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Objectives To explore the value of detecting the peri-device leak (PDL) and device endothelialization after left atrial appendage closure (LAAC) by cardiac computed tomography (CT) in patients with atrial fibrillation (AF), who underwent Watchman LAAC combined with radiofrequency ablation of atrial fibrillation (AFCA). Methods Patients with symptomatic drug-refractory atrial fibrillation at high risk of stroke (CHA2 DS2 -VASc Score ≥ 2), who underwent Watchman LAAC combined with AFCA in our center from March 2017 to December 2018 were enrolled. Maximum diameter of LAA orifice was determined by preoperative CCTA. A standardized view of Watchman device was obtained by postoperative CCTA multiplannar reconstruction to evaluate the PDL and device endothelialization. Results Approximately 84 patients post successful LAAC and AFCA were enrolled in this study. The satisfactory LAA occlusion rate was 100%. There was no death, bleeding, stroke, and device-related thrombus (DRT) events. At 6-month postprocedure, CCTA images evidenced complete endothelialization in 44 patients (no contrast enhancement in LAA); contrast enhancement in LAA and visible PDL in 33 patients; contrast enhancement in LAA but without PDL in seven patients (incomplete device endothelialization). Maximum diameter of LAA orifice could independently predict the occurrence of PDL (odds ratio, 1.31; 95% confidence interval, 1.11-1.55; p = .002), sensitivity was 69.7% and specificity was 80.4% with the cutoff value of maximum diameter of LAA orifice more than 28.2 mm on predicting PDL. Conclusions CCTA is feasible to evaluate PDL and device endothelialization after LAAC. The maximum diameter of LAA orifice derived from CT can independently predict the occurrence of post-LAAC PDL.

Aims The left atrial appendage (LAA) is one of the major sources of atrial tachycardias (ATs) in children. However, endocardial ablation in LAA may fail or even cause fatal tamponade; and epicardial ablation with subsequent surgical appendectomy (SAE) may be required. There is no relevant report in children. We aimed to evaluate the feasibility of epicardial ablation with SAE in children. Methods and results The epicardial ablation with SAE was performed in a 12-year-old girl with an incessant AT. Endocardial mapping demonstrated endocardial activation time of −112 msec and −105 msec (relative to the onset of the A wave at CS9-10) in the right ventricular outflow tract and LAA, respectively. But multiple ablation attempts at these sites did not terminate the AT. After the left-side pericardium opened, the earliest activation (−120 msec) during AT was found at the apex of upper lobe. At this site, ablation eliminated the tachycardia within 5 seconds of onset of energy. After ablation, the LAA was excited, followed by a continuous over and over suture to definitely close the resection line. The free of AT and a decrease in LAD and NT-proBNP were achieved during the 12-month follow-up. Conclusion The epicardial ablation with subsequent SAE was successfully performed in a child. The heart function of the patient improved after a 12-month follow-up. The excision of LAA may be an ideal strategy for children with incessant AT originating from epicardial LAA. However, the long-term safety and efficacy of SAE in children should be further estimated.

Background Recently, left bundle branch area pacing (LBBAP) has been shown to be feasible. However, the right ventricular (RV) implantation site for LBBAP remains elusive. We believe that the RV implantation site should be located at the posteromedial basal septum, and in this paper, we propose a new method to help guide lead implantation. The aim of this study is to demonstrate the feasibility of the proposed method. Methods The RV implantation site was positioned by a combination of a nine-grid system on fluoroscopy and the use of intracardiac echocardiogram (ICE) and then verified by ICE. Results Fifteen patients were enrolled for LBBAP using our method. The acute success rate was 86.7% (13/15), which demonstrated that our method is useful for assisting with lead implantation. According to ICE, the distance between the implantation site and apex (the front) and the distance between the implantation site and tricuspid annulus (the back) were 44.9 ± 10.7 and 33.2 ± 10.4 mm, respectively, and the ratio of the front and the back was 1.57 ± 0.80. The distance between the implantation site and the front junction point of the left-right ventricle (the upper) and the distance between the implantation site and the back junction point (the lower) were 33.4 ± 10.6 and 24.5 ± 10.2 mm, respectively. The ratio of the upper to the lower was 1.76 ± 1.36. These results suggest that the implantation site was at the posteromedial basal septum. The width of the QRS duration increased from 110.4 ± 33.1 ms at baseline to 114.1 ± 16.1 ms post LBBAP (P > 0.05). The operation time was 133 ± 32.9 min. The time of X-ray fluoroscopy was 21.2 ± 5.9 min. The mean time for lead positioning during LBBAP was 33.8 ± 16.6 min. During a follow-up of 3 months, the LBB capture threshold remained stable in 12 patients, except for one patient who had an increase in the LBB capture threshold to 3.0 v/0.4 ms. Conclusions Our preliminary results indicate that the posteromedial basal septum could be seen as the implantation site for LBBAP. As a technique for LBBAP, ICE is a useful method for assisting with lead implantation. It is feasible and safe to use a nine-grid system combined with ICE for LBBAP.

ObjectivesWe aimed to describe the feasibility of a surgical left thoracotomy for catheter ablation of scar-related ventricular tachycardia (VT) in patients with inaccessible pericardial access.BackgroundPericardial adhesion due to prior cardiac surgery or previous epicardial ablation procedures limits epicardial access in patients with drug-refractory VT originated from the epicardium.MethodsSix patients who underwent a surgical left lateral thoracotomy epicardial access for catheter ablation of VT after failed subxiphoid percutaneous epicardial access were reviewed. Patients’ baseline characteristics and procedural characteristics including epicardial access, mapping, and ablation were described. Epicardial access was successfully obtained in all patients by a surgical left lateral thoracotomy.ResultsThe reasons of pericardial adhesion were prior cardiac surgery (n = 3, 50%) and previous epicardial ablation procedures (n = 3, 50%). Epicardial mapping of the lateral and inferior left ventricle was acquired, and a total of 15 different VTs originated from those regions were abolished. Unless one patient with ST elevation myocardial infarction due to periprocedural occlusion of the posterior descending artery no further complications occurred. All patients were discharged 10.2 ± 4 days after the procedure. VT recurred in 1 patient (17%) and was controlled with oral amiodarone therapy during follow-up (median follow-up: 479 days).ConclusionsA surgical left lateral thoracotomy is feasible and safe for selected patients. This approach provides epicardial ablation in patients with VT located at the infero-lateral left ventricle and pericardial adhesions due to previous cardiac surgery or previous ablation procedures.Graphic abstract

Background Both atrial fibrillation (AF) and early repolarization (ER) are highly prevalent in patients with Wolff–Parkinson–White (WPW) syndrome. Methods We retrospectively identified 123 WPW patients with manifest accessory pathway (mAP) and 105 patients with concealed accessory pathways (cAP) who underwent successful ablation of the APs. AF history prior to the ablation was investigated. The presence of ER was evaluated from the 12-lead electrocardiograms performed both before and immediately after the ablation. Patients were further followed up for AF occurrence after the AP ablation. Results Compared with cAP patients, WPW patients presented with higher incidence of previous AF, as well as ER after the AP ablation. Compared with those without AF history, WPW patients with comorbid AF were more prone to presenting ER, especially in the inferior leads, after the mAP ablation. Regression analysis suggested that the post-ablation ER in the inferior leads was strongly associated with AF in WPW patients [OR = 5.85; 95% confidence interval (CI): 2.29–14.96], even after adjusting for age and left atrial diameter (OR = 5.14; 95% CI: 1.80–14.74). Moreover, post-ablation inferior-lead ER was predictive of AF recurrence after mAP ablation during the follow-up of 22.6 ± 11.1 months. In comparison, ER was correlated with neither AF history nor AF recurrence in patients undergoing cAP ablation. Conclusions ER in the inferior leads after the mAP ablation is highly correlated with AF history and recurrence in WPW patients.

Background Pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (AF) is associated with a non-negligible long-term recurrence rate. Objectives The aim of this study was to investigate whether PVI combined with six short ablation lines on the PVI circumferences (PVI+6L group) yields higher success rates than PVI alone (PVI group). Methods In this multicenter, single-blind, randomized trial, a total of 390 patients with paroxysmal AF were randomly assigned into PVI group (n=193) or PVI+6L group (n=197). The primary endpoint was freedom from AF/atrial tachycardia recurrence between 91 and 365 days. The secondary endpoints included AF burden, procedural parameters, and complications. Results Freedom from atrial tachyarrhythmia was achieved in in 160 of 197 patients (81.2%) in the PVI+6L group and 142 of 193 patients (73.6%) in the PVI group (hazard ratio, 0.61; 95% confidence interval, 0.39 to 0.97; P=0.040). Mean AF burden tended to be lower in PVI+6L group as compared to PVI group (1.95% vs. 0.53%, P=0.097). Procedure and ablation time were slightly longer in the PVI+6L group than in the PVI group (130 ± 25 vs. 121 ± 28 min, P=0.002, and 46 ± 14 vs. 41 ± 16 min, P=0.001, respectively) while X-ray exposure was similar (60 ± 54 vs. 61 ± 60 s, P=0.964). Complications occurred in three patients (1.6%) in the PVI group and in three patients (1.5%) in the PVI+6L group. Conclusions In patients with paroxysmal AF undergoing catheter ablation, adding six short ablation lines on the PVI circumferences could reduce recurrence rate of AF.

Background: The aim of this study was to investigate the efficacy of left atrial appendage closure (LAAC) for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF).Methods: This pilot study enrolled 36 patients with HCM and AF who underwent LAAC between April 2017 and December 2019, of whom 22 were for primary stroke prevention and 14 were for secondary prevention.Results: The patients enrolled in this study had non-obstructive (86.1%) or mild obstructive (13.9%) HCM. Patients in the Secondary Prevention Group had higher CHA2DS2-VASc scores (5.1 ± 1.4 vs. 2.6 ± 1.6, P < 0.001) and higher HAS-BLED scores (2.8 ± 1.0 vs. 1.5 ± 0.9, P < 0.001) compared with those in the Primary Prevention Group. Successful closure with satisfactory seals (residual leak ≤ 5 mm) was achieved in all patients, with complete occlusion in 86.4% of the Primary Prevention Group and 92.9% of the Secondary Prevention Group. Procedural-related complications included one pericardial effusion and one groin hematoma. One device-related thrombus was identified in the Secondary Prevention Group and resolved after anticoagulation. During a mean follow-up time of 28.4 months, one bleeding event was recorded. There were no thromboembolic events or deaths in either group, with 97.2% of the patients achieving freedom from anticoagulation therapy.Conclusions: Initial results suggest that LAAC can be a safe and feasible alternative for primary and secondary stroke prevention in selected patients with HCM and AF. Further studies with larger samples are required.

Background Post cardiac injury syndrome (PCIS) is a troublesome but not uncommon complication following catheter ablation of arrhythmias. We aimed to study the clinical features of ablation-associated PCIS. Methods For this purpose, we conducted a computerised literature search that identified 19 published cases, and we additionally included another two new cases from our centres. Twenty-one (21) cases of PCIS following ablation were analysed. Results Among the 21 cases, PCIS most commonly occurred after atrial flutter/fibrillation (AFL/AF) ablation (71.4%), followed by atrioventricular re-entrant tachycardia (AVRT) ablation (9.5%), atrioventricular node (AVN) ablation (9.5%), atrioventricular nodal re-entrant tachycardia (AVNRT) ablation (4.8%) and ventricular tachycardia (VT) ablation (4.8%). Thirty-eight (38) per cent of PCIS was suggested to be secondary to cardiac perforation. Specific symptoms or features include pleuritic chest pain (76.2%), fever (76.2%), elevated markers of inflammation (76.2%), pericardial effusion (90.5%), pleural effusion (71.4%) and pulmonary infiltrates (28.6%). Interestingly, all the six cases with pulmonary infiltrates were following AFL/AF ablation (6/15, 40%). Serious clinical manifestations include cardiac tamponade, massive pleural effusion with hypoalbuminaemia and hyponatraemia, and massive pulmonary infiltrates with hypoxaemia. Notably, empiric antibiotic therapy was used in seven cases including five with pulmonary infiltrates but failed to work. No mortality occurred during a mean follow-up of 4.1 ± 5.3 (1 to 19) months. Conclusions Catheter ablation of AFL/AF was most commonly involved in ablation-associated PCIS. Pulmonary infiltrate is an important feature of PCIS following AFL/AF ablation and may be misdiagnosed as pneumonia. Although PCIS is troublesome and even dangerous, it does carry a benign prognosis.

Background: Recently, the impact of fine particulate matter pollution on cardiovascular system is drawing considerable concern worldwide. The association between ambient fine particulate and the cardiac arrhythmias is not clear now. Objective: To study associations of ambient fine particulate with incidence of arrhythmias in outpatients. Methods: Data was collected from the remote electrocardiogram (ECG) system covering 282 community hospitals in Shanghai from June 24th, 2014 to June 23rd, 2016. ECG was performed for patients admitted to above hospitals with complaining of chest discomfort or palpitation, or for regular check-ups. Air quality data during this time period was obtained from China National Environment Monitoring Center. A generalized additive quasi-Poisson model was established to examine the associations between PM2.5 and cardiac arrhythmias. Results: Cardiac arrhythmias were detected in 202,661 out of 1,016,579 outpatients (19.9%) and fine particulate matter ranged from 6 to 219 μg/m3 during this period. Positive associations were evidenced between fine particulate matter level and prevalence of cardiac arrhythmia by different lag models. Per 10 μg/m3 increase in fine particulate matter was associated with a 0.584%(95%CI:0.346-0.689%, p

Left atrial appendage (LAA) closure (LAAC) has emerged as an alternative therapeutic approach to medical therapy for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, complex LAA anatomy may preclude its use. LAmbre is a new, self-expanding LAA occluder, and is highly adaptable to different LAA morphologies. We explored the feasibility, safety, and efficacy of LAAC using LAmbre device in NVAF patients with or without prior catheter ablation (CA). LAAC using LAmbre device was applied in NVAF patients with (group C) or without (group N) prior CA. Transesophageal echocardiography (TEE) was performed at 3, and 12 months post-LAAC. Among 17 LAAC patients (group C, 6 & group N, 11), 4 cases were implanted with special type devices, 5 were implanted with large devices. Besides one case of cardiac tamponade (N group), there were two minor peri-procedural complications only. Successful sealing of the LAA was documented in all the patients (100%) by TEE both post LAAC and at 3 months. At 3 months, no residual flow was achieved in 11 patients (64.7%); six patients (35.3%) had residual flow 0.05). LAAC with LAmbre device, subsequent to prior CA for AF, can be performed successfully and safely. The design and distinguishing features of this device could be of help in patients with complex anatomy of LAA.

The relationship between electrocardiographic-left ventricular hypertrophy (ECG-LVH) and stroke has been well established in the Western population with limited information in the Chinese population. This study evaluated the association between ECG-LVH and stroke outcome. A total of 19,815 (95.7%) subjects from the China Stroke Primary Prevention Trial (CSPPT) with baseline ECG were included. ECG-LVH by sex-unspecific Sokolow-Lyon criteria was detected in 1599 participants (8.1%) at baseline. After a mean follow-up of 4.5 years, 605 (3.1%) subjects were detected with new-onset stroke over the total population, baseline ECG-LVH was present in 72 (4.5%) of them during follow-up. After adjusting for various cofounders, ECG-LVH remained as an independent risk factor for stroke events in the total population (HR = 1.43; 95% CI, 1.10-1.84; P = 0.007) and male population (HR = 1.47; 95% CI, 1.07-2.03; P = 0.019). Subgroup analysis showed that baseline ECG-LVH was a risk factor for stroke in individuals younger than 65 years of age(HR = 1.80, 95% CI, 1.31-2.47 vs. HR = 1.02, 95% CI, 0.66-1.59, P value for interaction = 0.047). In summary, LVH diagnosed by ECG is associated with an excess risk for stroke in Chinese hypertensive population, especially in the age group of younger than 65 years.

Tissue expansion has been widely used for plastic, reconstructive, and esthetic surgeries. A mouse scalp expansion model can effectively mimic the characteristics of human skin expansion. However, a detailed study of the histological features and ultrastructural characteristics of expanded scalp is lacking, especially early ultrastructural changes. Here, a mouse scalp expansion model was established and the expanded scalp samples were obtained on day 2 (group I) and 4 (group II) post final injection. Histological analysis revealed epidermal thickening, dermal thinning, subcutaneous fat thinning, and capsule formation in the expanded samples. Ultrastructural evaluation showed the presence of keratinocytes with numerous tonofibrils and damaged mitochondria, and several ruptured collagen fibers and increased number of active fibroblasts and myofibroblasts were observed in the dermis and capsules. Adipocyte dedifferentiation was detected in the expanded samples of both groups, but formation of autophagosomes was only detected in the dermal fibroblasts of group I. Thus, early changes in expanded tissue should be carefully monitored, as it may help avoid dermal thinning and promote expanded tissue regeneration.

Aim. The feasibility and safety of performing the combined procedure of catheter ablation (CA) and left atrial appendage closure (LAAC) for atrial fibrillation (AF) have been reported by observational studies without controls. The aim of this study was to compare the procedural and long-term outcomes of combined procedures with isolated CA or LAAC. Methods and Results. This study included patients who underwent combined CA and LAAC (combined group), CA alone (CA-only group), or LAAC alone (LAAC-only group). Propensity score matching was used to select controls from the CA-only and LAAC-only groups. Each group contained 76 subjects. The procedures were successfully performed in all the patients. Procedure-related complications of the combined group included one pericardial effusion and two groin haematomas, which did not differ significantly with those of the CA-only group (3.9% vs. 2.6%, P=0.650) or the LAAC-only group (3.9% vs. 2.6%, P=0.650), respectively. The AF-free rate of the combined group was comparable with that of the CA-only group after a mean of 2 years follow-up (67.1% vs. 69.7%, P=0.727). Compared with the LAAC-only group, the combined group achieved similar complete occlusion rate at implant (94.7% vs. 93.4%) and at 45 days (82.9% vs. 85.5%). At the end of follow-up, ischemic stroke and bleeding events of the combined group were low (3.9%) and were comparable with those of the CA-only group (5.3%) and the LAAC-only group (2.6%). Conclusions. The combination of AF-CA and LAAC is safe and efficacious compared with single procedures alone.

Background. Premature ventricular complexes (PVCs) exhibit circadian fluctuation. We determine if PVCs of different origin exhibit specific circadian patterns. Methods. We analyzed Holter recordings from patients with monomorphic PVCs who underwent catheter ablation. PVC circadian patterns were classified as fast-heart rate- (HR-) dependent (F-PVC), slow-HR-dependent (S-PVC), or HR-independent (I-PVC). PVC origins were determined intraprocedurally. Results. In a retrospective cohort of 407 patients, F-PVC and S-PVC typically exhibited diurnal and nocturnal predominance, respectively. Despite decreased circadian fluctuation, I-PVC generally had heavier nocturnal than diurnal burden. PVCs of left anterior fascicle origin were predominantly S-PVC, while those of posterior hemibranch origin were mostly F-PVC. PVCs originating from the aortic sinus of Valsalva (ASV) were predominantly I-PVC, while most PVCs arising from the left ventricular outflow tract (LVOT) were F-PVC. Using a diurnal/nocturnal PVC burden ratio of 0.92 as the cutoff value to distinguish LVOT from ASV origin achieved 97% sensitivity and, as further verification, an accuracy of 89% (16/18) in a prospective cohort of patients with PVCs originating from either ASV or LVOT. In contrast, PVCs originating from right ventricles, such as right ventricular outflow tract, did not show distinct circadian patterns. Conclusions. The circadian patterns exhibit origin specificity for PVCs arising from left ventricles. An analysis of Holter monitoring provides useful information on PVC localization in ablation procedure planning.

Aims We evaluated the feasibility of left atrial appendage (LAA) closure guided by the image fusion of integrating fluoroscopy into 3D computed tomography (CT). Methods and results A total of 117 consecutive patients who underwent LAA closure with or without the image fusion were matched (1:2). Each LAA closure step of the Image fusion group was guided by the preprocedure CT and image fusion, especially in the plan of LAA measurement and transseptal puncture. All patients were successfully implanted with a WATCHMAN closure device. Comparing the two groups, the mean number of recapture times and the number of devices per patient of the Image fusion group were significantly lower (0.4 ± 0.5 vs. 0.7 ± 0.8, P = 0.031 and 1.0 ± 0.2 vs. 1.1 ± 0.3, P = 0.027, respectively). The one-time successful deployment rate by the support of the image fusion was higher than in the control group (66.7% vs. 44.9%, P = 0.026). Each case of the Image fusion group was completely occluded with one transseptal puncture, while five of the Non-image fusion group required redo transseptal punctures. During the 45-day follow-up, both group cases presented occlusion efficiency and no major adverse cardiac events were observed. Conclusion Image fusion technique integrating fluoroscopy into the 3D CT is safe and feasible which can be easily incorporated into the procedural work-flow of percutaneous LAA closure. The fusion image can play an important alternative role in the plan of LAA measurement and transseptal puncture site for improving the LAA closure procedure.

INTRODUCTION Catheter ablation of atrial fibrillation (AFCA) and left atrial appendage closure (LAAC) exert opposite effects on left atrial (LA) size. We aim to observe the net impact of combined AFCA and LAAC strategy on LA size and explore those factors which might affect the postprocedure LA structural remodeling. METHODS A total of 53 patients, who underwent combined AFCA and Watchman LAAC in our center from March to December 2017, were enrolled. Atrial fibrillation (AF) recurrence was monitored after the procedure. Left atrial volume (LAV) and left atrial appendage volume (LAAV) were measured by Mimics based on dual-source computed tomography images. RESULTS At 6 months, sinus rhythm (SR) was maintained in 79.2% patients. LAV was significantly reduced (130.2 ± 36.3 mL to 107.1 ± 30.0 ml; P

Background It has been suggested that endocardial and epicardial ablation of ventricular tachycardia ( VT ) improves outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia. We investigated our sequential approach for VT ablation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia in a single center. Methods and Results We included 47 patients (44±16 years) with definite (81%) or borderline (19%) arrhythmogenic right ventricular cardiomyopathy/dysplasia between 1998 and 2016. Our ablation strategy was to target the endocardial substrate. Epicardial ablation was performed in case of acute ablation failure or lack of an endocardial substrate. Single and multiple procedural 1‐ and 5‐year outcome data for the first occurrence of the study end points (sustained VT /ventricular fibrillation, heart transplant, and death after the index procedure, and sustained VT /ventricular fibrillation for multiple procedures) are reported. Eighty‐one radiofrequency ablation procedures were performed (mean 1.7 per patient, range 1–4). Forty‐five (56%) ablation procedures were performed via an endocardial, 11 (13%) via an epicardial, and 25 (31%) via a combined endo‐ and epicardial approach. Complete acute success was achieved in 65 (80%) procedures, and partial success in 13 (16%). After a median follow‐up of 50.8 (interquartile range, [18.6; 99.2]) months after the index procedure, 17 (36%) patients were free from the primary end point. After multiple procedures, freedom from sustained VT /ventricular fibrillation was 63% (95% CI , 52–75) at 1 year, and 45% (95% CI , 34–61) at 5 years, with 36% of patients receiving only endocardial radiofrequency ablation. A trend (log rank P =0.058) towards an improved outcome using a combined endo‐/epicardial approach was observed after multiple procedures. Conclusion Endocardial ablation can be effective in a considerable number of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with VT , potentially obviating the need for an epicardial approach.

Previous studies showed that genetic variants of the angiotensinogen (AGT) gene conferred higher risk for acquired atrial fibrillation (AF). The present study investigated whether AGT variants correlate with the clinical outcome in patients with acquired AF after catheter ablation (CA).A total of 150 acquired symptomatic drug-refractory AF patients (mean age 63.7±11.0 years, 24.6% non-paroxysmal AF) with acquired AF underwent a single CA procedure in our department and were included in this retrospective analysis. Eight tagging single nucleotide polymorphisms (tSNPs) in the AGT gene were genotyped. Standard electrocardiographs (ECGs) and 24-hour Holter recordings were performed during a median follow-up period of 57.5 months to detect AF recurrence.Sixty-one patients (40.7%) suffered AF recurrences after a single CA procedure during follow up. Of the eight tSNPs, the frequency of the M allele of M235T was significantly higher in the recurrence group (28%) compared to the non-recurrence group (18%) (p=0.042). The recurrence rates of patients with the TT, MT, and MM genotypes were 34.4%, 50%, and 55.6%, respectively (ptrend=0.049). After adjusting for age, sex, body mass index, hypertension, left atrial volume index (LAVI) and other covariates, M235T increased the risk of AF recurrence in additive and dominant models with odds ratios of 2.023 (95% confidence interval (CI): 1.034-3.926, p=0.033) and 2.601 (95% CI: 1.102-6.056, p=0.025), respectively. However, in multiple correction analyses, the p values of multiple comparisons were not statistically significant (pcorrect0.05).The M allele of M235T might be associated with an increased risk of AF recurrence after CA. Genotyping may thus be helpful on identifying patients with higher risks of AF recurrence after CA and developing optimal follow-up strategies. These strategies may differ and should be individualized according to patients' genotype. Future studies are warranted to validate the potential effect of AGT M235T on AF recurrence post CA.

Atrial fibrosis, the hallmark of structural remodeling associated with atrial fibrillation (AF), is characterized by abnormal proliferation of atrial fibroblasts and excessive deposition of extracellular matrix. Transforming growth factor-β1 (TGF-β1)/activin receptor-like kinase 5 (ALK5)/Smad2/3/4 pathway has been reported to be involved in the process. Recent studies have implicated both activin A and its specific downstream component activin receptor-like kinase 4 (ALK4) in stimulating fibrosis in non-cardiac organs. We recently reported that ALK4 haplodeficiency attenuated the pressure overload- and myocardial infarction-induced ventricular fibrosis. However, the role of activin A/ALK4 in the pathogenesis of atrial fibrosis and vulnerability to AF remains unknown. Our study provided experimental and clinical evidence for the involvement of activin A and ALK4 in the pathophysiology of atrial fibrosis and AF. Patients with AF had higher activin A and ALK4 expression in atriums as compared to individuals devoid of AF. After angiotensin-II (Ang-II) stimulation which mimicked atrial fibrosis progression, ALK4-deficient mice showed lower expression of ALK4 in atriums, reduced activation of atrial fibroblasts, blunted atrial enlargement and atrial fibrosis, and further reduced AF vulnerability upon right atrial electrophysiological studies as compared to wild-type littermates. Moreover, we found that apart from the well-known TGF-β1/ALK5 pathway, the activation of activin A/ALK4/smad2/3 pathway played an important role in the pathogenesis of Ang-II-mediated atrial fibrosis and inducibility of AF, suggesting that targeting ALK4 might be a potential therapy for atrial fibrosis and AF.

The impact of angiotensin II receptor blockers (ARBs) on electrical remodelling after myocardial infarction (MI) remains unclear. The purpose of the present study was to evaluate the effect of valsartan on incidence of ventricular arrhythmia induced by programmed electrical stimulation (PES) and potential link to changes of myocardial connexins (Cx) 43 expression and distribution in MI rats. Fifty-nine rats were randomly divided into three groups: Sham (n = 20), MI (n = 20) and MI + Val (20 mg/kg/day per gavage, n = 19). After eight weeks, the incidence of PES-induced ventricular tachycardia (VT) and fibrillation (VF) was compared among groups. mRNA and protein expressions of Cx43, angiotensin II type 1 receptor (AT1R) in the LV border zone (BZ) and non-infarct zone (NIZ) were determined by real-time PCR and Western blot, respectively. Connexins 43 protein and collagen distribution were examined by immunohistochemistry in BZ and NIZ sections from MI hearts. Valsartan effectively improved the cardiac function, reduced the prolonged QTc (163.7 ± 3.7 msec. versus 177.8 ± 4.5 msec., P < 0.05) after MI and the incidence of VT or VF evoked by PES (21.1% versus 55%, P < 0.05). Angiotensin II type 1 receptor expression was significantly increased in BZ and NIZ sections after MI, which was down-regulated by valsartan. The mRNA and protein expressions of Cx43 in BZ were significantly reduced after MI and up-regulated by valsartan. Increased collagen deposition and reduced Cx43 expression in BZ after MI could be partly attenuated by Valsartan. Valsartan reduced the incidence of PES-induced ventricular arrhythmia, this effect was possibly through modulating the myocardial AT1R and Cx43 expression.

Objectives The aim of this study was to evaluate the effects of pulse high-volume hemofiltration (PHVHF) in patients with severe sepsis. Methods Twenty-two patients with severe sepsis admitted to XiJing hospital between January 2009 and January 2010 were included in the present study. Patients were randomly divided into the control group (conventional treatment) and the PHVHF group. Patients in the PHVHF group received 72 h of PHVHF treatment in addition to conventional treatment after admission. PHVHF was conducted as follows: HVHF 85 ml/kg per hour for 6 h followed by continuous venovenous hemofiltration 35 ml/kg per hour for 18 h with an AN69 membrane. The hemofilter was replaced every 24 h and PHVHF was performed with 250 to 300 ml/min blood flow rate. The blood samples were taken to measure the changes of plasma cytokines (TNF-α, IL-1, IL-4, IL-6 and IL-10). Results With 72 h of PHVHF treatment, there was an improvement in clinical features and hemodynamics variables in PHVHF-treated patients. All plasma cytokines after PHVHF treatment were significantly lower than those at the start of PHVHF treatment (pConclusions Our findings suggest that PHVHF is a feasible adjuvant modality in the treatment of patients with severe sepsis. With the application of PHVHF treatment, plasma cytokines are effectively removed. Considering the lower cost and better feasibility than continuous high-volume hemofiltration (CHVF), PHVHF shows promising prospects for the future.

Background Purkinje cells (PCs) have a steeper rate dependence of repolarization and are more susceptible to arrhythmic activity than do ventricular myocytes (VMs). Late sodium current (I NaL ) is rate dependent and contributes to rate dependence of repolarization. Objective This study sought to test our hypothesis that PCs have a larger rate dependence of I NaL , contributing to their steeper rate dependence of repolarization and higher susceptibility to arrhythmic activity, than do VMs. Methods I NaL was recorded in isolated rabbit PCs and VMs with the whole-cell patch clamp technique. Action potential was examined using the microelectrode technique. Results Compared with VMs, PCs exhibited a significantly larger rate dependence of I NaL with a larger I NaL to basic cycle length (BCL) slope. Moreover, PCs had a larger rate dependence of I NaL decay and slower recovery kinetics. Interestingly, the larger rate dependence of I NaL matched to a steeper rate dependence of action potential duration (APD) in PCs. The I NaL blocker tetrodotoxin significantly blunted, while the I NaL enhancer anemone toxin (ATX-II) significantly increased, the rate dependence of I NaL and APD in PCs and VMs. In the presence of ATX-II, the rate dependence of I NaL in PCs was markedly larger than that in VMs, causing a much steeper rate dependence of APD in PCs. Accordingly, PCs exhibited greater rate-dependent electrical instability and were more prone to ATX-II–induced early afterdepolarizations, which were completely inhibited by the I NaL inhibitor ranolazine. Conclusion PCs have a significantly larger rate dependence of I NaL than do VMs because of distinctive I NaL decay and recovery kinetics, which contributes to their larger rate adaptation, and simultaneously predisposes them to a higher risk of arrhythmogenesis.

Background: Patients with manifest atrioventricular accessory pathways (mAPs) have a greater tendency to develop atrial fibrillation (AF) compared with patients with concealed atrioventricular accessory pathways (cAPs). However, the risk factors of developing AF in patients with various atrioventricular accessory pathways (APs) are not clear. Methods: This retrospective study included 460 symptomatic patients with either cAPs (n = 246) or mAPs (n = 214) who underwent electrophysiological study and successful radiofrequency catheter ablation of APs. Clinical and electrophysiological characteristics were compared between cAPs and mAPs and between AF and non-AF groups with cAPs or mAPs. Independent risk factors of AF were analyzed using multivariate logistic regression. Results: AF was more frequent in mAPs group than in cAPs group (23.4% vs 9.8%, p

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

To investigate whether resveratrol suppressed oxidative stress-induced arrhythmogenic activity and Ca(2+) overload in ventricular myocytes and to explore the underlying mechanisms.Hydrogen peroxide (H2O2, 200 μmol/L)) was used to induce oxidative stress in rabbit ventricular myocytes. Cell shortening and calcium transients were simultaneously recorded to detect arrhythmogenic activity and to measure intracellular Ca(2+) ([Ca(2+)]i). Ca(2+)/calmodulin-dependent protein kinases II (CaMKII) activity was measured using a CaMKII kit or Western blotting analysis. Voltage-activated Na(+) and Ca(2+) currents were examined using whole-cell recording in myocytes.H2O2 markedly prolonged Ca(2+) transient duration (CaTD), and induced early afterdepolarization (EAD)-like and delayed afterdepolarization (DAD)-like arrhythmogenic activity in myocytes paced at 0.16 Hz or 0.5 Hz. Application of resveratrol (30 or 50 μmol/L) dose-dependently suppressed H2O2-induced EAD-like arrhythmogenic activity and attenuated CaTD prolongation. Co-treatment with resveratrol (50 μmol/L) effectively prevented both EAD-like and DAD-like arrhythmogenic activity induced by H2O2. In addition, resveratrol markedly blunted H2O2-induced diastolic [Ca(2+)]i accumulation and prevented the myocytes from developing hypercontracture. In whole-cell recording studies, H2O2 significantly enhanced the late Na(+) current (I(Na,L)) and L-type Ca(2+) current (I(Ca,L)) in myocytes, which were dramatically suppressed or prevented by resveratrol. Furthermore, H2O2-induced ROS production and CaMKII activation were significantly prevented by resveratrol.Resveratrol protects ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca(2+) overload through inhibition of I(Na,L)/I(Ca,L), reduction of ROS generation, and prevention of CaMKII activation.

The aim of this study was to investigate the impacts of continuous veno-venous hemofiltration (CVVH) on plasma cytokines and monocyte human leukocyte antigen-DR (HLA-DR) expression and to evaluate the relationship between them during CVVH treatment in septic patients. Forty septic patients were enrolled in this study. They were randomly divided into control group (who received conventional treatment, n=20) and CVVH group (who received conventional treatment and CVVH treatment, n=20). The blood samples were taken to measure the changes of plasma cytokines (IFN-gamma, TNF-alpha, IL-1, IL-2, IL-4, IL-6, IL-10 and IL-13) and HLA-DR expression on monocytes. After CVVH treatment, the plasma levels of IFN-gamma, IL-1, IL-2, IL-4, IL-10 and IL-13 in septic patients were markedly decreased (P0.05), while the levels of TNF-alpha and IL-6 were only lowered to some extent without significant difference (P0.05). HLA-DR expression on monocytes improved in CVVH treated patients (P0.05). No matter pre-treatment or post-treatment of CVVH, there was a negative correlation between plasma IL-10 and monocyte HLA-DR expression (P0.05). In contrast, no obvious change was shown in control patients. Our findings suggest that CVVH is effective in removal of many plasma cytokines and in improvement of monocyte HLA-DR expression in septic patients.

The arrhythmogenic effect of intracardiac skeletal myoblast (SKM) transplantation may be related to the differentiation state of SKMs. We tested the hypothesis that lentivirus mediated siRNA against the loop region of miRNA-181a could upregulate the SKMs differentiation repressor homeobox protein A11 (Hox-A11) and reduce the arrhythmias post SKM transplantation into ischemic myocardium of rats. Primary cultured SKMs were transfected with Lenti-siR-miR-181 (recombined lentivirus expressing the unique siRNA against miR-181a, LV group). Real-time PCR showed that miRNA-181a level was significantly decreased and Hox-A11 protein level significantly increased in LV group than in control group at days 5 and days 7 post Lentivirus transfection. Knockdown of miRNA-181a significantly promoted SKMs' growth and attenuated the connexin43 downregulation in SKMs in vitro. Seven days after left coronary artery ligation, rats were randomized to receive intramyocardial injection of either 5 × 106 SKMs transfected with Lenti-siR-miR-181 (MI-SKMLV), 5 × 106 Lenti-siLUC SKMs (MI-SKM) or PBS (MI-PBS). Systolic function was significantly improved in both MI-SKM and MI-SKMLV groups fourteen days after injection. Incidence of inducible self-terminating ventricular tachycardia was significantly lower in MI-SKMLV than that in MI-SKM group. Engraftments of SKMs with knockdowned miRNA-181a similarly improved cardiac function as SKM transplantation but significantly decreased the arrhythmogenic effect of SKM transplantation in rats with experimental myocardial infarction.

Aims Myocardial infarction (MI) induces neural remodelling of the left stellate ganglion (LSG), which may contribute to ischaemia-induced arrhythmias. The neural chemorepellent Semaphorin 3a (Sema3a) has been identified as a negative regulator of sympathetic innervation in the LSG and heart. We previously reported that overexpression of Sema3a in the border zone could reduce the arrhythmogenic effects of cardiac sympathetic hyperinnervation post-MI. This study investigated whether Sema3a overexpression within the LSG confers an antiarrhythmic effect after MI through decreasing extra- and intra-cardiac neural remodelling. Methods and results Sprague-Dawley rats were subjected to MI, and randomly allocated to intra-LSG microinjection of either phosphate-buffered saline (PBS), adenovirus encoding green fluorescent protein (AdGFP), or adenovirus encoding Sema3a (AdSema3a). Sham-operated rats served as controls. Two weeks after infarction, MI-induced nerve sprouting and sympathetic hyperinnervation in the LSG and myocardium were significantly attenuated by intra-LSG injection with AdSema3a, as assessed by immunohistochemistry and western blot analysis of growth-associated protein 43 and tyrosine hydroxylase. This was also confirmed by sympathetic nerve function changes assessed by cardiac norepinephrine content. Additionally, intra-LSG injection with AdSema3a alleviated MI-induced accumulation of dephosphorylated connexin 43 in the infarct border zone. Furthermore, Sema3a overexpression in the LSG reduced the incidence of inducible ventricular tachyarrhythmia by programmed electrical stimulation post-MI, and arrhythmia scores were significantly lower in the AdSema3a group than in the PBS and AdGFP groups. Conclusion Semaphorin 3a overexpression in the LSG ameliorates the inducibility of ventricular arrhythmias after MI, mainly through attenuation of neural remodelling within the cardiac-neuraxis.