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Background: Atrial fibrillation (AF) is a common cardiovascular disease often observed in diabetes mellitus, and there is currently no satisfactory therapeutic option. Ubiquitin-specific protease 38 (USP38) has been implicated in the degradation of numerous substrate proteins in the myocardium. Herein, we aim to investigate the role of USP38 in AF induced by diabetes., Methods: Cardiac-specific transgenic USP38 mice and cardiac-specific knockout USP38 mice were constructed, and streptozotocin was used to establish diabetic mouse model. Functional, electrophysiological, histologic, biochemical studies were performed., Results: The expression of USP38 was upregulated in atrial tissues of diabetic mice and HL-1 cells exposed to high glucose. USP38 overexpression increased susceptibility to AF, accompanied by aberrant expression of calcium-handling protein, heightened iron load and oxidation stress in diabetic mice. Conversely, USP38 deficiency reduced vulnerability to AF by hampering ferroptosis. Mechanistically, USP38 bound to iron regulatory protein 2 (IRP2), stabilizing it and remove K48-linked polyubiquitination chains, thereby increasing intracellular iron overload, lipid peroxidation, and ultimately contributing to ferroptosis. In addition, reduced iron overload by deferoxamine treatment alleviated oxidation stress and decreased vulnerability to AF in diabetic mice., Conclusion: Overall, our findings reveal the detrimental role of USP38 in diabetes-related AF, manifested by increased level of iron overload and oxidation stress., Competing Interests: Declaration of competing interest We would like to submit the enclosed manuscript entitled “Ubiquitin-specific protease 38 promotes atrial fibrillation in diabetic mice by stabilizing iron regulatory protein 2”, which we wish to be considered for publication in “Free Radical Biology and Medicine”. No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Despite advances in technology and techniques, the recurrence rate of persistent atrial fibrillation (AF) following catheter ablation remains high. The Shensong Yangxin (SSYX) capsule, a renowned traditional Chinese medicine formula, is used in the treatment of cardiac arrhythmias. This trial aimed to investigate whether the SSYX can improve clinical outcomes in patients who have undergone catheter ablation for persistent AF., Methods: A multi-centre, randomized, double-blind, placebo-controlled clinical trial was conducted at 66 centres in China among 920 patients with persistent AF undergoing first ablation. Participants were randomized to oral SSYX, 1.6 g (.4 g/granule) thrice daily (n = 460), or matched placebo (n = 460) for 12 months. The primary endpoint was recurrent atrial tachyarrhythmias lasting for ≥30 s following a blanking period of 3 months. Secondary endpoints included time to first documented atrial tachyarrhythmias, AF burden, cardioversion, stroke/systemic embolism, changes in echocardiographic parameters, and quality-of-life (QoL) score. Analyses were performed according to the intention-to-treat principle., Results: A total of 920 patients underwent randomization (460 assigned to SSYX group and 460 assigned to placebo group). During the follow-up of 12 months, patients assigned to SSYX had a higher event-free rate from recurrent atrial tachyarrhythmias when compared with the placebo group (12-month Kaplan-Meier event-free rate estimates, 85.5% and 77.7%, respectively; hazard ratio, .6; 95% confidence interval .4-.8; P = .001). Patients assigned to receive SSYX had a better QoL score at 12 months compared to those randomized to placebo. There was no significant difference in the incidence of serious adverse events between the two groups., Conclusions: Treatment with SSYX following radiofrequency catheter ablation for persistent AF reduced the incidence of recurrent atrial tachyarrhythmias and led to clinically significant improvements in QoL during a 12-month follow-up in a Chinese population., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China., Objectives: The present study aimed to understand the variation and disparity in awareness of AF in China., Methods: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire., Results: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease., Conclusions: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations., Competing Interests: Declaration of competing interest All authors have no conflict to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: Cardiovascular disease is the leading cause of death worldwide. Anxiety disorders are common psychiatric conditions associated with cardiovascular outcomes. This two-sample Mendelian randomization (MR) study investigated the causal relationship between anxiety disorders and coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF)., Methods: Single nucleotide polymorphisms (SNPs) associated with anxiety disorders (16 730 cases; 101 021 controls) were obtained from the UK Biobank genome-wide association study (GWAS). Cardiovascular outcome data were derived from the FinnGen study (CHD: 21 012 cases and 197 780 controls; MI: 12 801 cases and 187 840 controls; HF: 23 397 cases and 194 811 controls; and AF: 22 068 cases and 116 926 controls). Inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode analyses examined causality., Results: IVW analysis demonstrated significant causal relationships between anxiety disorders and increased risk of CHD [odds ratio (OR): 4.496; 95% confidence interval (CI): 1.777-11.378; P = 0.002], MI (OR: 5.042; 95% CI: 1.451-17.518; P = 0.011), and HF (OR: 3.255; 95% CI: 1.461-7.252; P = 0.004). No relationship was observed with AF (OR: 1.775; 95% CI: 0.612-5.146; P = 0.29). Other methods showed non-significant associations. Two-way analysis indicated no reverse causality., Conclusions: Anxiety disorders were causally associated with greater risk of CHD, MI, and HF but not AF among individuals of European descent. Further research on mediating mechanisms and in diverse populations is warranted., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Phenylacetylglutamine (PAGln), a gut metabolite is substantially elevated in heart failure (HF). The increase of PAGln in plasma is associated with atrial fibrillation (AF), and contributes to AF pathogenesis. However, the role of PAGln in AF with HF remains uncertain. Therefore, this study aimed to determine the effect of PAGln on AF after HF. Thoracic aortic coarctation (TAC) created overpressure-induced HF mice for 4 weeks. Histopathology, biochemical, echocardiographic for assessment of cardiac function, and electrophysiological examination of several electrophysiological indexes (ERP, SNRT, and the occurrence rate of AF) were performed at the end of the HF mice model. We found that plasma PAGln levels were significantly elevated in PAGln-treated HF mice and that PAGln aggravated maladaptive structural remodeling and electrical remodeling, which aggravated the vulnerability of AF, shortened the ERP duration, prolonged the SNRT, increased the occurrence rate of AF in HF mice. Mechanistically, PAGln exacerbated ROS accumulation and increased the levels of phosphorylated PLB and CAMK II. Overall, PAGln played a vital role in promoting the occurrence of AF in HF mice by activating the CAMK II signaling pathway.

Aims: Atrial structural and electrical remodelling is a major reason for the initiation and perpetuation of atrial fibrillation (AF). Ubiquitin-specific protease 38 (USP38) is a deubiquitinating enzyme, but its function in the heart remains unknown. The aim of this study was to investigate the effect of USP38 in pressure overload-induced AF., Methods and Results: Cardiac-specific knockout USP38 and cardiac-specific transgenic USP38 mice and their corresponding control mice were used in this study. After 4 weeks with or without aortic banding (AB) surgery, atrial echocardiography, atrial histology, electrophysiological study, and molecular analysis were assessed. Ubiquitin-specific protease 38 knockout mice showed a remarkable improvement in vulnerability to AF, atrial weight and diameter, atrial fibrosis, and calcium-handling protein expression after AB surgery. Conversely, USP38 overexpression further increased susceptibility to AF by exacerbating atrial structural and electrical remodelling. Mechanistically, USP38 interacted with and deubiquitinated nuclear factor-kappa B (NF-κB), and USP38 overexpression increased the level of p-NF-κB in vivo and in vitro, accompanied by the upregulation of NOD-like receptor protein 3 (NLRP3) and inflammatory cytokines, suggesting that USP38 contributes to adverse effects by driving NF-κB/NLRP3-mediated inflammatory responses., Conclusion: Overall, our study indicates that USP38 promotes pressure overload-induced AF through targeting NF-κB/NLRP3-mediated inflammatory responses., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear., Methods: In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms., Results: Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent., Conclusions: USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI., (© 2023. The Author(s).)

Aims: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have made considerable progress in the field of heart failure, but their application in arrhythmia remains to be in-depth. Right heart disease (RHD) often leads to right heart dysfunction and is associated with atrial fibrillation (AF). Here, we explored the possible electrophysiologic effect of dapagliflozin (a type of SGLT2is) in the development of AF in rats with RHD., Methods and Results: Rats in the experimental group were intraperitoneally injected with a single dose of 60 mg/kg monocrotaline (MCT group, n = 32) on the first day of the experiment, whereas rats in the control group were injected with vehicle (CTL group, n = 32). Rats in the treatment subgroup were treated with dapagliflozin solution orally (MCT + DAPA and CTL + DAPA groups) for a total of 4 weeks, whereas rats in the rest of subgroups were given sterile drinking water. After 4 weeks, echocardiography demonstrated that MCT group rats developed obvious pulmonary arterial hypertension and right heart dysfunction. In addition, there were also obvious inflammatory infiltration, fibrosis, and muscularization in right atrial and pulmonary arteries. The P-wave duration (17.00 ± 0.53 ms, vs. 14.43 ± 0.57 ms in CTL; 14.00 ± 0.65 ms in CTL + DAPA; 14.57 ± 0.65 ms in MCT + DAPA; P < 0.05), RR interval (171.60 ± 1.48 ms, vs. 163.10 ± 1.10 ms in CTL; 163.30 ± 1.19 ms in CTL + DAPA; 163.10 ± 1.50 ms in MCT + DAPA; P < 0.05), Tpeak-Tend interval (65.93 ± 2.55 ms, vs. 49.55 ± 1.71 ms in CTL; 48.27 ± 3.08 ms in CTL + DAPA; P < 0.05), and corrected QT interval (200.90 ± 2.40 ms, vs. 160.00 ± 0.82 ms in CTL; 160.40 ± 1.36 ms in CTL + DAPA; 176.6 ± 1.57 ms in MCT + DAPA; P < 0.01) were significantly prolonged in the MCT group after 4 weeks, whereas P-wave amplitude (0.07 ± 0.0011 mV, vs. 0.14 ± 0.0009 mV in CTL; 0.14 ± 0.0011 mV in CTL + DAPA; 0.08 ± 0.0047 mV in MCT + DAPA; P < 0.05) and T-wave amplitude (0.04 ± 0.002 mV, vs. 0.13 ± 0.003 mV in CTL; 0.13 ± 0.003 mV in CTL + DAPA; P < 0.01) were decreased, and atrial 90% action potential duration (47.50 ± 0.93 ms, vs. 59.13 ± 2.1 ms in CTL; 59.75 ± 1.13 ms in CTL + DAPA; 60.63 ± 1.07 ms in MCT + DAPA; P < 0.01) and effective refractory periods (41.14 ± 0.88 ms, vs. 62.86 ± 0.99 ms in CTL; 63.14 ± 0.67 ms in CTL + DAPA; 54.86 ± 0.70 ms in MCT + DAPA; P < 0.01) were shortened. Importantly, the inducibility rate (80%, vs. 0% in CTL; 10% in CTL + DAPA; 40% in MCT + DAPA; P < 0.05) and duration of AF (30.85 ± 22.90 s, vs. 0 ± 0 s in CTL; 0.24 ± 0.76 s in CTL + DAPA; 5.08 ± 7.92 s in MCT + DAPA; P < 0.05) were significantly increased, whereas the expression levels of cardiac ion channels and calcium-handling proteins such as potassium/calcium channels and calmodulin were decreased. Mechanistically, 'NACHT, LRR, and PYD domain-containing protein 3' inflammasome-related pathway was significantly activated in the MCT group. Nevertheless, in the MCT + DAPA group, the above abnormalities were significantly improved., Conclusions: Dapagliflozin reduces pulmonary vascular damage and right heart dysfunction, as well as the susceptibility to AF in RHD rats., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Calciphylaxis is a rare and life-threatening condition in patients with end-stage kidney disease (ESKD). In this case report, we reported a 72-year-old female who had undergone aortic and mitral mechanical valve replacement 22 years ago due to rheumatic aortic and mitral stenosis. Following the valve replacement, she initiated warfarin treatment. Five years ago, she received a diagnosis of uremia and has since been undergoing regular hemodialysis. Ten months prior to her current admission, she experienced excruciating pain and was diagnosed with calciphylaxis. Additionally, an electrocardiogram revealed atrial fibrillation, while echocardiography indicated that the aortic and mitral mechanical valves were appropriately positioned, with normal perivalvular surroundings and good valve leaflet activity. No noticeable thrombosis was observed in the left atrium or left atrial appendage. Color Doppler imaging showed moderate stenosis in the lower extremity arteries, with no venous thromboembolism present. Extensive eggshell-like calcification within the arterial media was detected. The patient was managed with regular hemodialysis, symptomatic treatments (including anticoagulation and analgesia), and sodium thiosulfate. Unfortunately, symptomatic management provided limited relief, and during the one-month follow-up period, the patient passed away due to septic shock. Currently, there is insufficient conclusive evidence regarding alternative influential anticoagulants or appropriate prosthetic valve selection. For individuals with ESKD receiving maintenance hemodialysis, early identification, diagnosis, and treatment of calciphylaxis are of paramount importance.

Background: Obesity is a significant risk factor for atrial fibrillation (AF), and the gut microbiota is closely related to obesity-induced diseases. However, whether the gut microbiota is involved in regulating obesity-induced AF has not been studied. This study investigated whether gut microbiota dysbiosis affects obesity-related AF., Methods: Fecal microbes derived from normal diet (ND)-fed and high-fat diet (HD)-fed mice were transplanted into those fed normally. Morphologic, biochemical, functional, histologic, electrophysiological studies, molecular analysis, 16S rRNA gene amplicon sequencing, and RNA-sequencing were performed., Results: Transplantation of the HD gut microbes in ND-maintained (THD) mice led to a significant increase in the susceptibility to AF. Gut microbiota analysis showed a significant increase in Desulfovibrionaceae, which generated metabolic endotoxemia in THD mice. Transplantation with HD microbes also resulted in significantly increased levels of circulating lipopolysaccharide (LPS), significant disruption in the histologic architecture of the intestinal tissue, and significantly increased proinflammatory cytokines in the left atrium, indicating that atrial inflammation likely contributed to AF susceptibility. RNA-sequencing showed that the THD group had enhanced activation of ferroptosis and TLR4/NF-κB/NLRP3 inflammasome signalling pathway. Inhibiting the ferroptosis or NLRP3 inflammasome signalling pathway significantly improved atrial fibrosis and reduced susceptibility to obesity-related gut dysbiosis-induced AF., Conclusions: This study provides evidence showing an original causal role of gut microbiota dysbiosis in the pathogenesis of obesity-related AF, which showed elevated LPS and dysregulation of atrial pathologic remodelling by activating ferroptosis and the TLR4/NF-κB/NLRP3 inflammasome signalling pathway., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Shensong Yangxin (SSYX) is a traditional Chinese medicine been widely used clinically to treat various arrhythmias including atrial fibrillation (AF). However, the role and precise mechanism of SSYX in MS-induced AF have not yet been elucidated., Purpose: To elucidate the protective effects of SSYX on MS-induced AF and its possible mechanisms of action., Methods: Male Wistar rats (180-220 g) were fed a 16-week high-carbohydrate, high-fat (HCHF) diet together with 25% fructose in drinking water to produce a MS model. Low-concentration (SSYX-L, 0.4 g/kg) and high-concentration (SSYX-H, 0.8 g/kg) of SSYX were given by daily gavage 8-weeks following HCHF diet for 8-weeks. In vivo electrophysiological study, histological analysis, RNA-sequence (RNA-Seq) and gene ontology (GO) analysis, qRT-PCR and western blot were performed., Results: Both low-concentration and high-concentration of SSYX could inhibit MS-induced AF susceptibility, electrical remodeling and structural remodeling. Results from RNA-sequence analysis revealed intracellular iron homeostasis mediated the protective effect of SSYX against MS. In vivo and in vitro experiments both demonstrated that SSYX up-regulated ferroportin (Fpn) expression and ameliorated intracellular iron overload induced by MS. To verified whether Fpn is the target of SSYX and intracellular iron overload mediated the protective effect of SSYX against MS, adeno-associated virus type 9 (AAV9) delivery system was used. Knocking down Fpn (AAV9-shFpn) markedly aggravated the reactive oxygen species (ROS) production, electrical remodeling and atrial fibrosis induced by MS, leading to a further increase of AF susceptibility induced by MS., Conclusion: Our study demonstrated for the first time that SSYX reduced AF susceptibility, inhibited electrical remodeling and structural remodeling via up-regulating Fpn, decreasing intracellular iron overload and reducing ROS production. These results suggest that SSYX might be a potential therapeutic agent for the treatment of MS-induced AF., (Copyright © 2022. Published by Elsevier GmbH.)

Both long-term and short-term alcohol consumption can cause internal homeostasis imbalance, and they have been proved to be related to the initiation and development of atrial fibrillation (AF). Ferroptosis is an iron-dependent form of non-apoptotic oxidative death which also regulate the cell death homeostasis, but whether it involves in AF induced by alcohol consumption remains unclear. Here, we report a study on the effect of ferroptosis on susceptibility to AF at different alcohol consumption frequencies. We divided the mice into single or frequent excessive alcohol consumption group which given sterile drinking water or alcohol by gavage at different frequencies. Meanwhile, the experimental group was given an intraperitoneal injection of ferroptosis inhibitor (Fer-1) before alcohol drinking. It was found that once exposure to 5 g/kg/d frequent excessive alcohol consumption, compared with the single excessive alcohol consumption group, the mice serum non-heme iron concentration, accumulation of iron and oxidative stress reaction in atrial tissues were increased, while the body weight, heart weight and heart weight to tibia length (HW/TL) ratio were decreased. In addition, the inducibility rate of AF increased, while RR interval, effective refractory periods (ERPs) and 90 % action potential duration (APD 90 ) shortened, as well as QTc interval prolonged. Furthermore, the protein and mRNA expression levels of GPx4, FTL, FTH1, Kv1.5, Kv2.1, Kv4.3, Cav1.2, Serca2α, p-PLB were down-regulated, while PTGS2 was up-regulated. Most of the changes can be partially or completely reversed by Fer-1. These results suggest that frequent excessive alcohol consumption activates ferroptosis and increases the inducibility rate of AF. Nevertheless, inhibition of ferroptosis can balance iron overload disorders and reduce the generation of reactive oxygen species (ROS), eventually decrease the susceptibility to AF. Our results highlight the importance of guidance and warnings for unhealthy alcohol-abuse lifestyle., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Sepsis is a known risk factor for new-onset atrial fibrillation (AF), and previous studies have demonstrated that ferroptosis participates in sepsis-induced organ injury development. Nevertheless, the role of ferroptosis in new-onset AF with sepsis remains largely unknown. This study aims to investigate the underlying mechanisms linking ferroptosis and AF caused by sepsis. LPS-induced endotoxemia is often used to model the acute inflammatory response associated with sepsis. Herein, we reported that ferroptosis was significantly activated in LPS-induced endotoxemia rat model. We also observed that ferroportin (Fpn), the only identified mammalian non-heme iron exporter, was downregulated in the atrium of endotoxemia model. Vulnerability to AF was also significantly increased in a endotoxemia rat model. Additionally, Fpn knockdown by shFpn further increased intracellular iron concentration and oxidative stress and exaggerated the AF vulnerability, which was alleviated by ferroptosis inhibition. Mechanistically, silencing Fpn worsened the alterations in calcium handling proteins expression in a endotoxemia rat model. These findings suggest that Fpn-mediated ferroptosis is involved in the new-onset AF with LPS-induced endotoxemia via worsening the calcium handling proteins dysregulation and provides a novel and promising strategy for preventing AF development in sepsis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: The roles of radiofrequency catheter ablation (RFCA) and pharmacotherapy in treating persistent and long-standing persistent atrial fibrillation (AF) have not been sufficiently investigated. We conducted a multicentre, randomized, controlled trial to compare the effects of RFCA and pharmacotherapy on the prognosis of these patients., Methods and Results: A total of 648 patients with persistent and long-standing persistent AF were enrolled from 30 centres and randomized to either the ablation group (n = 327) or the pharmacotherapy group (n = 321). After 54.2 ± 10.6 months of follow-up, the primary endpoints occurred significantly more rarely in the ablation group than in the pharmacotherapy group (10.4% vs. 17.4%; hazard ratio 0.59, 95% confidence interval 0.48-0.75; P < 0.001). The incidence of stroke/transient ischaemic attack (TIA) was significantly lower in the ablation group (4.2% vs. 7.2%, P < 0.001). Likewise, the incidence of new-onset congestive heart failure (CHF) was lower in the ablation group (2.8% vs. 7.2%, P < 0.001). More patients had sinus rhythm in the ablation group than in the pharmacotherapy group (60.6% vs. 20.9%, P < 0.001), but fewer patients were on antiarrhythmic drugs (24.4% vs. 41.6%, P < 0.001) and warfarin (60.8% vs. 83.9%, P = 0.001). Both the 6-min walk distance and the quality of life (QoL) were improved in the ablation group at the end of follow-up., Conclusion: In patients with persistent and long-standing persistent AF, RFCA-based treatment was superior to pharmacotherapy in decreasing stroke/TIA and new-onset CHF and improving QoL., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

This study aims to explore the intraventricular pressure difference (IVPD) within left ventricle in patients with paroxysmal atrial fibrillation (PAF) by using the relative pressure imaging (RPI) of vector flow mapping (VFM). Twenty patients with paroxysmal atrial fibrillation (PAF) and thirty control subjects were enrolled in the study. Systolic and diastolic IVPD derived from VFM within left ventricle and conventional echocardiographic parameters were analyzed. It was found that the B-A IVPD of left ventricle in PAF patients showed the same pattern as controls-single peak and single valley during systole and double peaks and double valleys during diastole. Basal IVPD was the main component of base to apex IVPD (B-A IVPD). The isovolumetric systolic IVPD was associated with early systolic IVPD, early systolic IVPD was associated with late systolic IVPD, and late systolic IVPD was associated with isovolumic diastolic IVPD (all P < 0.05). The B-A IVPD and basal IVPD during isovolumetric systole, early systole, late systole and isovolumetric diastole in PAF patients significantly decreased (all P < 0.05). The study shows that the B-A IVPD pattern of the PAF group is the same as controls, but systolic B-A IVPD and basal IVPD are significantly reduced in PAF patients. VFM-derived RPI can evaluate left ventricular IVPD in PAF patients, providing a visually quantitative method for evaluating left ventricular hemodynamic mechanics in the patients with PAF.

Background: In the present study, we sought to explore the incidence, risk factors, and clinical impact of peridevice leaks (PDLs), following LAmbre-assisted left atrial appendage closure (LAAC)., Methods: We performed transesophageal echocardiography (TEE) on patients participating in the LAmbre multicenter study, at Day 1 postimplantation, then at 3 and 12 months to assess PDL, device-related thrombus, left atrial appendage (LAA) thrombus, and left atrial thrombus. Clinical events were recorded during follow-up., Result: A total of 152 patients with atrial fibrillation successfully completed LAAC. At 3 months follow-up, 123 patients underwent TEE, with 21 (17%) of them presenting PDL. Among the 121 patients who underwent TEE at 12 months follow-up, 19 (15.7%) presented PDL. Patients with PDL exhibited larger LAA orifice diameters and larger device sizes compared to those in the no leak group. In addition, we found no significant differences in thromboembolic events between patients in the PDL and no leak groups., Conclusion: LAmbre-assisted LAA closure resulted in a relatively low PDL occurrence, and its rate decreased over time. In addition, PDL was more prominent in patients with larger LAA orifice diameter and larger device size. However, the condition was not associated with an increased risk for thromboembolic events., (© 2020 Wiley Periodicals LLC.)

Background: Left atrial appendage closure (LAAC) using the LAmbre device has been associated with prevention of stroke in patients with nonvalvular atrial fibrillation (AF). Here, we interrogated the long-term safety and efficacy of using the LAmbre device in percutaneous LAAC., Methods: We analyzed 56 records of patients with nonvalvular AF undergoing LAAC procedures with the LAmbre device. We collected and analyzed the data to define the safety and efficacy of the LAmbre device implantation., Result: The LAAC was successfully occluded in the 56 patients. Our data showed no serious residual leak or pericardial effusion occurred during the perioperative period. At a mean follow-up of 37.8 ± 23.5 months, there were 7.1%, 3.6%, and 3.6% rates of death, stroke, and device-related thrombus, respectively. There were no cases of severe residual leak or systemic embolism., Conclusion: Taken together, we demonstrate that execution of LAAC with the LAmbre device has high procedural success and prevents AF-related stroke. However, further large-scale trials might be required to confirm our findings., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Guangji Wang et al.)

Aims: Myeloid differentiation protein 1 (MD1) is expressed in the mammalian heart and exerts an anti-arrhythmic effect. Atrial fibrillation (AF) is closely related to heart failure with preserved ejection fraction (HFpEF). The potential impact of MD1 on AF vulnerability in an HFpEF model is not clear., Methods and Results: MD1 knock-out and wild-type (WT) mice were subjected to uninephrectomy and continuous saline or d-aldosterone infusion and given 1% sodium chloride drinking water for 4 weeks. Echocardiographic and haemodynamic measurements, electrophysiological studies, Masson staining, and molecular analysis were performed. Aldosterone-infused WT mice develop HFpEF with left ventricular hypertrophy, moderate hypertension, pulmonary congestion, and diastolic dysfunction. Aldosterone infusion increased the vulnerability of WT mice to AF, as shown by a prolonged interatrial conduction time, shortened effective refractory period, and higher incidence of AF. In addition, aldosterone infusion increased myocardial fibrosis and inflammation, decreased sarcoplasmic reticulum Ca 2+ -ATPase 2a protein expression and the phosphorylation of phospholamban at Thr17, and increased sodium/calcium exchanger 1 protein expression and the phosphorylation of ryanodine receptor 2 in WT mice. All of the above adverse effects of aldosterone infusion were further exacerbated in MD1 knock-out mice compare with WT mice. Mechanistically, MD1 deletion increased the activation of the toll-like receptor 4/calmodulin-dependent protein kinase II signalling pathway in in vivo and in vitro experiments., Conclusions: MD1 deficiency increases the vulnerability of HFpEF mice to AF. This is mainly caused by aggravated maladaptive left atrial fibrosis and inflammation and worsened dysregulation of calcium handling, which is induced by the enhanced activation of the toll-like receptor 4/calmodulin-dependent protein kinase II signalling pathway., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: The CHADS 2 and CHA 2 DS 2 -VASc scoring systems have been proved efficacy to stratify stroke and thromboembolism risk in patients with atrial fibrillation (AF). Whether CHADS 2 and CHA 2 DS 2 -VASc score has predictive value for the prognosis in lacunar stroke (LS) patients remains unclear., Methods: A total of 763 consecutive patients with LS (mean age: 66 ± 12 years; 464 male) were enrolled in this study between January 2013 and December 2014. Patients were divided into LS without AF (LS; n = 679) and LS with AF (LS-AF; n = 84) groups. Measures of performance for the risk scores were evaluated at predicting mortality and restroke in LS-AF and LS without AF patients. All patients were evaluated with respect to clinical features and in-hospital clinical results., Results: During the mean follow-up period of 20 ± 5.8 months, 29 patients (3.8%) experienced all-cause death, 105 patients (13.8%) experienced recurrence of ischemic stroke. Multivariate analysis revealed that CHADS 2 and CHA 2 DS 2 -VASc score were independently associated with all-cause death (all P < .05). On receiver operating characteristic curve analysis, area under the curve (AUC) for CHADS2 score was .942 with a similar accuracy of the CHA2DS2-VASc score (AUC: .908) in predicting mortality in LS-AF patients. Kaplan-Meier curves were conducted according to the cut-off value of CHA 2 DS 2 -VASc score. When CHADS 2 score greater than or equal to 4 point or CHA 2 DS 2 -VASc score greater than or equal to 5 point, the mortality in LS-AF patients was significantly higher compared with those CHADS 2 score less than 4 point or CHA 2 DS 2 -VASc score less than 5 point. However, after adjusting for clinical covariates, CHADS 2 and CHA 2 DS 2 -VASc score could not predict both mortality and restroke in LS without AF patients., Conclusions: The CHADS 2 and CHA 2 DS 2 -VASc score have excellent predictive value for mortality in LS-AF patients but could not predict both mortality and restroke in LS without AF patients., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Early atrial fibrillation (AF) recurrences are common and have been shown to predict AF recurrences late after AF ablation during follow-up. Neiguan point acupuncture has been recognized to be therapeutic in treating AF in clinical practice., Methods and Results: Eighty-five patients were enrolled in succession due to persistent AF. All patients were randomized divided into control group and acupuncture group. In the control group (n = 45), amiodarone was orally taken from the first day after pulmonary vein isolation (PVI). In the acupuncture group (n = 40), patients were treated with Neiguan point acupuncture for 7 days and amiodarone was prescribed as same as the control group after PVI. The levels of inflammatory factors were analyzed before operation, 1 week after the operation and 3 months later. After 3 months, the acupuncture group had a lower rate of early recurrences than the control group (5/40 [12.5%] vs 15/45 [33.3%], P = 0.039). The inflammatory factors level in the two groups were significantly increased after ablation. However, compared with the control group, the levels of TNF-α, IL-6, CRP, TGF-β1, MMP2 in the acupuncture group significantly lower (P < 0.05). In a multivariate analysis, acupuncture was an independent factor associated with a lower rate of early recurrences during the blanking period (odds ratio, 0.17; 95% confidence interval, 0.05-0.63; P = 0.008)., Conclusion: Neiguan point acupuncture combined with amiodarone is superior to amiodarone alone in reducing early recurrences of patients with persistent AF after PVI. The efficacy of Neiguan acupuncture therapy on the early recurrence is associated with the decreased inflammation factors., (© 2019 Wiley Periodicals, Inc.)

Recent years, the role of long non-coding RNAs (lncRNAs) in atrial fibrillation (AF) has been gradually elucidated. In the current study, we measured the expression of ten AF-related lncRNAs to do qRT-PCR analysis. LncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1) was found to be significantly upregulated in AF model and Ang-II-induced mice heart. CACNA1C has been reported as a biomarker in atrial fibrillation. Here, we found that the expression pattern of CACNA1C was consistent with that of KCNQ1OT1. Electrophysiological study was conducted to demonstrate the effect of KCNQ1OT1 and CACNA1C on the Effective refractory period (ERP), interatrial conduction time (IACT), incidence of AF and AF duration of Ang-II-induced mice heart. Mechanically, KCNQ1OT1 contributed to the upregulation of CACNA1C by binding with miR-384. Furthermore, YY1 could activate the transcription of KCNQ1OT1 and CACNA1C. In conclusion, the present study revealed that YY1-induced upregulation of lncRNA KCNQ1OT1 regulates angiotensin II-induced atrial fibrillation by regulating miR-384/CACNA1C axis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The authors sought to assess the clinical outcomes of left atrial appendage (LAA) closure with the LAmbre closure system in patients with nonvalvular atrial fibrillation (NVAF)., Background: Over 90% of thrombi are located in the LAA in NVAF patients., Methods: A prospective, multicenter study was conducted in 153 NVAF patients with CHADS 2 score ≥1., Results: The LAA was successfully occluded in 152 patients. Serious complications occurred in 5 patients. During the 12-month follow-up, ischemic stroke occurred in 2 patients, 1 patient had incomplete LAA sealing, and there was no device embolization., Conclusions: LAA closure with the LAmbre device shows encouraging results for stroke prevention., (Copyright © 2017. Published by Elsevier Inc.)

Atropine (ATr) is well known as a cholinergic antagonist, however, at low concentrations ATr could paradoxically accentuate the parasympathetic actions of acetylcholine (ACh). In 22 pentobarbital anesthetized dogs, via a left and right thoracotomy, a leak-proof barrier was attached to isolate the atrial appendages (AAs) from the rest of the atria. In group 1 (Ach+ATr+Ach), ACh, 100 mM, was placed on the AA followed by the application of ATr, 2 mg/mL. The average atrial fibrillation (AF) duration was 17 ± 7 minutes. After ATr was applied to the AA and ACh again tested, the AF duration was markedly attenuated (2 ± 2 minutes, P < 0.05). In group 2 (ATr+Ach), ATr was initially applied to the AA followed by the application of ACh, 100 mM. There was no significant difference in AF duration (16 ± 4 minutes vs. 18 ± 2 minutes, P = NS). The inhibitory effect of ATr on induced HR reduction (electrical stimulation of the anterior right ganglionated plexi and vagal nerves) was similar between groups 1 and 2. These observations suggest that when ATr is initially administered it attaches to the allosteric site of the muscarinic ACh receptor (M2) leaving the orthosteric site free to be occupied by ACh. The M3 receptor that controls HR slowing does not show the same allosteric properties.

Background: The recurrence rate of atrial fibrillation (AF) after cryoballoon ablation in drug refractory AF patients is high. Late-recurrence of AF has various predictors., Aim: The aim of the study was to explore the related risk factors that can effectively predict late AF recurrence after cryoballoon-based pulmonary vein isolation., Methods: The PubMed and Web of Science databases were searched from 1 January 2013 to 1 August 2016, and studies were chosen that met the pre-stated inclusion criteria. The reference lists of the retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies. The strength of the relationship between different risk factors and late recurrence was assessed by the adjusted hazard ratio., Results: A total of 16 papers met the inclusion criteria and were included in the meta-analysis. The hazard ratio of late atrial arrhythmia recurrence in patients with early recurrence was 4.19 compared with the reference group (95% CI 2.73-6.44, p < 0.00001); that of increased left atrial diameter was 1.25 (95% CI 1.12-1.3, p < 0.0001); that of a long duration of AF before ablation was 1.10 (95% CI 1.04-1.17, p < 0.0009); and that of persistent AF was 2.44 (95% CI 1.30-4.58, p < 0.006). However, there exists significant heterogeneity for each indicator, and a slight publication bias was observed., Conclusions: Our study suggests that early recurrence in the blanking period, increased left atrial size, a longduration of AF before ablation and persistent AF are independent predictors of late recurrence after cryoballoon ablation.

Background: Low-level carotid baroreflex stimulation (LL-CBS) appears to have a potential antiarrhythmogenic effect., Objective: The purpose of this study was to investigate effects of short-term LL-CBS on an atrial fibrillation (AF) canine model., Methods: Group 1 (LL-CBS in the 6 hour-rapid atrial pacing model): Anesthetized dogs underwent 6 hours of rapid atrial pacing (RAP) with concomitant LL-CBS in last 3 hours (LL-CBS group; n = 7) or without (control group; n = 6). Effective refractory period (ERP), ERP dispersion, and window of vulnerability to AF were determined. Left stellate ganglion (LSG) neural activity and heart rate variability were analyzed. Group 2 (LL-CBS on electrically or mechanically induced AF with acetylcholine): In subgroup 1, sustained AF was induced by injecting acetylcholine (Ach; 10 mM) into the anterior right ganglionated plexus at baseline and after 3-hour LL-CBS (n = 7) or sham operation (n = 6). In subgroup 2, Ach was applied onto the right atrial appendage. The time of duration of AF and the average AF cycle length were determined in both subgroups., Results: Group 1: LL-CBS reversed the RAP-induced ERP shortening and increase in ERP dispersion and window of vulnerability (P < .05). The activation of LSG, decrease in high frequency, and increase in low frequency and low frequency/high frequency ratio induced by RAP were also reversed by LL-CBS (P < .05). After 6-hour RAP, plasma norepinephrine and angiotensin II concentrations were significantly lower in the LL-CBS group than in the control group (P < .05). Group 2: The AF duration was shortened and the average AF cycle length was prolonged markedly in both subgroups (P < .01) by LL-CBS., Conclusion: LL-CBS can reverse RAP-induced atrial electrical remodeling and suppress electrically or mechanically induced AF with Ach, and the anti-AF effect is attributed to attenuation of autonomic nerve remodeling, including inhibition of the LSG activity., (Copyright © 2016 Heart Rhythm Society. All rights reserved.)

Objectives: This study investigated whether the serum matrix metalloproteinase-9 level is an independent predictor of recurrence after catheter ablation for persistent atrial fibrillation., Methods: Fifty-eight consecutive patients with persistent atrial fibrillation were enrolled and underwent catheter ablation. The serum matrix metalloproteinase-9 level was detected before ablation and its relationship with recurrent arrhythmia was analyzed at the end of the follow-up., Results: After a mean follow-up of 12.1±7.2 months, 21 (36.2%) patients had a recurrence of their arrhythmia after catheter ablation. At baseline, the matrix metalloproteinase-9 level was higher in the patients with recurrence than in the non-recurrent group (305.77±88.90 vs 234.41±93.36 ng/ml, respectively, p=0.006). A multivariate analysis showed that the matrix metalloproteinase-9 level was an independent predictor of arrhythmia recurrence, as was a history of atrial fibrillation and the diameter of the left atrium., Conclusion: The serum matrix metalloproteinase-9 level is an independent predictor of recurrent arrhythmia after catheter ablation in patients with persistent atrial fibrillation.

Aims: The aim of the present study was to explore the effect of renal sympathetic denervation (RSD) on the progression of paroxysmal atrial fibrillation (AF) in canines with long-term intermittent atrial pacing., Methods and Results: Nineteen beagles were randomly divided into sham-operated group (six dogs), control group (six dogs), and RSD group (seven dogs). Sham-operated group were implanted with pacemakers without pacing; control group were implanted with pacemakers with long-term intermittent atrial pacing; and RSD group underwent catheter-based RSD bilaterally and were simultaneously implanted with pacemakers. Atrial pacing was maintained for 8 h a day and a total of 12 weeks in the control group and RSD group. Echocardiography showed that the left atrial structure and function were significantly improved in the RSD group compared with the control group (P < 0.05). Compared with the control group, the RSD group had fewer incidences of AF and a shorter duration of AF (P < 0.05) after long-term intermittent atrial pacing. In addition to increased atrial effective refractory period (AERP) and AF cycle length, AERP dispersion and P-wave duration and dispersion were significantly decreased in the RSD group compared with the control group (P < 0.05). Atrial morphological evaluation suggested that fibrosis and ultrastructural changes induced by long-term intermittent atrial pacing were markedly suppressed in the RSD dogs compared with controls (P < 0.05). Immunohistochemistry results showed that connexin 43 distribution in RSD mid-myocardial was significantly fewer heterogeneous than that in control mid-myocardial (P < 0.05)., Conclusion: Renal denervation inhibits the progression of paroxysmal AF, which might be related to the suppression of atrial electrophysiology and structural heterogeneity., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Recent studies have identified a variant, rs4845625, in the interleukin-6 receptor (IL6R) gene associated with Atrial Fibrillation (AF). Levels of circulating interleukin-6 and other proinflammatory molecules have consistently been associated with a risk for AF and its recurrence after catheter ablation. This study tested the hypothesis that variant rs4845625 is associated with AF recurrence after catheter ablation in a Chinese Han population., Methods: A total of 278 consecutive patients (mean age 59.4±11.5 years, 43% female) with paroxysmal (36.0%), persistent (59.7%), and permanent (4.3%) AF who underwent catheterablation from 2007-2011, were included in this study. Patients were monitored for 12 months for a recurrence of AF. The SNP rs4845625 was genotyped using high resolution melting analysis., Results: In our study cohort, an early recurrence of AF (ERAF), defined as a recurrence within the first 4 weeks, was observed in 42.8% of the patients, whereas late recurrence of AF (LRAF) (between 3 and 12 months) occurred in 25.9% of the patients. No significant differences in baseline clinical or echocardiographic characteristics were observed between patients with ERAF and LRAF. In contrast, the presence of the T allele of rs4845625 was associated with an increase in the risk for both ERAF (odds ratio [OR]: 1.84, 95% confidence interval [CI]: 1.31-2.59, p = 4.10×10-4) and LRAF (OR: 1.92, 95% CI: 1.30-2.81, p = 0.001). Furthermore, this association was significant after adjustments for age, sex, hypertension, diabetes and other risk factors. No significant relationship between rs4845625 and serum levels of IL6 was observed., Conclusions: In this study, a variant of the IL6R gene, rs4845625, was found confer risk to AF recurrence after catheter ablation in a Chinese Han population. Our findings indicated that the IL6R pathway or inflammation may play important rols in the recurrence of AF after catheter ablation.

Background: The left atrial appendage (LAA) is thought to be the main source of thrombi in patients with atrial fibrillation (AF). The purpose of this study was to describe the LAA orifice diameter, LAA length, and morphologic type of the LAA in Chinese patients with AF as well as to evaluate whether these LAA parameters are associated with a history of stroke in patients with AF from a single center in China., Methods: The study population consisted of 219 consecutive patients with drug-refractory, symptomatic paroxysmal, or persistent AF scheduled to undergo radiofrequency catheter ablation in our single center. All patients underwent extensive clinical assessment and multidetector computed tomography to fully explore the anatomy of the LAA., Results: Of the 219 patients who underwent catheter ablation procedures, chicken wing LAA morphology was found in 114 patients (52.2%), windsock in 52 (23.9%), cauliflower in 29 (13.0%), and cactus in 24 (10.9%). Compared with the windsock LAA morphology, cactus had a larger left atrial diameter ((42.40 ± 3.68) and (37.91 ± 4.32) mm, P = 0.005) and LAA orifice diameter ((27.38 ± 3.70) and (24.14 ± 3.58) mm, P = 0.048). The LAA length was significantly larger in the chicken wing morphology than in the windsock ((37.50 ± 6.74) and (31.33 ± 3.92) mm, P = 0.015) and cauliflower morphologies ((37.50 ± 6.74) and (31.33 ± 3.92) mm, P = 0.015). According to their medical records, 26 patients (11.9%) had suffered a prior stroke. Compared with patients who had no history of stroke, the prior-stroke patients were older (62.04 ± 8.07 and 58.24 ± 9.24, P = 0.047) and there were fewer patients with chicken wing (23.1% and 59.1%, P = 0.001) and more patients with cauliflower (26.9% and 9.8%, P = 0.046). Multivariate Logistic regression analysis demonstrated that age (odds ratio (OR) 1.26; 95% confidence interval (CI) 1.08-1.47; P = 0.003), non-chicken wing morphology (OR 5.82; 95% CI 1.61-21.03; P = 0.007), and LAA orifice diameter (OR 1.25; 95% CI 1.05-1.49; P = 0.014) were independent predictors of stroke after adjusting for all parameters that emerged as potential confounders with univariate analysis., Conclusion: LAA analysis can potentially be used to inform guidance on the implication for stroke risk assessment.

Background: The effects of anxiety and depression on the recurrence of persistent atrial fibrillation (AF) after circumferential pulmonary vein ablation (CPVA) are not clear. Whether CPVA can alleviate the anxiety and depression symptoms of persistent AF patients is unknown., Methods: One hundred and sixty-four patients with persistent AF, of which 43 treated with CPVA (CPVA group) and 103 treated with anti-arrhythmics drugs (medicine group), were enrolled. The Zung Self-Rating Anxiety Scale (SAS), and Zung Self-Rating Depression Scale (SDS) were assessed before and 12 months after treatment in all patients., Results: The scores of SAS (40.33 ± 7.90 vs. 49.76 ± 9.52, P < 0.01) and SDS (42.33 ± 8.73 vs. 48.17 ± 8.77, P < 0.01) decreased 12 months after CPVA. Over 12 months follow-up, AF relapsed in 17 patients in CPVA group. Compared with the data in the recurrent group (17 patients), the scores of SAS and SDS were significantly lower in the non-recurrent group (26 patients) at baseline. The results of multivariate Logistic regression analysis showed normal scores of SAS and SDS were the independent risk factors of AF recurrence after CPVA., Conclusions: Anxiety and depression increase the recurrence risk of persistent AF after CPVA. CPVA can ameliorate the anxiety and depression symptoms in patients with persistent AF.

Unlabelled: Effect of Anxiety and Depression on the Recurrence of Paroxysmal Atrial Fibrillation., Introduction: Whether circumferential pulmonary vein ablation (CPVA) can alleviate anxiety and depression symptoms is unknown and the effect of anxiety and depression on the recurrence of atrial fibrillation (AF) after CPVA is not clear., Methods: Two hundred and ten patients with a diagnosis of paroxysmal AF were admitted in the study. Ninety-eight patients (CPVA group) and 102 patients (medicine group) were treated with CPVA and antiarrhythmic drugs, respectively. All patients were followed up for 1 year. Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), and Short-Form life survey-36 items (SF-36) were assessed before and after follow-up., Results: In CPVA group, the scores of SAS and SDS decreased (41.69 ± 8.32 vs 37.66 ± 4.82, P < 0.001 and 45.01 ± 9.71 vs 40.05 ± 8.56, P < 0.001, respectively) and SF-36 score improved (565.29 ± 143.37 vs 606.84 ± 102.84, P = 0.021) after follow-up. Compared with the data in recurrent patients, the SAS and SDS scores were significantly lower in nonrecurrent patients at baseline (44.68 ± 8.40 vs 38.10 ± 7.55, P < 0.001 and 51.75 ± 9.41 vs 43.96 ± 8.95, P < 0.001, respectively). The results of multivariate logistic regression analysis showed normalized scores of SAS (OR = 3.20, 95% CI [3.05, 3.48], P = 0.023) and SDS (OR = 3.26, 95% CI [3.12, 3.49], P = 0.023) were the independent risk factor of AF recurrence after CPVA., Conclusions: CPVA can ameliorate anxiety and depression, which may contribute to improvement of quality of life in patients with paroxysmal AF. Anxiety and depression increase the recurrence risk of AF after CPVA., (© 2012 Wiley Periodicals, Inc.)

Background: Studies have shown that increased levels of serum uric acid (SUA) are associated with atrial fibrillation (AF). However, less is known about the prognostic value of SUA levels for AF in patients with chronic heart failure (CHF). The aim of the study was to examine the prognostic value of SUA levels for AF in patients with CHF., Methods: Sixteen thousand six hundred and eighty-one patients diagnosed with CHF from 12 hospitals were analyzed. Patients were categorized into AF group and non-AF group, death group, and survival group according to the results of the patients' medical records and follow-up. Univariate and multivariate Cox proportional hazards analyses were performed to examine the risk of AF. The sensitivity and specificity of SUA level in predicting the prognosis were examined by multivariate Cox models and receiver operating characteristic (ROC) curves., Results: The results of univariate predictors in overall patients showed that the higher SUA level was associated with AF. SUA level (HR, 1.084; 95%CI, 1.017 - 1.144; P < 0.001), diuretics (HR, 1.549; 95%CI, 1.246 - 1.854; P < 0.001), and New York Heart Association (NYHA) (HR, 1.237; 95%CI, 1.168 - 1.306; P < 0.001) function class were the independent risk factors for AF. The sensitivity and specificity of the models were 29.6% and 83.8% respectively for predicting AF. When SUA level was added to these models, it remained significant (Wald c(2), 1494.88; P < 0.001 for AF); 58.8% (95%CI, 57.7% - 60.0%) of the observed results were concordant with the separate model., Conclusion: Higher SUA level is associated strongly with AF in patients with CHF. SUA level can increase the sensitivity and specificity in predicting AF.

Background: Previous randomized studies have reported conflicting results on the efficacy of omega-3 fatty acids in preventing atrial fibrillation (AF) recurrences after cardioversion., Objective: A systematic review and meta-analysis of the role of omega-3 fatty acids in the prevention of atrial fibrillation recurrences after cardioversion was conducted., Methods: PubMed, Cochrane Library, Elsevier, Science Online database were searched up to the end of January 2012 to identify all of the studies in human subjects that reported the effects of omega-3 fatty acids on the prevention of atrial fibrillation recurrences after cardioversion., Results: Overall, omega-3 fatty acids had no significant effect on the prevention of AF recurrences after cardioversion (OR: 0.63,95% CI 0.35-1.13; p=0.12). The heterogeneity among the studies was significant (p=0.01, I(2)=66%). Subgroup analysis showed that by administering omega-3 fatty acids at least 4 weeks prior to cardioversion and continuing thereafter, the recurrence rate of AF is significantly low (OR: 0.39, 95% CI 0.25-0.61; p<0.0001)., Conclusion: In the subgroup administered omega-3 fatty acids at least 4 weeks prior to cardioversion and continued thereafter, the recurrence rate of AF was significantly low. More double-blind, randomized, placebo-controlled, multicenter studies with high quality and longer follow-up periods are needed to affirm our conclusion.

Background: Epicardial ganglionated plexi (GP) ablation can prevent atrial fibrillation inducibility. However, the long-term effects of GP ablation on atrial fibrillation have not been elucidated., Methods: Thirteen adult dogs of either sex, weighing 13-17kg, were randomly assigned to a sham-operated group (n=6) or a GP ablation group (n=7). After right thoracotomy, the atrial effective refractory period (AERP) was measured and atrial fibrillation was induced by right atrial rapid burst pacing. Atrial fibrillation and AERP were remeasured after anterior right and inferior right GP ablation in the GP ablation group. The animals were allowed to recover for 8 weeks, after which atrial fibrillation and AERP were measured again. Concentrations of C-reactive protein, tumour necrosis factor-alpha (TNF-α) and interleukin-6 were measured in the blood and atrial tissues., Results: After 8 weeks, atrial fibrillation was induced in all animals in the GP ablation group. AERP and dispersion of AERP (dAERP; maximum AERP minus minimum AERP) were increased after GP ablation but AERP recovered after 8 weeks. There were no significant differences in the concentrations of C-reactive protein, TNF-α or interleukin-6 in venous blood between the two groups and the concentration of C-reactive protein in the atrium did not change before and after GP ablation. However, the concentrations of TNF-α and interleukin-6 in the atrium increased significantly 8 weeks after GP ablation (P<0.05)., Conclusion: Increased concentrations of TNF-α and interleukin-6 in the atrium after GP ablation provide a new causative factor in terms of atrial fibrillation vulnerability., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Background: Previous studies have investigated the technique of linear ablation at the mitral isthmus (MI) in patients with idopathic atrial fibrillation (AF), but MI ablation in patients with prosthetic natural mitral valves (MVs) was not described in detail. Present study sought to summarize our initial experience of ablating MI in patients with prosthetic MVs, Methods: Patients with drug refractory AF and prosthetic MVs were eligible for this study, and the patients with natural MVs but received MI ablation served as control group. Left atrium (LA) mapping and ablation was carried out guided by CARTO system. The anatomy of MI was assessed via computer topography scan., Results: During the study period, a consecutive of 19 patients (male/female = 12/7, mean age of (48 ± 6) years) with prosthetic MVs (16 with metal valves, 3 with biologic valves) entered for AF ablation, other 35 patients served as control group. In study group, mapping along MI documented lower voltages ((2.0 ± 1.0) vs. (3.1 ± 1.3) mV, P = 0.002), more fragmented potentials (19/19 vs. 20/15, P < 0.001), and higher impedance ((132 ± 34) vs. (110 ± 20) Ω, P = 0.004). After initial ablation, more residual gaps along the MI lesions were found in study group (2.4 ± 0.4 vs. 1.7 ± 0.3, P < 0.001). The mean length of MI ((6.2 ± 3.3) vs. (7.1 ± 2.3) cm, P = 0.25) was comparable between 2 groups, but the MI in study group was much thicker ((3.1 ± 1.8) vs. (2.1 ± 1.07) cm, P = 0.01) and all were found as pouch type (19/19 vs. 2/35, P < 0.001). The follow-up results were comparable (65.1% vs. 72.3%, P = 0.30)., Conclusion: For patients with prosthetic MVs, linear ablation at MI could be successfully carried out despite anatomical and pathological changes.

Aims: The effects of ganglionated plexi (GP) ablation on atrial fibrillation (AF) inducibility and atrial autonomic innervation remodelling have not been elucidated., Methods and Results: Thirteen dogs were randomly divided into sham-operated group and GP ablation group. All animals underwent a right thoracotomy at the fourth intercostal space. Atrial fibrillation inducibility was assessed by burst rapid pacing at right atrium (RA). After anterior right GP and inferior right GP ablation, AF inducibility was assessed in the GP ablation group. The animals were allowed to recover for 8 weeks, after which, AF was measured again. The levels of atrial natriuretic peptide (ANP) in blood and atrial tissues were examined by radioimmunoassay. Immunocytochemical staining of cardiac nerves was performed in tissues from the dogs. Atrial fibrillation was induced easily in the GP ablation group after 8 weeks although AF was not observed in the sham-operated group, and after instant GP ablation. Compared with that in the sham-operated group, the levels of ANP in the blood and RA increased significantly 8 weeks after GP ablation (111.4 +/- 18.2 vs. 175.1 +/- 25.9; 184.9 +/- 36.3 vs. 299.1 +/- 32.5; P < 0.05). In the GP ablation group, the density of growth-associated protein 43-positive, tyrosine hydroxylase-positive, and choline acetyltransferase-positive nerves in the RA was 821 +/- 752, 481 +/- 627, and 629 +/- 644 per mm(2), respectively, which was significantly (P < 0.01) lower than the nerve density in sham-operated tissues (2590 +/- 841, 1752 +/- 605, and 3147 +/- 886 per mm(2), respectively)., Conclusion: Atrial autonomic innervations remodelling may be the mechanism of induced AF after GP ablation.

Background: The crista terminalis (CT) is known to initiate and maintain atrial arrhythmia, and is affected by autonomic tone, but the underlying mechanisms are poorly understood. This study sought to study the relation between autonomic innervation in CT and atrial arrhythmia., Methods: Thirty adult canines were used in the present study. Tissues of the CT and the pectinate muscles (PM) were obtained from 10 dogs for electrophysiology studies. Furthermore, tissues of the superior CT, the inferior CT, and the PM were obtained from 10 dogs for immunohistochemistrical studies. Anti-growth-associated protein 43 (GAP43), anti-tyrosine hydroxylase (TH), and choline acetyltransferase (ChAT) antibodies for immunocytochemical staining of cardiac nerves were performed to test the densities of autonomic nerve. Densities of I K,ACh in the superior CT, the inferior CT, and the PM cells were measured by patch clamp in the other 10 dogs., Results: With the pacing cycle length decreased, the amplitude of delayed after depolarization (DAD) increased and DAD-induced triggered activity was induced in the CT but not in PM with norepinephrine administration. GAP-43 and TH-positive nerves in the superior CT and the inferior CT were all significantly higher than in the PM (GAP-43: 6,250 +/- 1,928 vs 1,247 +/- 747, 2,855 +/- 1,579 vs 1,247 +/- 747; TH: 3,140 +/- 1,240 vs 690 +/- 720, 1,210 +/- 980 vs 690 +/- 720; P < 0.01). Furthermore, the GAP-43 and TH-positive nerves in the superior CT were higher than in the inferior CT. However, there were no significant differences in ChAT-positive nerves and I K,ACh in the superior CT, the inferior CT, and the PM., Conclusions: The higher densities of adrenergic nerve in the CT play an important role in the genesis of atrial arrhythmia.

Atrial fibrillation (AF) is the most commonly sustained arrhythmia in clinical practice. Despite the extensive studies, the pathophysiology of AF, however, remains incompletely understood. Studies have demonstrated that oxidative stress may be involved in cardiac structural and electrical remodeling. More recently, a growing body of evidence suggests that oxidative stress is associated with the development of AF. The evidence for the hypotheses included that: (1) histological studies have demonstrated oxidative damage in both AF patients and animal models of AF; (2) oxidative stress markers are increased in AF patients, and are associated with the presence of AF; (3) drugs that have antioxidant properties show beneficial effects on AF development. Although the studies suggest the association between oxidative stress and AF, the exact pathogenesis of oxidative stress in AF development remains elusive and requires further investigation. Specifically, the causality between oxidative stress and AF; the levels of the oxidative stress in various types of AFs and their role in the pathogenesis of AF; the effects of strategies to reduce oxidative stress on atrial structural and electrical remodeling, and their exact role in the development of AF. Oxidative stress may provide a scientific basis for further research on the underlying mechanisms of AF and may target for pharmacological interruption of AF.

Objective: This prospective and randomize-controlled trial was designed to investigate the effects of antiarrhythmic drug use (AADs) on atrial fibrillation (AF) recurrence in atrial fibrillation patients post circumferential pulmonary vein ablation (CAPV)., Methods: Seventy-four consecutive AF patients underwent CAPV (41 paroxysmal and 33 drug refractory AF) were randomly assigned to receive placebo (Group A) or AADs (Group B) for 3 months. Monthly standard electrocardiograms (ECG) and Holter monitoring were performed to assess AF recurrences during 17 - 28 months follow-up., Results: CAPV was successful in all patients. The recurrence rate of AF in Group B was significantly lower than that in Group A at 3 months post CAPV (13.5% vs. 37.8%, P < 0.01) and similar thereafter (29.7% vs. 24.3% at 12 months and 8.1% vs. 8.1% at more than 12 months, all P > 0.05). There was also no significant difference in terms of total recurrence rate between the two groups (37.8% vs. 32.4%, P > 0.05)., Conclusion: Post CAPV antiarrhythmic drug therapy could only decrease the early AF recurrence rate but was not effective for decreasing AF recurrence rate on later stage.

Introduction: It has been demonstrated that pulmonary veins (PVs) play an important role in initiation and maintenance of paroxysmal atrial fibrillation (AF). However, it is not clearly known whether a single PV acts as electrophysiological substrate for paroxysmal AF., Methods and Results: This study included five patients with paroxysmal AF. All patients underwent complete PV isolation with continuous circular lesions (CCLs) around the ipsilateral PVs guided by a three-dimensional mapping system. Irrigated radiofrequency (RF) delivery was performed during AF on the right-sided CCLs in two patients and on the left-sided CCLs in three patients. The incomplete CCLs resulted in a change from AF to atrial tachycardia (AT), which presented with an identical atrial activation sequence and P wave morphology. Complete CCLs resulted in AF termination with persistent PV tachyarrhythmias within the isolated PV in all five patients. PV tachyarrhythmia within the isolated PV was PV fibrillation from the left common PV (LCPV) in two patients, PV tachycardia from the right superior PV (RSPV) in two patients, and from the left superior PV in one patient. All sustained PV tachyarrhythmias persisted for more than 30 minutes, needed external cardioversion for termination in four patients and a focal ablation in one patient. After the initial procedure, an AT from the RSPV occurred in a patient with PV fibrillation within the LCPV, and was successfully ablated., Conclusion: In patients with paroxysmal AF, sustained PV tachyarrhythmias from a single PV can perpetuate AF. Complete isolation of all PV may provide good clinical outcome during long-term follow-up.

Background: Pulmonary veins (PVs) can be completely isolated with continuous circular lesions (CCLs) around the ipsilateral PVs. However, electrophysiological findings have not been described in detail during ablation of persistent atrial fibrillation (AF)., Methods and Results: Forty patients with symptomatic persistent AF underwent complete isolation of the right-sided and left-sided ipsilateral PVs guided by 3D mapping and double Lasso technique during AF. Irrigated ablation was initially performed in the right-sided CCLs and subsequently in the left-sided CCLs. After complete isolation of both lateral PVs, stable sinus rhythm was achieved after AF termination in 12 patients; AF persisted and required cardioversion in 18 patients. In the remaining 10 patients, AF changed to left macroreentrant atrial tachycardia in 6 and common-type atrial flutter in 4 patients. All atrial tachycardias were successfully terminated during the procedure. Atrial tachyarrhythmias recurred in 15 of 40 patients at a median of 4 days after the initial ablation. A repeat ablation was performed at a median of 35 days after the initial procedure in 14 patients. During the repeat study, recovered PV conduction was found in 13 patients and successfully abolished by focal ablation of the conduction gap of the previous CCLs. After a mean of 8+/-2 months of follow-up, 38 (95%) of the 40 patients were free of AF., Conclusions: In patients with persistent AF, CCLs can result in either AF termination or conversion to macroreentrant atrial tachycardia in 55% of the patients. In addition, recovered PV conduction after the initial procedure is a dominant finding in recurrent atrial tachyarrhythmias and can be successfully abolished.

Aims Atrial structural and electrical remodelling is a major reason for the initiation and perpetuation of atrial fibrillation (AF). Ubiquitin-specific protease 38 (USP38) is a deubiquitinating enzyme, but its function in the heart remains unknown. The aim of this study was to investigate the effect of USP38 in pressure overload-induced AF. Methods and results Cardiac-specific knockout USP38 and cardiac-specific transgenic USP38 mice and their corresponding control mice were used in this study. After 4 weeks with or without aortic banding (AB) surgery, atrial echocardiography, atrial histology, electrophysiological study, and molecular analysis were assessed. Ubiquitin-specific protease 38 knockout mice showed a remarkable improvement in vulnerability to AF, atrial weight and diameter, atrial fibrosis, and calcium-handling protein expression after AB surgery. Conversely, USP38 overexpression further increased susceptibility to AF by exacerbating atrial structural and electrical remodelling. Mechanistically, USP38 interacted with and deubiquitinated nuclear factor-kappa B (NF-κB), and USP38 overexpression increased the level of p-NF-κB in vivo and in vitro , accompanied by the upregulation of NOD-like receptor protein 3 (NLRP3) and inflammatory cytokines, suggesting that USP38 contributes to adverse effects by driving NF-κB/NLRP3-mediated inflammatory responses. Conclusion Overall, our study indicates that USP38 promotes pressure overload-induced AF through targeting NF-κB/NLRP3-mediated inflammatory responses. [ABSTRACT FROM AUTHOR]

Aims: The roles of radiofrequency catheter ablation (RFCA) and pharmacotherapy in treating persistent and long-standing persistent atrial fibrillation (AF) have not been sufficiently investigated. We conducted a multicentre, randomized, controlled trial to compare the effects of RFCA and pharmacotherapy on the prognosis of these patients.Methods and Results: A total of 648 patients with persistent and long-standing persistent AF were enrolled from 30 centres and randomized to either the ablation group (n = 327) or the pharmacotherapy group (n = 321). After 54.2 ± 10.6 months of follow-up, the primary endpoints occurred significantly more rarely in the ablation group than in the pharmacotherapy group (10.4% vs. 17.4%; hazard ratio 0.59, 95% confidence interval 0.48-0.75; P < 0.001). The incidence of stroke/transient ischaemic attack (TIA) was significantly lower in the ablation group (4.2% vs. 7.2%, P < 0.001). Likewise, the incidence of new-onset congestive heart failure (CHF) was lower in the ablation group (2.8% vs. 7.2%, P < 0.001). More patients had sinus rhythm in the ablation group than in the pharmacotherapy group (60.6% vs. 20.9%, P < 0.001), but fewer patients were on antiarrhythmic drugs (24.4% vs. 41.6%, P < 0.001) and warfarin (60.8% vs. 83.9%, P = 0.001). Both the 6-min walk distance and the quality of life (QoL) were improved in the ablation group at the end of follow-up.Conclusion: In patients with persistent and long-standing persistent AF, RFCA-based treatment was superior to pharmacotherapy in decreasing stroke/TIA and new-onset CHF and improving QoL. [ABSTRACT FROM AUTHOR]

Endocrine disorders are associated with various tachyarrhythmias, including atrial fibrillation (AF), ventricular tachycardia (VT), ventricular fibrillation (VF), and bradyarrhythmias. Along with underlying arrhythmia substrate, electrolyte disturbances, glucose, and hormone levels, accompanying endocrine disorders contribute to development of arrhythmia. Arrhythmias may be life-threatening, facilitate cardiogenic shock development and increase mortality. The knowledge on the incidence of tachy- and bradyarrhythmias, clinical and prognostic significance as well as their management is limited; it is represented in observational studies and mostly in case reports on management of challenging cases. It should be also emphasized, that the topic is not covered in detail in current guidelines. Therefore, cardiologists and multidisciplinary teams participating in care of such patients do need the evidence-based, or in case of limited evidence expert-opinion based recommendations, how to treat arrhythmias using contemporary approaches, prevent their complications and recurrence in patients with endocrine disorders. In recognizing this close relationship between endocrine disorders and arrhythmias, the European Heart Rhythm Association (EHRA) convened a Task Force, with representation from Asia-Pacific Heart Rhythm Society (APHRS) and Sociedad Latinoamericana de Estimulación Cardíaca y Electrofisiología (SOLAECE), with the remit of comprehensively reviewing the available evidence and publishing a joint consensus document on endocrine disorders and cardiac arrhythmias, and providing up-to-date consensus recommendations for use in clinical practice. [ABSTRACT FROM AUTHOR]