0 ≤ BMI < 30.0), or obese (BMI ≥ 30.0) based on BMI. Diabetes were categorized as non-diabetic, impaired fasting glucose (IFG), new-onset diabetes, diabetes < 5 years, and diabetes ≥ 5 years. Primary outcome end point was new-onset AF. New-onset AF was defined as one inpatient or two outpatient records of International Classification of Disease, Tenth Revision (ICD-10) codes in patients without prior AF diagnosis., Results: During 80,130,161 patient*years follow-up, a total of 196,136 new-onset AF occurred. Obese [hazard ration (HR) = 1.327], overweight (HR = 1.123), upper normal (HR = 1.040), and underweight (HR = 1.055) patients showed significantly increased risk of new-onset AF compared to the normal reference group. Gradual escalation in the risk of new-onset AF was observed along with advancing diabetic stage. Body weight status and diabetes were independently associated with new-onset AF and at the same time, had synergistic effects on the risk of new-onset AF with obese diabetic patients having the highest risk (HR = 1.823)., Conclusions: Patients with obesity, overweight, underweight, and diabetes had significantly increased risk of new-onset AF. Body weight status and diabetes had synergistic effects on the risk of new-onset AF. The risk of new-onset AF increased gradually with advancing diabetic stage. This study suggests that maintaining optimal body weight and glucose homeostasis might prevent new-onset AF.

Ischemic stroke after radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients is a great challenge for electrophysiologists. We performed this retrospective study to evaluate clinical and echocardiographic characteristics associated with increased risk of ischemic stroke following RFCA. A total of 2,352 consecutive patients with AF who underwent first-time RFCA were analyzed. Among 10,023 patient*year follow up, ischemic stroke occurred in 49 patients (0.49% per year). Late recurrence after last RFCA was significantly associated with ischemic stroke (3.8% vs. 12.9%, p < 0.001). Old age (≥60 years old) (3.2% vs. 15.4%, p = 0.001), non-paroxysmal AF (hazard ratio = 1.91, p = 0.024), left atrium (LA) size ≥45.0 mm (6.6% vs. 11.7%, p < 0.001), E over E' ≥10 (4.3% vs. 20.1%, p < 0.001), dense spontaneous echo contrast (SEC) (5.2% vs. 19.0%, p = 0.006), and decreased left atrial appendage (LAA) flow velocity (≤40 cm/sec) (4.1% vs. 10.8%, p < 0.001) were also associated with increased risk of ischemic stroke. The REVEEAL score derived from the risk factors identified in this study was superior to CHA 2 DS 2 -VASc score (p < 0.001) for the prediction of ischemic stroke. In conclusion, the risk factors for ischemic stroke in post-RFCA AF patients are not identical to RFCA naive AF patients and different approach to stratify the risk of ischemic stroke is needed.

The benefits of radiofrequency catheter ablation (RFCA) for patients with atrial fibrillation (AF) significantly decrease with late recurrence (LR). We aimed to develop a scoring system to identify patients at high and low risk for LR following RFCA, based on a comprehensive evaluation of multiple risk factors for AF recurrence, including echocardiographic parameters. We studied 2,352 patients with AF undergoing first-time RFCA in a single institution. The LR-free survival rate up to 5 years was measured using a Kaplan-Meier analysis. The influence of clinical and echocardiographic parameters on LR was calculated with a Cox-regression analysis. Duration of AF ≥4 years (hazard ratio [HR] = 1.75; p < 0.001), non-paroxysmal AF (HR = 3.18; p < 0.001), and diabetes (HR = 1.34; p = 0.015) were associated with increased risk of LR. Left atrial (LA) diameter ≥45 mm (HR = 2.42; p < 0.001), E/e' ≥ 10 (HR = 1.44; p < 0.001), dense SEC (HR = 3.30; p < 0.001), and decreased LA appendage flow velocity (≤40 cm/sec) (HR = 2.35; p < 0.001) were echocardiographic parameters associated with increased risk of LR following RFCA. The LR score based on the aforementioned risk factors could be used to predict LR (area under curve = 0.717) and to stratify the risk of LR (HR = 1.45 per 1 point increase in the score; p < 0.001). In conclusion, LR after RFCA is affected by multiple clinical and echocardiographic parameters. This study suggests that combining these multiple risk factors enables the identification of patients with AF at high or low risk for having arrhythmia recurrence.

Aims: Findings regarding efficacy of substrate modification for non-paroxysmal atrial fibrillation (AF) are inconsistent. We prospectively compared clinical outcomes of complex fractionated atrial electrogram (CFAE)-guided focal ablation (CFA) and CFAE-guided linear ablation (CLA) in patients with non-paroxysmal AF., Methods and Results: We randomized 150 patients with non-paroxysmal AF into CFA and CLA groups in a 1:1 ratio. Complex fractionated atrial electrogram distribution was evaluated using an automated algorithm of a three-dimensional mapping system. After pulmonary vein isolation (PVI), CFAE-guided ablation was performed in the left atrium and then in the right atrium (RA). When compared with conventional CFA, CLA was performed based on conventional lines, with additional lines. Atrial fibrillation was not induced after PVI alone or with cavotricuspid isthmus ablation in 20.7% of patients. To achieve the endpoint, additional CFAE-guided RA ablation was required in 42.7% and 36.0% of patients undergoing CFA and CLA, respectively (P = 0.403). Atrial fibrillation was terminated during CFAE-guided ablation in 72.9% and 75.0% of patients undergoing CFA and CLA, respectively (P = 0.792). Termination of atrial tachycardia (AT) or non-inducibility of AF/AT was achieved in 61.3% and 68.0% of patients undergoing CFA and CLA, respectively (P = 0.393). The CLA group showed decreased 1-year freedom from AF/AT recurrence (60.0%, CFA vs. 47.3%, CLA; log rank P = 0.085), but no significant difference throughout the follow-up (22.2 ± 21.0 months) (67.1%, CFA vs. 68.9%, CLA; log rank P = 0.298)., Conclusion: Long-term efficacy of CFAE-guided ablation was unaffected by the ablation technique in patients with non-paroxysmal AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Blood stasis in left atrium (LA) or LA appendage (LAA) is thought to be the main cause of thrombus formation and systemic embolism in atrial fibrillation (AF) patients. Paroxysmal and non-paroxysmal AF differ significantly in various aspects. Impact of cardiac hemodynamics on systemic embolism might also differ between the 2 distinct AF entities. This study was performed to evaluate the influence of cardiac hemodynamics on systemic embolism in both paroxysmal and non-paroxysmal AF. Consecutive AF patients undergoing radiofrequency catheter ablation (RFCA) in Korea University Medical Center Anam Hospital between June 1998 and February 2018 were analyzed. Among 2,801 patients who underwent first-time RFCA, a total of 231 patients had either previous ischemic stroke, transient ischemic attack, or arterial embolism. In paroxysmal AF, LA diameter, LA volume (measured with magnetic resonance imaging), left ventricular (LV) ejection fraction, E/e', LAA flow velocity, and prevalence of spontaneous echocontrast (SEC) and dense SEC were significantly different between patients with and without thromboembolic events. However, only E/e' was different between patients with and without thromboembolic events in non-paroxysmal AF. The influence of LA diameter, LA volume, LV EF, LAA flow velocity, and dense SEC on thromboembolic events was significantly moderated by the type of AF. In conclusion, paroxysmal and non-paroxysmal AF might have a different mechanism responsible for thrombus formation and consequent embolic events. Relative contribution of hemodynamic parameters and other factors such as atrial myopathy to thromboembolic events in paroxysmal versus non-paroxysmal AF needs further evaluation., Competing Interests: The authors have declared that no competing interests exist.

Background: Electrical isolation of the left atrial appendage (LAA) is associated with a lower rate of atrial fibrillation (AF) recurrence in patients undergoing radiofrequency catheter ablation. However, LAA isolation can significantly impair LAA contractility., Objective: This study was performed to evaluate whether electrical isolation of the LAA is associated with an increased risk of ischemic stroke or transient ischemic attack (TIA)., Methods: Consecutive patients with AF undergoing radiofrequency catheter ablation at Korea University Medical Center Anam Hospital were analyzed., Results: Of 2352 patients, 39 (1.7%) had LAA isolation. Patients with LAA isolation had a significantly higher rate of ischemic stroke or TIA than did those without LAA isolation (log-rank, P < .001; hazard ratio 23.6; P < .001). There were significant differences in the baseline characteristics of the 2 groups, including type of AF (34 [87.2%] and 911 [39.4%] patients with and without LAA isolation had nonparoxysmal AF, respectively). After multivariate adjustment, LAA isolation was found to be a significant risk factor for ischemic stroke or TIA (adjusted hazard ratio 11.3; P < .001). Propensity score-matched analysis also revealed an increased risk of ischemic stroke or TIA in patients with LAA isolation compared with those without LAA isolation (log-rank, P = .001). The LAA flow velocity of post-LAA isolation status was not significantly different between patients who did and did not experience ischemic stroke or TIA (30.3 ± 17.7 cm/s vs 33.9 ± 17.9 cm/s; P = .608)., Conclusion: A significantly increased risk of ischemic stroke or TIA was observed in patients with electrical isolation of the LAA. In addition, postisolation LAA flow velocity is not a reliable marker to predict future ischemic events., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients can cause various complications and atrioesophageal (AE) fistula is one of the most catastrophic complications of RFCA., Methods and Results: RFCA registries from 3 cardiovascular centers in the Republic of Korea consisted of 5721 patients undergoing 6724 procedures. Before undergoing RFCA, patients underwent either computed tomography or magnetic resonance imaging. We evaluated clinical, anatomical, and procedural characteristics of patients who developed AE fistula after RFCA. A total of 10 patients developed AE fistula after RFCA (0.15% per procedure). All AE fistulas occurred during first-time RFCA. Eight patients died and mortality rate was 80.0%. No patients had any gastrointestinal symptom at the time of discharge and mean duration time from RFCA to symptom onset was 23.4 days. Six patients (60.0%) had paroxysmal AF. Substrate modification in addition to pulmonary vein isolation was performed in 4 patients (40.0%). Patients with old age, low body weight, and high CHA 2 DS 2 -VASc score were at increased risk of AE fistula. Baseline imaging evaluation revealed that esophagus had closest contact with LA posterior wall near left inferior pulmonary vein rather than left superior pulmonary vein and all documented AE fistulas were located near left inferior pulmonary vein., Conclusion: Posterior wall of LA near left inferior pulmonary vein was the most vulnerable location for AE fistula. Pulmonary vein isolation was the main lesion set associated with AE fistula and old age, low body weight, and high CHA 2 DS 2 -VASc score were significant risk factors for AE fistula., (© 2018 Wiley Periodicals, Inc.)

Atrial fibrillation (AF) is known to cause adverse remodeling of left atrium (LA). Radiofrequency catheter ablation (RFCA) of AF is associated with decrease in LA volume. However, the impact of RFCA on left atrial appendage (LAA) volume and hemodynamic function is not fully understood. We analyzed 123 patients who underwent cardiac magnetic resonance imaging (MRI) evaluation before and after RFCA in Korea University Anam Hospital. LA and LAA volume were measured before and after RFCA based on cardiac MRI. Baseline LA volume was 99.5 ± 38.4 cm 3 and decreased to 74.6 ± 28.5 cm 3 after RFCA (p < 0.001). LA diameter measured with transthoracic echocardiography was also decreased after RFCA (43.3 ± 6.2 mm at baseline and 39.9 ± 5.9 mm at follow up; p < 0.001). However, LAA volume was significantly increased after RFCA (19.4 ± 8.5 cm 3 at baseline and 23.7 ± 13.3 cm 3 at follow up; p < 0.001). Total ablation time and additional substrate modification was associated with change in LA volume. After RFCA, average LAA velocity measured by transesophageal echocardiography was increased to 51.0 cm/sec from 41.1 cm/sec (p < 0.001). In conclusion, LAA volume was increased after RFCA in contrast to LA volume. Our data raise a concern about worsening hemodynamics of LA and LAA following RFCA and long term clinical significance of enlarged LAA after RFCA needs further evaluation.

Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed. The prevalence of SEC and thrombus were compared between patients who received NOAC and those who took warfarin. NOAC included direct thrombin inhibitor and factor Xa inhibitors. Among 1,050 patients who were considered for DCCV, 424 patients anticoagulated with warfarin or NOAC underwent TEE prior to DCCV. Eighty patients who were anticoagulated for less than 21 days were excluded. Finally, 344 patients were included for the analysis (180 warfarin users vs. 164 NOAC users). No significant difference in the prevalence of SEC (44.4% vs. 43.9%; p = 0.919), dense SEC (13.9% vs. 15.2%; p = 0.722), or thrombus (2.2% vs. 4.3%; p = 0.281) was observed between the warfarin group and the NOAC group. In multivariate analysis, there was no association between NOAC and risk of SEC (odds ratio [OR]: 1.4, 95% CI: 0.796-2.297, p = 0.265) or thrombus (OR: 3.4, 95% CI: 0.726-16.039, p = 0.120). In conclusion, effectiveness of NOAC is comparable to warfarin in preventing SEC and thrombus in patients with AF or AFL undergoing DCCV. However, numerical increase in the prevalence of thrombus in NOAC group warrants further evaluation.

Background/Objectives: Pulmonary vein isolation (PVI) using radiofrequency catheter ablation with contact force (CF)-sensing technology has improved long-term outcomes in patients with atrial fibrillation. This prospective randomized study aimed to assess the efficacy and safety of CF-sensing technology for additional left atrial (LA) linear ablation of persistent AF (PerAF). Methods: After PVI, anteromitral (AM) line and roof line ablation were performed using a CF-sensing catheter. Patients were randomly assigned to either the CF-sensing (CFS) group or the CF-blind control (Blind) group. The primary endpoint was atrial arrhythmia recurrence. LA late gadolinium enhancement (LA-LGE) MRI was conducted at baseline and 1-year follow-up for long-term lesion evaluation. Results: A total of 62 patients with drug-refractory PerAF were enrolled (mean age: 58 ± 10 years; 77% male). The success rates of AM and roof line block were 97% and 100% in the CFS group (n = 33) and 93% and 90% in the Blind group (n = 29). The time to achieve block was reduced in the CFS group (AM: 36 ± 22 vs. 48 ± 28 min, p = 0.068; roof: 19 ± 14 vs. 27 ± 15 min, p = 0.031). The maximum CF for safety endpoints was significantly lower in the CFS group (AM: 42 vs. 69 g, p < 0.001; roof: 33 vs. 49 g, p = 0.003). Full linear LA-LGE formation on 1-year MRI did not differ significantly between the groups (AM: 17 vs. 36%; roof; 29 vs. 24%, both p = NS). Kaplan–Meier estimates of AF/AT-free survival after ablation procedures were 63.6% in the CFS group and 58.6% in the Blind group (log-rank p = 0.837). Conclusions: In patients with PerAF, additional LA linear ablation following PVI using CF-sensing technology improved procedural safety and reduced the time needed to achieve conduction block. However, it did not significantly influence clinical outcomes or the formation of permanent full linear lesions. [ABSTRACT FROM AUTHOR]

The application of artificial intelligence (AI) algorithms to 12-lead electrocardiogram (ECG) provides promising age prediction models. We explored whether the gap between the pre-procedural AI-ECG age and chronological age can predict atrial fibrillation (AF) recurrence after catheter ablation. We validated a pre-trained residual network-based model for age prediction on four multinational datasets. Then we estimated AI-ECG age using a pre-procedural sinus rhythm ECG among individuals on anti-arrhythmic drugs who underwent de-novo AF catheter ablation from two independent AF ablation cohorts. We categorized the AI-ECG age gap based on the mean absolute error of the AI-ECG age gap obtained from four model validation datasets; aged-ECG (≥10 years) and normal ECG age (<10 years) groups. In the two AF ablation cohorts, aged-ECG was associated with a significantly increased risk of AF recurrence compared to the normal ECG age group. These associations were independent of chronological age or left atrial diameter. In summary, a pre-procedural AI-ECG age has a prognostic value for AF recurrence after catheter ablation. [ABSTRACT FROM AUTHOR]

Aims Evidence of an association between atrial fibrillation (AF) and sudden cardiac arrest (SCA) in young adults is limited. In this study, we aim to evaluate this association in a general population aged between 20 and 39 years. Methods and results Young adults who underwent health check-ups between 2009 and 2012 were screened from a nationwide healthcare database in South Korea. A history of AF diagnosis before the health check-ups was identified based on the relevant International Classification of Diseases, 10th edition codes reported in the database. Associations between an established diagnosis of AF and the risk of SCA during follow-up were examined. A total of 6 345 162 young people were analysed with a mean follow-up duration of 9.4 years. The mean age was 30.9 ± 5.0 years, and 5875 (0.09%) individuals were diagnosed with AF. During follow-up, SCA occurred in 5352 (0.08%) individuals, and the crude incidence was 0.56 and 0.09 events per 1000 person-years for participants with and without AF, respectively. Individuals with AF had a 3.0-fold higher risk in a multivariate model adjusted for age, sex, lifestyle, anthropometric data, and medical comorbidities (adjusted hazard ratio 2.96, 95% confidence interval 1.99–4.41, P < 0.001). Both incident and prevalent AFs were associated with an increased risk of SCA, with no significant differences between the two groups. Conclusion Atrial fibrillation was associated with a significantly higher risk of SCA developing in healthy young adults. Whether the rate or rhythm control influences the risk of SCA in young patients with AF remains to be examined. [ABSTRACT FROM AUTHOR]

Background: Adenosine can cause dormant electrical conduction between the pulmonary vein and left atrium after pulmonary vein isolation (PVI). Adenosine can also induce atrial fibrillation (AF) during catheter ablation. However, the clinical outcomes and effects of additional ablation for the trigger sites of adenosine-induced AF (AIAF) are unknown. This study therefore aimed to evaluate the clinical significance of AIAF. Methods: Between January 2010 and September 2019, we analyzed 616 consecutive patients with paroxysmal AF (PAF) who underwent radiofrequency catheter ablation (RFCA), including wide-area circumferential pulmonary vein isolation (PVI) and post-PVI adenosine testing. Results: Among 616 patients, 134 (21.7%) and 34 (5.5%) showed dormant conduction and AIAF, respectively. Eight patients (1.3%) had both dormant conduction and AIAF. The AF recurrence rate was not significantly different between patients with and without AIAF (16.7% vs. 18.6%, log-rank p = 0.827) during a mean follow-up period of 17.9 ± 18 months. Additional RFCA for the trigger site was attempted in 10 patients with AIAF; however, the recurrence rate of atrial arrhythmias was also not different between the groups with and without additional ablation (20% vs. 16.7%, log-rank p = 0.704). Conclusions: AIAF after PVI was not clinically associated with recurrence during long-term follow-up. Ablation of the trigger site in AIAF did not improve the clinical outcomes. [ABSTRACT FROM AUTHOR]

Aims: An epicardial approach is an effective means to detect and eliminate residual potentials in non-transmural lesions created during prior endocardial ablation. We sought to determine the impact of a combined epicardial and endocardial approach compared with a conventional endocardial approach, on recurrence-free survival after redo ablation.Methods and Results: Participants with recurred persistent atrial fibrillation after prior endocardial ablation were randomized (1:1) to undergo treatment with the combined approach (epicardial followed by endocardial ablation) for the treatment group or conventional approach (endocardial ablation only) for the control group. The primary outcome was the time to recurrence of atrial fibrillation or atrial tachycardia following a 90-day blanking period within 12 months after the procedure. The secondary safety outcome was the occurrence of procedure-related complications within 24 h after the procedure. Of 100 randomized participants {median age, 59.0 [(interquartile range (IQR): 53.8-64.3] years, including 16% women, with one prior ablation (IQR: 1-1)}, 93 (93%) completed the trial. Events relevant to the primary outcome occurred in 16 patients in the treatment group and in 21 patients in the control group {Kaplan-Meier estimator percentages, 32 vs. 42%; hazard ratio, 0.71 [95% confidence interval (CI): 0.37-1.37]}. The periprocedural complication rate was lower in the treatment group [2 vs. 16%; odds ratio, 0.11 (95% CI: 0.00-0.87)] with similar achievement of the procedural endpoint in the two groups.Conclusion: In the redo procedure for persistent atrial fibrillation, the combined approach had no significant difference of recurrence-free survival and a lower procedural complication rate compared with the conventional approach. [ABSTRACT FROM AUTHOR]

Background: A substantial proportion of cardiac arrhythmias are paroxysmal in nature, and 12-lead electrocardiography (ECG) and Holter monitoring often fail to detect paroxysmal arrhythmias. We designed and evaluated a watch-type, electrocardiograph-recording, wearable device (w-ECG) to overcome the limitations of 12-lead ECG and Holter monitoring. Methods: We prospectively enrolled 96 patients with symptoms assumed to be related to cardiac arrhythmias. Electrocardiography recording was performed with both the w-ECG and Holter monitoring. Detection of any arrhythmia was the primary outcome endpoint and was compared between the w-ECG and Holter monitoring. Results: Any arrhythmia was detected in 51 (53.1%) and 27 (28.1%) patients by the w-ECG and Holter monitoring, respectively (odds ratio (OR) = 2.9, p < 0.001). The w-ECG was superior to Holter monitoring for the detection of clinically significant arrhythmias (excluding atrial premature contraction, ventricular premature contraction, and non-sustained atrial tachyarrhythmia) (OR = 2.34, p = 0.018). In 27 (28.1%) patients, cardiac arrhythmias were detected only by the w-ECG, with atrial fibrillation being the most frequent case (13 patients). Based on ECGs recorded by using the w-ECG, 17 patients (17.7%) received therapeutic interventions, including radiofrequency catheter ablation. Conclusions: The w-ECG is capable of recording ECGs of good quality, with a discernable P wave and distinguishable QRS morphology. The ability of the w-ECG to detect cardiac arrhythmias was significantly better than that of Holter monitoring, and a significant proportion of patients received therapeutic intervention based on ECGs recorded by the w-ECG. [ABSTRACT FROM AUTHOR]

(1) Background: We hypothesized that female sex would have a differential impact on left atrial (LA) low-voltage areas (LVAs) according to CHA2DS2-VA scores. (2) Methods: This study included 553 patients who underwent radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). LVAs were defined as regions with bipolar peak-to-peak voltages of <0.5 mV. The proportion of LVAs was calculated by dividing the total LVA by the LA surface area. (3) Results: There was no sex-related difference in LA LVAs among patients with a CHA2DS2-VA scores ≤ 2. The proportion of LVAs was significantly higher in females among patients with CHA2DS2-VA scores of 3 or 4 (10.1 (4.7–15.1)% vs. 15.8 (9.2–32.1)%; p = 0.027). Female sex was significantly associated with extensive LVAs (LVA proportion ≥ 30%). Females had odd ratios of 27.82 (95% confidence interval (CI) 3.33–756.8, p = 0.01), and 1.53 (95% CI 0.81–2.83, p = 0.184) for extensive LAVs in patients with CHA2DS2-VA scores ≥ 3 and CHA2DS2-VA scores < 3, respectively. In the multiple regression model, female patients with a CHA2DS2-VA ≥3 were significantly associated with a higher proportion of LVAs (β = 8.52, p = 0.039). (4) Conclusions: Female sex was significantly associated with extensive LVAs, particularly when their CHA2DS2-VA scores were ≥3. This result suggests that female sex has a differential effect on the extent of LVAs based on the presence of additional risk factors. [ABSTRACT FROM AUTHOR]

Aims: Heavy consumption of alcohol is a known risk factor for new-onset atrial fibrillation (AF). We aimed to evaluate the relative importance of frequent drinking vs. binge drinking.Methods and Results: A total of 9 776 956 patients without AF who participated in a national health check-up programme were included in the analysis. The influence of drinking frequency (day per week), alcohol consumption per drinking session (grams per session), and alcohol consumption per week were studied. Compared with patients who drink twice per week (reference group), patients who drink once per week showed the lowest risk [hazard ratio (HR) 0.933, 95% confidence interval (CI) 0.916-0.950] and those who drink everyday had the highest risk for new-onset AF (HR 1.412, 95% CI 1.373-1.453), respectively. However, the amount of alcohol intake per drinking session did not present any clear association with new-onset AF. Regardless of whether weekly alcohol intake exceeded 210 g, the frequency of drinking was significantly associated with the risk of new-onset AF. In contrast, when patients were stratified by weekly alcohol intake (210 g per week), those who drink large amounts of alcohol per drinking session showed a lower risk of new-onset AF.Conclusion: Frequent drinking and amount of alcohol consumption per week were significant risk factors for new-onset AF, whereas the amount of alcohol consumed per each drinking session was not an independent risk factor. Avoiding the habit of consuming a low but frequent amount of alcohol might therefore be important to prevent AF. [ABSTRACT FROM AUTHOR]

Aims: The impact of persistent left superior vena cava (PLSVC) in atrial fibrillation (AF) patients undergoing radiofrequency catheter ablation (RFCA) is not well known. We performed this analysis to evaluate the electrophysiological characteristics of PLSVC and its role in triggering and maintaining AF.Methods and Results: Patients with AF referred to two tertiary hospitals were screened and patients with PLSVC in pre-RFCA imaging studies were enrolled. Among 3967 patients, PLSVC was present in 36 patients (0.9%). There were four morphological types of PLSVC: type 1, atresia of the right superior vena cava (SVC) (n = 2); type 2A, dual SVCs with an anastomosis between right and left SVCs (n = 15); type 2B, dual SVCs without an anastomosis (n = 16); type 3, PLSVC draining into the left atrium (LA; n = 2); and unclassified in one patient. Thirty-two patients underwent RFCA and electrophysiology study focusing on PLSVC: PLSVC was the trigger of AF in 48.4% of patients and the driver of AF in 46.9% of patients. Cumulatively, PLSVC was a trigger or driver of AF in 22 patients (68.8%). Whether to ablate PLSVC was determined by the results of electrophysiology study, and no significant difference in the late recurrence rate was observed between patients who did and did not have either trigger or driver from PLSVC.Conclusion: Pre-RFCA cardiac imaging revealed PLSVC in 0.9% of AF patients. This study demonstrated that PLSVC has an important role in initiating and maintaining AF in substantial proportion of patients. Electrophysiology study focusing on PLSVC can help to decide whether to ablate PLSVC. [ABSTRACT FROM AUTHOR]

Aims: Findings regarding efficacy of substrate modification for non-paroxysmal atrial fibrillation (AF) are inconsistent. We prospectively compared clinical outcomes of complex fractionated atrial electrogram (CFAE)-guided focal ablation (CFA) and CFAE-guided linear ablation (CLA) in patients with non-paroxysmal AF.Methods and Results: We randomized 150 patients with non-paroxysmal AF into CFA and CLA groups in a 1:1 ratio. Complex fractionated atrial electrogram distribution was evaluated using an automated algorithm of a three-dimensional mapping system. After pulmonary vein isolation (PVI), CFAE-guided ablation was performed in the left atrium and then in the right atrium (RA). When compared with conventional CFA, CLA was performed based on conventional lines, with additional lines. Atrial fibrillation was not induced after PVI alone or with cavotricuspid isthmus ablation in 20.7% of patients. To achieve the endpoint, additional CFAE-guided RA ablation was required in 42.7% and 36.0% of patients undergoing CFA and CLA, respectively (P = 0.403). Atrial fibrillation was terminated during CFAE-guided ablation in 72.9% and 75.0% of patients undergoing CFA and CLA, respectively (P = 0.792). Termination of atrial tachycardia (AT) or non-inducibility of AF/AT was achieved in 61.3% and 68.0% of patients undergoing CFA and CLA, respectively (P = 0.393). The CLA group showed decreased 1-year freedom from AF/AT recurrence (60.0%, CFA vs. 47.3%, CLA; log rank P = 0.085), but no significant difference throughout the follow-up (22.2 ± 21.0 months) (67.1%, CFA vs. 68.9%, CLA; log rank P = 0.298).Conclusion: Long-term efficacy of CFAE-guided ablation was unaffected by the ablation technique in patients with non-paroxysmal AF. [ABSTRACT FROM AUTHOR]

Background: The main purpose of performing radiofrequency catheter ablation (RFCA) in atrial fibrillation (AF) patients is to improve the quality of life (QoL) and alleviate AF-related symptoms. We aimed to determine the qualitative and quantitative effects of RFCA on the QoL in AF patients. Methods: We performed a systemic review and meta-analysis using a random effects model. We searched for the studies that reported the physical component summary score (PCS) and mental component summary score (MCS) of the short form-36, a validated system to assess and quantify the QoL, before and after RFCA in AF patients. PCS and MCS are T-scores with a mean of 50 and standard deviation of 10. Results: Of the 470 studies identified through systematic search, we included 13 studies for pre-RFCA vs. the post-RFCA analysis and 5 studies for treatment success vs. AF recurrence analyses. In the pre-RFCA vs. post-RFCA analysis, RFCA was associated with a significant increase in both the PCS (weighted mean difference [WMD] = 6.33 [4.81–7.84]; p < 0.001) and MCS (WMD = 7.80 [6.15–9.44]; p < 0.001). The ΔPCS (post-RFCA PCS–pre-RFCA PCS) and ΔMCS values were used for the treatment success vs. AF recurrence analysis. Patients with successful ablation had a higher ΔPCS (WMD = 7.46 [4.44–10.49]; p < 0.001) and ΔMCS (WMD = 7.59 [4.94–10.24]; p < 0.001). Conclusions: RFCA is associated with a significant increase in the PCS and MCS in AF patients. Patients without AF recurrence after RFCA had a better improvement in the PCS and MCS than patients who had AF recurrence. [ABSTRACT FROM AUTHOR]

Prediction of recurrences after catheter ablation of atrial fibrillation (AF) remains challenging. We sought to investigate the long-term outcomes after AF catheter ablation. A total of 2221 consecutive patients who underwent catheter ablation for symptomatic AF were included in this study (mean age 55 ± 11 years, 20.3% women, and 59.0% paroxysmal AF). Extensive ablation, in addition to circumferential pulmonary vein isolation, was more often accomplished in patients with non-paroxysmal AF than in those with paroxysmal AF (87.4% vs. 25.3%, p < 0.001). During a median follow-up of 54 months, sinus rhythm (SR) was maintained in 67.1% after index procedure. After redo procedures in 418 patients, 83.3% exhibited SR maintenance. Recurrence rates were similar for single and multiple procedures (17.4% vs. 16.7%, p = 0.765). Subanalysis showed that the extent of late gadolinium enhancement (LGE), as assessed by cardiac magnetic resonance, is greater in patients with recurrence than in those without recurrence (36.2 ± 23.9% vs. 21.8 ± 13.7%, p < 0.001). Cox-regression analysis revealed that non-paroxysmal AF (hazard ratio (HR) 2.238, 95% confidence interval (CI) 1.905–2.629, p < 0.001), overweight (HR 1.314, 95% CI 1.107–1.559, p = 0.020), left atrium dimension ≥ 45 mm (HR 1.284, 95% CI 1.085–1.518, p = 0.004), AF duration (HR 1.020 per year, 95% CI 1.006–1.034, p = 0.004), and LGE ≥ 25% (HR 1.726, 95% CI 1.330–2.239, p < 0.001) are significantly associated with AF recurrence after catheter ablation. This study showed that repeated catheter ablation improves the clinical outcomes of patients with non-paroxysmal AF, suggesting that AF substrate based on LGE may underpin the mechanism of recurrence after catheter ablation. [ABSTRACT FROM AUTHOR]

The Cockcroft-Gault (CG) formula is recommended to guide clinicians in the choice of the appropriate dosage for direct oral anticoagulants (DOACs). However, the performance of the CG formula varies depending on the patient's age, weight, and degree of renal function. We aimed to compare the validity of the CG formula with that of Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) formulae for dosing DOACs. A total of 6268 consecutive patients on anticoagulants for atrial fibrillation (AF) were retrospectively investigated. Among underweight and elderly patients, the CG formula underestimated renal function compared with the non-CG formulae. However, the concordant rate of drug indications between the CG and the non-CG formulae was approximately 94%. On-label uses under the three formulae were associated with a lower risk of major bleeding (but not thromboembolism) compared to warfarin. Although we found differences in estimating renal function and the proportions of drug indications between the CG and non-CG formulae, the risks of thromboembolism and major bleeding were similar to those with warfarin regardless of which formula was used. [ABSTRACT FROM AUTHOR]