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Purpose@#Advanced chronic kidney disease (CKD), including end-stage renal disease (ESRD) on dialysis, increases thromboembolic risk among patients with atrial fibrillation (AF). This study examined the comparative safety and efficacy of direct-acting oral anticoagulant (DOAC) compared to warfarin or no oral anticoagulant (OAC) in AF patients with advanced CKD or ESRD on dialysis. @*Materials and Methods@#Using data from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, 260 non-valvular AF patients with advanced CKD (defined as estimated glomerular filtration rate <30 mL/min per 1.73/m2 ) or ESRD on dialysis were enrolled from June 2016 to July 2020. The study population was categorized into DOAC, warfarin, and no OAC groups; and differences in major or clinically relevant non-major (CRNM) bleeding, stroke/systemic embolism (SE), myocardial infarction/critical limb ischemia (CLI), and death were assessed. @*Results@#During a median 24 months of follow-up, major or CRNM bleeding risk was significantly reduced in the DOAC group compared to the warfarin group [hazard ratio (HR) 0.11, 95% confidence interval (CI) 0.01 to 0.93, p=0.043]. In addition, the risk of composite adverse clinical outcomes (major or CRNM bleeding, stroke/SE, myocardial infarction/CLI, and death) was significantly reduced in the DOAC group compared to the no OAC group (HR 0.16, 95% CI 0.03 to 0.91, p=0.039). @*Conclusion@#Among AF patients with advanced CKD or ESRD on dialysis, DOAC was associated with a lower risk of major or CRNM bleeding compared to warfarin and a lower risk of composite adverse clinical outcomes compared to no OAC.ClinicalTrials.gov (NCT02786095)
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Background and Objectives@#Atrial fibrillation (AF) is associated with decreased cardiac resynchronization therapy (CRT) benefits compared to sinus rhythm (SR). Effective biventricular (BiV) pacing is a determinant of CRT success, but AF can interfere with adequate BiV pacing and affect clinical outcomes. We investigated the effect of device-detected AF on clinical outcomes and optimal BiV pacing in patients with heart failure (HF) treated with CRT. @*Methods@#We retrospectively analyzed 174 patients who underwent CRT implantation between 2012 and 2019 at a tertiary center. The optimal BiV pacing percentage was defined as ≥98%. Device-detected AF was defined as an atrial high-rate episode ≥180 beats per minute lasting more than 6 minutes during the follow-up period. We stratified the patients without preexisting AF at pre-implantation into device-detected AF and no-AF groups. @*Results@#A total of 120 patients did not show preexisting AF at pre-implantation, and 54 had AF. Among these 120 patients, 19 (15.8%) showed device-detected AF during a median follow-up of 25.1 months. The proportion of optimal BiV pacing was significantly lower in the device-detected AF group than in the no-AF group (42.1% vs. 75.2%, p=0.009). The devicedetected AF group had a higher incidence of HF hospitalization, cardiovascular death, and all-cause death than the no-AF group. The device-detected AF and previous AF groups showed no significant differences regarding the percentage of BiV pacing and clinical outcomes. @*Conclusions@#For HF patients implanted with CRT, device-detected AF was associated with lower optimal BiV pacing and worse clinical outcomes than no-AF.
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Background@#The prognostic significance of resting heart rate and its therapeutic target in atrial fibrillation (AF) is uncertain. We sought to investigate the relationship between resting heart rate and cardiovascular outcomes in patients with non-paroxysmal AF (non-PAF). @*Methods@#In this propensity score-weighted, multi-center prospective cohort study, 3217 patients with non-PAF were analyzed. Patients were categorized according to the baseline resting heart rate and cardiovascular outcomes were accessed for a median follow-up of 30 months. The primary outcome was a composite of cardiovascular death, heart failure hospitalization, and myocardial infarction/critical limb ischemia. @*Results@#Freedom from primary outcome was longest among patients with resting heart rate 80–99 beats per minute (bpm) whereas shortest among those with ≤ 59 bpm (weighted log rank, p = 0.008). Compared with heart rate ≥ 100 bpm, resting heart rate 80–99 and 60–79 bpm was associated with reduced risk of primary outcome (weighted hazard ratio [WHR] 0.52, 95% confidence interval [CI] 0.32–0.84, p = 0.008 and WHR 0.58, 95% CI 0.37–0.92, p = 0.021 for heart rate 80–99 and 60–79 bpm, respectively). Using weighted restricted cubic spline curves, there was a U-shaped association between the resting heart rate and primary outcome with reduced risk of primary outcome in heart rate range of 68–99 bpm. This association was maintained regardless of atrioventricular node (AVN) blocker use or persistent/permanent AF (p for interaction 0.767 for AVN blocker use and 0.720 for AF type). @*Conclusion@#Resting heart rate was associated with cardiovascular outcomes in patients with non-PAF and those with resting heart rate between 68 and 99 bpm had lower risk of adverse cardiovascular events regardless of AVN blocker use or persistent/permanent AF.
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Background@#It has become important to identify and manage risk factors for subclinical atrial fibrillation (AF) with an increase in its detection rate. Thus, this research aimed to investigate whether alcohol consumption contrib‑ utes to the development of subclinical AF. @*Methods@#This prospective study enrolled 467 patients without AF from a multicenter pacemaker registry. The incidence of subclinical AF (episodes of atrial rate > 220 beats per minute without symptoms) was compared between alcohol-drinking and non-drinking groups. @*Results@#During followup (median 18 months), the incidence and risk of long-duration atrial high-rate episodes (AHRE) ≥ 24 h were increased in the alcohol group compared to the non-alcohol group [5.47 vs. 2.10 per 100 personyears, adjusted hazard ratio (HR), 2.83; 95% confidence interval (CI), 1.14–7.04; P = 0.03]. After propensity score match‑ ing, the incidence and risk of long-duration AHRE were higher in the alcohol group (6.97 vs. 1.27 per 100 personyears, adjusted HR, 7.84; 95% CI, 1.21–50.93; P = 0.03). The mean burden of long-duration subclinical AF was higher in the alcohol group than in the non-alcohol group (0.18 vs. 1.61% during follow-up, P = 0.08). @*Conclusion@#Alcohol consumption was associated with an increased risk of subclinical AF. Long-duration AHRE inci‑ dence and AHRE burden were higher in alcohol drinkers than in non-drinkers.
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Background@#Traditional right ventricular apical pacing can cause electrical–mechanical dyssynchrony. Therefore, physiological conduction system pacing was considered and became the reason for developing His bundle pacing (HBP). Recently, left bundle branch area pacing (LBBAP) has been implemented, which overcomes the shortcomings of HBP. Most initial large LBBAP studies reported that LBBAP was achieved through a lumenless pacing lead (LLL) with a fixed helix design; however, it is unavailable in Korea. LBBAP delivery sheaths using a conventional standard styletdriven pacing lead (SDL) with an extendable helix design are currently available in Korea. In this review, we describe the methods and procedural skills required to perform the LBBAP using conventional SDL.Main body LBBAP has emerged as a new physiological CSP modality and has shown a stable and lower capture threshold and achieved a similarly paced QRS duration compared to HBP. It has also demonstrated stable early outcomes for feasibility and safety with a high success rate. Furthermore, the application of LBBAP has recently been extended to a resynchronization strategy. The LBBAP with SDL requires different handling and lead preparation owing to differences in lead and helix designs. Reported procedure-related acute complications of LBBAP include septal per‑ foration during the procedure, pneumothorax, pocket infection, pocket hematoma, and lead dislodgements occur‑ ring during follow-up. @*Conclusion@#LBBAP with conventional SDL has similar implant success rates, procedural safety, and pacing character‑ istics as LBBAP with LLL. However, LBBAP with SDL requires different handling and lead preparation from that of LLL owing to the differences in the lead and helix designs.
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Rhythm control therapy is used in atrial fibrillation (AF) management to improve AF-related symptoms along with rate control. AF catheter ablation is effective in maintaining sinus rhythm and has an acceptable complication rate. Compared with antiarrhythmic drugs, AF catheter ablation is superior with respect to arrhythmia-free survival and improvement in the quality of life. Therefore, AF ablation is recommended for rhythm control after the failure of antiarrhythmic drugs and is sometimes considered a first-line therapy for AF patients. Radiofrequency and cryoballoon ablation show similar efficacy, with slightly different complication profiles. Surgery for AF is also an effective rhythm control therapy and should be considered in patients undergoing cardiac surgery or in those with failed catheter ablation. For patients undergoing AF catheter ablation, performing ablation under uninterrupted warfarin or non-vitamin K oral anticoagulant treatment is recommended for periprocedural stroke risk management. Here, we review existing data and discuss the general principles of AF catheter and surgical ablation in patients with AF.
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For almost 20 years, data regarding the effect of rhythm control therapy for atrial fibrillation (AF) on cardiovascular prognosis in comparison with rate control therapy has not been conclusive. The safety of rhythm control and anticoagulation therapy has generally improved. Recently, it was revealed that a rhythm-control strategy reduced the risk of adverse cardiovascular events than usual rate control in patients with recent AF (diagnosed within 1 year). Within 1 year after the AF diagnosis, early initiation of rhythm control led to more favorable cardiovascular outcomes than rate control. Early rhythm control reduced the risks of stroke and heart failure-related admission than rate control. Moreover, rhythm control was associated with lower dementia risk than rate control. Finally, early rhythm control treatment was also effective in patients with asymptomatic AF but less effective in older adults. Therefore, in patients with AF, rhythm control should be considered at earlier stages, regardless of symptom.
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Background and Objectives@#In patients with atrial fibrillation (AF), females taking vitamin K antagonist are at higher risk of stroke or systemic embolism (SSE), bleeding and all-cause death than males. This study investigated the relationship between sex and adverse clinical events in a contemporary AF patient cohort taking anticoagulation. @*Methods@#This prospective multicenter AF registry study comprised 6,067 patients with AF (mean age, 70±9 years; men, 59%) with intermediate to high risk of stroke (CHA 2 DS 2-VAscore ≥1) and receiving oral anticoagulation therapy. Adverse clinical outcomes, including SSE, bleeding, death were evaluated in patients stratified by sex and anticoagulation patterns. @*Results@#Women were older and used more direct oral anticoagulants (85% vs. 78%, p<0.001) than men. During a median (25 the and 75 the percentiles) follow-up of 30 (24, 38) months, the incidence rate and risk of SSE (0.7 in women vs. 0.7 in men per 100 person-years) and major bleeding (0.1 in women vs. 0.1 in men per 100 person-years) were not different between the sexes. However, women had a lower all-cause death rate (0.4 in women vs. 0.6 in men per 100 person-years, hazard ratio: 0.48, 95% confidence interval: 0.25–0.91, p=0.025) than men. @*Conclusions@#In contemporary anticoagulation for AF, SSE and major bleeding risks did not differ between sexes. However, women showed a lower risk of all-cause death rate than men, indicating that the use of oral anticoagulants for treating AF in females does not appear to be a risk factor for adverse clinical events.
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Background@#Conventional modality requires several days observation by Holter monitor to differentiate atrial fibril‑ lation (AF) between Paroxysmal atrial fibrillation (PAF) and Non-paroxysmal atrial fibrillation (Non-PAF). Rapid and practical differentiating approach is needed. @*Objective@#To develop a machine learning model that observes 10-s of standard 12-lead electrocardiograph (ECG) for real-time classification of AF between PAF versus Non-PAF. @*Methods@#In this multicenter, retrospective cohort study, the model training and cross-validation was performed on a dataset consisting of 741 patients enrolled from Severance Hospital, South Korea. For cross-institutional validation, the trained model was applied to an independent data set of 600 patients enrolled from Ewha University Hospital, South Korea. Lasso regression was applied to develop the model. @*Results@#In the primary analysis, the Area Under the Receiver Operating Characteristic Curve (AUC) on the test set for the model that predicted AF subtype only using ECG was 0.72 (95% CI 0.65–0.80). In the secondary analysis, AUC only using baseline characteristics was 0.53 (95% CI 0.45–0.61), while the model that employed both baseline characteris‑ tics and ECG parameters was 0.72 (95% CI 0.65–0.80). Moreover, the model that incorporated baseline characteristics, ECG, and Echocardiographic parameters achieved an AUC of 0.76 (95% CI 0.678–0.855) on the test set. @*Conclusions@#Our machine learning model using ECG has potential for automatic differentiation of AF between PAF versus Non-PAF achieving high accuracy. The inclusion of Echocardiographic parameters further increases model per‑ formance. Further studies are needed to clarify the next steps towards clinical translation of the proposed algorithm.
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Purpose@#The incidence of stroke and/or systemic thromboembolism (SSE) has not been properly evaluated in well-anticoagulated atrial fibrillation (AF) patients. This study investigated the incidence of SSE according to CHA2DS2-VASc score in contemporary well-anticoagulated Korean AF patients. @*Materials and Methods@#From the prospective multicenter COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation (CODE-AF) registry, we identified 9503 patients with non-valvular AF (mean age, 68±8 years; female 35.5%) enrolled between June 2016 and May 2020 with eligible follow-up visits. Stroke incidence in the CODE-AF registry was compared with that in an oral anticoagulant (OAC)-naïve AF cohort from the Korean National Health Insurance database. @*Results@#The usage rates of OACs and antiplatelet agents were 73.5% (non-vitamin K OACs, 56.4%; warfarin, 17.1%) and 23.8%, respectively. During a mean follow-up period of 26.3±9.6 months, 163 (0.78 per 100 person-years) patients had SSE. The incidence rate (per 100 person-years) of SSE was 0.77 in the total population, 0.26 in low-risk patients [CHA2DS2-VASc score 0 (male) or 1 (female)], and 0.88 in high-risk patients (CHA2DS2-VASc score ≥2). Contemporary AF patients had a stroke rate that was about one-fifth the stroke rate reported in a Korean OAC-naïve AF cohort. In this cohort, most risk factors for CHA2DS2-VASc score showed significant associations with SSE. Female sex was not associated with an increased risk of stroke/SSE in well-anticoagulated AF patients. @*Conclusion@#Contemporary AF patients have a stroke rate about one-fifth that in OAC-naïve AF patients and exhibit different stroke risk factors.
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Background@#Cardiac resynchronization therapy (CRT) is an effective treatment option for patients with heart failure (HF) and left ventricular (LV) dyssynchrony. However, the problem of some patients not responding to CRT remains unresolved. This study aimed to propose a novel in silico method for CRT simulation. @*Methods@#Three-dimensional heart geometry was constructed from computed tomography images. The finite ele‑ ment method was used to elucidate the electric wave propagation in the heart. The electric excitation and mechani‑ cal contraction were coupled with vascular hemodynamics by the lumped parameter model. The model parameters for three-dimensional (3D) heart and vascular mechanics were estimated by matching computed variables with measured physiological parameters. CRT effects were simulated in a patient with HF and left bundle branch block (LBBB). LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), LV ejection fraction (LVEF), and CRT responsiveness measured from the in silico simulation model were compared with those from clinical observation. A CRT responder was defined as absolute increase in LVEF ≥ 5% or relative increase in LVEF ≥ 15%. @*Results@#A 68-year-old female with nonischemic HF and LBBB was retrospectively included. The in silico CRT simu‑ lation modeling revealed that changes in LVEDV, LVESV, and LVEF by CRT were from 174 to 173 mL, 116 to 104 mL, and 33 to 40%, respectively. Absolute and relative ΔLVEF were 7% and 18%, respectively, signifying a CRT responder.In clinical observation, echocardiography showed that changes in LVEDV, LVESV, and LVEF by CRT were from 162 to 119 mL, 114 to 69 mL, and 29 to 42%, respectively. Absolute and relative ΔLVESV were 13% and 31%, respectively, also signifying a CRT responder. CRT responsiveness from the in silico CRT simulation model was concordant with that in the clinical observation. @*Conclusion@#This in silico CRT simulation method is a feasible technique to screen for CRT non-responders in patients with HF and LBBB.
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Background@#Sudden cardiac arrest (SCA) has not been well studied in Asian countries. This study investigated the temporal trends in the incidence and outcomes of SCA and the impact of age, gender, economic state, and urbaniza‑ tion on SCA using a nationwide population-based sample cohort of South Korea. @*Methods@#In the Korean National Health Insurance Service—Sample Cohort consisting of one million persons from 2003 through 2013, we identified 5,675 (0.56%) patients with SCA using ICD-10 code I46 and I49.0. We evaluated the impact of the age, gender, household income, and urbanization level on the incidence and outcome of SCA. @*Results@#During the study period, the overall age- and gender-adjusted annual incidence of SCA increased by 46.9% from 30.9 in 2003 to 45.4 in 2013 (per 100,000 person-years, p < 0.001 for trend). The medical cost per 100,000 personyears also greatly increased about four times (p < 0.001 for trend). The overall adjusted survival to hospital discharge rate increased from 8.9% in 2003 to 13.2% in 2013 (adjusted rate ratio per year 1.05; p < 0.001 for trend). Old age and low household incomes of the population was related to increased SCA and poor survival to hospital discharge rate. The proportion of patients with intensive or advanced therapeutic modalities after SCA greatly increased from 1.6% in 2003 to 10.0% in 2013 (p < 0.001 for trend). This increase was consistent regardless of age, gender, economic state, and urbanization level. @*Conclusions@#Although the incidence of SCA was increased, the outcome was improved for the decade. However, in the elderly and low-income population, the incidence of SCA continued to rise and survival outcome was not improved.
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Optimized management of atrial fibrillation requires patient-oriented decision making with a multidisciplinary approach. This report incorporates recent authoritative studies to provide detailed recommendations for managing atrial fibrillation in specific clinical settings. The principles of the Atrial fibrillation Better Care (ABC) pathway apply in these clinical settings. In addition, specific considerations are discussed for each of these conditions and populations.
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Atrial fibrillation (AF) is a strong risk factor for ischemic stroke and systemic embolism. To prevent thromboembolic events in patients with AF, anticoagulation therapy is essential. The anticoagulant strategy is determined after stroke and bleeding risk assessments using the CHA2DS2-VASc and HAS-BLED scores, respectively; both consider clinical risk factors. Vitamin K antagonists (VKAs) are the sole anticoagulant option in AF patients with a prosthetic mechanical valve or moderate-severe mitral stenosis; in all other AF patients VKA or non-vitamin K antagonist oral anticoagulants are therapeutic options. However, antiplatelet therapy should not be used for stroke prevention in AF patients. Anticoagulation is not needed in AF patients with low stroke risk but strongly recommended in those with a with low bleeding risk. Left atrial appendage (LAA) occlusion offers an alternative in AF patients in whom long-term anticoagulation is contraindicated. Surgical occlusion or the exclusion of LAA can be considered for stroke prevention in AF patients undergoing cardiac surgery. In this article, we review existing data for stroke prevention and suggest optimal strategies to prevent stroke in AF patients.
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Atrial fibrillation (AF) is a strong risk factor for embolic stroke. In patients with AF, optimal anticoagulation therapy, administered according to the stroke risk scoring system, can effectively reduce the stroke risk. However, AF episodes are frequently asymptomatic, with a significant number of them detected after a stroke event. Therefore, the early detection of subclinical AF and the subsequent administration of optimal oral anticoagulation therapy is expected to reduce the risk of stroke. However, this strategy requires more effective screening for the detection of AF in the asymptomatic stage, which accounts for the recent research interest in silent/subclinical AF. Today, the widespread use of cardiac implantable electronic devices and wearable rhythm monitors has enabled the detection of atrial high-rate episodes/subclinical AF in a substantial number of patients. The risk of stroke appears to be related to the duration of this phenomenon. Subclinical AF increases the risk of stroke, but generally not as much as clinical AF, but whether long-term anticoagulation therapy is required in patients with subclinical AF is unclear. Here we review existing data on the epidemiology, clinical significance, and suggest guidelines on management of subclinical AF and the optimal screening strategies aimed at its detection.
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Background and Objectives@#Atrial high-rate episodes (AHREs) can be continuously detected by cardiovascular implantable electronic devices (CIEDs); however, the predictors of clinically relevant AHREs are unclear. @*Methods@#This prospective multicenter study monitored 816 patients (median age 73 years, 40.4% male) without atrial fibrillation (AF) from September 2017 to July 2020. AHREs was defined as a programmed atrial detection rate >220 beats/min. The reference values of 6 minutes and 6 hours were set to analyze clinical implication of AHREs based on previously published data that the 6 minutes excluded most episodes of oversensing. @*Results@#During a median follow-up of 18 months (interquartile interval 9–26 months), AHREs with the longest durations of >15 seconds, >6 minutes, and >6 hours and clinically documented AF by electrocardiography were noted in 246 (30.1%), 112 (13.7%), 49 (6.0%), and 24 (2.9%) patients, respectively. Among patients developing AHREs >6 minutes, 102 (91.1%) of 112 patients were identified at the 6-month visit. Patients with AHREs >6 minutes had higher proportions of sick sinus syndrome, subjects with atrial premature beat >1% on Holter monitoring, and larger left atrium (LA) size than patients with AHREs ≤6 minutes.Multivariable logistic regression analysis showed that LA diameter >41 mm (odds ratio [OR], 2.08; 95% confidence interval [95% CI], 1.25–3.45), and sick sinus syndrome (OR, 3.22; 95% CI, 1.91–5.43) were associated with AHREs >6 minutes. @*Conclusions@#In patients with LA diameter >41 mm, and sick sinus syndrome before CIEDs implantation is associated with risk of developing AHREs >6 minutes.
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Background and Objectives@#Prior studies have shown that stroke patients treated with percutaneous left atrial appendage occlusion (LAAO) for non-valvular atrial fibrillation (NVAF) experience better outcomes than similar patients treated with warfarin. We investigated the impact of percutaneous left atrial appendage closure on post-stroke neurological outcomes in NVAF patients, compared with non-vitamin K antagonist oral anticoagulant (NOAC) therapy. @*Methods@#Medical records for 1,427 patients in multiple registries and for 1,792 consecutive patients at 6 Korean hospitals were reviewed with respect to LAAO or NOAC treatment.Stroke severity in patients who experienced ischemic stroke or transient ischemic attack after either treatment was assessed with modified Rankin Scale (mRS) scoring at hospital discharge and at 3 and 12 months post-stroke. @*Results@#mRS scores were significantly lower in LAAO patients at 3 (p<0.01) and 12 months (p<0.01) post-stroke, despite no significant differences in scores before the ischemic cerebrovascular event (p=0.22). The occurrences of disabling ischemic stroke in the LAAO and NOAC groups were 36.7% and 44.2% at discharge (p=0.47), 23.3% and 44.2% at 3 months post-stroke (p=0.04), and 13.3% and 43.0% at 12 months post-stroke (p=0.01), respectively.Recovery rates for disabling ischemic stroke at discharge to 12 months post-stroke were significantly higher for LAAO patients (50.0%) than for NOAC patients (5.6%) (p<0.01). @*Conclusions@#Percutaneous LAAO was associated with more favorable neurological outcomes after ischemic cerebrovascular event than NOAC treatment.
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Background and Objectives@#Cavotricuspid isthmus (CTI) block is easily achieved, and prophylactic ablation can be performed during atrial fibrillation (AF) ablation. However, the previous study was too small and short-term to clarify the efficacy of this block. @*Methods@#Patients who underwent catheter ablation for paroxysmal AF were enrolled, and patients who had previous or induced atrial flutter (AFL) were excluded. We randomly assigned 366 patients to pulmonary vein isolation (PVI) only and prophylactic CTI ablation (PVI vs. PVI+CTI). @*Results@#There was no significant difference in procedure time between the two groups because most CTI blocks were performed during the waiting time after the PVI (176.8±72.6 minutes in PVI vs. 174.2±76.5 minutes in PVI+CTI, p=0.75). All patients were followed up for at least 18 months, and the median follow-up was 3.4 years. The recurrence rate of AF or AFL was not different in the 2 groups (25.7% in PVI vs. 25.7% in PVI+CTI, p=0.92). The recurrence rate of any AFL was not significantly different in the 2 groups (3.3% in PVI vs. 1.6% in PVI+CTI, p=0.31). The recurrence rate of typical AFL also was not different (0.5% in PVI vs. 0.5% in PVI+CTI, p=0.99). @*Conclusions@#In this large and long-term follow-up study, prophylactic CTI ablation had no benefit in patients with paroxysmal AF without typical AFL.
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Background and Objectives@#Ambient particulate matter (PM) in real urban air pollution (RUA) is an environmental health risk factor associated with increased cardiac events. This study investigated the threshold level to induce arrhythmia, as well as arrhythmogenic mechanism of RUA that mainly consisted of PM <2.5 μm in aerodynamic diameter close to ultrafine particles. @*Methods@#RUA was artificially produced by a lately developed pyrolysis based RUA generator.C57BL/6 mice were divided into 4 groups: a control group (control, n=12) and three groups with exposure to RUA with the concentration of 200 µg/㎥ (n=12), 400 µg/㎥ (n=12), and 800 µg/㎥ (n=12). Mice were exposed to RUA at each concentration for 8 hr/day and 5 day/week to mimic ordinary human activity during 3 weeks. @*Results@#The QRS and QTc intervals, as well as intracellular Ca2+ duration, apicobasal action potential duration (APD) gradient, fibrosis, and inflammation of left ventricle of mouse hearts were increased dose-dependently with the increase of RUA concentration, and significantly increased at RUA concentration of 400 µg/㎥ compared to control (all p<0.001). In mice exposed to RUA concentration of 800 µg/㎥ , spontaneous ventricular arrhythmia was observed in 42%, with significant increase of inflammatory markers, phosphorylated Ca2+ /calmodulindependent protein kinase II (CaMKII), and phospholamban (PLB) compared to control. @*Conclusions@#RUA could induce electrophysiological changes such as APD and QT prolongation, fibrosis, and inflammation dose-dependently, with significant increase of ventricular arrhythmia at the concentration of 400 µg/㎥ . RUA concentration of 800 µg/㎥ increased phosphorylation of CaMKII and PLB.
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Atrial fibrillation (AF) is the most common form of arrhythmia in the elderly population and increases stroke risk by a factor of 4- to 5-fold. There is increasing evidence to suggest that incident AF may contribute to the development of dementia, independent of overt stroke. In particular, relatively younger patients with AF are more prone to dementia development than older patients with AF. Evidence is accumulating regarding the possible treatment strategies for preventing dementia in patients with AF. Oral anticoagulation may be effective for reducing the risk of dementia, even in patients with low stroke risks. Among oral anticoagulants, the use of non-vitamin K antagonists have been associated with a considerably decreased risk of dementia than warfarin. Moreover, successful catheter ablation for AF has also been associated with decreased dementia risk compared to medical therapy, suggesting that restoration of sinus rhythm, and not the ablation procedure itself, as the important mechanism in the prevention of AF-associated dementia. Among midlife patients with AF, there appeared to be a U-shaped association of blood pressure (BP) and a linear association of hypertension with dementia risk.A BP of 120 to 129/80 to 84 mmHg has been identified as the optimal range. Finally, integrated management of AF was associated with a reduced risk of dementia in AF patients.