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Objectives: The relationship between left atrial (LA) size and atrial fibrillation (AF) is well-established. However, the specifics of LA regional remodeling and its connection to left atrial tachycardia (LA-AT) post-ablation in patients with non-paroxysmal AF are less understood. This study aims to explore how LA dimensions are related to the development of LA-AT following AF ablation procedures in these patients. Methods: This study focused on 73 patients with non-paroxysmal atrial fibrillation (average age 52, predominantly male, with a nearly even split between persistent and long-lasting persistent AF), all undergoing their first catheter ablation for AF. Prior to the ablation, left atrial dimensions were determined through computed tomography, measuring the maximal transverse, anteroposterior, and superoinferior diameters. Results: Over an average follow-up period of 23 months, 31.5% of the patients (Group 1) experienced left atrial tachycardia (LA-AT) that required a second linear ablation procedure. This group had significantly larger left atrial (LA) dimensions in terms of transverse, anteroposterior, and superoinferior measurements compared to the other group (Group 2). However, the recurrence of atrial fibrillation (AF) was not linked to any specific LA diameter. The anteroposterior diameter was identified as a significant predictor (p=0.002, HR 2.3, 95% CI 1.3-3.8) for LA-AT occurrence through multivariate analysis. Conclusions: Eccentric dilatation involving the anteroposterior diameter is a significant predictor for the occurrence of LA-AT in patients with non-paroxysmal AF after catheter ablation. Keywords Atrial fibrillation; Atrial flutter; Atrial tachycardia; Left atrial diameter; Catheter ablation; Computed tomography

Abstract Background Myocarditis substantially increases the risk of ventricular arrhythmia. Approximately 30% of all ventricular arrhythmia cases in patients with myocarditis originate from the right ventricular outflow tract (RVOT). However, the role of NLRP3 signaling in RVOT arrhythmogenesis remains unclear. Methods Rats with myosin peptide–induced myocarditis (experimental group) were treated with an NLRP3 inhibitor (MCC950; 10 mg/kg, daily for 14 days) or left untreated. Then, they were subjected to electrocardiography and echocardiography. Ventricular tissue samples were collected from each rat’s RVOT, right ventricular apex (RVA), and left ventricle (LV) and examined through conventional microelectrode and histopathologic analyses. In addition, whole-cell patch-clamp recording, confocal fluorescence microscopy, and Western blotting were performed to evaluate ionic currents, intracellular Ca2+ transients, and Ca2+-modulated protein expression in individual myocytes isolated from the RVOTs. Results The LV ejection fraction was lower and premature ventricular contraction frequency was higher in the experimental group than in the control group (rats not exposed to myosin peptide). Myocarditis increased the infiltration of inflammatory cells into cardiac tissue and upregulated the expression of NLRP3; these observations were more prominent in the RVOT and RVA than in the LV. Furthermore, experimental rats treated with MCC950 (treatment group) improved their LV ejection fraction and reduced the frequency of premature ventricular contraction. Histopathological analysis revealed higher incidence of abnormal automaticity and pacing-induced ventricular tachycardia in the RVOTs of the experimental group than in those of the control and treatment groups. However, the incidences of these conditions in the RVA and LV were similar across the groups. The RVOT myocytes of the experimental group exhibited lower Ca2+ levels in the sarcoplasmic reticulum, smaller intracellular Ca2+ transients, lower L-type Ca2+ currents, larger late Na+ currents, larger Na+–Ca2+ exchanger currents, higher reactive oxygen species levels, and higher Ca2+/calmodulin-dependent protein kinase II levels than did those of the control and treatment groups. Conclusion Myocarditis may increase the rate of RVOT arrhythmogenesis, possibly through electrical and structural remodeling. These changes may be mitigated by inhibiting NLRP3 signaling.

Abstract Background In post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies. Methods This study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone. Results The risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p

IntroductionSignal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM.Methods and resultsThis retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence.ConclusionIn our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

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Abstract Background Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF. Methods A one-group pretest–posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients’ recognition of SDM, and a 5-point scoring method was used, where “very much” was scored as 5 points, and “totally not” was scored as 1 point. Results Fifty-two patients with AF were enrolled. In terms of patients’ recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of “very much.” The patients’ anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points (p

Background: High-power short-duration (HPSD) and cryoballoon ablation (CBA) has been used for pulmonary vein isolation (PVI). Objective: We aimed to compare the efficacy of PVI between CBA and HPSD ablation in patients with paroxysmal atrial fibrillation (PAF). Methods: We retrospectively analyzed 251 consecutive PAF patients from January 2018 to July 2020. Of them, 124 patients (mean age 57.2 ± 10.1 year) received HPSD and 127 patients (mean age 59.6 ± 9.4 year) received CBA. In HPSD group, the radiofrequency energy was set as 50 W/10 s at anterior wall and 40 W/10 s at posterior wall. In CBA group, 28 mm s generation cryoballoon was used for PVI according the guidelines. Results: There was no significant difference in baseline characteristics between these 2 groups. The time to achieve PVI was significantly shorter in cryoballoon ablation group than in HPSD group (20.6 ± 1.7 min vs 51.8 ± 36.3, P = 0.001). The 6-month overall recurrence for atrial tachyarrhythmias was not significantly different between the two groups (HPSD:14.50% vs CBA:11.0%, P = 0.40). There were different types of recurrent atrial tachyarrhythmia between these 2 groups. Recurrence as atrial flutter was significantly more common in CBA group compared to HPSD group (57.1% vs 12.5%, P = 0.04). Conclusion: In PAF patients, CBA and HPSD had a favourable and comparable outcome. The recurrence pattern was different between CBA and HPSD groups.

A challenge in accurately identifying and classifying left ventricular hypertrophy (LVH) is distinguishing it from hypertrophic cardiomyopathy (HCM) and Fabry disease. The reliance on imaging techniques often requires the expertise of multiple specialists, including cardiologists, radiologists, and geneticists. This variability in the interpretation and classification of LVH leads to inconsistent diagnoses. LVH, HCM, and Fabry cardiomyopathy can be differentiated using T1 mapping on cardiac magnetic resonance imaging (MRI). However, differentiation between HCM and Fabry cardiomyopathy using echocardiography or MRI cine images is challenging for cardiologists. Our proposed system named the MRI short-axis view left ventricular hypertrophy classifier (MSLVHC) is a high-accuracy standardized imaging classification model developed using AI and trained on MRI short-axis (SAX) view cine images to distinguish between HCM and Fabry disease. The model achieved impressive performance, with an F1-score of 0.846, an accuracy of 0.909, and an AUC of 0.914 when tested on the Taipei Veterans General Hospital (TVGH) dataset. Additionally, a single-blinding study and external testing using data from the Taichung Veterans General Hospital (TCVGH) demonstrated the reliability and effectiveness of the model, achieving an F1-score of 0.727, an accuracy of 0.806, and an AUC of 0.918, demonstrating the model’s reliability and usefulness. This AI model holds promise as a valuable tool for assisting specialists in diagnosing LVH diseases.

IntroductionCatheter ablation is an effective and safe strategy for treating atrial fibrillation patients. Nevertheless, studies on the long-term outcomes of catheter ablation in patients with dilated cardiomyopathy are limited. This study aimed to assess the electrophysiological characteristics of atrial fibrillation patients with dilated cardiomyopathy and compare the long-term clinical outcomes between patients undergoing catheter ablation and medical therapy.MethodPatient baseline characteristics and electrophysiological parameters were examined to identify the predictors of atrial fibrillation recurrence following catheter ablation. The clinical outcomes of catheter ablation and medical therapy were compared using the propensity score matched method.ResultsA total of 343 patients were enrolled, with 46 in the catheter ablation group and 297 in the medical therapy group. Among the catheter ablation group, 58.7% (n = 27) had persistent atrial fibrillation. The recurrence rate of atrial arrhythmia was 30.4% (n = 14) after an average follow-up duration of 7.7 years following catheter ablation. The only predictive factor for atrial fibrillation recurrence after catheter ablation was the left atrial diameter. When compared to medical therapy, catheter ablation demonstrated significantly better outcomes in terms of overall survival, freedom from heart failure hospitalization, improvement in left ventricular ejection fraction, and a greater reduction in left ventricular diameter and left atrial diameter after propensity score matching.ConclusionsTherefore, catheter ablation proves to be effective in providing long-term control of atrial fibrillation in patients with dilated cardiomyopathy. In addition to standard heart failure care, catheter ablation significantly enhanced both morbidity and mortality outcomes and reversed structural remodeling when compared to heart failure medication alone.

Abstract Renal denervation (RDN) suppresses the activity of the renin–angiotensin–aldosterone system and inflammatory cytokines, leading to the prevention of cardiac remodeling. Limited studies have reported the effects of renal denervation on ventricular electrophysiology. We aimed to use optical mapping to evaluate the effect of RDN on ventricular structural and electrical remodeling in a tachycardia-induced cardiomyopathy rabbit model. Eighteen rabbits were randomized into 4 groups: sham control group (n = 5), renal denervation group receiving RDN (n = 5), heart failure group receiving rapid ventricular pacing for 1 month (n = 4), and RDN-heart failure group (n = 4). Rabbit hearts were harvested for optical mapping. Different cycle lengths were paced (400, 300, 250, 200, and 150 ms), and the results were analyzed. In optical mapping, the heart failure group had a significantly slower epicardial ventricular conduction velocity than the other three groups. The RDN-heart failure, sham control, and RDN groups had similar velocities. We then analyzed the 80% action potential duration at different pacing cycle lengths, which showed a shorter action potential duration as cycle length decreased (P for trend

Background: Gender is a well-recognized risk factor in atrial fibrillation (AF)-related ischemic stroke. The association of gender with the use of oral anticoagulants (OACs) and prognosis remains unknown. Methods: The National Health Insurance Research Database in Taiwan identified 203,775 patients with AF aged ≥20 years from 2012 to 2018, with 55.4% of males. Our main study cohort included 67,426 patients using OACs. The study endpoints include death, ischemic stroke, intracranial hemorrhage, major bleeding, and composite adverse events. Results: Significant differences were found in baseline characteristics between sexes. Female patients with AF were older and had higher CHA2DS2-VASc and HAS-BLED scores. Non-vitamin K antagonist oral anticoagulant (NOAC) use was more prominent in females while the use of warfarin was similar in both sexes. The distribution of baseline characteristics between the warfarin and NOAC groups in both sexes was much alike. Among the whole study cohort, NOAC was associated with a decreased risk of clinical endpoints compared to warfarin, which remained the same in subgroup analyses of both sexes. Additionally, a greater risk reduction of ischemic stroke with NOAC was observed in female patients compared to male patients (adjusted hazard ratio: 0.517 in males, 0.425 in females, interaction p = 0.040). Conclusions: This nationwide cohort demonstrated the differences between male and female patients with AF, including baseline characteristics, risk profiles, and medication use. Despite great differences in baseline demographic data, NOAC was associated with better clinical outcomes compared to warfarin in both sexes, and females benefited more than males in preventing ischemic stroke using NOACs.

BackgroundAtrial fibrillation (AF) and mitral regurgitation (MR) have a complex interplay. Catheter ablation (CA) of AF may be a potential method to improve the severity of MR in AF patients.MethodsPatients with symptomatic AF and moderate to severe MR who underwent catheter ablation from 2011 to 2021 were retrospectively included in the study. Patients' baseline characteristics and electrophysiological features were examined. These patients were classified as group 1 with improved MR and group 2 with refractory MR after CA.ResultsFifty patients (age 60.2 ± 11.6 years, 29 males) were included in the study (32 in group 1 and 18 in group 2). Group 1 patients had a lower CHA2DS2-VASc score (1.7 ± 1.5 vs. 2.7 ± 1.5, P = 0.005) and had a lower incidence of hypertension (28.1% vs. 66.7%, P = 0.007) and diabetes mellitus (3.1% vs. 22.2%, P = 0.031) as compared to group 2 patients. Electroanatomic three-dimensional (3D) mapping showed that group 1 patients demonstrated less scars on the posterior bottom of the left atrium compared to group 2 patients (12.5% vs. 66.7%, P

Abstract Background Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. Methods Twenty‐five drug‐refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1–3, and 6–12 months after PVI. After 8.2 ± 2.5 months of follow‐ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non‐recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). Results The non‐recurrence group, but not the recurrence group, had decreased high‐frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1–3 months after PVI and increased DFAslope2 6–12 months after PVI. The non‐recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1–3 and 6–12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. Conclusions Significantly reduced vagal tone 1–3 months after PVI, increased long‐term fractal complexity 6–12 months after PVI, and decreased sympathetic tone as well as short‐term fractal complexity 1–3 and 6–12 months after PVI led to a better AF‐free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

Abstract Aims The efficacy of catheter ablation (CA) on clinical outcomes and cardiac structural remodelling in atrial fibrillation (AF) patients with HF with mildly reduced or mid‐range ejection fraction (HFmrEF) remains unclear. We aimed to compare the efficacy of CA with medical therapy (MT) in AF patients with HFmrEF. Methods and results We retrospectively screened a total of 36 879 patients with AF between 2005 and 2020. Patients who were initially diagnosed with echocardiography‐proved HFmrEF and had follow‐up echocardiography were enrolled. After applying propensity score matching in a 1:1 ratio, 72 patients treated by CA (Group 1) and 72 patients receiving MT (Group 2) were taken into further analysis. The co‐morbidities were similar between the two groups, except for hyperlipidaemia. After a mean follow‐up duration of 58.9 ± 42.6 months, Group 1 had a lower HF hospitalization and all‐cause mortality compared with Group 2 (hazard ratio (HR), 0.089 [95% confidence interval (CI), 0.011–0.747]; P = 0.026 and HR, 0.121 [95% CI, 0.016–0.894]; P = 0.038, respectively). As for cardiac structural remodelling, the Group 1 had a better improvement in left ventricular ejection fraction (LVEF) and a more decreased left atrium (LA) diameter than Group 2 (+25.0% ± 18.0% vs. +6.2% ± 21.6%, P =

BackgroundCatheter ablation (CA) is a treatment strategy for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). We investigated the electrophysiological characteristics of recurrence in a tertiary referral center and compared long-term clinical outcomes after CA therapy with patients who did not undergo CA.MethodsPatients with HCM and AF who underwent CA (group 1, n = 60) or pharmacological treatment (group 2, n = 298) between 2006 and 2021 were enrolled in this study. The baseline characteristics and electrophysiological characteristics of group 1 patients were examined to elucidate the reason for the recurrence of AF after CA therapy. The clinical results of the patients in Group 1 and Group 2 were compared using a propensity score (PS)-matched method.ResultsThe most common cause of recurrence was pulmonary vein reconnection (86.5%), followed by non-pulmonary vein triggers (40.5%), cavotricuspid isthmus flutter (29.7%), and atypical flutter (24.3%). Thyroid disease (HR, 14.713; P

BackgroundKnowledge of the risk of death in patients with dementia is essential for planning preventive strategies. This study aimed to evaluate the effect of atrial fibrillation (AF) on death risks and other factors associated with death in patients with dementia and AF.MethodsWe conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database. We identified subjects with dementia diagnosed for the first time and AF diagnosed concomitantly between 2013 and 2014. Subjects under the age of 18 years were excluded. Age, sex, and CHA2DS2-VASc scores were 1: 4 matched for AF patients (N = 1,679) and non-AF controls (N = 6,176) using the propensity score technique. The conditional Cox regression model and competing risk analysis were applied. The risk of mortality was tracked till 2019.ResultsAF history was associated with higher risks of all-cause death (hazard ratio [HR]: 1.208; 95% confidence interval [CI]: 1.142–1.277) and cardiovascular death (subdistribution HR: 1.210; 95% CI: 1.077–1.359) in dementia patients than patients without a diagnosis of AF. For patients with both dementia and AF, they had a higher risk of death due to higher age, diabetes mellitus, congestive heart failure, chronic kidney disease, and prior stroke. Anti-arrhythmic drugs and novel oral anticoagulants significantly reduced the risk of death in patients with AF and dementia.ConclusionThis study found that AF is a risk factor for mortality in patients with dementia and explored several risk factors for AF-related mortality. This study highlights the importance of controlling AF especially in patients with dementia.

Abstract Long QT syndrome (LQTS) is commonly presented with life-threatening ventricular arrhythmias (VA). Renal artery denervation (RDN) is an alternative antiadrenergic treatment that attenuates sympathetic activity. We aimed to evaluate the efficacy of RDN on preventing VAs in LQTS rabbits induced by drugs. The subtypes of LQTS were induced by infusion of HMR-1556 for LQTS type 1 (LQT1), erythromycin for LQTS type 2 (LQT2), and veratridine for LQTS type 3 (LQT3). Forty-four rabbits were randomized into the LQT1, LQT2, LQT3, LQT1-RDN, LQT2-RDN, and LQT3-RDN groups. All rabbits underwent cardiac electrophysiology studies. The QTc interval of the LQT2-RDN group was significantly shorter than those in the LQT2 group (650.08 ± 472.67 vs. 401.78 ± 42.91 ms, p = 0.011). The QTc interval of the LQT3-RDN group was significantly shorter than those in the LQT3 group (372.00 ± 22.41 vs. 335.70 ± 28.21 ms, p = 0.035). The VA inducibility in all subtypes of the LQT-RDN groups was significantly lower than those in the LQT-RDN groups, respectively (LQT1: 9.00 ± 3.30 vs. 47.44 ± 4.21%, p

BackgroundAmiodarone is commonly used during therapeutic hypothermia (TH) following cardiac arrest due to ventricular arrhythmias. However, electrophysiological changes and proarrhythmic risk after amiodarone treatment have not yet been explored in TH.MethodsEpicardial high-density bi-ventricular mapping was performed in pigs under baseline temperature (BT), TH (32-34°C), and amiodarone treatment during TH. The total activation time (TAT), conduction velocity (CV), local electrogram (LE) duration, and wavefront propagation from pre-specified segments were analyzed during sinus rhythm (SR) or right ventricular (RV) pacing (RVP), along with tissue expression of connexin 43. The vulnerability to ventricular arrhythmias was assessed.ResultsCompared to BT, TH increased the global TAT, decreased the CV, and generated heterogeneous electrical substrate during SR and RVP. During TH, the CV reduction and LE duration prolongation were greater in the anterior mid RV than in the other areas, which changed the wavefront propagation in all animals. Compared to TH alone, amiodarone treatment during TH further increased the TAT and LE duration and decreased the CV. Heterogeneous conduction was partially attenuated after amiodarone treatment. After TH and amiodarone treatment, the connexin 43 expression in the anterior mid RV was lower than that in the other areas, compatible with the heterogeneous CV reduction. The animals under TH and amiodarone treatment had a higher incidence of inducible ventricular arrhythmias than those under BT or TH without amiodarone.ConclusionElectrical heterogeneity during amiodarone treatment and TH was associated with vulnerability to ventricular arrhythmias.

Background A previously underrecognized phenotype of left ventricular apical aneurysm (LVAA) has been increasingly identified in Fabry disease. This study explored LVAA's clinical prevalence and its prognostic implications over a long‐term follow‐up. Methods and Results We retrospectively analyzed 268 consecutive patients with Fabry disease at a tertiary medical center. Patients with increased left ventricular mass index were recognized as having left ventricular hypertrophy (LVH). LVAA was identified using either echocardiography or cardiovascular magnetic resonance imaging. Two patients with ischemic LVAA were excluded. The primary end point was a composite of cardiovascular events, including heart failure hospitalization, sustained ventricular tachycardia, ischemic stroke, and all‐cause mortality. Of 266 enrolled patients, 105 (39.5%) had LVH (age 58.5±11.9 years, 48.6% men), and 11 (10.5%) had LVAA. Over 49.3±34.8 months of follow‐up, 25 patients with LVH experienced composite events, including 9 heart failure hospitalizations, 4 sustained ventricular tachycardia, 6 ischemic strokes, and 15 mortalities. In patients with LVH, those with LVAA had a significantly higher risk of composite events and lower event‐free survival than those without LVAA (8 [72.7%] versus 17 [18.1%], log‐rank P

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy caused by defective desmosomal proteins. The typical histopathological finding of ARVC is characterized by progressive fibrofatty infiltration of the right ventricle due to the dysfunction of cellular adhesion molecules, thus, developing arrhythmogenic substrates responsible for the clinical manifestation of ventricular tachycardia/fibrillation (VT/VF). Current guidelines recommend implantable cardiac defibrillator (ICD) implantation to prevent sudden cardiac death (SCD) in ARVC, especially for those experiencing VT/VF or aborted SCD, while antiarrhythmic drugs, despite their modest effectiveness and several undesirable adverse effects, are frequently used for those experiencing episodes of ICD interventions. Given the advances in mapping and ablation technologies, catheter ablation has been implemented to eliminate drug-refractory VT in ARVC. A better understanding of the pathogenesis, underlying arrhythmogenic substrates, and putative VT isthmus in ARVC contributes to a significant improvement in ablation outcomes through comprehensive endocardial and epicardial approaches. Regardless of ablation strategies, there is a diversity of arrhythmogenic substrates in ARVC, which could partly explain the nonuniform ablation outcome and long-term recurrences and reflect the role of potential factors in the modification of disease progression and triggering of arrhythmic events.

IntroductionUnsuccessful endocardial ablation for perimitral atrial flutter (AFL) could be attributed by the epicardial bridging.ObjectiveThis study aimed to investigate the electrophysiological characteristics of epicardial breakthrough during catheter ablation of perimitral AFL.Materials and methodsThis retrospective study recruited 40 patients who received successful catheter ablation of perimitral AFL from January 2016 to June 2021. The patients were divided into two groups: group 1 (n = 18) successful endocardial ablation, and group 2 (n = 22) successful epicardial ablation following unsuccessful endocardial ablation owing to incomplete mitral block or unachievable termination AFL. The local electrogram (EGM) interval of coronary sinus (CS) duration perimitral AFL was measured before catheter ablation.ResultsThere was no significant difference in the baseline characteristics between the two groups. In group 2, 60% of successful epicardial ablation was performed in intra-CS ablation and 40% in VOM ethanol infusion. Group 2 patients had a longer EGM interval of distal CS than that in group 1 (CS1-2: 64.2 17.5 vs. 42.4 0.09 ms, P = 0.008, CS3-4: 57.13 19.4 vs. 43.8 7.5 ms; P = 0.001). The conduction velocity at successful site was slower in group 2 compared to group 1 (0.18 0.05 vs. 0.75 0.19 m/s, P = 0.040). In the multivariate analysis, distal EGM interval (CS1-2) was identified as independent predictor of the need of epicardial ablation with the optimal cutoff of 49 ms.ConclusionLonger EGM interval in distal CS during perimitral AFL was observed in perimitral AFL patients with epicardial breakthrough following endocardial-failed ablation, which may be associated with the need of epicardial ablation.

Abstract Diabetes mellitus is associated with cardiovascular disease and cardiac arrhythmia. Accumulation of advanced glycation end products closely correlates with cardiovascular complications through mitochondrial dysfunction or oxidative stress and evoke proliferative, inflammatory, and fibrotic reactions, which might impair cardiac electrophysiological characteristics and increase the incidence of cardiac arrhythmia. This study examined the mechanisms how advanced glycation end products may contribute to arrhythmogenesis of right ventricular outflow tract—a unique arrhythmogenic substrate. A whole‐cell patch clamp, conventional electrophysiological study, fluorescence imaging, Western blot, and confocal microscope were used to study the electrical activity, and Ca2+ homeostasis or signaling in isolated right ventricular outflow tract myocytes with and without advanced glycation end products (100 μg/ml). The advanced glycation end products treated right ventricular outflow tract myocytes had a similar action potential duration as the controls, but exhibited a lower L‐type Ca2+ current, higher late sodium current and transient outward current. Moreover, the advanced glycation end products treated right ventricular outflow tract myocytes had more intracellular Na+, reverse mode Na+–Ca2+ exchanger currents, intracellular and mitochondrial reactive oxygen species, and less intracellular Ca2+ transient and sarcoplasmic reticulum Ca2+ content with upregulated calcium homeostasis proteins and advanced glycation end products related signaling pathway proteins. In conclusions, advanced glycation end products modulate right ventricular outflow tract electrophysiological characteristics with larger late sodium current, intracellular Na+, reverse mode Na+–Ca2+ exchanger currents, and disturbed Ca2+ homeostasis through increased oxidative stress mediated by the activation of the advanced glycation end products signaling pathway.

Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced atrial fibrillation risk, but the mechanisms underlying this association remain unclear. The GLP-1 receptor agonist directly impacts cardiac Ca2+ homeostasis, which is crucial in pulmonary vein (PV, the initiator of atrial fibrillation) arrhythmogenesis. This study investigated the effects of the GLP-1 receptor agonist on PV electrophysiology and Ca2+ homeostasis and elucidated the potential underlying mechanisms. Conventional microelectrodes and whole-cell patch clamp techniques were employed in rabbit PV tissues and single PV cardiomyocytes before and after GLP-1 (7-36) amide, a GLP-1 receptor agonist. Evaluations were conducted both with and without pretreatment with H89 (10 μM, an inhibitor of protein kinase A, PKA), KN93 (1 μM, an inhibitor of Ca2+/calmodulin-dependent protein kinase II, CaMKII), and KB-R7943 (10 μM, an inhibitor of Na+/Ca2+ exchanger, NCX). Results showed that GLP-1 (7-36) amide (at concentrations of 1, 10, and 100 nM) reduced PV spontaneous activity in a concentration-dependent manner without affecting sinoatrial node electrical activity. In single-cell experiments, GLP-1 (7-36) amide (at 10 nM) reduced L-type Ca2+ current, NCX current, and late Na+ current in PV cardiomyocytes without altering Na+ current. Additionally, GLP-1 (7-36) amide (at 10 nM) increased sarcoplasmic reticulum Ca2+ content in PV cardiomyocytes. Furthermore, the antiarrhythmic effects of GLP-1 (7-36) amide on PV automaticity were diminished when pretreated with H89, KN93, or KB-R7943. This suggests that the GLP-1 receptor agonist may exert its antiarrhythmic potential by regulating PKA, CaMKII, and NCX activity, as well as modulating intracellular Ca2+ homeostasis, thereby reducing PV arrhythmogenesis.

The right ventricular outflow tract (RVOT) is the major origin of ventricular arrhythmias, including premature ventricular contractions, idiopathic ventricular arrhythmias, Brugada syndrome, torsade de pointes, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy. The RVOT has distinct developmental origins and cellular characteristics and a complex myocardial architecture with high shear wall stress, which may lead to its high vulnerability to arrhythmogenesis. RVOT myocytes are vulnerable to intracellular sodium and calcium overload due to calcium handling protein modulation, enhanced CaMKII activity, ryanodine receptor phosphorylation, and a higher cAMP level activated by predisposing factors or pathological conditions. A reduction in Cx43 and Scn5a expression may lead to electrical uncoupling in RVOT. The purpose of this review is to update the current understanding of the cellular and molecular mechanisms of RVOT arrhythmogenesis.

Abstract Background Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. Methods Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25–30 W, force–time integral = 400 g s, n = 40) or with HPSD (power control: 40–50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. Results 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007.

This report describes a young patient with paroxysmal atrial fibrillation (AF) with termination pause. Primary mediastinal large B-cell lymphoma with pericardial and right atrial involvement was diagnosed, and he was free of AF after chemotherapy. Therefore, for young patients with tachy-brady syndrome, thorough evaluation for other causes is recommended. (Level of Difficulty: Beginner.)

Abstract Aims Cardiac implanted electronic devices (CIEDs) can detect atrial high‐rate episodes (AHREs) and challenge current management of subclinical atrial fibrillation (AF). Methods To characterize the anatomic and functional remodeling of cardiac structures between patients with subclinical AF (SCAF) and clinical AF. The predictors for AHREs ≥6 min were also investigated. Results We compared the atrial volume, dynamic function, and peri‐atrial fat between 104 CIEDs (AHREs = 0, n = 12; SCAF, n = 66; CIEDs with AF, n = 26) and 40 paroxysmal AF patients who were planning for catheter ablation (AF for ablation) using 256‐slice multidetector computed tomography for the duration of the AHREs. The maximal volume of the left atrium (LA) and LA appendage (LAA) were significantly smaller; the total emptying fraction (EF) and active EF of the LA and LAA were significantly better in the patients with SCAF than in those with clinical AF. Less peri‐atrial fat (p

Abstract Mechanoelectrical feedback is an important factor in the pathophysiology of atrial fibrillation (AF). Ectopic electrical activity originating from pulmonary vein (PV) myocardial sleeves has been found to trigger and maintain paroxysmal AF. Dilated PVs by high stretching force may activate mechanoelectrical feedback, which induces calcium overload and produces afterdepolarization. These results, in turn, increase PV arrhythmogenesis and contribute to initiation of AF. Paracrine factors, effectors of the renin‐angiotensin system, membranous channels, or cytoskeleton of PV myocytes may modulate PV arrhythmogenesis directly through mechanoelectrical feedback or indirectly through endocardial/myocardial cross‐talk. The purpose of this review is to present laboratory and translational relevance of mechanoelectrical feedback in PV arrhythmogenesis. Targeting mechanoelectrical feedback in PV arrhythmogenesis may shed light on potential opportunities and clinical concerns of AF treatment.

Objective(s): Drug-induced atrial fibrillation (AF) is considered an adverse effect of chemotherapeutic drugs. AF is a crucial risk factor for stroke, heart failure, myocardial infarction, and mortality. Pulmonary veins (PVs) are considered triggers inducing AF, and the sinoatrial node (SAN) may modulate PV activity and participate in AF genesis. AF was associated with early discontinuation of trastuzumab in patients with breast cancer. However, whether trastuzumab directly modulates the electrophysiological characteristics of PV and SAN remains unclear. Materials and Methods: ECG and conventional microelectrode system were used to record rabbit heart rhythm in vivo and electrical activities in vitro from isolated SAN, PV, and SAN-PV preparations. Results: Trastuzumab reduced the beating rate in isolated PV and SAN preparations at 1, 10, and 30 μM (particularly in isolated SAN preparations) and induced burst firings in isolated PV preparations at 10 μΜ. In addition, trastuzumab (10 μM) induced SAN-PV conduction block and burst firings, which were blocked by wortmannin (a PI3K inhibitor, 100 nM). Similarly, ECG recordings showed that acute intravenous administration of trastuzumab (10 mg/kg) reduced rabbit heart rates. Conclusion: Trastuzumab increased PV arrhythmogenesis through interfering with PI3K signaling, which may contribute to the genesis of AF.

Abstract Background Studies specifically examining the association between glycated hemoglobin A1c (HbA1c) levels and ischemic stroke/systemic thromboembolism (IS/SE) risk in atrial fibrillation (AF) patients are limited. Here, we investigated the association between HbA1c levels and the risk of IS/SE, as well as major bleeding, among AF patients with or without oral anticoagulants (OACs). We also compared the effectiveness and safety of warfarin and direct oral anticoagulants (DOACs) in different HbA1c categories. Methods We utilized medical data from a multi-center healthcare provider in Taiwan, which included 34,036 AF patients with serum HbA1c data available within 3 months after AF being diagnosed. Patients were divided into seven study groups according to their HbA1c levels: 0.05). Conclusion For AF patients, IS/SE risk significantly increased once HbA1c levels exceeded 6.5%, and OACs may attenuate these associations. Compared with warfarin, DOACs were more effective and safer across broad HbA1c categories. Therefore, in addition to prescribing DOACs when indicated, more aggressive glycemic control to achieve an HbA1c level

Background/Purpose: Currently, data on the real-world use of dronedarone, an antiarrhythmic drug for atrial fibrillation (AF), are contradictory and often based on patient populations comprised of Caucasians. We prospectively investigated the efficacy and safety of dronedarone and risk factors related to treatment outcomes in a real-world use setting. Methods: The prospective, observational, single-arm, multi-center study included a total of 824 Taiwanese patients with a diagnosis of paroxysmal or persistent AF and receiving dronedarone treatment. Risk factors analysis, efficacy, and safety of dronedarone were assessed with a follow-up of six months. Results: Of the 824 patients enrolled (mean age, 75.3 ± 7.2 years), 95.2% had at least one cardiovascular risk factor. An increase in the proportion of patients with sinus rhythm following treatment was seen (52.1% at baseline vs. 67.4% at 6 months). A decrease in the mean duration of AF episodes (388.4 min vs. 62.3 min) and an increase in total AFEQT (65.4 ± 16.2 vs. 74.0 ± 11.8) were also observed after 6 months of treatment. Females, those under the age of 75, and those with symptomatic AF had higher odds of treatment success. At 6 months, 10.5% of patients reported treatment-related AEs. However, only 0.2% of the AEs were both severe in nature and causally related to dronedarone. Conclusion: This six-month study showed dronedarone to be relatively safe and efficacious and to improve quality-of-life in Taiwanese patients with atrial fibrillation. Odds of treatment success were related to the patient's gender, age, and AF type. Keywords: Atrial fibrillation, Dronedarone, Observational, Safety, Quality of life

RationaleAtrial fibrillation is a critical health burden. Targeting calcium (Ca2+) dysregulation and oxidative stress are potential upstream therapeutic strategies. Fibroblast growth factor (FGF) 1 can modulate Ca2+ homeostasis and has antioxidant activity. The aim of this study was to investigate whether FGF1 has anti-arrhythmic potential through modulating Ca2+ homeostasis and antioxidant activity of pulmonary vein (PV) and left atrium (LA) myocytes.MethodsPatch clamp, western blotting, confocal microscopy, cellular and mitochondrial oxidative stress studies were performed in isolated rabbit PV and LA myocytes treated with or without FGF1 (1 and 10 ng/mL). Conventional microelectrodes were used to record electrical activity in isolated rabbit PV and LA tissue preparations with and without FGF1 (3 μg/kg, i.v.).ResultsFGF1-treated rabbits had a slower heart rate than that observed in controls. PV and LA tissues in FGF1-treated rabbits had slower beating rates and longer action potential duration than those observed in controls. Isoproterenol (1 μM)-treated PV and LA tissues in the FGF1-treated rabbits showed less changes in the increased beating rate and a lower incidence of tachypacing (20 Hz)-induced burst firing than those observed in controls. FGF1 (10 ng/mL)-treated PV and LA myocytes had less oxidative stress and Ca2+ transient than those observed in controls. Compared to controls, FGF1 (10 ng/mL) decreased INa−L in PV myocytes and lowered Ito, IKr−tail in LA myocytes. Protein kinase C (PKC)ε inhibition abolished the effects of FGF1 on the ionic currents of LA and PV myocytes.ConclusionFGF1 changes PV and LA electrophysiological characteristics possibly via modulating oxidative stress, Na+/Ca2+ homeostasis, and the PKCε pathway.

BackgroundWe have proposed the Taiwan AF score consisting of age, male sex, hypertension, heart failure, coronary artery disease, end-stage renal disease, and alcoholism to predict incident atrial fibrillation (AF) in Asian population. We hypothesized that the modified Taiwan AF score (mTaiwan AF score) excluding alcoholism remained useful for predicting new onset AF.MethodsA total of 7,220,654 subjects aged ≥ 40 years without a past history of cardiac arrhythmia were identified from a national cohort, and 438,930 incident AF occurred during a 16-year follow-up with an incidence of 0.42 per 100 person-years. The mTaiwan AF score ranging between −2 and 14 and its predictive accuracy of incident AF was analyzed.ResultsThe areas under the receiver operating characteristic curve (AUCs) of the mTaiwan AF scores in predicting AF are 0.861 for 1-year follow-up, 0.829 for 5-year follow-up, 0.795 for 10-year follow-up, and 0.751 for 16-year follow-up. The risk of incident AF increased from 0.05%/year for patients with a score of −2 to 6.98%/year for those having a score of 14. Patients were classified into three groups based on the tertile values of the mTaiwan AF scores—group 1 (score −2-3), group 2 (score 4-9) and group 3 (score 10-14). The annual risks of incident AF were 0.20, 1.33, and 3.36% for group 1, 2, and 3, respectively. Compared to patients in group 1, the hazard ratios of incident AF were 5.79 [95% confidence interval (CI) 3.75-7.75] for group 2 and 8.93 (95% CI 6.47-10.80) for group 3.ConclusionsWe demonstrated that the mTaiwan AF score based on age and clinical comorbidities could be used to predict incident AF in Asian population.

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn’t have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00–0.02; p

Cirrhotic cardiomyopathy (CMP) is associated with altered cardiac electrophysiological (EP) properties, which leads to the risk of ventricular arrhythmias (VAs). We aimed to evaluate the EP properties, autonomic, and structural remodeling in a rabbit model with early liver cirrhosis (LC). Twelve rabbits were assigned to the sham and LC groups. The early-stage LC was induced by the ligation of the common bile duct. All rabbits received an EP study, VA inducibility test, myocardial, and liver histology staining. Western blot analyses of protein expression and tyrosine hydroxylase stain for sympathetic nerves were performed. The effective refractory period the LC group was significantly longer than the sham group [i.e., left ventricle (LV) 205.56 ± 40.30 vs. 131.36 ± 7.94 ms; right ventricle (RV) 206.78 ± 33.07 vs. 136.79 ± 15.15 ms; left atrium (LA) 140.56 ± 28.75 vs. 67.71 ± 14.29 ms; and right atrium (RA) 133.78 ± 40.58 vs. 65.43 ± 19.49 ms, all p < 0.01], respectively. The VA inducibility was elevated in the LC group when compared with the sham group (i.e., 21.53 ± 7.71 vs. 7.76 ± 2.44%, p = 0.013). Sympathetic innervation (102/μm2/mm2) was increased in all cardiac chambers of the LC group compared with the sham group (i.e., LV 9.11 ± 4.86 vs. 0.17 ± 0.15, p < 0.01; RV 4.36 ± 4.95 vs. 0.18 ± 0.12, p = 0.026; LA 6.79 ± 1.02 vs. 0.44 ± 0.20, p = 0.018; and RA 15.18 ± 5.12 vs. 0.10 ± 0.07, p = 0.014), respectively. Early LC is presented with an increased ventricular vulnerability, structural heterogeneity, and sympathetic innervation. Close monitoring for fatal arrhythmias is warranted in patients with early stages of LC.

Background: Although direct oral anticoagulants (DOACs) for patients with atrial fibrillation (AF) are considered to be safe, over or under anticoagulation and increased bleeding or thromboembolic risk are still considered individually. We aimed to investigate whether there is an association between prothrombin time and international normalized ratio (PT-INR) or activated partial thromboplastin time (aPTT) ratio, and the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding among AF patients taking rivaroxaban or dabigatran. Methods: This multi-center cohort study in Taiwan included 3192 AF patients taking rivaroxaban and 958 patients taking dabigatran for stroke prevention where data about PT-INR and aPTT were available. Results: For patients treated with rivaroxaban, a higher INR level was not associated with a higher risk of major bleeding compared to an INR level < 1.1. The risk of IS/SE was lower for patients having an INR ≥ 1.5 compared to those with an INR < 1.1 (aHR:0.57; [95%CI: 0.37–0.87]; p = 0.01). On-label dosing of rivaroxaban and use of digoxin were independent factors associated with an INR ≥ 1.5 after taking rivaroxaban. For patients taking dabigatran, a higher aPTT ratio was not associated with a higher risk of major bleeding. The risk of IS/SE was lower for patients having an aPTT ratio of 1.1–1.2 and 1.3–1.4 than those with an aPTT ratio < 1.1. Conclusions: In AF patients, rivaroxaban with an INR ≥ 1.5 was associated with a lower risk of IS/SE. PT-INR or aPTT ratios were not associated with bleeding events for rivaroxaban or dabigatran. INR may help predict the outcome of AF patients who take rivaroxaban.

Background Although several risk schemes have been proposed to predict new‐onset atrial fibrillation (AF), clinical prediction models specific for Asian patients were limited. In the present study, we aimed to develop a clinical risk score (Taiwan AF score) for AF prediction using the whole Taiwan population database with a long‐term follow‐up. Methods and Results Among 7 220 654 individuals aged ≥40 years without a past history of cardiac arrhythmia identified from the Taiwan Health Insurance Research Database, 438 930 incident AFs occurred after a 16‐year follow‐up. Clinical risk factors of AF were identified using Cox regression analysis and then combined into a clinical risk score (Taiwan AF score). The Taiwan AF score included age, male sex, and important comorbidities (hypertension, heart failure, coronary artery disease, end‐stage renal disease, and alcoholism) and ranged from −2 to 15. The area under the receiver operating characteristic curve of the Taiwan AF scores in the predictions of AF are 0.857 for the 1‐year follow‐up, 0.825 for the 5‐year follow‐up, 0.797 for the 10‐year follow‐up, and 0.756 for the 16‐year follow‐up. The annual risks of incident AF were 0.21%/year, 1.31%/year, and 3.37%/year for the low‐risk (score −2 to 3), intermediate‐risk (score 4 to 9), and high‐risk (score ≥10) groups, respectively. Compared with low‐risk patients, the hazard ratios of incident AF were 5.78 (95% CI, 3.76–7.75) for the intermediate‐risk group and 8.94 (95% CI, 6.47–10.80) for the high‐risk group. Conclusions We developed a clinical AF prediction model, the Taiwan AF score, among a large‐scale Asian cohort. The new score could help physicians to identify Asian patients at high risk of AF in whom more aggressive and frequent detections and screenings may be considered.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL.Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence.Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence.Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Adrenomedullin, a peptide with vasodilatory, natriuretic, and diuretic effects, may be a novel agent for treating heart failure. Heart failure is associated with an increased risk of atrial fibrillation (AF), but the effects of adrenomedullin on atrial arrhythmogenesis remain unclear. This study investigated whether adrenomedullin modulates the electrophysiology of the atria (AF substrate) or pulmonary vein (PV; AF trigger) arrhythmogenesis. Conventional microelectrode or whole-cell patch clamps were used to study the effects of adrenomedullin (10, 30, and 100 pg/mL) on the electrical activity, mechanical response, and ionic currents of isolated rabbit PV and sinoatrial node tissue preparations and single PV cardiomyocytes. At 30 and 100 pg/mL, adrenomedullin significantly reduced the spontaneous beating rate of the PVs from 2.0 ± 0.4 to 1.3 ± 0.5 and 1.1 ± 0.5 Hz (reductions of 32.9% ± 7.1% and 44.9 ± 8.4%), respectively, and reduced PV diastolic tension by 12.8% ± 4.1% and 14.5% ± 4.1%, respectively. By contrast, adrenomedullin did not affect sinoatrial node beating. In the presence of L-NAME (a nitric oxide synthesis inhibitor, 100 μM), adrenomedullin (30 pg/mL) did not affect the spontaneous beating rate or diastolic tension of the PVs. In the single-cell experiments, adrenomedullin (30 pg/mL) significantly reduced the L-type calcium current (ICa-L) and reverse-mode current of the sodium–calcium exchanger (NCX). Adrenomedullin reduces spontaneous PV activity and PV diastolic tension by reducing ICa-L and NCX current and thus may be useful for treating atrial tachyarrhythmia.

Lithium intoxication induces Brugada-pattern ECG, ventricular arrhythmia, and sudden death with the predominant preference for the male over the female gender. This study investigated the mechanisms of gender difference in lithium-induced arrhythmogenesis. The ECG parameters were recorded in male and female rabbits before and after the intravenous administration of lithium chloride (LiCl) (1, 3, 10 mmol/kg). Patch clamps were used to study the sodium current (INa) and late sodium current (INa-late) in the isolated single male and female right ventricular outflow tract (RVOT) cardiomyocytes before and after LiCl. Male rabbits (n = 9) were more prone to developing lithium-induced Brugada-pattern ECG changes (incomplete right bundle branch block, ST elevation and QRS widening) with fatal arrhythmia (66.7% vs. 0%, p = 0.002) than in female (n = 7) rabbits at 10 mmol/kg (but not 1 or 3 mmol/kg). Compared to those in the female RVOT cardiomyocytes, LiCl (100 μM) reduced INa to a greater extent and increased INa-late in the male RVOT cardiomyocytes. Moreover, in the presence of ranolazine (the INa-late inhibitor, 3.6 mg/kg iv loading, followed by a second iv bolus 6.0 mg/kg administered 30 min later, n = 5), LiCl (10 mmol/kg) did not induce Brugada-pattern ECG changes (p < 0.005). The male gender is much predisposed to lithium-induced Brugada-pattern ECG changes with a greater impact on INa and INa-late in RVOT cardiomyocytes. Targeting INa-late may be a potential therapeutic strategy for Brugada syndrome-related ventricular tachyarrhythmia.

Atrial arrhythmias are considered prominent phenomena in pulmonary arterial hypertension (PAH) resulting from atrial electrical and structural remodeling. Endothelin (ET)-1 levels correlate with PAH severity and are associated with atrial remodeling and arrhythmia. In this study, hemodynamic measurement, western blot analysis, and histopathology were performed in the control and monocrotaline (MCT, 60 mg/kg)-induced PAH rabbits. Conventional microelectrodes were used to simultaneously record the electrical activity in the isolated sinoatrial node (SAN) and right atrium (RA) tissue preparations before and after ET-1 (10 nM) or BQ-485 (an ET-A receptor antagonist, 100 nM) perfusion. MCT-treated rabbits showed an increased relative wall thickness in the pulmonary arterioles, mean cell width, cross-sectional area of RV myocytes, and higher right ventricular systolic pressure, which were deemed to have PAH. Compared to the control, the spontaneous beating rate of SAN–RA preparations was faster in the MCT-induced PAH group, which can be slowed down by ET-1. MCT-induced PAH rabbits had a higher incidence of sinoatrial conduction blocks, and ET-1 can induce atrial premature beats or short runs of intra-atrial reentrant tachycardia. BQ 485 administration can mitigate ET-1-induced RA arrhythmogenesis in MCT-induced PAH. The RA specimens from MCT-induced PAH rabbits had a smaller connexin 43 and larger ROCK1 and phosphorylated Akt than the control, and similar PKG and Akt to the control. In conclusion, ET-1 acts as a trigger factor to interact with the arrhythmogenic substrate to initiate and maintain atrial arrhythmias in PAH. ET-1/ET-A receptor/ROCK signaling may be a target for therapeutic interventions to treat PAH-induced atrial arrhythmias.

Arrhythmogenic cardiomyopathy (ACM) is a group of arrhythmogenic disorders of the myocardium that are not caused by ischemic, hypertensive, or valvular heart disease. The clinical manifestations of ACMs may overlap those of dilated cardiomyopathy, complicating the differential diagnosis. In several ACMs, ventricular tachycardia (VT) has been observed at an early stage, regardless of the severity of the disease. Therefore, preventing recurrences of VT can be a clinical challenge. There is a wide range of efficacy and side effects associated with the use of antiarrhythmic drugs (AADs) in the treatment of VT. In addition to AADs, patients with ACM and ventricular tachyarrhythmias may benefit from catheter ablation, especially if they are drug-refractory. The differences in pathogenesis between the various types of ACMs can lead to heterogeneous distributions of arrhythmogenic substrates, non-uniform ablation strategies, and distinct ablation outcomes. Ablation has been documented to be effective in eliminating ventricular tachyarrhythmias in arrhythmogenic right ventricular dysplasia (ARVC), sarcoidosis, Chagas cardiomyopathy, and Brugada syndrome (BrS). As an entity that is rare in nature, ablation for ventricular tachycardia in certain forms of ACM may only be reported through case reports, such as amyloidosis and left ventricular noncompaction. Several types of ACMs, including ARVC, sarcoidosis, Chagas cardiomyopathy, BrS, and left ventricular noncompaction, may exhibit diseased substrates within or adjacent to the epicardium that may be accountable for ventricular arrhythmogenesis. As a result, combining endocardial and epicardial ablation is of clinical importance for successful ablation. The purpose of this article is to provide a comprehensive overview of the substrate characteristics, ablation strategies, and ablation outcomes of various types of ACMs using endocardial and epicardial approaches.

BackgroundDuring pandemics, acquiring outpatients’ travel, occupation, contact, and cluster histories is one of the most important measures in assessing the disease risk among incoming patients. Previous means of acquiring this information in the examination room have been insufficient in preventing disease spread. ObjectiveThis study aimed to demonstrate the deployment of an automatic system to triage outpatients over the internet. MethodsAn automatic system was incorporated in the existing web-based appointment system of the hospital and deployed along with its on-site counterpart. Automatic queries to the virtual private network travel and contact history database with each patient’s national ID number were made for each attempt to acquire the patient’s travel and contact histories. Patients with relevant histories were denied registration or entry. Text messages were sent to patients without a relevant history for an expedited route of entry if applicable. ResultsA total of 127,857 visits were recorded. Among all visits, 91,195 were registered on the internet. In total, 71,816 of them generated text messages for an expedited route of entry. Furthermore, 65 patients had relevant histories, as revealed by the virtual private network database, and were denied registration or entry. ConclusionsAn automatic triage system to acquire outpatients’ relevant travel and contact histories was deployed rapidly in one of the largest academic medical centers in Taiwan. The updated system successfully denied patients with relevant travel or contact histories entry to the hospital, thus preventing long lines outside the hospital. Further efforts could be made to integrate the system with the electronic medical record system.

ALDH2 gene is coded for the aldehyde dehydrogenase (ALDH), which is an enzyme involved in alcohol metabolism. Compared to normal aldehyde dehydrogenases, a homozygous point mutation on exon 12 from G to A significantly reduces its efficiency. In this study, we have reported the generation of IBMS-iPSC-021-04, IBMS-iPSC-022-01, and IBMS-iPSC-023-03 as induced pluripotent stem cell (iPSC) lines carrying the homozygous form of ALDH2 with the rs671 genetic polymorphism (E487K mutation). These cell lines were characterized in terms of pluripotency and differentiation potential. They serve as useful platforms to study alcohol metabolism and other chronic diseases associated with alcohol consumption.

Atrial fibrillation is the most common heart disease in the world, with around 35 million patients in 2020. Here we reported the generation of IBMS-iPSC-015-06, IBMS-iPSC-016-06, and IBMS-iPSC-017-02 as human induced pluripotent stem cell (iPSC) lines from patients’ peripheral blood mononuclear cells (PBMCs) with atrial fibrillation. The cell lines expressed properties of pluripotent stem cells, including pluripotent markers and the ability to differentiate into three germ layers. These cell lines served as suitable models for studying alternative therapies of atrial fibrillation.

Background: The stroke risk scoring system for atrial fibrillation (AF) patients can vary considerably based on patients’ status while receiving ablation. This study aimed to demonstrate a novel scoring system for stroke risk stratification based on the status of catheter ablation. Methods: First, 787 patients with AF undergoing ablation were matched according to age, sex, and underlying diseases with the same number of patients not undergoing ablation using the propensity-score (PS)-matched cohort. Multivariate Cox model-derived coefficients were used to construct a simple point-based clinical model using the PS-matched cohort. Thereafter, the novel model (AF-CA-Stroke score) was validated in a nationwide AF cohort. Results: The AF-CA-Stroke score was calculated based on age (point = 5), ablation status (point = 4), prior history of stroke (point = 4), chronic kidney disease (point = 2), diabetes mellitus (point = 1), and congestive heart failure (point = 1). Risk function to predict the 1-, 5-, 10-year absolute stroke risks was reported. The estimated area under the receive operating characteristic curve of the AF-CA-Stroke score in the PS-matched cohort was 0.845 (95% confidence interval: 0.824–0.865) to predict long-term stroke. A validation study showed that discrimination abilities in the AF-CA-Stroke scores were significantly higher than those in the CHADS2/CHA2DS2-VASc scores. The best cut-off value of the AF-CA-Stroke score to predict future strokes was ≥ 5. Conclusions: This novel model-based point scoring system effectively identifies stroke risk using clinical factors and AF ablation status of patients with AF. Various age stratifications and AF ablation should be considered in AF management.

Abstract Background Atrial fibrillation (AF) frequently coexists with congestive heart failure (HF) and arginine vasopressin (AVP) V1 receptor antagonists are used to treat hyponatremia in HF. However, the role of AVP in HF-induced AF still remains unclear. Pulmonary veins (PVs) are central in the genesis of AF. The purpose of this study was to determine if AVP is directly involved in the regulation of PV electrophysiological properties and calcium (Ca2+) homeostasis as well as the identification of the underlying mechanisms. Methods Patch clamp, confocal microscopy with Fluo-3 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, Ca2+ homeostasis, and Ca2+ regulatory proteins in isolated rabbit single PV cardiomyocytes incubated with and without AVP (1 μM), OPC 21268 (0.1 μM, AVP V1 antagonist), or OPC 41061 (10 nM, AVP V2 antagonist) for 4–6 h. Results AVP (0.1 and 1 μM)-treated PV cardiomyocytes had a faster beating rate (108 to 152%) than the control cells. AVP (1 μM) treated PV cardiomyocytes had higher late sodium (Na+) and Na+/Ca2+ exchanger (NCX) currents than control PV cardiomyocytes. AVP (1 μM) treated PV cardiomyocytes had smaller Ca2+ i transients, and sarcoplasmic reticulum (SR) Ca2+ content as well as higher Ca2+ leak. However, combined AVP (1 μM) and OPC 21268 (0.1 μM) treated PV cardiomyocytes had a slower PV beating rate, larger Ca2+ i transients and SR Ca2+ content, smaller late Na+ and NCX currents than AVP (1 μM)-treated PV cardiomyocytes. Western blot experiments showed that AVP (1 μM) treated PV cardiomyocytes had higher expression of NCX and p-CaMKII, and a higher ratio of p-CaMKII/CaMKII. Conclusions AVP increases PV arrhythmogenesis with dysregulated Ca2+ homeostasis through vasopressin V1 signaling.