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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 Fever is associated with the manifestation of Brugada phenotype and ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS). The thermal effect on the pathogenesis of functional substrates in BrS remains unknown. Objective This study aimed to elucidate the thermal effect on BrS phenotype, VT/VF, and electrophysiological characteristics of epicardial functional substrates in BrS. Methods We consecutively studied 15 patients with BrS receiving radiofrequency catheter ablation for drug-refractory ventricular tachyarrhythmias. Baseline characteristics, electrocardiographic features, and changes in epicardial functional substrates before and after epicardial warm water instillation (n = 6) were recorded and analyzed. Results A total of 15 male patients (mean age 41.3 ± 10.3 years) with type 1 BrS presenting with ventricular tachyarrhythmias were consecutively enrolled. Epicardial mapping in 11 patients demonstrated a significantly larger epicardial scar/low-voltage zone (LVZ) area within the right ventricular outflow tract and anterior right ventricular free wall than within the endocardium (6.32 ± 12.74 cm2 vs 52.91 ± 45.25 cm2; P = .007). Epicardial warm water instillation in 6 patients led to a significant enlargement of the functional scar/LVZ area (123.83 ± 35.26 cm2 vs 63.53 ± 40.57 cm2; P = .03), accelerated conduction velocity of the endocardium and epicardium without scar/LVZ area, and increased VT/VF inducibility (16.7% vs 100%; P = .02). Ablation by targeting premature ventricular complexes and/or epicardial abnormal substrates rendered noninducibility of VT/VF and prevented the recurrences of VT/VF. Conclusion Epicardial warm water instillation enhanced functional epicardial substrates, which contributed to the increased inducibility of ventricular tachyarrhythmias in BrS. Ablation by targeting the triggers and abnormal epicardial substrates provided an effective strategy for preventing ventricular tachyarrhythmia recurrences in BrS.

Aims Whether the distribution of scar in arrhythmogenic right ventricular cardiomyopathy (ARVC) plays a role in predicting different types of ventricular arrhythmias is unknown. This study aimed to investigate the prognostic value of scar distribution in patients with ARVC. Methods and results We studied 80 consecutive ARVC patients (46 men, mean age 47 ± 15 years) who underwent an electrophysiological study with ablation. Thirty-four patients receive both endocardial and epicardial mapping. Abnormal endocardial substrates and epicardial substrates were characterized. Three groups were defined according to the epicardial and endocardial scar gradient ( 20%: horizontal, as groups 1, 2, and 3, respectively). Sinus rhythm electrograms underwent a Hilbert-Huang spectral analysis and were displayed as 3D Simultaneous Amplitude Frequency Electrogram Transformation (SAFE-T) maps, which represented the arrhythmogenic potentials. The baseline characteristics were similar between the three groups. Group 3 patients had a higher incidence of fatal ventricular arrhythmias requiring defibrillation and cardiac arrest during the initial presentation despite having fewer premature ventricular complexes. A larger area of arrhythmogenic potentials in the epicardium was observed in patients with horizontal scar. The epicardial-endocardial scar gradient was independently associated with the occurrence of fatal ventricular arrhythmias after a multivariate adjustment. The total, ventricular tachycardia, and VF recurrent rates were higher in Group 3 during 38 ± 21 months of follow-up. Conclusion For ARVC, the epicardial substrate that extended in the horizontal plane rather than transmurally provided the arrhythmogenic substrate for a fatal ventricular arrhythmia circuit.

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.

We herein report a case of atrial tachycardia (AT) originating from the dilated coronary sinus (CS) connected to a persistent left superior vena cava. The earliest activation site of AT was localized at the superior CS ostium, identified using a novel ultra-rapid high-density mapping system (Rhythmia™). Successful ablation was performed at the corresponding position. This report demonstrated the utility of an ultra-rapid high-density mapping system in identifying arrhythmogenic foci in adult cases of congenital heart disease.

Background Autonomic imbalance with increased sympathetic and decreased parasympathetic activities is observed in patients after myocardial infarction (MI). We aimed to investigate sleep-related changed in autonomic regulation in left coronary artery (LCA) ligation rats. Methods Wireless transmission of polysomnographic recording was performed in sham and LCA ligation male rats during normal daytime sleep with and without atenolol treatment. Spectral analyses of the electroencephalogram (EEG) and electromyogram (EMG) were evaluated to define active waking (AW), quiet and paradoxical sleeps (QS, PS). Cardiac autonomic activities were measured by analyzing the power spectrum of heart rate variability (HRV). EEG, EMG and HRV were recorded over 6h for consecutive 3days in all groups. Results In LCA ligation group, there were higher LF and LF/HF ratio on QS phase, but not AW and PS phases, compared to atenolol treated sham and LCA ligation groups, respectively. The HF component was not significantly changed on all groups in both sleep and awake phases. Sleep interruption was more frequent in LCA ligation rats compared to sham, and it was not found in LCA ligation with atenolol treatment group. Increased AW, PS and decreased QS time were noted in LCA ligation group, compared to sham and it was restored to baseline in LCA ligation with atenolol treatment group. Conclusions Our results demonstrate significant sleep fragmentations with sympathetic hyperactivity during QS stages after MI, and atenolol could restore the autonomic dysfunction and sleep disturbance. The finding explains the cause of sleep-related fetal arrhythmia and sudden cardiac death after MI.

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.

Whether ectopic atrial rhythm (EAR) is a high-risk cardiovascular phenotype (eg, the manifestation of a diseased sinoatrial node) or just a benign accelerated ectopic pacemaker remains unclear.We aimed to analyze the cardiovascular outcomes and underlying mechanisms in patients with EAR.From a 12-lead electrocardiogram hospital-based electrocardiogram database, a total of 2896 adults with EAR were propensity score matched at 1:5 with 14,480 patients with sinus rhythm (SR). Patients were retrospectively followed up for cardiovascular mortality (the primary outcome) and permanent pacemaker implantation (the secondary outcome). Heart rate variability was analyzed to compare autonomic function between patients with EAR and those with SR.The prevalence of EAR was 1.13%, which increased with age. Compared with the matched patients, those with EAR had a higher risk of cardiovascular mortality (adjusted hazard ratio 1.93; 95% confidence interval 1.52-2.44; P.0001) and permanent pacemaker implantation (adjusted hazard ratio 5.94; 95% confidence interval 3.89-9.09; P.0001) according to the Cox proportional hazards regression model. The risk of cardiovascular mortality was similar across the subgroups on the basis of age, sex, hypertension, type 2 diabetes mellitus, congestive heart failure, myocardial infarction, stroke, and chronic kidney diseases. In patients with EAR, the low frequency/high frequency and standard deviation of the mean normal-to-normal intervals/root mean square of successive RR interval differences ratios for heart rate variability were both lower than those in patients with SR. This implied autonomic imbalance in patients with EAR.Patients with EAR have a higher risk of cardiovascular mortality and permanent pacemaker implantation, which was associated with autonomic imbalance.

BACKGROUND: The location of the accessory pathway (AP) can be precisely identified on surface electrocardiography (ECG) in adults with Wolff-Parkinson-White (WPW) syndrome. However, current algorithms to locate the AP in pediatric patients with WPW syndrome are limited. OBJECTIVE: To propose an optimal algorithm that localizes the AP in pediatric patients with WPW syndrome. METHODS: From 1992 to 2016, 180 consecutive patients aged below 18 years with symptomatic WPW syndrome were included. After the exclusion of patients with non-descriptive electrocardiography (ECG), multiple APs, congenital heart diseases, non-inducible tachycardia, and those who received a second ablation, 104 patients were analyzed retrospectively. Surface ECG was obtained before ablation and evaluated by using previously documented algorithms, from which a new pediatric algorithm was developed. RESULTS: Previous algorithms were not highly accurate when used in pediatric patients with WPW syndrome. In the new algorithm, the R/S ratio of V1 and the polarity of the delta wave in lead I could distinguish right from the left side AP with 100% accuracy. The polarity of the delta wave of lead V1 could distinguish free wall AP from septal AP with an accuracy of 100% in left-side AP, compared to 88.6% in leads III and V1 for right-side AP. The overall accuracy was 92.3%. CONCLUSIONS: This simple, novel algorithm could differentiate left from right AP and septal from free wall AP in pediatric patients with WPW syndrome.

Signal-averaged electrocardiogram (SAECG) provides not only diagnostic information but also the prognostic implication of ablation in arrhythmogenic right ventricular cardiomyopathy (ARVC).This study aimed to validate the role of SAECG in identifying arrhythmogenic substrates requiring an epicardial approach in ARVC.Ninety-one patients with a definite diagnosis of ARVC who underwent successful ablation for drug-refractory ventricular arrhythmia were enrolled and classified into 2 groups: group 1 who underwent successful ablation at the endocardium only and group 2 who underwent successful ablation requiring an additional epicardial approach. The baseline characteristics of patients and SAECG parameters were obtained for analysis.Male predominance, worse right ventricular (RV) function, higher incidence of syncope, and depolarization abnormality were observed in group 2. Moreover, the number of abnormal SAECG criteria was higher in group 2 than in group 1. After a multivariate analysis, the independent predictors of the requirement of epicardial ablation included the number of abnormal SAECG criteria (odds ratio 2.8, 95% confidence interval 1.4-5.4; P = .003) and presence of syncope (odds ratio 11.7; 95% confidence interval 2.7-50.4; P = .001). In addition, ≥2 abnormal SAECG criteria were associated with larger RV endocardial unipolar low-voltage zone (P.001), larger RV endocardial/epicardial bipolar low-voltage zone/scar (P.05), and longer RV endocardial/epicardial total activation time (P.001 and P = .004, respectively).The number of abnormal SAECG criteria was correlated with the extent of diseased epicardial substrates and could be a potential surrogate marker for predicting the requirement of epicardial ablation in patients with ARVC.

BACKGROUND Telomere length is a biologic aging marker. This study investigated leukocyte telomere length (LTL) as a new biomarker to predict recurrence after paroxysmal atrial fibrillation (PAF) ablation.Methods and Results:A total of 131 participants (26 healthy individuals and 105 symptomatic PAF patients) were enrolled. PAF patients (54.1±10.8 years) who received catheter ablation therapy were divided into 2 groups: recurrent AF (n=25) and no recurrent AF after catheter ablation (n=80). Peripheral blood mononuclear cells were collected from all subjects to measure LTL. Under 50 years old, LTL in healthy individuals (n=17) was longer than in PAF patients (n=31; 7.34±0.58 kbp vs. 6.44±0.91 kbp, P=0.01). In PAF patients, LTL was positively correlated with left atrial bipolar voltage (R=0.497, P

Aims The stroke risk of patients with atrial fibrillation (AF) is not static, since AF patients get older and accumulate more comorbidities after AF is diagnosed. Therefore, the stroke risk of AF patients given certain comorbidities in different age strata should ideally be analysed using an assessment which considers incident comorbidities and the actual age when ischaemic stroke occurred. The goal of the present study is to report the age treatment thresholds for the use of non-vitamin K antagonist oral anticoagulants (NOACs) for AF patients without or with only one comorbidity of the CHA2DS2-VASc score, based on an ‘ideal method’ of stroke risk assessments. Methods and results The study cohort included 31 039 and 39 020 AF patients who did not have any or had only one risk factor comorbidity of the CHA2DS2-VASc score except for age and sex. The risks of ischaemic stroke in each age strata for each comorbidities were analysed in three ways, as follows: (i) the conventional way (based on baseline risk factors and age), (ii) dynamic method (patients were censored when new comorbidities occurred), and (iii) an ideal method (patients were censored when new comorbidities occurred and the stroke risk was related to the actual age when stroke happened). The tipping point for the use of NOACs was set at a stroke risk of 0.9%/year. The overall risk of ischaemic stroke using the conventional way was overestimated compared to the dynamic or ideal assessment with the incidence rate ratio of 1.24 for patients with hypertension, 1.20 for heart failure, 1.37 for diabetes mellitus, and 1.38 for vascular diseases; all P-values Conclusion Ischaemic stroke risk in AF is heterogeneous, depending on different risk factors with age being as an important driver of stroke risk. Age thresholds for the use of NOACs were different for AF patients having different single risk factors beyond sex despite the same CHA2DS2-VASc score point (1 for males and 2 for females); that is, 35 years for heart failure, 50 years for hypertension or diabetes, and 55 years for vascular diseases.

Background Acute failure of radiofrequency ablation (RFA) of ventricular arrhythmias (VAs) occur in 10%-20% of patients and is partly attributed to inadequate lesion depth acquired with standard ablation protocols. Half-normal saline (HNS)-irrigation is a promising strategy to improve the success rate of VA ablation. Objective This study investigated the efficacy of HNS-irrigated ablation after a failed standard plain normal saline solution (PNSS)-irrigated ablation on idiopathic outflow tract ventricular arrhythmia (OT-VA). Method This is a prospective observational study of consecutive patients undergoing RFA of idiopathic OT-VA comparing the efficacy of additional HNS-irrigated ablation for failed standard PNSS-irrigated ablation. Acute failure was defined as persistence of spontaneous VA or persistent inducibility of the clinical VA. Results Out of 160 OT-VA cases (51 ± 15-year-old, 62 males), 31 underwent HNS irrigation after a failed standard PNSS-irrigated ablation. The HNS group had a significantly longer procedure time (60.06 ± 43.83 vs 37.51 ± 33.40 minutes; P = .013) and higher radiation exposure (31.45 ± 20.24 vs 17.22 ± 15.25 minutes; P = .001) than the PNSS group but provided an additional acute success in 21 of 31 (67.7%) patients. Over a follow-up duration of 7.8 ± 4.6 months, 24 recurrences were identified, including 8 (25.8%) in the HNS and 16 (12.4%) in the PNSS group, with lower freedom from recurrence in the HNS group (log rank P = .009). No major complication was observed. Conclusion HNS-irrigated ablation after failed standard PNSS-irrigated ablation is safe and additionally improves acute ablation success by 67.7% for idiopathic OT-VA but with a higher rate of recurrence on follow-up. Whether the application of HNS as initial irrigant could result in better outcome requires further investigation.

Aims Both obesity and heart failure (HF) are associated with sudden cardiac death. The current study aimed to investigate the effects of overweight and HF on the substrate for ventricular fibrillation (VF), and whether renal denervation (RDN) can protect the heart from sympathetic activation and cardiac remodelling in HF rabbits fed with high-fat diet (HFD). Methods and results Twenty-four rabbits randomized into control group fed with regular diet (Control), HFD, HFD-HF, and HFD-HF-RDN groups. Rapid ventricular pacing of 400 b.p.m. for 4 weeks was applied in HFD-HF and HFD-HF-RDN. Surgical and chemical RDNs were approached through bilateral retroperitoneal flank incisions in HFD-HF-RDN. All rabbits received electrophysiological study and a VF inducibility test. The ventricular myocardium was harvested for trichrome stain. After 3 months, mean body weight was heavier in HFD, compared with control (3.5 ± 0.1 kg vs. 2.6 ± 0.1 kg, P Conclusion Our results suggest that overweight and HF increase sympathetic activity, structural remodelling, and VF inducibility, but RDN prevents them.

Background For patients with atrial fibrillation (AF) receiving cardiac implantable electronic device (CIED) implantations, current consensus recommends uninterrupted non-vitamin K antagonist oral anticoagulant (NOAC) considering low incidence of bleeding or thrombo-embolic events. It remains unknown whether uninterrupted strategy outweighs discontinuation method for patients receiving NOAC. Methods From January 1, 2013 to June 1, 2017, we enrolled 100 patients (mean age 78.3 ± 10.2 years, 58% male) with AF taking NOAC for stroke prevention eligible for CIED implantation in a tertiary medical center, Taipei, Taiwan. NOAC was continued without skipping any doses during the surgery. The baseline characteristics, underlying diseases, CHA2DS2-VASc score, and clinical course of every patient were reviewed and analyzed. Results Among these patients, 28 were on dabigatran, 61 on rivaroxaban, 10 on apixaban, and one on edoxaban, respectively. There were no adverse events except one case of pericardial effusion and another one with large pocket hematoma. One patient receiving implantable cardioverter defibrillator implantation had late onset of pericardial effusion with impending tamponade necessitating pericardiocentesis. Another patient had large pocket hematoma, which spontaneously resolved within 1 month without further intervention. No periprocedural mortality and stroke occurred. Conclusion Uninterrupted NOAC during CIED implantations may be an acceptable option especially in patients with high risk for thromboembolism. However, special caution should be paid during defibrillator implantation considering relatively higher risk of bleeding, perhaps due to the larger size of the defibrillator lead.

BACKGROUND The relationship between gastroesophageal reflux disease (GERD) and atrial fibrillation (AF) has been previously reported. However, the detailed mechanism remains unknown. In this study, we investigated the effects of acid reflux on the intrinsic cardiac autonomic nervous system, atrial/ventricular electrophysiology, and AF inducibility. METHODS Eighteen rabbits were randomized into three groups: acid reflux (group 1, n = 6), control (group 2, n = 6), and acid reflux with periesophageal vagal blockade (group 3, n = 6). Atrial and ventricular effective refractory periods (ERPs) and AF inducibility were checked at baseline and then hourly until 5 hours after the experiment. RESULTS Three hours after the experiment, atrial ERP prolongation was noted in groups 2 and 3 (P

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.

INTRODUCTION: Adjunctive driver-guided ablation in addition to pulmonary vein isolation has been proposed as a strategy to improve procedural success and outcomes for various populations with atrial fibrillation (AF). First, this study aimed to evaluate the different mapping techniques for driver/rotor identification and second to evaluate the benefits of driver/rotor-guided ablation in patients with paroxysmal and persistent AF (PerAF). METHODS: We searched the electronic database in PubMed using the keywords “atrial fibrillation,” “rotor,” “rotational driver,” “atrial fibrillation source,” and “drivers” for both randomized controlled trials and observational controlled trials. Clinical studies reporting efficacy or safety outcomes of driver-guided ablation for paroxysmal AF or (PerAF) were identified. We performed subgroup analyses comparing different driver mapping methods in patients with PerAF. The odds ratios (ORs) with random effects were analyzed. RESULTS: Out of 175 published articles, seven met the inclusion criteria, of which two were randomized controlled trials, one was quasiexperimental study, and four observational studies (three case-controlled studies and one cross-sectional study). Overall, adjunctive driver-guided ablation was associated with higher rates of acute AF termination (OR: 4.62, 95% confidence interval [CI]: 2.12–10.08; P < 0.001), lower recurrence of any atrial arrhythmia (OR: 0.44, 95% CI: 0.30–0.065; P < 0.001), and comparable complication incidence. CONCLUSIONS: Adjunctive driver-guided catheter ablation suggested an increased freedom from AF/AT relative to conventional strategies, irrespective of the mapping techniques. Furthermore, phase mapping appears to be superior to electrogram-based driver mapping in PerAF ablation.

Background Pulmonary vein isolation (PVI) is commonly performed in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (PAF). However, the very long-term follow-up result is limited. Objective We aimed to investigate 10-year ablation outcomes in patients with PAF and long-term follow-up results after PVI. Methods This study retrospectively enrolled 176 (131 men, mean age 51.2 ± 12.1 years) patients with drug-refractory symptomatic PAF who underwent electroanatomic-guided PVI. Ten-year follow-up was completed using medical records or telephonic interviews. Procedural characteristics at index procedures and long-term clinical outcomes were investigated. Results After a mean follow-up period of 130.0 ± 10.8 months, sinus rhythm was achieved in 102 (58%) patients after a single procedure (including 14 (8%) patients on antiarrhythmic medications) and in 88% patients after multiple procedures (including 17 (10%) patients on antiarrhythmic medications). Left atrial diameter (odds ratio 1.067; 95% confidence interval 1.009–1.127; P = .023) was the predictor of recurrent atrial tachyarrhythmia after a single ablation procedure. The single-procedure recurrence-free rates were similar between circumferential PVI and segmental PVI (59% and 50%; log-rank, P = .251). The recurrence patterns of both groups regarding the role of non–pulmonary vein and pulmonary vein triggers were similar. Conclusion The single-procedure long-term efficacy was modest, with freedom from atrial fibrillation at 10 years being 58%. Those who had enlarged left atrial diameters have more atrial tachyarrhythmia recurrences. Ten-year single-procedure outcomes of the effects of circumferential PVI and segmental PVI in patients with PAF were similar.

Pulmonary veins (PVs) are a major source of ectopic beats that initiate AF. PV isolation from the left atrium is an effective therapy for the majority of paroxysmal AF. However, investigators have reported that ectopy originating from non-PV areas can also initiate AF. Patients with recurrent AF after persistent PV isolation highlight the need to identify non-PV ectopy. Furthermore, adding non-PV ablation after multiple AF ablation procedures leads to lower AF recurrence and a higher AF cure rate. These findings suggest that non-PV ectopy is important in both the initiation and recurrence of AF. This article summarises current knowledge about the electrophysiological characteristics of non-PV AF, suitable mapping and ablation strategies, and the safety and efficacy of catheter ablation of AF initiated by ectopic foci originating from non-PV areas.

Predictors of AF Progression After AblationIntroduction Although rare, some paroxysmal atrial fibrillations (AF) still progress despite radiofrequency (RF) ablation. In the study, we evaluated the long-term efficacy of RF ablation and the predictors of AF progression. Methods A total of 589 paroxysmal AF patients (404 men and 185 women; aged 54 ± 12 years) who received 3-dimensional mapping and ablation were enrolled. Their clinical parameters and electrophysiological characteristics were collected. They were divided into Group 1 (N = 13, with AF progression) and Group 2 (N = 576, no AF progression). AF progression was defined as recurrence of persistent AF. Results Group 1 patients had larger left atrial (LA) diameter, larger left ventricle (LV) end-systolic and end-diastolic diameters, poorer LV systolic function, and more amiodarone use at baseline. After 1.2 ± 0.5 procedures, 123 (21%) patients experienced recurrence during 56 ± 29 months’ follow-up. In the multivariate analysis, LA diameter (P = 0.018, HR = 1.12, 95% CI = 1.02–1.24) and LV end-systolic diameter (P = 0.005, HR = 1.10, 95% CI = 1.03–1.17) independently predicted AF progression. LA diameter >43 mm and LV end-systolic diameter >31 mm were the best cut-off values for predicting AF progression by ROC analysis. AF progression rate achieved 19% if they had both larger LA diameter (>43 mm) and LV end-systolic diameter (>31 mm). Conclusion RF ablation prevents the progression of paroxysmal AF effectively, except in patients with increased LA diameter and LV end-systolic diameter on echocardiogram, suggesting more aggressive rhythm control therapies should be considered in these patients.

Objectives This prospective study compared the efficacy of atrial substrate modification guided by a nonlinear phase mapping technique with that of conventional substrate ablation. Background The optimal ablation strategy for persistent atrial fibrillation (AF) was unknown. Methods In phase 1 study, we applied a cellular automation technique to simulate the electrical wave propagation to improve the phase mapping algorithm, involving analysis of high-similarity electrogram regions. In addition, we defined rotors and focal AF sources, using the physical parameters of the divergence and curvature forces. In phase 2 study, we enrolled 68 patients with persistent AF undergoing substrate modification into 2 groups, group-1 (n = 34) underwent similarity index (SI) and phase mapping techniques; group-2 (n = 34) received complex fractionated atrial electrogram ablation with commercially available software. Group-1 received real-time waveform similarity measurements in which a phase mapping algorithm was applied to localize the sources. We evaluated the single-procedure freedom from AF. Results In group-1, we identified an average of 2.6 ± 0.89 SI regions per chamber. These regions involved rotors and focal sources in 65% and 77% of patients in group-1, respectively. Group-1 patients had shorter ablation procedure times, higher termination rates, and significant reduction in AF recurrence compared to group-2 and a trend toward benefit for all atrial arrhythmias. Multivariate analysis showed that substrate mapping using nonlinear similarity and phase mapping was the independent predictor of freedom from AF recurrence (hazard ratio: 0.26; 95% confidence interval: 0.09 to 0.74; p = 0.01). Conclusions Our study showed that for persistent AF ablation, a specified substrate modification guided by nonlinear phase mapping could eliminate localized re-entry and non-pulmonary focal sources after pulmonary vein isolation.

Background and Purpose— The age threshold for an increased stroke risk for patients with atrial fibrillation may be different for Asians and non-Asians. We hypothesized that a modified CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65–74 years, female) scheme, mCHA 2 DS 2 -VASc, which assigned one point for patients aged 50 to 74 years, may perform better than CHA 2 DS 2 -VASc score for stroke risk stratification in Asians. Methods— This study used the Taiwan National Health Insurance Research Database, which included 224 866 newly diagnosed atrial fibrillation patients. The predictive accuracies of ischemic stroke of CHA 2 DS 2 -VASc and mCHA 2 DS 2 -VASc scores were compared among 124 271 patients without antithrombotic therapies. From the whole cohort, 15 948 patients had a CHA 2 DS 2 -VASc score 0 (males) or 1 (females), and 8654 patients had an mCHA 2 DS 2 -VASc score 1 (males) or 2 (females). The latter were categorized into 3 groups, that is, no treatment, antiplatelet therapy, and warfarin, and the risks of ischemic stroke and intracranial hemorrhage (ICH) were compared. Results— During a follow-up of 538 653 person-years, 21 008 patients experienced ischemic stroke. The mCHA 2 DS 2 -VASc performed better than CHA 2 DS 2 -VASc score in predicting ischemic stroke assessed by C indexes and net reclassification index. For 8654 patients having an mCHA 2 DS 2 -VASc score of 1 (males) or 2 (females) because of the resetting of the age threshold, use of warfarin was associated with a 30% lower risk of ischemic stroke and a similar risk of ICH compared with nontreatment. Net clinical benefit analyses also favored the use of warfarin in different weighted models. Conclusions— In this Asian atrial fibrillation cohort, the mCHA 2 DS 2 -VASc score performed better than the CHA 2 DS 2 -VASc and would further identify atrial fibrillation patients who may derive a positive net clinical benefit from oral anticoagulation.

Collateral damage to periesophageal vagal plexus associated with symptomatic gastric hypomotility and associated symptoms are not uncommon after catheter ablation of atrial fibrillation (AF). The injury may indicate transmural ablation lesions.The purpose of this study was to evaluate the periesophageal vagal plexus injury (PNI) and long-term outcome after catheter ablation of AF.A total of 441 consecutive patients with AF (mean age 54.71 ± 10.52 years; 134 women) who underwent catheter ablation (paroxysmal AF, n = 312; persistent AF, n = 129) were retrospectively enrolled from 2011 to 2013; group 1 was defined as patients with PNI and associated symptoms (n = 88), and group 2 was defined as patients without PNI or associated symptoms (n = 353). Baseline characteristics and electrophysiological properties were collected to analyze the relationship between PNI and clinical outcome. The association of AF recurrence after catheter ablation and PNI symptoms was also investigated.During a mean follow-up period of 37.3 ± 0.94 months, group 1 had longer AF-freedom days in sinus rhythm after AF ablation and had less recurrence after the blanking period compared with group 2 (mean recurrence days, 1254.22 ± 45.26 days vs 1065.21 ± 33.35 days; P.01). Multivariate analysis also revealed that PNI was an independently protective predictor of AF recurrence (hazard ratio 0.527; 95% confidence interval 0.289-0.959; P = .036). There was no difference in baseline characteristics, CHA2DS2-VASc score, or echocardiography follow-up duration.PNI and associated symptoms are not uncommon after catheter ablation of AF. A better long-term outcome is thereby independently predicted, suggesting transmural ablation lesions during pulmonary vein isolation.

Background Ventricular arrhythmia originating from the papillary muscle (VA-PM) is characterized by multiple exits and morphologic alternations. The conventional ablation strategy relies on activation mapping, but the results might be suboptimal. Objective The purpose of this study was to propose a novel pacemapping strategy aimed at multiple exits using high-output software as a complementary approach to the conventional strategy. Methods A consecutive 13 patients with VA-PM were enrolled in this study. Novel pacemapping based on an automatic matching algorithm and integrated electroanatomic mapping was used to quantify the morphology variation in these patients and to identify the potential exits of VA-PM. Complementary ablation targeting at the best matching site of each morphology was performed. Results Twelve of 13 patients (92%) experienced morphologic alternation, and a total of 34 morphologies were detected (2.6 ± 1.0 per patient). A total of 23 (68%) morphologies were detected as spontaneous pleomorphic ventricular premature complexes (VPCs) before procedure, and 4 morphologies (12%) were induced under isoproterenol infusion. Another 7 of 34 morphologies (21%) could be found only after radiofrequency ablation attempts. Exits with a high pacemapping correlation index for corresponding morphology would be mapped, so preferential exits could be identified. Mean interexit distance was 15.1 ± 5.9 mm. Acute success rate was 100%. During mean follow-up of 12.2 ± 6.9 months, only 1 case recurred with ventricular tachycardia. Although 3 cases recurred with different VPC morphologies, the VPC burden decreased from 16.3% ± 8.8% to 2.6% ± 1.7%. Conclusion This novel pacemapping strategy could effectively eliminate multiple exits as a complementary approach to the conventional strategy.

Atrial fibrillation (AF) can be associated with an increased risk of developing coronary artery disease (CAD) due to mechanisms of inflammation, endothelial dysfunction and adverse atrial remodelling. It is unclear if adverse coronary events can be further reduced after successful catheter ablation of AF. We hypothesise that AF ablation and sinus maintenance could reduce future adverse cardiac events in patients with underlying CAD.A total of 310 patients with drug-refractory paroxysmal AF and prior history of percutaneous coronary intervention (PCI) for underlying CAD were recruited in the retrospective case control study. Of these, 155 patients underwent AF ablation (the Ablation Group), while 155 patients received medical treatment (the Medical Group). All patients were followed up for major adverse cardiac events, including acute coronary syndrome requiring hospitalisation, stroke, pulmonary embolism and mortality.The clinical characteristics were comparable between the two groups, except for higher antiarrhythmic drug use in the Medical Group. During a follow-up duration of 61±32 months, all-cause mortality (8.4% vs. 1.3%, p=0.004) and the overall major adverse events (47.7% vs. 12.3%, p0.001) were significantly higher in the Medical Group than the Ablation Group. There were also more instances of stroke (10.3% vs. 3.2%, p=0.013) and acute coronary syndrome requiring hospitalisation (29% vs. 7.1%, p0.001) in the Medical Group than the Ablation Group. Multivariate analysis confirmed that non-ablation was an independent risk factor for major adverse events (p0.001, HR 3.4, 95% confidence interval 1.9-5.9).In PAF patients with established CAD who underwent PCI, catheter ablation could lead to fewer major adverse cardiac events compared to medical therapy.

Special circumstances may require the measurement of the anticoagulant effect of dabigatran etexilate. No data currently link any given coagulation test to bleeding outcomes in patients receiving dabigatran etexilate for atrial fibrillation. Nonvalvular atrial fibrillation patients receiving dabigatran etexilate of 110 mg (DE110) or 150 mg (DE150) were consecutively enrolled. The hemoclot thrombin inhibitor (HTI) assay, prothrombin time, and activated partial thromboplastin time (APTT) measurements were correlated with bleeding events during a prospective follow-up. There were 17 bleeding events (8.2%) in 208 patients (74.7 ± 10.3 years old, 67.9% male, median follow-up: 364 days), whereas 15 patients with bleeding events used DE110. Compared with DE110, the patients receiving DE150 were younger and more often male and had lower HAS-BLED and CHA2DS2VASc scores and better renal function. Patients' HTI levels were very variable (DE110, 10-90th percentile: 20.5-223.9 ng/ml). A receiver-operator characteristic curve gave a median cutoff HTI level of 117.7 ng/ml to predict bleeding events (C-statistics: 0.65; P = 0.036), but no cutoff could be determined for prothrombin time or APTT. Based on the Kaplan-Meier analysis, a dabigatran etexilate level greater than 117.7 ng/ml was associated with a higher bleeding rate (15.4% vs. 4.9%, P = 0.01). After multivariate Cox regression analysis, HTI levels, history of stroke, and male sex were independent risk factors for bleeding events. Dabigatran etexilate-HTI levels were independently associated with bleeding in patients receiving routine clinical care. Blood sampling at multiple time points might be needed to increase reliability because of high variation of dabigatran etexilate-HTI levels.

Background Radiofrequency ablation of ventricular arrhythmias (VAs) originating from the continuum between the aortic sinus of Valsalva (ASV) and the left ventricular (LV) summit is a challenge. Objectives The objectives of this study were to investigate the electrocardiographic, electrophysiological, and anatomical characteristics of VAs and to develop an algorithm for predicting the successful ablation site. Methods We recruited 66 patients (mean age, 47 ± 15 years; 42 male patients) with symptomatic VAs originating from the continuum between the ASV and the LV summit who underwent radiofrequency ablation. Patients were classified into 4 groups (group 1: ASV, n=20; group 2: subvalvular region, n=15; group 3: great cardiac vein/anterior interventricular vein [GCV/AIV], n=16; group 4: epicardium requiring pericardial access, n=15). The QRS morphological characteristics of VAs were compared between the 4 groups. Results Electrocardiographic analysis revealed that the aVL/aVR Q-wave ratio is useful in the prediction of successful ablation sites in the ASV, subvalvular area, GCV/AIV, and epicardium requiring pericardial access at cutoff values of ≤1.415, 1.416–1.535, 1.536–1.740, and >1.740, respectively. The aVL/aVR Q-wave ratio was well correlated with the distance between the successful ablation site and the tip of the LV summit. A distance of >18.9 mm and an LV myocardial thickness of >9.1 mm predicted the need for the epicardial or GCV/AIV approaches. There were no major procedural complications. Eight patients (12.1%) developed VA recurrence during a mean follow-up of 15.9 months (interquartile range 9.2–24.2 months). Conclusion The aVL/aVR Q-wave ratio is a useful parameter for predicting the successful ablation sites of VAs originating from the continuum between the ASV and the LV summit.

Objective: It remains unknown whether catheter ablation for atrial fibrillation (AF) reduces future acute coronary syndrome (ACS) risk or whether the CHA2DS2-VASc score has a role in predicting this risk. We aimed to compare very long-term risk of ACS between patients who received catheter ablation to AF or antiarrhythmic medications and controls without AF. Methods: Propensity scores were calculated for each patient and used to assemble a cohort of 787 patients undergoing AF ablation in 2003–2012. Patients were compared to an equal number of AF patients treated with antiarrhythmic medications and a control group without AF. Patients with previous coronary events were excluded. The primary endpoint was ACS occurrence. Results: Baseline clinical characteristics were comparable. After a mean 9.1 ± 3.2-year follow-up, the ablation group had lower incidence of new onset ACS than the medication and non-AF control groups (annual incidence: 0.15%. 0.78%, and 0.35%; with 2.67, 4.16, and 10.44 cases/1000 person-years, respectively; P

This cohort study in Taiwan compares the clinical outcomes of warfarin use and non–vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation with a history of intracranial hemorrhage using a nationwide cohort with atrial fibrillation., Key Points Question Are non–vitamin K antagonist oral anticoagulants (NOACs) associated with greater clinical benefit than warfarin sodium among patients with atrial fibrillation with a history of intracranial hemorrhage? Findings In this cohort study, 4540 patients were identified with prior intracranial hemorrhage who received warfarin or NOACs. The use of NOACs was associated with statistically significantly lower rates of all-cause mortality, intracranial hemorrhage, and major bleeding compared with the use of warfarin, whereas the rate of ischemic stroke was similar in the 2 groups. Meaning Among patients with atrial fibrillation with prior intracranial hemorrhage, NOACs could be the preferred choice for stroke prevention., Importance Current guidelines recommend the use of non–vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in patients with atrial fibrillation (AF). Data regarding warfarin sodium use compared with NOAC use in patients with AF with a history of intracranial hemorrhage (ICH) are limited. Objective To compare the clinical outcomes of warfarin use and NOAC use in patients with AF with a history of ICH using a nationwide cohort with AF. Design, Setting, and Participants A nationwide cohort study from January 1, 2012, to December 31, 2016, was performed using data from the Taiwan National Health Insurance Research Database. The dates of analysis were July 1 to September 1, 2019. The study population comprised patients with AF with a history of ICH and a CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥75 years [doubled], diabetes, prior stroke/transient ischemic attack/thromboembolism [doubled], vascular disease [prior myocardial infarction, peripheral artery disease], age 65-74 years, sex category [female]) of at least 1 for men or at least 2 for women who had received warfarin or NOACs. The clinical outcomes were examined using Cox proportional hazards regression analyses among the study population before and after propensity score matching. Exposures Oral anticoagulation with warfarin or NOACs. Main Outcomes and Measures The clinical outcomes measured were all-cause mortality, ischemic stroke, ICH, major bleeding, and adverse events. Results The study cohort included 4540 patients (mean [SD] age, 76.0 [10.5] years; 2653 men [58.4%]), with 1047 patients receiving warfarin (mean [SD] age, 75.1 [11.4] years; 571 men [54.5%]) and 3493 patients receiving NOACs (mean [SD] age, 76.3 [10.2] years; 2082 men [59.6%]). Compared with warfarin use, NOAC use was associated with statistically significantly lower risk of all-cause mortality (adjusted hazard ratio [aHR], 0.517; 95% CI, 0.457-0.585), ICH (aHR, 0.556; 95% CI, 0.389-0.796), and major bleeding (aHR, 0.645; 95% CI, 0.525-0.793), whereas the rate of ischemic stroke was similar in the 2 groups (aHR, 0.879; 95% CI, 0.678-1.141). These results were generally consistent after propensity score matching among 973 patients in each group. Conclusions and Relevance Among patients with AF with prior ICH, NOAC use was associated with lower rates of ICH and major bleeding compared with warfarin use, whereas the rate of ischemic stroke was similar in the 2 groups. Among patients with AF with prior ICH, NOACs could be the preferred choice for stroke prevention.

Aims Most left atrial tachycardia (LAT) is associated with atrial fibrillation (AF). The clinical and electrophysiological characteristics and outcomes of LAT without AF have not been investigated. This study sought to determine the long-term ablation outcomes and predictors of recurrence of isolated LAT. Methods This is a single-center study of consecutive patients with isolated LAT. Atrial arrhythmia recurrence was determined from follow-up records of patients who underwent LAT ablation from 2008 to 2017. Clinical and electrophysiologic characteristics associated with atrial arrhythmia recurrence were identified. Results A total of 50 patients (53 ± 19 years, 46% male) with 59 LAT (1.16 ± 0.47 per patient) were enrolled. Over a mean follow-up of 37 ± 33 months, atrial arrhythmia recurrence occurred in 22 (44%) patients, 11 with atrial tachycardia (AT) only, five with AF only, and six with concurrent AT and AF. The incidence of pulmonary vein (PV) origins increased significantly in the repeat procedure (P = 0.036). Multivariate analysis identified left ventricular ejection fraction (LVEF) as the only predictor of any atrial arrhythmia recurrence and LAT recurrence, while smoking and identified macroreentrant LAT in the index procedure predicted AF recurrence. Conclusion This study demonstrated a higher rate of atrial arrhythmia recurrence, including AF, among patients with initially isolated LAT. A lower LVEF predicted any atrial arrhythmia and LAT recurrence, whereas smoking and index macroreentrant AT mechanism predicted long-term AF. PV ATs were frequently observed in recurrent patients irrespective of index procedure origin.

J wave syndrome and myocardial ischemia are related with malignant ventricular arrhythmia (VA). The characteristics of dynamic J wave in patients with early phase of acute myocardial infarction (AMI) and subsequent VA or electrical storm (ES) have not been well evaluated.We investigated the utility of J wave in the prediction of VA and ES in patients within the early phase of AMI.This study retrospectively enrolled 208 patients (mean age 69±15 years, 171 males) with AMI. Of them, 50 patients had experienced VA during hospitalization and 24 had ES. The clinical and electrocardiographic characteristics of these patients with and without VA were compared.Patients with VA had a higher incidence of chronic kidney disease (CKD) and J wave compared with those without VA. The hazard ratio (HR) of J wave for VA was 4.31 (p0.01) and CKD was 2.64 (p0.01). In the VA group, ES patients had a higher incidence of diabetes mellitus (DM) (HR 2.73, p=0.02) and J wave (HR 4.21, p0.01). If the AMI patients had J wave, the OR for mortality was 2.14 (p=0.03), VA events was 6.23 (p0.01), and ES events was 12.15 (p0.01). If VA patients had J wave, the mortality rate will significantly increase (OR 68.62, p=0.01).The AMI patients who develop VA in the early phase of AMI had a higher incidence of J wave and CKD, and those who develop ES had a higher incidence of J wave and DM. It seems that J wave in AMI patients is a poor prognostic factor, and we found that J wave will increase mortality, VA events, and ES events. The majority locations of J wave were inferior leads although there was no relationship between the locations and VA incidence. If the VA patients had inferior or lateral J wave, it would further increase the risk of mortality.

BACKGROUND The reason for recurrence of ventricular arrhythmia (VA) after catheter ablation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is not clear. METHODS In this study, 91 ARVC patients (age, 47 ± 13 years; 47 men) who underwent catheter ablation for drug-refractory ventricular arrhythmia (VA) were enrolled. The patients were categorized into single or multiple procedures (n = 28). The baseline characteristics and electrophysiological features of the patients were examined to elucidate the reason of the VA recurrences. RESULTS A total of 186 VAs were induced during the index procedure and 176 (94.6%) were eliminated. Successful, partially successful, and failed ablations were achieved in 89.0%, 8.8%, and 2.2% of the patients, respectively. During a mean follow-up period of 32 ± 26 months, 35 patients had VA recurrences. Forty-two repeat procedures were performed for 81 induced VAs in 28 patients. Of the 42 repeat procedures, successful, partially successful, and failed ablations were achieved in 37, 4, and 1 of the procedures, respectively. Most of the recurrent VAs (70 [72.9%]) originated from the newly-developed circuits owing to the scar progression. The patients with repeat procedure had worsening right ventricular remodeling. The multivariate analysis revealed that history as endurance athlete significantly predicted the need of a repeat procedure in spite of the initially successful endocardial/epicardial ablation and negative inducibility (hazard ratio: 3.014, 95% confidence interval: 1.493-6.084, P = 0.002). CONCLUSIONS In spite of the initial complete VA elimination, history as an athlete was associated with scar progression, RV remodeling, and VA recurrences from the newly developed arrhythmogenic substrates/circuit in ARVC.

Background Ambient fine particulate matter (PM2.5) exposure is associated with increased cardiovascular and cardiac arrhythmias events, but the detailed mechanism remains unclear. Objective We aimed to investigate the effect of PM2.5 (particulate matter Method Among 6912 patients who had underwent 24-hour Holter ECG recordings between Oct 1st 2015 and Oct 31st 2016, 46 (25 males, 69.3 ± 12.1 years old) were enrolled with confirmation of living in an environment with a reported PM2.5 level and were classified as elevated (Group 1, >36 μg/m3, 50.73 ± 8.50) or low (Group 2, Result The baseline characteristics including the comorbidities and medications were similar between the 2 groups. The Holter ECG parameters were also similar. There were no significant HRV differences between the two groups for the 24-hour interval analysis. However, the LF/HF ratio was significantly higher in Group 1 than Group 2 in the 9 am to 9 pm (p = 0.028), 8 am to 4 pm (p = 0.024), and 4 pm to 12 pm (p = 0.025) periods, respectively, but not for the nocturnal HRV parameters. Conclusion Our study demonstrated that an elevated PM2.5 exposure had a significant association with an increased daytime LF/HF ratio suggesting a diurnal difference in the response to PM2.5 exposure.

Background Long‐term cardiovascular risk in patients with intermediate pauses remains unclear. Whether asymptomatic patients with intermediate pauses have increased future cardiovascular events remains unknown. We hypothesize that intermediate pause is associated with increased cardiovascular risk and mortality. Methods and Results We retrospectively analyzed 5291 patients who have pauses of am –8:00 pm ), nighttime pause (8:00 pm –8:00 am ), and daytime plus nighttime pause groups depending on the occurring time of the pauses. The rest of the patients (pause P =0.008) and daytime plus nighttime pause (hazard ratio, 2.26; P =0.016) patients have a higher mortality rate than that in nighttime pause. Conclusions Patients with intermediate pause are associated with increased cardiovascular risk. Intermediate pauses occurring at daytime have a higher mortality rate than that at nighttime during long‐term follow‐up.

Sudden cardiac death (SCD), the most devastating manifestation of ventricular arrhythmias (VAs), is the leading cause of mortality in patients with atrial fibrillation (AF). We hypothesized that the CHA

Background We aimed to investigate the impact of interleukin (IL)-17 on ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an ischemic heart failure (HF) model. The expression of the proinflammatory cytokine IL-17 is upregulated during myocardial ischemia and plays a fundamental role in post-infarct inflammation. However, the influence of IL-17 on the genesis of VA has not yet been studied. Methods and results The level of inflammation and Th17 cell (CD4+IL-17+) expression in the rabbit model of ischemic HF were studied by flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute and chronic administration of IL-17 was determined using electrophysiological techniques and optical mapping. The expression of IL-17 target genes and related cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA, and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner. IL-17 decreased conduction velocity, lengthened action potential duration, and increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment led to fibrosis, collagen production and apoptosis in the LV. Furthermore, increased IL-17 signaling activated mitogen-activated protein kinase and increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1. An anti-IL-17 neutralizing antibody abolished the effects of IL-17. Conclusions The expression of IL-17 and its downstream target genes may play fundamental roles in inducing VA in ischemic HF.

In spite of several proposed predictors for premature ventricular complex (PVC)-induced cardiomyopathy (PVC-CMP), the specific ECG features of idiopathic right ventricular outflow tract (RVOT) PVC-CMP remain unknown.A total of 130 patients (49 males, mean age 44 years) with symptomatic and drug-refractory idiopathic RVOT PVCs undergoing radiofrequency catheter ablation (RFCA) were enrolled. The patients were categorized into two groups, including those with and without RVOT PVC-CMP (left ventricular ejection fraction (LVEF) 50%, n = 25 and LVEF ≥ 50%, n = 105, respectively). The 12-lead PVC morphologies were assessed.Patients with RVOT PVC-CMP had a lower LVEF (42 ± 5% vs. 60 ± 7%, P 0.01) and higher PVC burden (24 ± 14% vs. 15 ± 11%, P = 0.02) when compared to patients without RVOT PVC-CMP. The PVC features in those with PVC-CMP displayed a significantly wider QRS duration (143 ± 14 ms vs. 132 ± 17 ms, P 0.01) and higher peak deflection index (PDI; 0.60 ± 0.07 vs. 0.55 ± 0.08, P 0.01). A multivariate analysis demonstrated that the QRS duration (odds ratio (OR) 1.130, 95% confidence interval (CI) 1.020-1.253, P = 0.02) and PDI (OR 1.240, 95% CI 1.004-1.532, P = 0.04) were independently associated with RVOT PVC-CMP. Based on the receiver-operating characteristic analysis, a QRS duration 139 ms and PDI 0.57 could predict RVOT PVC-CMP (area under the curve (AUC) 0.710 and AUC 0.690, respectively). The elimination and suppression of PVCs by RFCA resulted in the recovery of the LVEF in RVOT PVC-CMP.The ECG parameters, including a wider QRS duration and higher PDI, could predict the development of RVOT PVC-CMP, which could be effectively treated by RFCA.

Background Myocardial infarction increases the risk of heart failure ( HF ) and atrial fibrillation. Renal denervation ( RDN ) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction. Methods and Results HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF ‐ RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF ‐ RDN . Left anterior descending coronary artery in HF and HF ‐ RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real‐time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF ‐ RDN by echocardiography compared with HF . Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF ‐ RDN compared with HF . The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, Kv LQT 1, phosphoinositide 3‐kinase, AKT , and endothelial nitric oxide synthase in HF ‐ RDN were significantly higher compared with HF . The effective refractory period and action potential duration of HF ‐ RDN were significantly shorter compared with HF . Decreased atrial fibrillation inducibility was noted in HF ‐ RDN compared with HF (50% versus 100%, P Conclusions RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3‐kinase/ AKT /endothelial nitric oxide synthase signaling pathway.

Background Ventricular tachycardia (VT) and ventricular premature complexes (VPCs) originating from the right ventricular outflow tract (RVOT) are generally considered as benign arrhythmias, with ECG morphology showing LBBB pattern and inferior axis. Pathogenic mechanisms in the genesis of RVOT VT/VPC remain largely unknown. We aimed to investigate the neural mechanism in RVOT ventricular arrhythmias in canine model. Methods Twelve mongrel dogs (13.7 ± 1.3 kg, 5 male dogs) were studied through midline thoracotomies. High-frequency stimulation (HFS) was applied to the proximal pulmonary artery (PA) to induce RVOT VT/VPC. An EnSite Array and a mapping catheter were used for electroanatomical mapping. The RVOT and PA were surgically excised for immunohistochemistry studies, including tyrosine hydroxylase (TH) stain for sympathetic nerves and choline acetyltransferase (ChAT) stain for parasympathetic nerves. Results In nine (75%) out of twelve dogs, HFS of the proximal PA induced RVOT VT/VPC. The density of TH-positive nerves was significantly higher than that of ChAT-positive nerves (6803 ± 700 vs. 670 ± 252 μm2/mm2, p Conclusions HFS of the proximal PA could induce RVOT VT/VPC. The sympathetic nerves were densely innervated to the origin of RVOT VT/VPC, indicating the critical role of sympathetic hyperactivity in the initiation and perpetuation of RVOT VT/VPC.

The detailed electrophysiological characteristics of patients with both atrioventricular nodal re-entrant tachycardia (AVNRT) and atrial flutter (AFL) have not been clarified. This study investigated the related electrophysiological differences in a large series of patients undergoing radiofrequency catheter ablation of AVNRT.A total of 1063 clinically documented AVNRT patients underwent catheter ablation were enrolled. Before the slow pathway (SP) ablation, 61 patients (5.7%) had inducible sustained cavotricuspid isthmus (CTI)-dependent AFL (Group 1), and the others (94.3%) without inducible sustained CTI-dependent AFL were defined as Group 2. The electrophysiological characteristics of these two groups and effect of the SP ablation on the inducibility of AFL were assessed. In Group 1, 36 patients (59%) had inducible/sustained AFL after the ablation of AVNRT and required a CTI ablation. The Group 1 patients had more AVNRT with continuous atrioventricular (AV) node function curves (P0.001, odds ratio = 7.55 [3.70-16.7], multivariate regression), and a younger age (P = 0.02, odds ratio = 1.02 [1.003-1.03], multivariate regression) than Group 2. The other characteristics were comparable between the two groups. The long-term follow-up (64.9 ± 34.9 months) revealed that the recurrence of AFL/atrial fibrillation was similar between the two groups (P0.05).Atrioventricular nodal re-entrant tachycardia patients with concomitant CTI-dependent AFL had more continuous AV node function curves. Forty-one per cent of these patients had non-inducible AFL after the SP ablation, indicating a slow conduction isthmus in the triangle of Koch area.

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 Recent studies from Asia have suggested that the risk of ischemic stroke for patients with atrial fibrillation (AF) with a “low-risk” congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74, female (CHA2DS2-VASc) score of 0 (for males) or 1 (for females) might be higher than that for non-Asians. Objectives This study hypothesized that the age threshold (65 years) used in the CHA2DS2-VASc system for initiating oral anticoagulants (OACs) might be lower in Taiwanese AF patients than in non-Asians. Methods We used the National Health Insurance Research Database in Taiwan to study 186,570 nonanticoagulated AF patients. There were 9,416 males with a CHA2DS2-VASc score of 0 and 6,390 females with a CHA2DS2-VASc score of 1. Their risk of ischemic stroke was analyzed with stratification on the basis of age. Results The annual risks of ischemic stroke for males (score 0) and females (score 1) were 1.15% and 1.12%, respectively, and continuously increased from younger to older age groups, with an increment in stroke risk evident for patients >50 years of age. At a cutoff of 50 years, patients could be further stratified into 2 subgroups with different stroke risks (>50 years of age: 1.78%/year; vs. Conclusions For Taiwanese patients 50 to 64 years of age, the annual stroke risk was 1.78%, which may exceed the threshold for OAC use for stroke prevention. The annual risk of ischemic stroke for AF patients

Characteristics of Multiple AF Ablation Procedures Background The recurrence of atrial fibrillation (AF) is not uncommon in the era of catheter ablation. This study aimed to evaluate the characteristics of AF patients who underwent multiple (>2) ablation procedures. Methods and Results Of 666 consecutive patients (53 ± 11 y/o, 484 men) who underwent catheter ablation of AF (paroxysmal AF, n = 530), 144 (22%) underwent 2 procedures and 52 (8%) underwent more than 2 procedures due to symptomatic recurrences refractory to medication during 48 ± 23 months of follow-up. Baseline and procedural characteristics at the index procedure were investigated to determine their impact on the necessity of multiple procedures. After 2 procedures, 48 (92%) of 52 patients had pulmonary vein (PV) ectopic beats initiating AF. Coexisting PV and non-PV triggers were found in 23 of 48 patients. In a multivariate analysis, the presence of non-PV triggers (P = 0.004; odds ratio 2.69, 95% CI 1.37–5.28) at the index procedure was the only independent predictor of necessary multiple procedures. Among patients with non-PV ectopic beats initiating AF at the index procedure, the presence of ligament of Marshall triggers (P = 0.001, odds ratio 6.74, 95% CI 2.13–21.32) could predict the necessity of multiple procedures. Conclusions The need for multiple catheter ablation procedures can be predicted by the presence of non-PV ectopic beats initiating AF at the index procedure. However, PV-initiated AF remains the major cause of AF recurrence despite multiple catheter ablation procedures.

Hyperthyroidism is a known reversible cause of atrial fibrillation (AF). However, some patients remain in AF despite restoration of euthyroid status.The purpose of this study was to compare the electrophysiologic characteristics and long-term ablation outcome in AF patients with and without history of hyperthyroidism.The study enrolled 717 consecutive patients with AF who underwent first AF ablation, which involved pulmonary vein (PV) isolation in paroxysmal AF and additional substrate modification in nonparoxysmal AF patients. Eighty-four patients (12%) with hyperthyroidism history were compared to those without. Euthyroid status was achieved for ≥3 months before ablation in hyperthyroid patients.Patients with hyperthyroid history were associated with older age, more female gender, lower mean right atrial voltage, higher number of PV ectopic foci (1.3 ± 0.4 vs 1.0 ± 0.2, P.01), and higher prevalence of non-PV foci (42% vs 23%, P.01). Ectopic foci from ligament of Marshall were demonstrated more often in hyperthyroid patients (7.1% vs 1.6%, P.01) in whom alcohol ablations were required. After propensity score matching for potential covariates, history of hyperthyroidism was an independent predictor of AF recurrence after single procedure (hazard ratio 2.07, 95% confidence interval 1.27-3.38). AF recurrence rates after multiple procedures were not different between patients with and those without hyperthyroid history.Patients with hyperthyroid history had a significantly higher number of PV ectopies and higher prevalence of non-PV ectopic foci compared to euthyroid patients, which resulted in a higher AF recurrence rate after a single procedure.

Atrial fibrillation (AF) is prevalent in end-stage renal disease (ESRD) patients and negatively impacts patient outcomes. We explored the incidence and risk factors for new-onset AF among patients with ESRD undergoing renal replacement therapy, without a prior history of AF, retrieved from Taiwan’s National Health Insurance Research Database (NHIRD). For each of 134,901 patients with ESRD, one age- and gender-matched control and one similarly matched patient with chronic kidney disease (CKD), a total of 404,703 patients, were selected from the NHIRD. The study endpoint was the occurrence of new-onset AF and patients were followed an average of 5.1 years. The incidence rates of AF were 12.1, 7.3, and 5.0 per 1000 person-years for ESRD, CKD, and control patients, respectively. Among patients with ESRD, age, hypertension, heart failure, coronary artery disease, peripheral arterial occlusive disease, and chronic obstructive pulmonary disease were significant risk factors for new-onset AF. Thus, patients with ESRD had a significantly higher risk of new-onset AF. The presence of multiple risk factors was associated with a higher possibility of AF occurrence.