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Background: Meta-analyses of large clinical trials investigating SGLT2 (sodium-glucose cotransporter-2) inhibitors have suggested their protective effects against atrial fibrillation in patients with type 2 diabetes. However, the results were predominantly driven from trials involving dapagliflozin., Methods and Results: We used a nationwide, population-based cohort of patients with type 2 diabetes who initiated either dapagliflozin or empagliflozin between May 2016 and December 2018. An active-comparator, new-user design was used, and the 2 groups of patients were matched using propensity scores. The primary outcome was incident nonvalvular atrial fibrillation, which was analyzed using both the main intention-to-treat and sensitivity analysis that censored patients who skipped their medications for ≥30 days. Men ≥55 years of age and women ≥60 years of age with ≥1 traditional risk factor or those with established cardiovascular disease were categorized as high cardiovascular risk group. Patients not included in the high-risk group were categorized as low risk. After 1:1 propensity-score matching, a total of 137 928 patients (mean age, 55 years; 58% men) were included and followed up for 2.2±0.6 years. The risk of incident atrial fibrillation was significantly lower in the dapagliflozin group in both the main (hazard ratio [HR], 0.885 [95% CI, 0.789-0.992]) and sensitivity analyses (HR, 0.835 [95% CI, 0.719-0.970]). Notably, this was consistent in both the low and high cardiovascular risk groups. There was no effect modification by age, sex, body mass index, duration of diabetes, or renal function., Conclusions: This real-world, population-based study demonstrates that patients with type 2 diabetes using dapagliflozin may have a lower risk of developing nonvalvular atrial fibrillation than those using empagliflozin.

Objective: We investigated the association between the use of ACEi, ARB, or non-renin-angiotensin-aldosterone system inhibitors (non-RASi) and incident cardiovascular events in an unselected nationwide hypertension cohort., Methods: The information regarding 2,025,849 patients who underwent general health checkup between 2010 and 2011 and were on antihypertensive medication was collected. Patients were allocated into ACEi, ARB, and non-RASi groups and followed until 2019. The outcomes of interest were myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause deaths., Results: Patients on ACEi and ARB showed unfavorable baseline characteristics compared to those on non-RASi. After adjusting for covariates, the ACEi group showed lower risks of MI, AF, and all-cause deaths (HR (95% CI): 0.94 (0.89-0.99), 0.96 (0.92-1.00), and 0.93 (0.90-0.96), respectively), but similar risks of IS and HF (0.97 (0.92-1.01) and 1.03 (1.00-1.06), respectively), compared to the non-RASi group. Likewise, the ARB group showed decreased risks of MI, IS, AF, HF, and all-cause deaths (HR (95% CI): 0.93 (0.91-0.95), 0.88 (0.86-0.90), 0.86 (0.85-0.88), 0.94 (0.93-0.96), and 0.84 (0.83-0.85)), compared to the non-RASi group. Sensitivity analysis of patients taking a single antihypertensive medication showed similar results. In the propensity score matching (PSM) cohort, the ARB group showed similar risks of MI and decreased risks of IS, AF, HF, and all-cause deaths compared to the ACEi group., Conclusions: ACEi and ARB users were associated with decreased risks of MI, IS, AF, HF, and all-cause deaths, compared to non-RASi users., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Aims: The outcomes of mitral valve replacement/repair (MVR) in severe degenerative mitral regurgitation (MR) patients depend on various risk factors. We aimed to develop a risk prediction model for post-MVR mortality in severe degenerative MR patients using machine learning., Methods and Results: Consecutive severe degenerative MR patients undergoing MVR were analysed (n = 1521; 70% training/30% test sets). A random survival forest (RSF) model was constructed, with 3-year post-MVR all-cause mortality as the outcome. Partial dependency plots were used to define the thresholds of each risk factor. A simple scoring system (MVR-score) was developed to stratify post-MVR mortality risk. At 3 years following MVR, 90 patients (5.9%) died in the entire cohort (59 and 31 deaths in the training and test sets). The most important predictors of mortality in order of importance were age, haemoglobin, valve replacement, glomerular filtration rate, left atrial dimension, and left ventricular (LV) end-systolic diameter. The final RSF model with these six variables demonstrated high predictive performance in the test set (3-year C-index 0.880, 95% confidence interval 0.834-0.925), with mortality risk increased strongly with left atrial dimension >55 mm, and LV end-systolic diameter >45 mm. MVR-score demonstrated effective risk stratification and had significantly higher predictability compared to the modified Mitral Regurgitation International Database score (3-year C-index 0.803 vs. 0.750, P = 0.034)., Conclusion: A data-driven machine learning model provided accurate post-MVR mortality prediction in severe degenerative MR patients. The outcome following MVR in severe degenerative MR patients is governed by both clinical and echocardiographic factors., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aims: To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA)., Methods and Results: This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0-70.0) years, 53.3% male]. The median LASr was 13.9% (10.5-20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr >14.4% (18.1% vs. 5.1%, P < 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879-0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337-8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P < 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2)., Conclusion: LASr was an independent predictor of NOAF in patients with ALCA., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Little is known about the determinants and outcomes of significant atrial functional tricuspid regurgitation (AFTR)., Objectives: The authors aimed to identify risk factors for significant TR in relation to atrial fibrillation-flutter (AF-AFL) and assess its prognostic implications., Methods: The authors retrospectively studied patients with mild TR with follow-up echocardiography examinations. Significant TR was defined as greater than or equal to moderate TR. AFTR was defined as TR, attributed to right atrial (RA) remodeling or isolated tricuspid annular dilatation, without other primary or secondary etiology, except for AF-AFL. The Mantel-Byar test was used to compare clinical outcomes by progression of AFTR., Results: Of 833 patients with mild TR, 291 (34.9%) had AF-AFL. During the median 4.6 years, significant TR developed in 35 patients, including 33 AFTRs. Significant AFTR occurred in patients with AF-AFL more predominantly than in those patients without AF-AFL (10.3% vs 0.6%; P < 0.001). In Cox analysis, AF-AFL was a strong risk factor for AFTR (adjusted HR: 8.33 [95% CI: 2.34-29.69]; P = 0.001). Among patients with AF-AFL, those who developed significant AFTR had larger baseline RA areas (23.8 vs 19.4 cm 2 ; P < 0.001) and RA area-to-right ventricle end-systolic area ratio (3.0 vs 2.3; P < 0.001) than those who did not. These parameters were independent predictors of AFTR progression. The 10-year major adverse cardiovascular event was significantly higher after progression of AFTR than before or without progression (79.8% vs 8.6%; Mantel-Byar P < 0.001)., Conclusions: In patients with mild TR, significant AFTR developed predominantly in patients with AF-AFL, conferring poor prognosis. RA enlargement, especially with increased RA area-to-right ventricle end-systolic area ratio, was a strong risk factor for progression of AFTR., Competing Interests: Funding Support and Author Disclosures This work was supported by the National Research Foundation of Korea of the Ministry of Science and ICT (NRF-2020R1C1C1010890). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA 2 DS 2 -VASc or HAS-BLED scores. There were 18 major bleeding events, 106 deaths, and 50 stroke events during a mean follow-up of 2.9 months. After multivariable adjustment, the use of NOAC was associated with a lower risk of incident ischemic stroke (HR 0.51, 95% CI 0.27-0.94), while there was no significant difference in risk for major bleeding or death compared with warfarin. These results suggest that NOACs have better effectiveness for stroke prevention and similar safety compared with warfarin in patients on concomitant anti-tuberculosis treatment. This is the first study assessing the safety and effectiveness of NOACs compared to warfarin in this clinical scenario., (© 2023. The Author(s).)

Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS) in hypertrophic cardiomyopathy (HCM), the risk of IS in HCM patients without documented AF is less recognized. This nationwide population-based cohort study using Korean National Health Insurance database included 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls between 2010 and 2016. The primary outcome was an incident IS. During a mean follow-up of 6.1 years, IS occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. The overall incidence of IS was 0.72/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.64; 95% CI 1.424-1.895; P &lt; 0.001). The overall incidence of IS was 1.36/100 person-years in HCM patients aged ≥ 65 and 2.32/100 person-years years in those with heart failure, respectively. In the HCM group, age ≥ 65 years (adjusted HR 2.74; 95% CI 2.156-3.486; P &lt; 0.001) and chronic heart failure (adjusted HR 1.75; 95% CI 1.101-2.745; P = 0.018) were independent risk factors for IS. HCM patients without documented AF are at a greater risk of IS, especially in those 65 years of age or older or those with chronic heart failure., (© 2022. The Author(s).)

Background: Non-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown., Methods: We retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death., Results: The mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56-2.34), major bleeding (HR 0.80, 95% CI 0.32-2.03) and all-cause death (HR 1.09, 95% CI 0.73-1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76-1.47). These outcomes were not different in various subgroups analyzed., Conclusion: In this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV., Competing Interests: The authors have declared that no competing interests exist.

Objective: Despite the benefits of weight loss on metabolic profiles in patients with type 2 diabetes mellitus (T2DM), its association with myocardial infarction (MI), ischemic stroke (IS), atrial fibrillation (AF), heart failure (HF), and all-cause death remains elusive., Research Design and Methods: Using the National Health Insurance Service Database, we screened subjects who underwent general health checkups twice in a 2-year interval between 2009 and 2012. After identifying 1,522,241 patients with T2DM without a previous history of MI, IS, AF, and HF, we followed them until December 2018. Patients were stratified according to the magnitude of weight changes between two general health checkups: ≤ -10%, -10 to ≤ -5%, -5 to ≤5%, 5 to ≤10%, and >10%., Results: During the follow-up (median 7.0 years), 32,106 cases of MI, 44,406 cases of IS, 34,953 cases of AF, 68,745 cases of HF, and 84,635 all-cause deaths occurred. Patients with weight changes of -5 to ≤5% showed the lowest risk of each cardiovascular event. Both directions of weight change were associated with an increased cardiovascular risk. Stepwise increases in the risks of MI, IS, AF, HF, and all-cause death were noted with progressive weight gain (all P < 0.0001). Similarly, the more weight loss occurred, the higher the cardiovascular risks observed (all P < 0.0001). The U-shaped associations were consistently observed in both univariate and multivariate analyses. Explorative subgroup analyses also consistently showed a U-shaped association., Conclusions: Both weight loss and gain >5% within a 2-year interval were associated with an increased risk of major cardiovascular events in patients with T2DM., (© 2022 by the American Diabetes Association.)

Aims: Diabetes mellitus (DM) often coexists in elderly hypertrophic cardiomyopathy (HCM) patients; however, its impact on clinical outcomes is unclear., Methods: We compared clinical outcomes according to the presence of DM in a nationwide HCM cohort., Results: In 9,883 HCM subjects (mean age 58.5 ± 13.1, men 71.7%), 1,327 (13.4%) had DM. During follow-up (mean 5.9 ± 2.5 years), end-stage renal disease (ESRD) progression, coronary events (myocardial infarction, coronary revascularization), heart failure (HF), cardiovascular mortality, and all-cause mortality occurred in 80 (0.8%), 365 (3.7%), 1,558 (15.8%), 354 (3.6%), and 877 (8.9%) subjects, respectively. DM HCM subjects had significantly higher risks of ESRD progression (HR 3.49, 95% CI 2.20-5.54) and HF (HR 1.15, 95% CI 1.01-1.32) compared to non-DM HCM subjects, independent of age, sex, ischemic heart disease, atrial fibrillation, and other comorbidities. There was a tendency for greater risk of ESRD progression, HF, and all-cause death in subjects with more advanced stage of DM (p-for-trend < 0.05 for all). Insulin-treated DM was associated with the highest risk., Conclusions: DM HCM subjects have higher risk of ESRD progression and HF. Considering the extended life expectancy of HCM and increasing number of elderly HCM subjects, active surveillance and management of DM-related outcomes should be highlighted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Backgroud There is a paucity of information on whether changes in metabolic syndrome (MetS) status affect the risk of new-onset atrial fibrillation (AF). We aimed to evaluate whether changes in MetS status and components of MetS affect AF risk using data from a nationwide observational cohort. Methods and Results A total of 7 565 531 adults without prevalent AF (mean age, 47±14 years) who underwent 2 serial health examinations by the Korean National Health Insurance Cooperation were identified. The patients were categorized into 4 groups according to the change in MetS status in serial evaluations, as follows: patients with persistent MetS (n=1 388 850), healthy patients newly diagnosed with MetS in the second evaluation (n=608 158), patients with MetS who were healthy in the second evaluation (n=798 555), and persistently healthy individuals (n=4 769 968). During a mean 7.9-year follow-up, incident AF was diagnosed in 139 305 (1.8%) patients. After multivariable adjustment, the AF risk was higher by 31% in the patients with persistent MetS , 26% in the patients with MetS who were healthy in the second evaluation, and 16% in the healthy patients newly diagnosed with MetS in the second evaluation compared with the persistently healthy individuals. Regardless of the MetS component type, the AF risk correlated with changes in the number of components. The risk of AF was strongly correlated with MetS status changes in the young and middle-age groups (20-39 years and 40-64 years, respectively) than in the elderly group (≥65 years). Conclusions Dynamic changes in MetS status and persistent MetS were associated with an increased risk of AF in a large-scale Asian population.

We evaluated the impacts of lifestyle behaviors, namely smoking, alcohol consumption, and physical activity, on the development of new-onset AF in patients with DM. Using the Korean Nationwide database, we identified subjects diagnosed with type 2 DM and without previous history of AF between 2009 and 2012. Self-reported lifestyle behaviors were analyzed. Among 2,551,036 included subjects, AF was newly diagnosed in 73,988 patients (median follow-up 7.1 years). Both ex-smokers (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.02-1.07) and current smokers (HR 1.06, 95% CI 1.03-1.08) demonstrated a higher risk of AF than never smokers. Patients with moderate (15-29 g/day) (HR 1.12, 95% CI 1.09-1.15) and heavy (≥ 30 g/day) (HR 1.24, 95% CI 1.21-1.28) alcohol consumption exhibited an increased risk of AF, while subjects with mild alcohol consumption (< 15 g/day) (HR 1.01, 95% CI 0.99-1.03) had an AF risk similar to that of non-drinkers. Patients who engaged in moderate-to-vigorous physical activity showed a lower risk of AF (HR 0.93, 95% CI 0.91-0.94) than those who did not. This study suggests that smoking, alcohol consumption, and physical activity are associated with new-onset AF in patients with DM, and lifestyle management might reduce the risk of AF in this population.

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disorder associated with various morbidities. Although the relationship between cardiovascular disease and PD has been studied, a paucity of information on PD and atrial fibrillation (AF) association exists. Thus, we aimed to investigate whether patients with PD have an increased risk of AF., Methods: This study included 57,585 patients with newly diagnosed PD (≥40-year-old, mean age 69.7 years, men 40.2%) and without a history of AF from the Korean National Health Insurance Service (NHIS) database between 2010 and 2015. Furthermore, an equal number of age- and sex-matched subjects without PD were selected for comparison. The primary outcome was new-onset AF., Results: During the mean follow-up period of 3.4 ± 1.8 years, AF was newly diagnosed in 3,665 patients. A significantly higher incidence rate of AF was noted among patients with PD than among patients without PD (10.75 and 7.86 per 1000 person-year, respectively). Multivariate Cox-regression analysis revealed that PD was an independent risk factor for AF (hazard ratio [HR]: 1.27, 95% confidence interval [CI]: 1.18-1.36). Furthermore, subgroup analyses revealed that AF risk was higher in the younger age subgroups, and compared with the non-PD group, the youngest PD group (age: 40-49 years) had a threefold increased risk of AF (HR: 3.06, 95% CI: 1.20-7.77)., Interpretation: Patients with PD, especially the younger age subgroups, have an increased risk of AF. Active surveillance and management of AF should be considered to prevent further complications., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Bodyweight variability is a risk factor for atrial fibrillation (AF). We aimed to examine the relationship between bodyweight variability and the risk of AF in patients with type 2 diabetes mellitus (DM), and whether this relationship was affected by baseline body mass index (BMI), weight change, or advanced diabetic stage., Methods: A nationwide population-based cohort of 670,797 patients with type 2 DM from the Korean National Health Insurance Service database without a history of AF and with ≥ 3 measurements of bodyweight over a 5-year period were followed up for AF development. Intra-individual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quintile with the highest variability with the lower four quintiles as reference., Results: During a median of 7.0 years of follow-up, 22,019 patients (3.3%) newly developed AF. After multivariate adjustment, those in the highest quintile of bodyweight variability showed a higher risk of incident AF (HR 1.16, 95% CI 1.12-1.20) compared to those in the lower 4 quintiles with reference bodyweight variability, irrespective of baseline BMI group and direction of overall weight change. This association was greater in magnitude in subjects with lower BMI, those on insulin, and those with a DM duration of greater than 5 years. In sensitivity analyses, high bodyweight variability was consistently associated with AF development using other indices of variability and adjusting for glycemic variability., Conclusions: High variability in bodyweight was associated with AF development, independently of traditional cardiovascular risk factors and baseline BMI. This association was stronger in underweight patients and with advanced diabetic stage. Weight fluctuation may interfere with the beneficial effects of weight loss and should be avoided when possible in weight control regimens for DM patients.

Background: Obesity and weight gain are established risk factors for atrial fibrillation (AF)., Objective: The purpose of this study was to investigate whether bodyweight variability is also a risk factor for AF development., Methods: A nationwide population-based cohort of 8,091,401 adults from the Korean National Health Insurance Service database without a history of AF and with ≥3 measurements of bodyweight over a 5-year period were followed up for incident AF. Intraindividual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quartile with the highest variability (Q4) with Q1-Q3 as reference., Results: During median 8.1 years of follow-up, each increase of 1 SD in bodyweight variability was associated with a 5% increased risk of AF development, and the quartile with the highest bodyweight variability showed 14% increased risk of AF development compared to the quartile with the lowest variability (hazard ratio 1.14; 95% confidence interval 1.12-1.15), after adjustment for baseline bodyweight, height, age, sex, lifestyle factors, and comorbidities. High bodyweight variability was significantly associated with AF development in all baseline body mass index (BMI) groups except the very obese (BMI ≥30), and this association was stronger in subjects with lower bodyweight. High bodyweight variability was associated with increased risk of incident AF in all weight change groups, with a stronger association in those who lost weight., Conclusion: Bodyweight fluctuation was independently associated with an increased risk of AF development, especially in individuals with low bodyweight, and regardless of weight gain or loss., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The relation of progression of type 2 diabetes and detailed fasting glucose level with risk of atrial fibrillation (AF) is not well known. A total of 6,199,629 subjects not diagnosed with AF who underwent health check-up in 2009 were included from the Korean National Health Insurance Service database. Risk of AF was compared among subjects with normal fasting glucose (NFG), subjects with impaired fasting glucose (IFG), patients with diabetes duration <5 years (early diabetes mellitus [DM]), and patients with diabetes duration ≥5 years (late DM). Next, risk of AF stratified by fasting glucose level per 10 mg/dL was assessed. During a mean follow-up of 7.2 years, the risk of AF significantly increased across the time course of type 2 diabetes (adjusted hazard ratio (aHR) 1.04, 95% confidence interval (CI) 1.02 to 1.05 for IFG; aHR 1.06, 95% CI 1.04 to 1.08 for early DM; aHR 1.09, 95% CI 1.07 to 1.11 for late DM). The risk of AF was significantly higher in subjects who progressed to type 2 diabetes in the IFG group. Risk of AF increased with a 10 mg/dL increment of fasting blood glucose (p-for-trend <0.0001). However, there was a U-shape relationship between fasting blood glucose and risk of AF in those who received antidiabetic medication. In conclusion, the risk of AF increased with the time course of type 2 diabetes. However, low blood glucose in antidiabetic medication user was associated with an increased risk of AF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background While high levels of lipids and lipid variability are established risk factors for atherosclerotic cardiovascular disease, their roles in the development of atrial fibrillation (AF) are unclear, with previous studies suggesting a "cholesterol paradox." Methods and Results A nationwide population-based cohort of 3 660 385 adults (mean age 43.4 years) from the Korean National Health Insurance Service database, with ≥3 annual lipid measurements from 2009 to 2012 and without a history of AF or prescription of lipid-lowering medication before 2012, were identified. Total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides levels were measured, and lipid variability was calculated using variability independent of the mean. The cohort was divided into quartiles by lipid levels and lipid variability and followed up for incident AF. During a median 5.4 years of follow-up, AF was newly diagnosed in 27 581 (0.75%). AF development was inversely associated with high lipid levels (for top versus bottom quartile; total cholesterol, HR 0.78, 95% CI 0.76-0.81; low-density lipoprotein cholesterol, HR 0.81, 95% CI 0.78-0.84; high-density lipoprotein cholesterol, HR 0.94, 95% CI 0.91-0.98; triglycerides, HR 0.88, 95% CI 0.85-0.92). Meanwhile, AF development was associated with high lipid variability (for top versus bottom quartile; total cholesterol, HR 1.09, 95% CI 1.06-1.13; low-density lipoprotein cholesterol, HR 1.12, 95% CI 1.08-1.16; high-density lipoprotein cholesterol, HR 1.08, 95% CI 1.04-1.12; triglycerides, HR 1.05, 95% CI 1.01-1.08). Men showed greater risk reduction with high triglyceride levels and greater risk with high triglyceride variability for incident AF. Conclusions Low cholesterol levels and high cholesterol variability were associated with a higher risk of AF development.

Although chronic kidney disease is known to increase the risk of atrial fibrillation (AF), the impact of the variability of renal function on the risk of incident AF is unknown. We aimed to evaluate the association between variability of renal function and the risk of developing AF among the general population. We evaluated a total of 3,551,249 adults who had three annual health check-ups provided by the National Health Insurance Service. The variability of renal function was defined as GFR-VIM, which is variability independent of the mean (VIM) of creatinine-based estimated glomerular filtration rate (eGFR). The study population was divided into four groups (Q1-4) based on the quartiles of GFR-VIM, and the risks of incident AF by each group were compared. During a mean of 3.2 ± 0.5 years follow-up, incident AF occurred in 15,008 (0.42%) subjects. The incidence rates of AF increased from Q1 to Q4 (0.98, 1.42, 1.27, and 1.63 per 1,000 person-years, respectively). Adjusting with multiple variables, Q4 showed an increased risk of incident AF compared to Q1 (hazard ratio (HR) 1.125, 95% confidence interval (CI) 1.071-1.181). Variability of serum creatinine or other definitions of variability showed consistent results. On subgroup analyses, Q4 in males or those with a decreasing trend of eGFR had significantly increased risks of incident AF compared to Q1 (HR 1.127, 95% CI 1.082-1.175; and HR 1.115, 95% CI 1.059-1.173, respectively). High variability of eGFR was associated with an increased risk of incident AF, particularly in males or those with decreasing trends of eGFR during follow-up.

Background: The association of lifetime exposure to endogenous sex hormone with incident atrial fibrillation (AF) and subsequent ischemic stroke has never been studied., Methods: This study involved 4 638 299 natural postmenopausal waomen aged ≥40 years without prior history of AF and with national breast cancer check-up between January 1, 2009 and December 31, 2014. The primary end point was incident AF, and the secondary end point was subsequent ischemic stroke once AF has developed. Cox proportional hazard regression analysis was used to estimate the risk of end points., Results: During the mean follow-up of 6.3 years, shorter total reproductive years (<30 years) were associated with 7% increased risk of AF after adjusting for confounding variables (adjusted hazard ratio [aHR], 1.07 [95% CI, 1.05-1.09]). Risk of AF declined progressively with every 5-yearly increment in total reproductive years ( P -for-trend <0.001). However, the prolonged (≥2 years) use of hormone replacement therapy after menopause was paradoxically associated with a 3% increase in AF risk (aHR, 1.03 [95% CI, 1.01-1.05]). For the secondary end point analysis, the risk of ischemic stroke after AF development significantly decreased with each 5-yearly increment in total reproductive years (with <30 years as reference; aHR, 0.93 [95% CI, 0.88-0.99] for 30-34 years; aHR, 0.84 [95% CI, 0.79-0.89] for 35-39 years; and aHR, 0.88 [95% CI, 0.80-0.97] for ≥40 years, P -for-trend <0.001)., Conclusions: In women with natural menopause, shorter lifetime exposure to endogenous sex hormone, that is, shorter total reproductive years, was significantly associated with a higher risk of AF and subsequent ischemic stroke. Paradoxically, prolonged exogenous hormone replacement therapy increased the risk of incident AF.

Background and Purpose- Hypertrophic cardiomyopathy patients with atrial fibrillation are at increased risk of stroke, and anticoagulation is strongly recommended. However, limited data are available regarding the safety and effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) for primary prevention of stroke. Methods- Using the Korean Health Insurance Review and Assessment Service database, we identified 2397 patients with hypertrophic cardiomyopathy and nonvalvular atrial fibrillation on oral anticoagulation from 2013 to 2016 without history of ischemic stroke, intracranial hemorrhage (ICH), or gastrointestinal bleeding (992 on warfarin and 1405 on NOACs). Inverse probability of treatment weighting with propensity scores was used to balance covariates between treatment groups. Risk for ischemic stroke, ICH, gastrointestinal bleeding, death, and their composite outcome associated with NOAC use was assessed with warfarin use as the reference. Results- During a mean follow-up of 1.6 years, the incidence rates of ischemic stroke, ICH, gastrointestinal bleeding, death, and composite outcome were all significantly lower in the NOAC than in the warfarin group (stroke, 2.8 versus 5.0; ICH, 0.5 versus 1.3; gastrointestinal bleeding, 2.3 versus 3.0; death, 3.0 versus 5.1; composite, 7.5 versus 12.5 events per 100 person-years). NOACs were associated with significantly lower risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.32-0.68), ICH (HR, 0.31; 95% CI, 0.14-0.69), gastrointestinal bleeding (HR, 0.62; 95% CI, 0.40-0.96), death (HR, 0.45; 95% CI, 0.31-0.65), and the composite outcome (HR, 0.48; 95% CI, 0.38-0.61) than warfarin. The same trend was observed regardless of the NOAC dose and across various high-risk subgroups. In analysis of individual NOACs, all NOACs were associated with lower risks of ischemic stroke and composite outcome. Conclusions- NOACs showed superior effectiveness and safety versus warfarin in the primary prevention of stroke versus warfarin in real-world Asian hypertrophic cardiomyopathy with atrial fibrillation.

Background: Advanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking., Objectives: The aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease., Methods: Using the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups., Results: DOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827)., Conclusions: In this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Proteinuria is one of the well-known risk factors for cardiovascular disease. However the impact of proteinuria on the incidence of atrial fibrillation (AF) is unclear. In this study, we investigated the association between proteinuria detected using urine dipstick test and the risk of AF. A total of 18,201,275 individuals were analyzed, who had no prior AF and had received biennial health checkups provided by the National Health Insurance Service between 2005 and 2008 in Korea. Incidences of AF were ascertained through the end of 2015. During a mean follow-up of 9.6 years, a total of 324,764 (1.8%) developed AF (1.86 per 1,000 person-years). In Cox regression models, proteinuria was associated with an increased risk of AF: adjusted HR and 95% CI of AF occurrence were 1.13 (1.10-1.16), 1.34 (1.31-1.38), 1.53 (1.48-1.58), 1.82 (1.71-1.94), and 1.86 (1.61-2.16) in individuals with trace, 1+, 2+, 3+, and 4+ proteinuria, respectively, compared with those without proteinuria. The result was consistent even after additional adjustment for estimated glomerular filtration rate. In addition, the risk of AF further increased or decreased according to the follow-up dipstick test results. Thus, proteinuria measured with a dipstick test might be considered a potent risk factor for AF development.

Background: Atrial fibrillation (AF) is prevalent among type 2 diabetic patients. However, the association between diabetic retinopathy (DR) and AF is controversial., Methods: We included 40,500 patients with type 2 diabetes (≥40years, mean age 62±11years, 53% men) without AF from the Korean National Insurance Service-National Sample Cohort (2002-2007). Subjects were classified without DR (non-DR, n=30,178), with DR (DR, n=8920), and with proliferative DR (PDR, n=1402)., Results: During a mean 5.9-year follow-up, 1261 (3.1%) patients were newly diagnosed as having AF (4.9, 6.0, and 8.3 per 1000 person-years in the non-DR, DR, and PDR groups, respectively). In multivariate Cox proportional hazard models, patients in the DR and PDR groups had a significantly higher risk of AF than those in the non-DR group (DR group: hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.00-1.30; PDR group: HR 1.46, 95% CI 1.13-1.87); p for trend <0.001). The risk of AF increased in patients with DR and end-stage renal disease (ESRD) (HR 2.39, 95% CI 1.31-3.96, p<0.001) and in those with PDR and ESRD (HR 3.59, 95% CI 1.96-5.97, p<0.001) compared to those without DR and ESRD., Conclusions: The presence and severity of DR was significantly associated with the incidence of AF. Also, the presence of ESRD had an impact on the incidence of AF in patients with DR., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aims The aim of this study was to investigate the prognostic utility of left ventricular (LV) global longitudinal strain (LV-GLS) in patients with hypertrophic cardiomyopathy (HCM) and an LV ejection fraction (LVEF) of 50–60%. Methods and results This retrospective cohort study included 349 patients with HCM and an LVEF of 50–60%. The primary outcome was a composite of cardiovascular death, including sudden cardiac death (SCD) and SCD-equivalent events. The secondary outcomes were SCD/SCD-equivalent events, cardiovascular death (including SCD), and all-cause death. The final analysis included 349 patients (mean age 59.2 ± 14.2 years, men 75.6%). During a median follow-up of 4.1 years, the primary outcome occurred in 26 (7.4%), while the secondary outcomes of SCD/SCD-equivalent events, cardiovascular death, and all-cause death occurred in 15 (4.2%), 20 (5.7%), and 34 (9.7%), respectively. After adjusting for age, atrial fibrillation, ischaemic stroke, LVEF, and left atrial volume index, absolute LV-GLS (%) was independently associated with the primary outcome [adjusted hazard ratio (HR) 0.88, 95% confidence interval (CI) 0.788–0.988, P = 0.029]. According to receiver operating characteristic analysis, 10.5% is an optimal cut-off value for absolute LV-GLS in predicting the primary outcome. Patients with an absolute LV-GLS ≤ 10.5% had a higher risk of the primary outcome than those with an absolute LV-GLS > 10.5% (adjusted HR 2.54, 95% CI 1.117–5.787, P = 0.026). Absolute LV-GLS ≤ 10.5% was an independent predictor for each secondary outcome (P < 0.05). Conclusions LV-GLS was an independent predictor of a composite of cardiovascular death, including SCD/SCD-equivalent events, in patients with HCM and an LVEF of 50–60%. Therefore, LV-GLS can help in risk stratification in these patients. [ABSTRACT FROM AUTHOR]

Aims To investigate whether left arterial reservoir strain (LASr) could predict new-onset atrial fibrillation (NOAF) in patients with light-chain-type cardiac amyloidosis (ALCA). Methods and results This study enrolled 427 patients with CA from two tertiary centres between 2005 and 2019. LASr was measured using a vendor-independent analysis programme. The primary outcome was NOAF. A total of 287 patients with ALCA were included [median age 63.0 (56.0–70.0) years, 53.3% male]. The median LASr was 13.9% (10.5–20.8%). During the median follow-up of 0.85 years, AF occurred in 34 patients (11.8%). In the receiver operating characteristics curve analysis, the optimal cut-off of LASr for predicting NOAF was 14.4%. Patients with LASr ≤14.4% had a higher risk of NOAF than those with LASr >14.4% (18.1% vs. 5.1%, P < 0.010). In the multivariate analysis adjusting for confounding factors, including left arterial volume index and left ventricular global longitudinal strain (LV-GLS), higher LASr (%) was independently associated with lower risk for NOAF [adjusted hazard ratio (aHR): 0.936, 95% confidence interval (95% CI): 0.879–0.997, P = 0.039]. Furthermore, LASr ≤14.4% was an independent predictor for NOAF (aHR: 3.370, 95% CI: 1.337–8.492, P = 0.010). This remained true after accounting for all-cause death as a competing risk. Compared with Model 1 (LV-GLS) and Model 2 (LV-GLS plus LAVI), Model 3, including LASr showed a better reclassification ability for predicting NOAF (net reclassification index = 0.735, P < 0.001 compared with Model 1; net reclassification index = 0.514, P = 0.003 compared with Model 2). Conclusion LASr was an independent predictor of NOAF in patients with ALCA. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. Methods: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013–2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. Results: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65–0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. Conclusion: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality. [ABSTRACT FROM AUTHOR]

Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications. [ABSTRACT FROM AUTHOR]

Background: Obesity and weight gain are established risk factors for atrial fibrillation (AF).Objective: The purpose of this study was to investigate whether bodyweight variability is also a risk factor for AF development.Methods: A nationwide population-based cohort of 8,091,401 adults from the Korean National Health Insurance Service database without a history of AF and with ≥3 measurements of bodyweight over a 5-year period were followed up for incident AF. Intraindividual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quartile with the highest variability (Q4) with Q1-Q3 as reference.Results: During median 8.1 years of follow-up, each increase of 1 SD in bodyweight variability was associated with a 5% increased risk of AF development, and the quartile with the highest bodyweight variability showed 14% increased risk of AF development compared to the quartile with the lowest variability (hazard ratio 1.14; 95% confidence interval 1.12-1.15), after adjustment for baseline bodyweight, height, age, sex, lifestyle factors, and comorbidities. High bodyweight variability was significantly associated with AF development in all baseline body mass index (BMI) groups except the very obese (BMI ≥30), and this association was stronger in subjects with lower bodyweight. High bodyweight variability was associated with increased risk of incident AF in all weight change groups, with a stronger association in those who lost weight.Conclusion: Bodyweight fluctuation was independently associated with an increased risk of AF development, especially in individuals with low bodyweight, and regardless of weight gain or loss. [ABSTRACT FROM AUTHOR]