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The presence of bipolar low-voltage zone (LVZ) is a predictor of AF recurrence after PV isolation (PVI). However, changes of wavefront and bipole directions may cause different electrogram characteristics. We aimed to investigate whether using omnipolar maximum voltage (Vmax) map derived from high density (HD) Grid mapping catheter could assess LVZ and AF ablation outcome accurately.Fifty paroxysmal AF patients (27 males, 57.8 ± 9.5 years old) who underwent 3D mapping guided PVI were enrolled. Left atrial voltage mapping during sinus rhythm before ablation was performed. The significant LVZ (0.5 mV with area 5 cmPVI was performed in all patients, and there were 2 patients (4%) who also received additional non-PV triggers ablation. After a follow-up of 11.4 ± 5.4 months, recurrence of AF occurred in 12 patients (24%). The presence of a significant LVZ was less detected by omnipolar Vmax map, compared to HD wave map (24.0% vs. 58.0%, p = 0.001). LVZ detected by omnipolar Vmax map independently predicted the AF recurrence (odds ratio 16.91; 95% CI, 3.17-90.10; p = 0.001).LVZ detected by omnipolar Vmax map accurately predicts the AF recurrence following ablation in paroxysmal AF, compared to conventional bipolar and HD wave maps, suggesting the omnipolar Vmax map can precisely define the atrial substrate property.

To evaluate the performance of a single‑lead, 14-day continuous electrocardiogram (ECG) patch for the detection of arrhythmias compared to conventional 24-h monitoring.This prospective clinical trial enrolled patients suspected of arrhythmias but not diagnosed by 12‑lead ECGs. Each patient underwent a 24-h Holter and 14-day ECG patch simultaneously. Seven types of arrhythmias were classified: supraventricular tachycardia (SVT, repetitive atrial beats4 beats), irregular SVT without P wave (4 beats), AF/AFL (irregular SVT without P wave ≥30 s), pause ≥3 s, atrioventricular block (AVB; Mobitz type II, third-degree, two to one or high degree AVB), ventricular tachycardia (VT), and polymorphic VT.A total of 158 patients were recruited (mean wear time:12.3 ± 3.2 days). The overall arrhythmia detection rate was higher with 14-day ECG patches (59.5%) compared to 24-h Holter (19.0%, P0.001). Up to 87.2% of arrhythmias recorded with 14-day ECG patches were not associated with symptoms. The 14-day ECG patch was associated with higher detection rates compared to the 24-h Holter in patients with SVT (52.5% versus 15.8%, P0.001), irregular SVT without P wave (12.7% versus 4.4%, P = 0.002), AF/AFL (9.5% versus 3.8%, P = 0.042), and critical arrhythmias (pause ≥3 s, AVB, VT, polymorphic VT) (16.5% versus 2.5%, P0.001). The 14-day ECG patch detected more than 2 types of arrhythmias in 5.1% of patients. No serious adverse events in patients wearing the 14-day ECG patch were reported.The 14-day ECG patch outperformed 24-h Holter to detect overall, asymptomatic, critical and multiple arrhythmias. It is safe and has the potential to identify individuals with hidden arrhythmias, especially those with critical arrhythmias.

Background Intracardiac electrogram recording is influenced by the electrode size and inter-electrode spacing. Smaller electrodes with a closer inter-electrode spacing may improve the mapping resolution and outcome. Methods Substrate mapping of the left atrium and residual pulmonary vein (PV) potentials during sinus rhythm was sequentially performed using a 3.5-mm electrode tip catheter and a 1-mm electrode multielectrode catheter in 33 patients (Group 1) that underwent repeat atrial fibrillation (AF) procedures. PV gap identification and electrophysiological characteristics were compared. Arrhythmia freedom was compared with a propensity matched (1:2) control group (66 patients, Group 2) undergoing repeat AF procedures guided by wide inter-electrode spacing catheter. Results In the Group 1 patients, the total area of residual PV potentials measured using the 1-mm catheter was larger than that measured by the 3.5-mm catheter. Overall 1.97 ± 0.59 (1–3) and 1.49 ± 0.62 (1–3) PVs were identified by the 1-mm electrode and 3.5 mm catheters, respectively (P = 0.02). The gaps not identified by the 3.5 mm catheter had a smaller width and lower voltage. Radiofrequency catheter ablation in the areas with residual PV potentials identified by the 1-mm catheter resulted in complete electrical isolation of the PVs. Arrhythmia freedom at one year of follow-up was achieved in 26 of 33 (78.8%) patients in Group 1, which was significantly higher than the matched control group (33/66 [50%], P Conclusion In the patients with a previous PV isolation, mapping with small, closely spaced electrodes can increase the detection rate of residual PV potentials and improve the outcome.

Background While modifiable bleeding risks should be addressed in all patients with atrial fibrillation (AF), use of a bleeding risk score enables clinicians to ‘flag up' those at risk of bleeding for more regular patient contact reviews. We compared a risk assessment strategy for major bleeding and intracranial hemorrhage (ICH) based on modifiable bleeding risk factors (referred to as a ‘MBR factors' score) against established bleeding risk stratification scores (HEMORR 2 HAGES, HAS-BLED, ATRIA, ORBIT). Methods A nationwide cohort study of 40,450 AF patients who received warfarin for stroke prevention was performed. The clinical endpoints included ICH and major bleeding. Bleeding scores were compared using receiver operating characteristic (ROC) curves (areas under the ROC curves [AUCs], or c-index) and the net reclassification index (NRI). Results During a follow up of 4.60±3.62years, 1581 (3.91%) patients sustained ICH and 6889 (17.03%) patients sustained major bleeding events. All tested bleeding risk scores at baseline were higher in those sustaining major bleeds. When compared to no ICH, patients sustaining ICH had higher baseline HEMORR 2 HAGES (p=0.003), HAS-BLED (p Conclusion All contemporary bleeding risk scores had modest predictive value for predicting major bleeding but the best predictive value and NRI was found for the HAS-BLED score. Simply depending on modifiable bleeding risk factors had suboptimal predictive value for the prediction of major bleeding in AF patients, when compared to the HAS-BLED score.

Background The changes of signal averaged ECG (SAECG) in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) undergoing radiofrequency catheter ablation (RFCA) of ventricular arrhythmias (VAs) remains unknown. Methods Between 2010 and 2014, a total of 81 ARVD/C patients underwent endocardial and/or epicardial RFCA for drug-refractory VAs. Seventy patients (mean age 46.2±14.1years, 37 males) achieving acute procedure success (negative inducibility) were enrolled. Baseline characteristics, non-invasive examinations and SAECG (before and 3months after RFCA) were collected retrospectively. Results After successful RFCA, the electrical parameters of SAECG changed in 39 patients (55.7%), including 28 patients (40%) with electrical regression (group 1), and 11 patients (15.7%) with electrical progression (group 3). Thirty-one patients (44.3%) showed no significant SAECG change (group 2). During a mean follow-up of 17.8±10.7months, 23 patients (32.9%) had VA recurrences, including 4 in group 1, 12 in group 2, and 7 in group 3. In comparisons with groups 2 and 3, group 1 patients had a significantly better VA recurrence-free survival ( P =0.02). In multivariable Cox regression analysis, electrical regression was found to be associated with fewer VA recurrences ( P =0.02, OR: 0.28, 95% CI: 0.10–0.83). Conclusions Electrical regression of SAECG after RFCA in ARVD/C was found to be associated with fewer VA recurrences.

Background Precise segmentation of the left atrium (LA) in computed tomography (CT) images constitutes a crucial preparatory step for catheter ablation in atrial fibrillation (AF). We aim to apply deep convolutional neural networks (DCNNs) to automate the LA detection/segmentation procedure and create three-dimensional (3D) geometries. Methods Five hundred eighteen patients who underwent procedures for circumferential isolation of four pulmonary veins were enrolled. Cardiac CT images (from 97 patients) were used to construct the LA detection and segmentation models. These images were reviewed by the cardiologists such that images containing the LA were identified/segmented as the ground truth for model training. Two DCNNs which incorporated transfer learning with the architectures of ResNet50/U-Net were trained for image-based LA classification/segmentation. The LA geometry created by the deep learning model was correlated to the outcomes of AF ablation. Results The LA detection model achieved an overall 99.0% prediction accuracy, as well as a sensitivity of 99.3% and a specificity of 98.7%. Moreover, the LA segmentation model achieved an intersection over union of 91.42%. The estimated mean LA volume of all the 518 patients studied herein with the deep learning model was 123.3 ± 40.4 ml. The greatest area under the curve with a LA volume of 139 ml yielded a positive predictive value of 85.5% without detectable AF episodes over a period of one year following ablation. Conclusions The deep learning provides an efficient and accurate way for automatic contouring and LA volume calculation based on the construction of the 3D LA geometry.

Catheter ablation is an effective treatment for atrioventricular nodal reentrant tachycardia (AVNRT). However, the characteristics of extremely late (3 years) recurrences of AVNRT after a successful initial ablation are not fully elucidated. We aimed to explore the electrophysiological characteristics of extremely late recurrences of AVNRT after a successful ablation.From 1991 to 2018, 3311 patients (mean age: 48.7 ± 17.4 years; men: 1328 [40.1%]) who underwent catheter ablation for AVNRT were investigated. Baseline characteristics of the patients, recurrence status, and detailed electrophysiological parameters of the index and repeat ablation procedures were obtained for analysis.After a mean follow-up period of 129.5 ± 58.0 months, 65 (2.0%) patients underwent repeat ablation for recurrences of AVNRT, of whom 17 (0.5%) presented with extremely late recurrences. The incidence of transient AV block was significantly higher in patients with extremely late recurrences (5.9%) than in those without recurrences (1.9%) but lower than that in patients with recurrences within3 years (12.5%, P .001). In addition, among patients with extremely late recurrences of AVNRT, the atrial-His bundle interval was significantly longer (99.1 ± 23.4 vs. 76.5 ± 13.1 ms, P .01) and the need for intravenous isoproterenol and/or atropine for the induction of AVNRT (88.2% vs. 47.1%, P = .03) was higher in the repeat ablation procedure than in the index ablation procedure.Recurrences of AVNRT can occur 3 years after a successful initial ablation. The electrophysiological features of the index and repeat ablation procedures differed between patients with extremely late recurrences of AVNRT and those with recurrences within3 years.

Aims Patients with atrial fibrillation (AF) may be at higher risk for cancer, possibly due to the presence of coexisting risk factors. In this study, we investigate the magnitude and predictors of this potential risk within a population-based study. Methods and results The study cohort included 332,555 AF patients aged ≥20 years without past history of cancer. Standardized incidence ratio (SIR) was used as a measure of relative risk, comparing observed cancer incidence among patients with AF with that expected based on cancer incidence in the Taiwanese population. During the observation period, 22,911 incident cancers occurred with an incidence of 1.65%/year. Compared with the general population, AF patients had a significantly higher cancer risk with a SIR of 1.37 (95%CI = 1.36–1.39). Patients with new-onset AF had an elevated cancer risk which was highest within 1 year (SIR = 2.30; 95%CI, 2.25–2.36) and persisted beyond 10 years after AF was diagnosed (SIR = 1.18; 95%CI, 1.11–1.25). Age ≥ 65 years, male gender, hypertension, diabetes, chronic obstructive pulmonary disease (COPD) and liver cirrhosis were significantly associated with development of cancers among AF patients. The hazard ratio of cancers increased from 1.40 (95%CI = 1.28–1.53) for patients having 1 risk factor to 5.14 (95%CI = 4.03–6.06) for patients with 6 risk factors, in comparison to those without any risk factors. Conclusion In the nationwide cohort study, we show that AF patients had a higher risk of cancer. Age, male gender, hypertension, diabetes, COPD and liver cirrhosis are important risk factors of cancer among AF patients. Prompt and detailed examinations may be considered for incident AF patients with multiple risk factors to early detect the occult malignancy.

Background Gender differences in the penetrance and clinical expression of genetic mutations have been reported in patients with arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C). Our study aimed at clarifying the impact of gender on ventricular substrates and clinical outcomes after radiofrequency catheter ablation (RFCA). Methods Patients with ARVD/C underwent RFCA for drug-refractory ventricular arrhythmias (VAs) were consecutively enrolled. Baseline characteristics, electrocardiograms, ventricular substrates, and VA recurrences after RFCA were extracted for comparison between genders. Results A total of 70 consecutive unselected patients with definite ARVD/C (36 men [51%], age 45±14years) were studied. Male patients had a higher incidence of sustained ventricular tachycardia and ventricular fibrillation or sudden cardiac arrest as initial manifestations. Electroanatomical mapping demonstrated that men with ARVD/C had a larger epicardial RV unipolar low-voltage zone, a larger endocardial and epicardial area with late potentials, and longer local abnormal ventricular activity. Cox regression analysis demonstrated that gender and late potential area predicted the recurrences of VAs. Conclusion Patients with ARVD/C displayed different characteristics of VAs and substrate properties between men and women. Male gender and the presence of larger area of abnormal electrograms independently predicted VA recurrences after RFCA.

Background Atrial fibrillation (AF) is associated with an increased risk of cognitive impairment and functional decline, and may contribute to development of dementia. Objectives Data from a nationwide large-scale population-based cohort study are lacking. Besides, how best to predict the occurrence of incident dementia among AF subjects remains uncertain. Methods A total of 332,665 AF subjects without dementia were identified as the study group from the "National Health Insurance Research Database" in Taiwan. For each study patient, one age- and sex-matched subject without AF and dementia was selected as the control group. The study end point was occurrence of dementia, and the usefulness of CHADS 2 and CHA 2 DS 2 -VASc scores in predicting dementia was analyzed. Results During the follow-up, 29,012 AF patients experienced dementia with an annual incidence of 2.12%, higher than non-AF subjects (1.50%). Patients with AF possessed a higher risk of dementia with a hazard ratio (HR) of 1.420 after adjustments for age, gender, baseline differences and medication use. Among AF patients, the CHADS 2 and CHA 2 DS 2 -VASc scores were significant predictors of dementia with an adjusted HR of 1.520 and 1.497 per 1 increment of the CHADS 2 and CHA 2 DS 2 -VASc scores, respectively. The c-index for CHA 2 DS 2 -VASc in predicting dementia (0.611, 95% confidence interval [CI]=0.608–0.614) was significantly higher than the CHADS 2 score (0.589, 95% CI=0.586–0.592) (DeLong test p Conclusions In this nationwide cohort study, AF was independently associated with a higher risk of dementia. The CHA 2 DS 2 -VASc score can be used to estimate the risk of dementia in AF patients.

Background Multiform premature ventricular complexes (PVCs) are common electrocardiographic abnormalities in patients with structurally normal hearts. However, the prognostic value of these complexes remains unclear. This study aimed to clarify the role of PVC polymorphism in predicting adverse outcomes. Methods and result We examined the database for 24-hour electrocardiography monitoring between January 1, 2002 and December 31, 2004. We analyzed 3351 individuals with apparently normal hearts. Kaplan–Meier curves and multivariate Cox proportional hazards models were employed to estimate the effect of multiform PVC and uniform PVC on the number of incident adverse events. Average follow-up time was 10±1years. Patients with multiform PVC were older and had a higher prevalence of comorbidities. In multivariate analysis, patients with multiform PVC had an increased incidence of mortality (hazard ratio [HR]: 1.642, 95% confidence interval [CI]: 1.327–2.031), hospitalization (HR: 1.196, 95% CI: 1.059–1.350), cardiovascular hospitalization (HR: 1.289, 95% CI: 1.030–1.613), new-onset heart failure (HF; HR: 1.456, 95% CI: 1.062–1.997), transient ischemic accident (HR: 1.411, 95% CI 1.063–1.873), and new-onset atrial fibrillation (AF; HR: 1.546, 95% CI: 1.058–2.258) compared to the group without PVC. Patients with multiform PVC had a higher rate of mortality (HR: 1.231, 95% CI: 1.033–1.468) and all cause-hospitalization (HR: 1.147, 95% CI: 1.025–1.283) compared with patients with uniform PVC. Conclusion The presence of multiform PVC was associated with a higher incidence of mortality, hospitalization, transient ischemic attack, new-onset AF, and new-onset HF independent of other clinical risk factors.

Vasovagal responses (VR) encountered during radiofrequency pulmonary vein isolation (PVI) in paroxysmal atrial fibrillation (PAF) suggest ablation of the atrial tissue subjacent to the ganglionic plexi (GP) and confer durability of PVI.We hypothesized that VR during cryoballoon PVI (CB-PVI) in PAF can predict mid-term AF recurrence.We enrolled 39 patients who underwent PVI using 2nd generation cryoballoon for PAF from November 2014 to July 2016. We evaluated the long term outcomes for those who had VR during index procedure.A total of 39 patients (76% male, mean age 57 ± 9 years) underwent CB-PVI for PAF and 66.67% (26/39) had VR. VR was frequently observed in the LSPV (100%), followed by RSPV (64%), LIPV (60%), and less frequently, RIPV (28%). Overall, the mean difference in the HR and SBP, and the relative differences in the HR and SBP were observed during CB-PVI in the LSPV (mean difference in HR, p 0.001; mean difference in SBP, p 0.001; relative difference in HR, p 0.001); relative difference in SBP, p 0.001). After PVI, 22/26 (84.62%) and 5/13 (38.46%) of patients in the VR and NVR group, respectively, maintained SR at 14 ± 6 months follow-up. The Kaplan-Meier analysis showed statistical difference in favor of patients with VR during CB-PVI (log rank p 0.01) with a better mid-term outcome.In a small cohort of patients, VR during CB-PVI in PAF is a surrogate marker for ablation of atrial tissue subjacent to the GP and predicts a favorable mid-term outcome for AF recurrence.

Signal averaged electrocardiogram (SAECG) is a specific and non-invasive tool useful for arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis. However, its role in risk stratification of patients with ARVC remains largely undefined.Sixty-four patients fulfilling Task Force ARVC criteria (mean age: 47 ± 14 years-old, 56% male, 50% definite ARVC) were enrolled. The baseline demographic, electrocardiographic, structural, and electrophysiological characteristics were collected. Patients with SAECG fulfilling all 3 Task Force criteria (3+ SAECG) were categorized into group 1, and those fulfilled 2 or less criterion were categorized into group 2. The study endpoints were unstable ventricular arrhythmia (VA), device detectable sustained fast VA (cycle lengths240 ms) and cardiovascular death.During a mean follow-up of 21 ± 20 months, 15 primary endpoints including 12 unstable VAs and 3 device-detected fast VAs were met. One patient died of electrical storm, and one patient underwent heart transplantation. The presence of 3+ SAECG predicted malignant events in all patients with definite and non-definite ARVC (p0.01, OR = 30.5, 95% CI = 2.5-373.7) and in patients with definite ARVC alone (p = 0.03, OR = 11.1, 95% CI = 1.3-93.9). Patients diagnosed with non-definite ARVC without 3+ SAECG were free from malignant events.SAECG fulfilling all 3 Task Force criteria was an independent risk predictor of malignant events in ARVC patients. SAECG may play a valuable role in ARVC risk stratification.

Background It is unclear whether atrial substrate with complex fractionated electrograms (CFAEs) is related to arrhythmogenesis. This study aimed to investigate the electrophysiology in CFAE and high dominant frequency (DF) areas. Methods and results Atrial fibrillation (AF) was induced by rapid atrial pacing in heart failure (HF) rabbits (4weeks after coronary artery ligation). Real-time substrate mapping, multielectrode array, and monophasic action potential recordings were used to study areas of CFAE and DF. Conventional microelectrode and western blot were used to record the action potentials (APs) and protein expression in isolated tissue preparations. CFAE site with high DF had the most depolarized resting membrane potential, highest incidence of early and delayed afterdepolarizations, and steepest maxima slope of 90% of AP duration (APD 90 ) restitution curve (RC) compared to CFAE site with low DF or non-CFAE sites. CFAE site with high DF exhibited the slowest conduction velocity and shortest wavelength than the other areas. Upregulation of the Na + –Ca 2+ exchanger (NCX), apamin-sensitive small-conductance Ca 2+ -activated K + channel type 2 (SK2) and sarcoplasmic reticulum Ca 2+ -ATPase, and downregulation of the Kir2.1 were found at CFAE site with high DF compared to that observed in the 3 other areas. Inhibition of the NCX and SK channels prolonged the APD 90 , flattened the maximum slope of RC, and suppressed AF. Conclusions CFAE site with high DF had an arrhythmogenic property differing significantly from the other areas of LA in an HF rabbit model, which may contribute to the genesis of AF.

Background Sudden cardiac death (SCD) occurs commonly after heart transplantation (HTX). The utilization of surface electrocardiography (ECG) to assess post-HTX SCD has not been investigated thoroughly. This study aimed to investigate the specific changes in surface ECG in HTX patients with SCD. Methods A total of 227 HTX patients (age 48±14y/o, mean donor age 34±14y/o, 173males) were followed up regularly at the outpatient clinic. Twelve-lead ECG's were recorded during 1–2 monthly visits. Serial ECG parameters and relevant clinical data were collected and analyzed. Results During the follow-up period of 96±51months, SCD occurred in 28 (12.3%) patients. The baseline ECG parameters were comparable between patients with and without SCD. Important ECG trends of rising rest heart rates and prolongation of corrected QT (QTc) and JT (JTc) intervals were observed prior to development of SCD. After adjustment for other clinical variables, the independent predictors for SCD were older donor age (p=0.014, OR 1.05, 95% CI 1.01–1.09), faster heart rate (p=0.006, OR 1.06, 95% CI 1.02–1.1) and longer JTc interval (p=0.015, OR 1.03, 95% CI 1.01–1.06). SCD occurred in 71.4% patients presenting with all three risk predictors. Conclusions Besides older donor age, important ECG signs, including prolongation of the JTc interval and increased heart rate during post HTX follow up, could predict SCD.

Although hyperuricemia was associated with several cardiovascular diseases, the role of uric acid (UA) in left atrial (LA) remodeling and new-onset atrial fibrillation (AF) has not been fully explored. The goal of the present study is to investigate the relationship between UA, LA diameter and the development of AF in the large-scale cohort.The study consisted of 2 parts. First, we investigated the association between serum UA and LA diameter in a single-center database (n = 3043). Second, we studied and compared the risk of new-onset AF among patients with and without hyperuricemia in the nationwide longitudinal cohort in Taiwan (n = 122,524).Elevated serum level of UA was associated with an increased systemic inflammation, and insulin resistance. The LA diameter was significantly correlated with serum UA (r = 0.341, p value0.001). The linear correlation between LA dimension and UA level remained significant after the adjustment for clinical, biochemical and echocardiographic variables. In the nationwide cohort, there were 2339 patients (1.9% of the study population) developing AF during the follow-up of 6.3 ± 3.0 years. The AF occurrence rate was higher in patients with hyperuricemia than those without it (2.1% versus 1.7%; p value0.001). Hyperuricemia was a significant risk factor of new-onset AF with a hazard ratio of 1.191 (95% confidence interval = 1.098-1.292, p value0.001) in the multivariate Cox regression analysis.Hyperuricemia was associated with a larger LA size and may be a novel risk factor for the development of AF.

Obesity is an important risk factor for atrial fibrillation (AF) and heart failure (HF). The effects of epicardial fat on atrial electrophysiology were not clear. This study was to evaluate whether HF may modulate the effects of epicardial fat on atrial electrophysiology.Conventional microelectrodes recording was used to record the action potential in left (LA) and right (RA) atria of healthy (control) rabbits before and after application of epicardial fat from control or HF (ventricular pacing of 360-400 bpm for 4 weeks) rabbits. Adipokine profiles were checked in epicardial fat of control and HF rabbits.The LA 90% of AP duration was prolonged by control epicardial fat (from 77 ± 6 to 87 ± 7 ms, p0.05, n=7), and by HF epicardial fat (from 78 ± 3 to 98 ± 4 ms, p0.001, n=9). However, control or HF epicardial fat did not change the AP morphology in RA. HF epicardial fat increased the contractility in LA (61 ± 11 vs. 35 ± 6 mg, p=0.001), but not in RA. Control fat did not change the LA or RA contractility. Moreover, control and HF epicardial fat induced early and delayed afterdepolarizations in LA and RA, but only HF epicardial fat provoked spontaneous activity and burst firing in LA (n=3/9, 33.3% vs. n=0/7, 0%, n=0/9, 0%, p0.05). Compared to control fat, HF epicardial fat, had lower resistin, C-reactive protein and serum amyloid A, but similar interleukin-6, leptin, monocyte chemotactic protein-1, adiponectin and adipsin.HF epicardial fat increases atrial arrhythmogenesis, which may contribute to the higher atrial arrhythmia in obesity.

There are limited literatures regarding the non-pulmonary vein (NPV) triggers in long-standing persistent atrial fibrillation (LSPAF). The goal of the present study was to investigate the characteristics and long-term outcome of catheter ablation among these patients.The study included 776 patients (age 53.59±11.38years-old, 556 males) who received catheter ablation for drug-refractory atrial fibrillation (AF). We divided these patients into 3 groups. Group 1 consisted of 579 patients with paroxysmal AF (PAF), group 2 consisted of 103 patients with persistent AF (PerAF) and group 3 consisted of 94 patients with long-standing persistent AF (LSPAF). The average follow-up duration was 28.53±23.21months.The clinical endpoint was the recurrence of atrial tachyarrhythmia. Among these 3 groups, higher percentages of male (93.6%, P0.001), NPV triggers (44.7%, P0.001), longer AF duration (6.65±6.72years, P=0.029), larger left atrium diameter (44.44±6.79mm, P0.001), and longer procedure time (181.94±70.02min, P0.001) were noted in LSPAF. After the first catheter ablation, the recurrence rate of AF was highest in LSPAF (Log Rank, P0.001). Larger left atrium diameters (LAD) (P=0.006; HR: 1.063; CI: 1.018-1.111) and NPV triggers (P=0.035; HR: 1.707; 1.037-2.809) independently predicted AF recurrence in LSPAF.Compared with PAF and PerAF, LSPAF had a higher incidence of NPV triggers and worse long-term outcome after catheter ablation. NPV triggers and LAD independently predicted AF recurrence after catheter ablation in LSPAF.

Aortic dilatation was frequently observed in patients with atrial fibrillation (AF) and non-pulmonary vein (PV) triggers are important for mapping and ablation of AF. We hypothesized that the aortic encroachment area over left atrium (LA) could contribute to the local substrate characteristics.We studied 32 consecutive patients of AF (age=57.34±8.07, male=30), including 26 paroxysmal and 6 persistent AFs. Anatomic relationship between LA and aorta, and electrophysiological characteristics of the encroachment areas were investigated. IRB approval was taken.The LA bipolar voltage (mean 0.49±0.26mV) was lower at aortic encroached area compared to global LA (mean 1.52±0.48mV) and it was statistically significant (p0.001). There was a linear correlation between the voltages of LA and distance from the aorta to the aortic encroachment area of LA (p0.001, R=0.616). Non-PV triggers were observed in 34.37% (n=11) of total patients. The initiation of AF in aortic encroached area was seen in 45.45% (n=5) of non-PV trigger and 15.62% of total patients. All the patients were followed up for 6months and 4 (14.81%) out of 27 patients without trigger at aortic encroached site of LA and 1 (20%) out of 5 patients with trigger at aortic encroached site of LA had recurrence of AF.The aorta contributed to low voltages on its encroachment area over the anterior wall of LA. Non-pulmonary vein triggers originating from the aortic encroachment area were found in 15.62% of total patients. Careful evaluation of the anatomical relationship between LA and aorta is important during AF ablation for a better long term outcome.

Background Heart failure (HF) causes atrial remodeling and increases the incidence of atrial fibrillation (AF). Renal denervation (RDN) has been shown to decrease the development of AF. This study aimed to identify the effects of RDN on the atrial arrhythmogenic substrates in HF. Methods Rabbits were classified into four groups: control (n=9), RDN (n=10), HF (n=6) and HF-RDN (n=9). Surgical and chemical RDN was approached through bilateral retroperitoneal flank incisions in RDN and HF-RDN. Rapid ventricular pacing of 400bpm for 4weeks was applied in HF and HF-RDN. After 4weeks, the rabbits were sacrificed and atrial myocardium were harvested for Western blot and Trichrome stain. Results The bi-atrial effective refractory period (ERP) of HF was significantly longer compared with that of control and RDN. In right atrium, the ERP of HF was also significantly longer compared with that of HF-RDN, but there was no significant difference in left atrial ERP. In bi-atrium, ion channel protein expressions of CaV1.2, NaV1.5, Kir2.1 SERCA2 and NCX were similar among 4 groups. However, the degree of atrial fibrosis was extensive in bi-atrium of HF, when compared to that of control, RDN and HF-RDN. Conclusion The ERP of HF-RDN is partially shortened by RDN compared with that of HF. There are no differences ionic channel protein expressions in bi-atrium among all groups. The degree of atrial fibrosis is severe in HF, but not in HF-RDN, suggesting that RDN may regulate the atrial arrhythmogenic substrates in HF mostly through reverse structural remodeling.

Sarcoidosis is an important diagnostic consideration in patients with ventricular tachycardia (VT) of unknown origin. The clinical course of VT as the primary presentation in patients with sarcoidosis is mostly unknown. This study aimed to investigate the incidence of life-threatening VT and mortality during long term follow-up in patients with sarcoidosis.We analyzed the epidemiological features of sarcoidosis in Taiwan using the National Health Insurance Research Database from 2000 to 2004. Patients with sarcoidosis were identified, and healthy controls without prior histories of structural heart disease were matched with a 1:1 propensity-score to the sarcoidosis group. The risk of life-threatening VT and mortality with sarcoidosis was analyzed.A total of 2237 sarcoidosis cases were enrolled with a matching number of healthy controls, and the baseline characteristics between the two groups were similar. After a mean follow-up of 11.4±2.15years (IQR: 12, 11.3-12), the VT incidence in the sarcoidosis group was higher than in healthy controls (0.94% [85 per 100,000 person-year] in the sarcoidosis group, and 0.09% [8 per 100,000 person-year] in healthy controls). After a multivariate adjustment including the sex, age, and other comorbidities, the VT risk was still higher in the sarcoidosis group (hazard ratio: 12.7, 95% confidence interval: 2.82-56.9; P0.001). The risk of defibrillator implantations for secondary prevention, cardiovascular death, and total mortality between the groups was equivalent.Sarcoidosis may increase the predisposition to ventricular arrhythmias with a cumulative incidence of 0.94% during a very long term follow-up of nearly 10years from initially diagnosing sarcoidosis.

a Division of Cardiovascular Medicine, Department of Internal Medicine, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan b Division of Cardiology and Cardiovascular Research Center, Taipei Veterans General Hospital, Taipei, Taiwan c Institute of Clinical Medicine, and Cardiovascular Research Institute, National Yang-Ming University, Taipei, Taiwan d Medical Department, Taipei City Hospital, Taipei, Taiwan e Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan f National Yang-Ming University Hospital, Taiwan

Atrial fibrillation (AF) is associated with cognitive decline and may contribute to an increased risk of dementia. The goal of the present study was to investigate whether statin use prevented non-vascular dementia in subjects with AF.Data from the National Health Insurance Research Database of Taiwan were used in this study. The study group comprised 51,253 AF subjects aged ≥ 60 years who had received statin treatment. For each study patient, four age- and sex-matched AF subjects without statin exposure were selected as the control group (n=205,012). The risk of non-vascular dementia was compared between the statin and control groups.During the follow-up period, 17,201 patients experienced non-vascular dementia. The annual incidence of non-vascular dementia was lower in the statin group than in the control group (1.89% vs. 2.20%; p0.001). Statin use exhibited a protective effect on the occurrence of non-vascular dementia, with an adjusted hazard ratio (HR) of 0.832 (95% confidence interval=0.801-0.864). Among statin types, the use of rosuvastatin was associated with the largest risk reduction (adjusted HR=0.661). Statin exposure duration was related inversely to the risk of non-vascular dementia.In this large-scale nationwide cohort study, statin use was associated with a lower risk of non-vascular dementia in AF. Use of more potent statin and longer exposure time may be associated with greater benefits.

arrhythmias, reducing hospitalizations and medical cost Yen-Chang Huang , Shih-Lin Chang ⁎, Yenn-Jiang Lin , Li-Wei Lo , Yu-Feng Hu , Tze-Fan Chao , Wen-Ling Sheen , Hui-Lun Chuang , Mei-Ling Chen , Huan-Chung Li , Fei-Lung Lin , Chih-Hsiang Liu , Shih-Ann Chen a,b a Division of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC b Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC c Department of Medicine, Taipei City Hospital, Taipei, Taiwan, ROC d Advanced Research Institute, Institute for Information Industry, Taipei, Taiwan, ROC

Background The clinical characteristics and prognostic value of early repolarization (ER) in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) and symptomatic ventricular arrhythmias remain unclear. We investigated the prevalence, clinical features, and cardiovascular outcomes of patients with symptomatic ARVD/C and ER. Methods A total of 59 consecutive ARVD/C patients hospitalized for catheter ablation, presenting with and without J-point elevations of ≥0.1mV in at least 2 inferior leads or lateral leads were enrolled. Clinical characteristics, electrophysiological study, substrate mapping, catheter ablation, and future clinical outcomes in a prospective patient registry were investigated. Results ER was observed in 38 patients (64.4%). Among these patients, ER was found in the inferior leads in 18 patients (47.4%), in the lateral leads in 2 patients (5.3%), and in both inferior and lateral leads in 18 patients (47.4%). Patients exhibiting ER were commonly men, had lower right ventricular ejection fraction, had higher incidence of clinical ventricular fibrillation or aborted sudden cardiac death, had more defibrillator implantations, had higher the need of epicardial ablation, and had more major criteria according to the task force criteria. Significant higher incidence of induced ventricular fibrillation and shorter tachycardia cycle length of induced ventricular tachycardia were found during procedure. The recurrence rate of ventricular arrhythmias did not differ between patients with and without ER after catheter ablation. Conclusions A high prevalence of electrocardiographic ER was found among symptomatic ARVD/C patients undergoing catheter ablation. ER in 12-lead ECG is associated with an increased risk of clinical fatal ventricular arrhythmias.

This study aimed to investigate the mechanism by which colchicine suppresses atrial fibrillation (AF) in a rabbit heart failure (HF) model.HF was induced by coronary ligation. Using the Langendorff perfusion system, monophasic action potentials were recorded in the left atrial appendage (LAA) of normal rabbits (n=6) and HF rabbits (n=6) treated with colchicine (100 μM) followed by colchicine (100 μM) plus paclitaxel (5 μM). Collagen content and mRNA and protein expression of ion channels through the PI3K/AKT/eNOS signaling pathway were evaluated in LAA of normal rabbits (n=6) and HF rabbits treated with vehicle (n=6) or colchicine (n=6) intraperitoneal injection for 2 days. Colchicine decreased action potential duration (74.1±2.6 vs 91.8±3.3 ms, P0.001), effective refractory period, and maximum slope of the restitution curve in HF LAA. However, these effects were reversed by paclitaxel. The incidence of early afterdepolarizations, delayed afterdepolarizations, and AF inducibility was significantly lower after colchicine perfusion than at baseline or after colchicine plus paclitaxel perfusion. Cardiac function increased and LA fibrosis decreased after colchicine treatment. mRNA and protein expression of Kir2.1, Kv1.4, Kv1.5, Kv7.1, Cav1.2, and SERCA2a were upregulated after colchicine treatment, as was mRNA expression of PI3K, AKT, and eNOS.Colchicine regulates ion channel gene expression and activates the PI3K/AKT/eNOS signaling pathway in HF rabbits, which may reverse atrial remodeling and suppress AF.

Background Although hyperuricemia has been reported to be a risk factor of stroke, the relationship between hyperuricemia and stroke in patients with atrial fibrillation (AF) remains uncertain. The goal of the present study was to investigate whether hyperuricemia could potentially refine clinical risk stratification in AF. Methods This study used the "National Health Insurance Research Database" in Taiwan. A total of 7601 AF patients who did not receive antiplatelet agents or oral anticoagulants were identified as the study population. Hyperuricemia was defined as having at least one episode of gout attack necessitating long-term treatment with uric acid-lowering agents. The association between hyperuricemia and ischemic stroke was analyzed. Results During the follow up of 3.0±2.7years, 1116 patients (14.7%) experienced ischemic stroke with an annual rate of around 4.9%. Hyperuricemia significantly predicts stroke, with a hazard ratio (HR) of 1.280 after adjusting for CHA 2 DS 2 -VASc score and other comorbidities. Among the 376 patients with a CHA 2 DS 2 VASc score of 0, hyperuricemia can further stratify them into 2 groups with different stroke rates (7.1% versus 1.3%, p=0.020). The adjusted HR of hyperuricemia in predicting ischemic stroke diminished from 7.491 for patients with a CHA 2 DS 2 -VASc score of 0 to 1.659 for those with a score of 3, and became insignificant for patients with a score ≥4. Conclusions Hyperuricemia was a significant risk factor of stroke which could potentially refine the clinical risk stratification in AF. It deserves a prospective trial to investigate whether it would change the current strategy for stroke preventions using oral anticoagulants.

Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The goal of the present study was to investigate whether exposure to non-steroidal anti-inflammatory drugs (NSAIDs) was a risk factor for AF, and to discern which patients were at the highest risk for AF due to NSAID use. Methods A total of 7280 patients with newly diagnosed AF from 2000 to 2009 were identified from the National Health Insurance Research Database. On the same date of enrollment, 10 patients without AF, who were matched for age, sex, and underlying disease for each study patient, were selected to be the control group. The relationship between NSAID exposure before enrollment and AF risk was analyzed. Results The NSAID use was associated with an increased AF risk, especially for new users (odds ratio [OR]=1.651). Among new users, subgroup analysis revealed that patients with heart failure were at the highest risk for AF (OR=1.920). For patients who were only exposed to selective cyclooxygenase 2 (COX2) inhibitors, no significant associations were found between AF and selective COX2 inhibitor use, except for patients with chronic kidney or pulmonary disease (OR=1.656 and 1.707, respectively). Conclusions New NSAID use may predispose patients to AF, and the risk is almost doubled in heart failure patients. Use of selective COX2 inhibitors was not significantly related to AF occurrence, except in patients with chronic kidney or pulmonary disease.

Background The components of CHADS 2 score were reported to be important risk factors for the development of atrial fibrillation (AF). The goal of the current study was to investigate whether the CHADS 2 score was a useful scheme in predicting new-onset AF. Furthermore, we aimed to use the CHADS 2 scoring system to estimate the individual risk in developing AF for patients with different comorbidities. Methods From January 1, 2000 to December 31, 2001, a total of 702,502 patients older than 18 years old and who had no history of cardiac arrhythmias were identified from the “National Health Insurance Research Database” released by the Taiwan National Health Research Institutes. The CHADS 2 score was calculated for every patient. Finally, 628,807 (score 0), 47,039 (score 1), 15,655 (score 2), 6843 (score 3), 3315 (score 4), 790 (score 5) and 53 (score 6) patients were studied and followed for the occurrences of AF. Results During a follow-up of 9.0 ± 2.2 years, there were 9187 (1.3%) patients experiencing new-onset AF. The incidence of AF was 1.5 per 1000 patient-years. The incidence increased from 0.8 per 1000 patient-years for patients with a CHADS 2 score of 0 to 34.6 per 1000 patient-years for those with a CHADS 2 score of 6. After an adjustment for the gender and comorbidities, the hazard ratio (95% confidence interval) of each increment of the CHADS 2 score in predicting AF was 2.342 (2.309–2.375; p Conclusions The CHADS 2 score, consisting of an age > 75 and several clinical risk factors was useful in risk estimation and stratification of new-onset AF.

Background The occurrence of eccentric retrograde atrial activation has been demonstrated to be from 6 to 8% in patients with atrioventricular nodal reentrant tachycardia (AVNRT) by several previous reports. However, most of those reports were limited by the absence of coronary sinus venography to confirm if the retrograde activation was truly left sided. The purposes of this study were to 1) determine the incidence of left sided retrograde atrial activation in our center, 2) determine the specific electrophysiologic characteristics of eccentric and concentric atrial activation and 3) determine the outcome of radiofrequency catheter ablation for AVNRT with eccentric retrograde atrial activation. Methods From November 2001 to July 2004, 290 consecutive patients with AVNRT who underwent an electrophysiologic study and radiofrequency ablation were included. Group 1 consisted of AVNRT patients with eccentric retrograde atrial activation; group 2 consisted of AVNRT patients with concentric retrograde atrial activation. The electrophysiologic characteristics of the group 1 and group 2 patients were then compared. Results The incidence of AVNRT with eccentric retrograde activation confirmed by CS venography was 6.5%. There were more females and atypical AVNRT in patients with retrograde eccentric conduction. There was more VA block after ablation and tachycardia induction by right ventricular pacing/extrastimuli in eccentric rather than concentric retrograde atrial activation. A shorter antegrade fast functional refractory period of the AV node was demonstrated in the atypical eccentric group as compared to the atypical concentric group. Conclusion This study demonstrated the different electrophysiologic characteristics between the AVNRT patients with eccentric and concentric retrograde atrial activation. Successful ablation sites were similar to the standard RA ablation sites in patients with retrograde eccentric conduction.

Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia in adulthood. Although selective ablation of the slow AV nodal pathway can cure AVNRT, accidental AV block may occur. The details on the electrophysiologic characteristics, quantitative data on the voltage inside Koch's triangle, and the use of three-dimensional noncontact mapping to facilitate the catheter ablation of AVNRT associated with a high-risk for AV block or other arrhythmias have been limited.Nine patients (M/F=5/4, 34+/-23 years, range 17-76) with clinically documented AVNRT were included. All patients had undergone previous sessions for slow AV nodal pathway ablation but they had failed, because of repetitive episodes of complete AV block during the RF energy applications. Further, one patient had a complex anatomy and 4 patients were associated with other tachycardias, respectively. The electrophysiologic studies revealed that 4 patients had the slow-fast, 4 the slow-intermediate and one the fast-intermediate form of AVNRT. Noncontact mapping demonstrated two types of antegrade AV nodal conduction, markedly differing sites of the earliest atrial activation during retrograde VA conduction, and a lower range of voltage within Koch's triangle. The lowest border of the retrograde conduction region was defined on the map, and the application of the RF energy was delivered below that border to prevent the occurrence of AV block. The distance between the successful ablation lesions and the lowest border of the retrograde conduction region was significantly shorter in the patients with the slow-intermediate form of AVNRT than in those with the slow-fast form (5.5+/-3.4 vs. 15+/-7.6 mm; p0.05). After the ablation procedure, either rapid pacing or extrastimulation could not induce any tachycardia, and there was no recurrence during the follow-up (10.3+/-5.4, 2 to 22 months).Noncontact mapping could effectively demonstrate the antegrade and retrograde atrionodal conduction patterns, electrophysiologic characteristics of Koch's triangle, and guide the successful catheter ablation in difficult AVNRT cases.

Background The significant role of bundle branch block during atrioventricular nodal reentrant tachycardia (AVNRT) is not clear. The purposes of this study were to study the effects of complete right bundle branch block (RBBB) on electrophysiological parameters during AVNRT and to define the significance of complete RBBB during AVNRT. Methods and results According to characteristics of electrocardiogram during sinus rhythm and AVNRT, 50 patients who underwent catheter ablation for slow–fast AVNRT were divided into three groups. Group I included 20 patients who had narrow QRS (≤110 ms) during sinus rhythm and AVNRT. Group II included 18 patients who had persistent RBBB (≥120 ms) during sinus rhythm and AVNRT. Group III included 12 patients who had narrow QRS during sinus rhythm, but they had narrow QRS and transient RBBB during AVNRT. The atrio-His (AH) interval (296±60 vs. 288±75 ms), His-ventricular (HV) interval (36±11 vs. 35±11 ms), His-atrial (HA) interval (72±24 vs. 71±28 ms), VA HRA interval (defined as the interval between the onset of ventricular depolarization and the onset of atrial activity of right high atrium; 34±24 vs. 37±25 ms), VA CSO interval (defined as the interval between the onset of ventricular depolarization and the onset of atrial activity of coronary sinus ostium; 13±28 vs. 26±23 ms) and tachycardia cycle length (TCL; 368±67 vs. 359±73 ms) during AVNRT were similar between group I and group II (all P >0.05). In group III, the AH interval (255±81 vs. 246±83 ms), HV interval (44±5 vs. 42±11 ms), HA interval (66±19 vs. 70±15 ms), VA HRA interval (27±15 vs. 29±16 ms), VA CSO interval (23±25 vs. 21±25 ms) and TCL (322±76 vs. 316±77 ms) were not significantly different between AVNRT with narrow QRS and those with transient RBBB (all P >0.05). Conclusions Persistent RBBB and transient RBBB have no significant effects on the electrophysiological parameters during AVNRT. These findings suggest that RBBB might not influence the conduction of lower common pathway or the circuit of AVNRT.