Understanding electrical pulmonary vein antrum for paroxysmal atrial fibrillation: Further look into superhigh-density electroanatomic mapping of the left atrium.

BACKGROUND: An isolation line placed at the pulmonary vein antrum (PVA) area is superior to ostium level in atrial fibrillation (AF) control. However, less is known about the electrophysiologic characteristics of the PVA. OBJECTIVE: The aim of this study was to describe the electrophysiologic properties of the PVA. METHODS: High-density mapping of the left atrium was performed in 18 paroxysmal AF (PAF) patients and 9 age- and sex-matched paroxysmal supraventricular tachycardia (PSVT) patients. Each PVA was divided into 8 segments, and the pulmonary vein (PV) was divided into 4 segments. The electrophysiologic properties included slow conduction, complex fractionated electrograms, and effective refractory period (ERP). RESULTS: Slow conduction was more prevalent at the PVA (43.2% ± 19.5% vs 14.7% ± 13.0%; P = .001) and PV (61.9% ± 16.4% vs 9.1% ± 9.0%; P < .001) in PAF patients than in PSVT patients during sinus rhythm. Similarly, the area with complex fractionated electrograms was significantly larger at the PVA (133.8 [61.6-233.2] mm2 vs 0.0 [0.0-41.4] mm2; P = .011) in PAF patients during sinus rhythm. The ERP of the PVA was longer in PAF patients than in control at the drive length of 600 ms (260 [230-280] ms vs 220 [190-250] ms; P = .001) and 400 ms (230 [205-250] ms vs 200 [190-220] ms; P = .007). The ERP net difference between the PV and PVA is larger in PAF patients than in control both at 600-ms pacing (40 [20-70] ms vs 10 [10-30] ms; P < .001) and at 400-ms pacing (40 [20-60] ms vs 20 [10-30] ms; P < .001). CONCLUSION: PAF patients have the PVA electrical substrate including slow conduction, complex fractionated electrograms, and ERP dispersion.

Single Exposed Zn (0002) Plane and Sustainable Zn-Oriented Growth Achieving Highly Reversible Zinc Metal Batteries.

To prevent dendrite growth and hydrogen evolution reaction, directional epitaxial growth of Zn2+ ions on Zn anode, especially along the lowest-surface-energy Zn (0002) plane, is pursued for highly reversible zinc metal batteries (ZMBs). However, designing single Zn (0002) exposed anodes for sustained uniaxial crystalline orientation of Zn electroplating faces challenges. Herein, we propose an anode engineering that utilizes a low lattice mismatch substrate and ordered Zn2+ migration channels to modify Zn anodes with single (0002) surface exposure and sustainable Zn-oriented growth, yielding highly reversible ZMBs. A vapor-deposited metal-organic framework Cu3(C6O6)2 film on brass foil shows low lattice mismatch (4.24 %) with electrodeposited Zn anodes, enabling the exposure of a single (0002) plane. Furthermore, the low desolvation energy (-1.36 eV) between solvated Zn2+ ions and the ordered porous Cu3(C6O6)2 film guides sustainable Zn-oriented nucleation along the Zn (0002) surface. Consequently, the Zn||Zn cells with brass-Cu3(C6O6)2 substrate shows a high average Coulombic efficiency of 99.55 % after 4,000 cycles at 10 mA cm-2. This work provides a new window to design highly reversible Zn metal anode with a single-exposed Zn (0002) plane and sustainable oriented growth for emerging ZMBs.

Lessons from ablation responses to preferential wavefront in typical atrial flutter.

BACKGROUND: The heterogeneous conduction properties through the cavotricuspid isthmus (CTI) in typical atrial flutter (AFL) have not yet been well elucidated. OBJECTIVE: We sought to investigate preferential conduction through the CTI and the efficacy of ablation targeting preferential wavefront (PW) guided by ultra-high-resolution mapping. METHODS: In retrospective study, 28 patients were enrolled. Wavefront propagation patterns through the CTI and ablation responses at the location of PW were evaluated. In the following prospective study, 23 patients with predominant PW across the CTI were enrolled and assigned to the arm of PW prior ablation and the arm of conventional ablation. RESULTS: Five activation patterns were noticed in the retrospective study. The termination sites were exactly located at the PW in 18 of 28 patients (64.3%). The width of the PW in direct termination group was significantly narrower than that in the CL prolongation before termination group (16.6 ± 1.0 mm vs. 23.3 ± 3.4 mm, respectively, p = 0.025). In the prospective study, the voltage of PW region was significantly higher than non-PW regions both from unipolar and bipolar mapping. 21 of 23 patients (91.3%) were terminated at PW. AFL could no longer be induced immediately after termination. The time from radiofrequency application to AFL termination and to achieve bidirectional conduction block was significantly shorter in PW prior ablation arm than that in conventional ablation group (p < 0.05). CONCLUSIONS: Ablation targeting the PW first could be more efficient to terminate typical AFL and to achieve the endpoint of bidirectional conduction block.

The feasibility of atrial Fibrillatory wave amplitude in predicting ablation outcomes in persistent atrial fibrillation.

BACKGROUND: Atrial fibrosis has a significant impact on the success rate of catheter ablation (CA) treatment of atrial fibrillation (AF). The fibrotic tissues could be reflected by the amplitude of the fibrillatory wave (F-wave). METHODS AND RESULTS: 704 patients with persistent AF and at least 1-year follow-up after CA were included as the internal group. 101 patients from another hospital were used as the external validation cohort. A 12­lead ECG was performed before CA and the maximum FWA in three ECG leads (aVL, aVF, V1) were measured. The FWA score (0 to 6 points according to the amplitude range of the three leads) of each patients was calculated. Five models including clinical features, FWA score, CHA2DS2-VASc score, APPLE score and the fusion of clinical features and FWA score were built. The FWA score was superior to the model constructed by clinical variables, CHA2DS2-VASc score and APPLE score. It not only had good predictive performance for AF recurrence, with an AUC value of 0.812 (95% CI 0.724-0.900), but also showed a significant predictive value for the recurrence rate according to F-wave amplitude. In the external validation cohort, the FWA score showed similar results (AUC 0.768, 95% CI 0.672-0.865). CONCLUSIONS: The present study reveals the significant predictive value of the FWA score for persistent AF ablation recurrence.

Deep learning-based multimodal fusion of the surface ECG and clinical features in prediction of atrial fibrillation recurrence following catheter ablation.

BACKGROUND: Despite improvement in treatment strategies for atrial fibrillation (AF), a significant proportion of patients still experience recurrence after ablation. This study aims to propose a novel algorithm based on Transformer using surface electrocardiogram (ECG) signals and clinical features can predict AF recurrence. METHODS: Between October 2018 to December 2021, patients who underwent index radiofrequency ablation for AF with at least one standard 10-second surface ECG during sinus rhythm were enrolled. An end-to-end deep learning framework based on Transformer and a fusion module was used to predict AF recurrence using ECG and clinical features. Model performance was evaluated using areas under the receiver operating characteristic curve (AUROC), sensitivity, specificity, accuracy and F1-score. RESULTS: A total of 920 patients (median age 61 [IQR 14] years, 66.3% male) were included. After a median follow-up of 24 months, 253 patients (27.5%) experienced AF recurrence. A single deep learning enabled ECG signals identified AF recurrence with an AUROC of 0.769, sensitivity of 75.5%, specificity of 61.1%, F1 score of 55.6% and overall accuracy of 65.2%. Combining ECG signals and clinical features increased the AUROC to 0.899, sensitivity to 81.1%, specificity to 81.7%, F1 score to 71.7%, and overall accuracy to 81.5%. CONCLUSIONS: The Transformer algorithm demonstrated excellent performance in predicting AF recurrence. Integrating ECG and clinical features enhanced the models' performance and may help identify patients at low risk for AF recurrence after index ablation.

Mechanisms of Rehmannioside A Against Systemic Lupus Erythematosus Based on Network Pharmacology, Molecular Docking and Molecular Dynamics Simulation.

The effect of rehmannioside A (ReA) on systemic lupus erythematosus (SLE) is not clear and needs further study. In this study, SLE-related targets were obtained from the DisGeNet and GeneCards databases, while ReA-related targets were obtained from the SwissTarget and SuperPred databases. A protein-protein interaction network of intersected targets was constructed using the STRING platform. After selecting the intersected targets, GO and KEGG enrichment analyses were performed via the R package "clusterProfiler". The relationships between ReA and various core targets were assessed via molecular docking, and molecular dynamics simulation was conducted for optimal core protein-compound complexes obtained by molecular docking. The top five targets in the ranking of degree value were HSP90AA1, HIF1A, PIK3CA, MTOR, and TLR4. Significant biological processes mainly included response to oxidative stress and response to reactive oxygen species. The potential pathways of ReA in the treatment of SLE mainly focused on the PI3K-Akt signaling pathway, neutrophil extracellular trap formation, and Apoptosis. Molecular docking showed that ReA had the highest binding affinity for mTOR, suggesting that mTOR is a key target of ReA against SLE. Molecular dynamics simulations revealed good binding abilities between ReA and mTOR. In conclusion, ReA exerts its effects on SLE through multiple targets and pathways, with mTOR being a key target of ReA against SLE.

An investigation of tomosynthesis on the diagnostic efficacy of spot compression mammography.

To explore the diagnostic efficacy of tomosynthesis spot compression (TSC) compared with conventional spot compression (CSC) for ambiguous findings on full-field digital mammography (FFDM). In this retrospective study, 122 patients (including 108 patients with dense breasts) with ambiguous FFDM findings were imaged with both CSC and TSC. Two radiologists independently reviewed the images and evaluated lesions using the Breast Imaging Reporting and Data System. Pathology or at least a 1-year follow-up imaging was used as the reference standard. Diagnostic efficacies of CSC and TSC were compared, including area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The mean glandular dose was recorded and compared for TSC and CSC. Of the 122 patients, 63 had benign lesions and 59 had malignant lesions. For Reader 1, the following diagnostic efficacies of TSC were significantly higher than those of CSC: AUC (0.988 vs. 0.906, P = 0.001), accuracy (93.4% vs. 77.8%, P = 0.001), specificity (87.3% vs. 63.5%, P = 0.002), PPV (88.1% vs. 70.5%, P = 0.010), and NPV (100% vs. 90.9%, P = 0.029). For Reader 2, TSC showed higher AUC (0.949 vs. 0.909, P = 0.011) and accuracy (83.6% vs. 71.3%, P = 0.022) than CSC. The mean glandular dose of TSC was higher than that of CSC (1.85 ± 0.53 vs. 1.47 ± 0.58 mGy, P < 0.001) but remained within the safety limit. TSC provides better diagnostic efficacy with a slightly higher but tolerable radiation dose than CSC. Therefore, TSC may be a candidate modality for patients with ambiguous findings on FFDM.

Ultrasound-electrochemistry assisted liquid-phase co-exfoliation of phosphorene decorated by Au-Ag bimetallic nanoparticles as nanozyme for smartphone-based portable sensing of 4-nitrophenol.

The stability of black phosphorene (BP) and its preparation and modification for developing and applying devices have become a hot topic in the interdisciplinary field. We propose ultrasound-electrochemistry co-assisted liquid-phase exfoliation as an eco-friendly one-step method to prepare gold-silver bimetallic nanoparticles (Au-AgNPs)-decorated BP nanozyme for smartphone-based portable sensing of 4-nitrophenol (4-NP) in different water sources. The structure, morphology, composition, and properties of Au-AgNPs-BP nanozyme are characterized by multiple instrumental analyses. Bimetallic salts are induced to efficiently occupy oxidative sites of BP to form highly stable Au-AgNPs-BP nanozyme and guarantee the integrity of the lamellar BP. The electrochemistry shortens the exfoliation time of the BP nanosheet and contributes to the loading efficiency of bimetallic nanoparticles on the BP nanosheet. Au-AgNPs-BP-modified screen-printed carbon electrode coupled with palm-sized smartphone-controlled wireless electrochemical analyzer as a portable wireless intelligent sensing platform was applied to the determination of 4-NP in a linear range of 0.6-10 µM with a limit of detection of 63 nM. It enables on-site determination of 4-NP content in lake water, river water, and irrigation ditch water. This work will provide a reference for an eco-friendly one-step preparation of bimetallic nanoparticle-decorated graphene-like materials as nanozymes and their smartphone-based portable sensing application outdoors.

Is it high time to leave the chronic disease care of rural older people to village doctors in China: Insights from a population-based atrial fibrillation screening study.

OBJECTIVE: No study has systematically investigated the quality of long-term care delivered to the rural older people with chronic diseases, such as atrial fibrillation (AF) in China. This study aims to provide contemporary data on the prevalence and awareness of AF among the older population in rural China and to evaluate healthcare knowledge and delivery by village doctors. DESIGN: A cross-sectional study. SETTING: Rural villages in Daqiao and Xiaoji towns of Jiangsu Province, China. PARTICIPANTS: Rural population aged ≥65 years. OUTCOME MEASURES: AF was identified using 12-lead electrocardiography in the first-step (government-led health examination) and single-lead electrocardiography in the second-step (in-house AF screening). Questionnaire surveys were designed for the AF patients and their village doctors. RESULTS: Among 31,342 permanent residents, 12,630 (40.3 %) declined, 7,956 (25.3 %) participated in the first-step and 10,756 (34.3 %) in the second-step. The overall AF detection rate was 4.3 % (810/18,712). Of the 810 AF patients (mean age 76.1±5.9 years; 51.4 % female), 51.5 % were illiterate, only 2.6 % could use smartphone applications, and 8.1 % lived with their children. Common risk factors were older age, men, hypertension, diabetes, prior stroke, vascular disease, and congestive heart failure. Among the 402 patients with known AF, 367 were at high risk of stroke and 10.9 % (40/367) were anticoagulated. Only 17.6 % patients with known hypertension had blood pressure level <140/90 mmHg, and 6.0 % with known diabetes had a fasting blood glucose level ≤6.1 mmol/L. Only 7.3 % (9/122) village doctors reported having the knowledge of integrated care AF management. CONCLUSIONS: This study identified AF in 4.3 %, but AF management was suboptimal in rural China. The current village doctor-dominant rural healthcare system is far from delivering standardized AF management for older patients in rural China. There is an urgent need to empower the village doctors in optimising the care of AF patients.

Infective endocarditis.

First described more than 350 years ago, infective endocarditis represents a global health concern characterised by infections affecting the native or prosthetic heart valves, the mural endocardium, a septal defect, or an indwelling cardiac device. Over recent decades, shifts in causation and epidemiology have been observed. Echocardiography remains pivotal in the diagnosis of infective endocarditis, with alternative imaging modalities gaining significance. Multidisciplinary management requiring expertise of cardiologists, cardiovascular surgeons, infectious disease specialists, microbiologists, radiologists and neurologists, is imperative. Current recommendations for clinical management often rely on observational studies, given the limited number of well conducted randomised controlled trials studying infective endocarditis due to the rarity of the disease. In this Seminar, we provide a comprehensive overview of optimal clinical practices in infective endocarditis, highlighting key aspects of pathophysiology, pathogens, diagnosis, management, prevention, and multidisciplinary approaches, providing updates on recent research findings and addressing remaining controversies in diagnostic accuracy, prevention strategies, and optimal treatment.

Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

RV1+RV3 Index to Differentiate Idiopathic Ventricular Arrhythmias Arising From Right Ventricular Outflow Tract and Aortic Sinus of Valsalva: A Multicenter Study.

BACKGROUND: This study aimed to investigate the predictive value of parameters of every precordial lead and their combinations in differentiating between idiopathic ventricular arrhythmias (IVAs) from the right ventricular outflow tract and aortic sinus of Valsalva (ASV). METHODS AND RESULTS: Between March 1, 2018, and December 1, 2021, consecutive patients receiving successful ablation of right ventricular outflow tract or ASV IVAs were enrolled. The amplitude and duration of the R wave and S wave were measured in every precordial lead during IVAs. These parameters were either summed, subtracted, multiplied, or divided to create different indexes. The index with the highest area under the curve to predict ASV IVAs was developed, compared with established indexes, and validated in an independent prospective multicenter cohort. A total of 150 patients (60 men; mean age, 45.3±16.4 years) were included in the derivation cohort. The RV1+RV3 index (summed R-wave amplitude in leads V1 and V3) had the highest area under the curve (0.942) among the established indexes. An RV1+RV3 index >1.3 mV could predict ASV IVAs with a sensitivity of 95% and a specificity of 83%. Its predictive performance was maintained in the validation cohort (N=109). In patients with V3 R/S transition, an RV1+RV3 index >1.3 mV could predict ASV IVAs, with an area under the curve of 0.892, 93% sensitivity, and 75% specificity. CONCLUSIONS: The RV1+RV3 index is a simple and novel criterion that accurately differentiates between right ventricular outflow tract and ASV IVAs. Its performance outperformed established indexes, making it a valuable tool in clinical practice.

Sex difference in atrial scar prevalence: What can we learn from the STABLE-SR-III trial?

BACKGROUND: Female sex has long been recognized to present a higher risk of stroke and atrial fibrillation (AF) recurrence after circumferential pulmonary vein isolation (CPVI) than in males. However, the underlying mechanisms and benefits of additional low-voltage area (LVA) modification in women remain unknown. OBJECTIVE: The purpose of this study was to investigate differences in atrial substrate and efficacy of additive LVA ablation between sex subgroups. METHODS: Patients with paroxysmal atrial fibrillation (PAF) aged 65-80 years were randomly assigned to either CPVI plus LVA modification (STABLE-SR) group or CPVI alone group. The primary outcome was freedom from atrial arrhythmias after a single ablation procedure. RESULTS: Of 414 patients included in STABLE-SR-III, 204 (49.3%) were women (mean age 70.5 ± 4.7 years). Women demonstrated significantly higher LVA prevalence (51.5% vs 32.9%; P <.001) and LVA burden (6.5% vs 2.9%; P <.001) than men. In the STABLE-SR group, additional LVA ablation was associated with a 63% reduction in recurrence for women compared with the CPVI alone group (10.8% vs 29.4%; adjusted hazard ratio 0.37; 95% confidence interval 0.18-0.75; P for interaction = .040). However, this finding was not observed in men (18.7% vs 18.5%). In the female subgroup, both group 1 (CPVI + LVA modification) and group 3 (CPVI alone in females without LVA) had similar clinical outcomes, which were much better than in Group 2 (CPVI alone in women with LVA) (90% vs 83.8% vs 63.6%; P = .003). CONCLUSION: In older patients with PAF, women demonstrated more advanced atrial substrate, including higher prevalence and burden of LVA compared with men. Women may receive greater benefit from additional LVA modification than men.

A Simple Score to Predict New-Onset Atrial Fibrillation After Ablation of Typical Atrial Flutter.

BACKGROUND: New-onset atrial fibrillation (NeAF) is common after cavotricuspid isthmus-dependent counterclockwise atrial flutter (CCW-AFL) ablation. This study aimed to investigate a simple predictive model of NeAF after CCW-AFL ablation. METHODS: From January 2013, to December 2017, consecutive patients receiving CCW-AFL ablation were enrolled from 3 centres. Clinical, echocardiographic, and electrocardiographic data were collected and followed. Patients from 2 centres and another centre were assigned into the derivation and validation cohorts, respectively. In the derivation cohort, logistic regression was performed to evaluate the ability of parameters to discriminate those with and without NeAF. A score system was developed and then validated. RESULTS: Two hundred seventy-one patients (mean 59.7 ± 13.6 age; 205 male) were analyzed. During follow-up (73.0 ± 6.5 months), 107 patients (39.5%) had NeAF; 190 and 81 patients were detected in the derivation and validation cohorts, respectively. Hypertension, age ≥ 70 years, left atrial diameter ≥ 42 mm, P-wave duration ≥ 120 ms and the negative component of flutter wave in lead II ≥ 120 ms were selected as the final parameters. A weighted score was used to develop the HAD-AF score ranging from 0 to 9. In the derivation cohort, area under the receiver operating characteristic curve (AUC) was 0.938 (95% confidence interval [CI], 0.902-0.974), superior to those of currently used CHA2DS2-VASC (0.679, 95% CI, 0.600-0.757) and HATCH scores (0.651, 95% CI, 0.571-0.730) (P < 0.001). Performance maintained in the validation cohort. CONCLUSIONS: Six years after CCW-AFL ablation, 39.5% of patients developed NeAF. HAD-AF score can reliably identify patients likely to develop NeAF after CCW-AFL ablation.

Anticoagulation Intensity during Appendage Occlusion: Lessons from Silent Cerebral Embolism.

INTRODUCTION: Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolism (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study was to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE. METHODS: It was a prospective observational cohort study. Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging before and after the procedure. RESULTS: A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW p = 0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence. CONCLUSION: Raising the peri-procedure ACT level to a stable 300 s could decrease the risk of the SCE without increasing the major bleeding events.

Mid-term outcome of catheter ablation of idiopathic non-outflow tract ventricular arrhythmias.

BACKGROUND: Catheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs. METHOD AND RESULTS: From 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546). CONCLUSION: Despite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

Cardiac-specific overexpression of CREM-IbΔC-X via CRISPR/Cas9 in mice presents a new model of atrial cardiomyopathy with spontaneous atrial fibrillation.

Atrial cardiomyopathy (ACM) forms the substrate for atrial fibrillation (AF) and underlies the potential for atrial thrombus formation and subsequent stroke. However, generating stable animal models that accurately replicate the entire progression of atrial lesions, particularly the onset of AF, presents significant challenges. In the present study, we found that the isoform of CRE-binding protein modulator (CREM-IbΔC-X), which is involved in the regulation of cardiac development and atrial rhythm, was highly expressed in atrial biopsies from patients with AF. Building upon this finding, we employed CRISPR/Cas9 technology to create a mouse model with cardiac-specific overexpression of CREM-IbΔC-X (referred to as CS-CREM mice). This animal model effectively illustrated the development of ACM through electrophysiological and structural remodelings over time. Proteomics and Chip-qPCR analysis of atrial samples revealed significant upregulation of cell-matrix adhesion and extracellular matrix structural components, alongside significant downregulation of genes related to atrial functions in the CS-CREM mice. Furthermore, the corresponding responses to anti-arrhythmia drugs, i.e., amiodarone and propafenone, suggested that CS-CREM mice could serve as an ideal in vivo model for drug testing. Our study introduced a novel ACM model with spontaneous AF by cardiac-specifically overexpressing CREM-IbΔC-X in mice, providing valuable insights into the mechanisms and therapeutic targets of ACM.

Increased formation of neutrophil extracellular traps induced by autophagy and identification of autophagy-related biomarkers in systemic lupus erythematosus.

Abnormal death of neutrophils and the subsequent ineffective clearance of cell fragments result in production of autoantigens that can lead to systemic lupus erythematosus (SLE). Excessive formation of neutrophil extracellular traps (NETs) can trigger the synthesis of pro-inflammatory cytokines such as type I interferons, leading to tissue damage and immune dysfunction in SLE patients. In this study, we found that a decrease in neutrophil counts in the peripheral blood was correlated with clinical parameters in SLE patients. Patients with low neutrophil counts had high renal activity index and chronicity index scores. NET formation and neutrophil autophagy in SLE patients were increased. The autophagy inhibitor hydroxychloroquine was shown to restrict NET formation. Using comprehensive bioinformatics analysis, we found that the expression of the autophagy-related gene, hypoxia-inducible factor 1A (HIF1A), was enhanced in peripheral neutrophils and in the renal glomeruli in SLE patients. Targeting HIF1A could be a potential therapeutic approach for SLE.

Vitamin D3 mitigates autoimmune inflammation caused by activation of myeloid dendritic cells in SLE.

Systemic lupus erythematosus (SLE) is an autoimmune disease in which defective T cells, immune complex deposition and other immune system alterations contribute to pathological changes of multiple organ systems. The vitamin D metabolite c is a critical immunomodulator playing pivotal roles in the immune system. Epidemiological evidence indicates that vitamin D deficiency is correlated with the severity of SLE. Our aim is to investigate the effects of 1,25(OH)2D3 (VitD3) on the activation of myeloid dendritic cells (mDCs) by autologous DNA-containing immune complex (DNA-ICs), and the effects of VitD3 on immune system balance during SLE. We purified DNA-ICs from the serum of SLE patients and isolated mDCs from normal subjects. In vitro studies showed that DNA-ICs were internalized and consumed by mDCs. VitD3 blocked the effects of DNA-ICs on RelB, IL-10 and TNF-α in mDCs. Further analysis indicated that DNA-ICs stimulated histone acetylation in the RelB promoter region, which was inhibited by VitD3. Knockdown of the histone deacetylase 3 gene (HDAC3) blocked these VitD3-mediated effects. Co-culture of mDCs and CD4+ T cells showed that VitD3 inhibited multiple processes mediated by DNA-ICs, including proliferation, downregulation of IL-10, TGF-ß and upregulation of TNF-α. Moreover, VitD3 could also reverse the effects of DNA-IC-induced imbalance of CD4+ CD127- Foxp3+ T cells and CD4+ IL17+ T cells. Taken together, our results indicated that autologous DNA-ICs stimulate the activation of mDCs in the pathogenesis of SLE, and VitD3 inhibits this stimulatory effects of DNA-ICs by negative transcriptional regulation of RelB gene and maintaining the Treg/Th17 immune cell balance. These results suggest that vitamin D may have therapeutic value for the treatment of SLE.