BACKGROUND:The variable-loop circular catheter (VLCC) showed promising outcomes in European and US studies, but evidence is limited in Asian populations. afIRE trial assessed 12-month safety and effectiveness of the VLCC in Chinese patients with symptomatic, drug-refractory paroxysmal atrial fibrillation (AF). METHODS:AfIRE was a prospective, multicenter, single-arm trial for adults undergoing first-time pulmonary vein isolation (PVI) with the VLCC. Primary effectiveness was 12-month freedom from atrial arrhythmia recurrence (systematically assessed by electrocardiogram and Holter monitoring at 3-, 6-, and 12-months post-ablation or when symptomatic), repeat ablation, procedural failure, or Class I/III antiarrhythmic drug use. Safety was defined by incidence of primary adverse events (PAEs). RESULTS:Of 142 patients enrolled, 123 (mean age 57.0 years, 45.5% female) comprised the main-stage cohort (patients treated with the VLCC after roll in). Median procedure, pulsed field ablation (PFA), and fluoroscopy times were 115.0, 36.1, and 5.0 min, respectively. Acute PVI was achieved in all patients, with 89.4% without acute reconnection and 11.4% undergoing non-PV ablation. Twelve-month primary effectiveness success and freedom from symptomatic recurrence were 74.8% and 87.0%, respectively. Safety was favorable, with PAEs in 2 patients (1.6%; vascular complications; unlikely device-related). Multivariable analysis of the primary endpoint showed that preserved left ventricular ejection fraction (≥ 60%) was associated with 86% reduction in odds of 12-month atrial arrhythmia recurrence; diabetes, ≥ 9 symptomatic AF episodes, and < 48 valid PFA applications (16 ablations) numerically increased odds of recurrence. CONCLUSION:The first Asian VLCC experience demonstrated favorable 12-month effectiveness and excellent safety, reinforcing reproducibility across global AF populations. CLINICAL TRIAL REGISTRATION:NCT05552963.

The rise of biologics, including recombinant proteins, gene therapies, and cell therapies, is reshaping the landscape of modern therapeutics, offering new strategies to address previously “undruggable” targets. Cardiovascular diseases (CVDs), the leading cause of mortality worldwide, remain inadequately managed by traditional therapies, but biologics offer a paradigm shift from symptom control to disease modification. This review provides a comprehensive analysis of biologics in cardiovascular medicine, focusing on five key biological processes: cardiac regeneration, cardiac reverse remodeling, genetic cardiomyopathy correction, vascular function modulation, and lipid metabolism modulation. Advances in cardiac regeneration are highlighted by the transplantation of pluripotent stem cells, direct reprogramming, stimulation of endogenous adult cardiomyocyte proliferation, and noncell strategies, all of which aim to restore cardiac tissue integrity. In reverse cardiac remodeling, therapies targeting key signaling pathways, metabolic processes, and contractility-enhancing agents offer promising new approaches for CVD management. The development of gene therapies targeting genetic cardiomyopathies, including gene replacement, genome editing, and gene silencing, is discussed. For vascular function modulation, therapies targeting angiotensinogen, natriuretic peptide receptor 1, and the gut microbiome have been explored as innovative approaches to regulate vascular tone and hemodynamics. Finally, lipid modulation therapies, including agents targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and atherogenic lipoproteins, have redefined the management of dyslipidemia and cardiovascular risk. Collectively, these advancements underscore the transformative potential of biologics to provide targeted, personalized, and disease-modifying treatments for CVD. By addressing both the pathophysiological roots and clinical manifestations of CVDs, biologics represent a promising frontier in cardiovascular medicine.

Cardiometabolic multimorbidity (CMM) is increasingly prevalent among patients with atrial fibrillation (AF), yet its independent impact on post-ablation outcomes, the underlying mechanistic pathways, and the optimal approach to risk prediction in this population remain incompletely defined. We analyzed three independent cohorts of patients undergoing AF catheter ablation: a derivation cohort (n = 3,308), an external validation cohort, and a prospective testing cohort. CMM was defined as the coexistence of two or more cardiometabolic conditions. Cox proportional hazards models and propensity score–matched analyses assessed the association between CMM and AF recurrence, all-cause death, and cardiovascular death. Mediation analysis quantified the contributions of structural, metabolic, and inflammatory pathways. Ten machine learning algorithms were developed and validated for predicting AF recurrence, and model performance was compared against eight established clinical risk scores. Time-dependent ROC analysis was used to evaluate discrimination across multiple follow-up horizons. Among 3,308 patients in the derivation cohort, 686 (20.7

BACKGROUND:Substrate mapping for atrial fibrillation (AF) ablation commonly relies on sinus rhythm (SR) maps, which may overlook rate-dependent electrophysiological changes. OBJECTIVE:This study aimed to evaluate the diagnostic and prognostic value of rate-dependent substrate characterization using high-density omnipolar mapping under rapid pacing. METHODS:In a prospective cohort of 46 patients (5 controls, 22 paroxysmal AF [PAF], 19 persistent AF [PeAF]), bi-atrial conduction velocity (CV) and low-voltage zones (LVZ) were assessed across seven mapping conditions: SR and graded pacing (600, 400, 300 ms) from the distal coronary sinus (CSD) and high right atrium (HRA). RESULTS:CV decreased with faster pacing across all cohorts. At 300 ms, PeAF patients exhibited significantly slower CV than PAF and controls (0.60 ± 0.07 vs. 0.72 ± 0.06 vs. 0.90 ± 0.05 m/s; p < 0.001). The global LVZ burden was greater in PeAF than PAF at 300 ms (58.71 [39.84-68.69] vs. 26.18 [20.94-37.40]; p = 0.009). Decremental pacing was associated with progressive bi-atrial conduction slowing in AF, most pronounced in PeAF (0.76 ± 0.08 vs. 0.74 ± 0.06 vs. 0.69 ± 0.02 vs. 0.60 ± 0.07 m/s; p < 0.001). Rapid pacing at 300 ms showed the numerically highest discriminative capacity. Patients with global CV < 0.67 m/s (AUC 0.749; p = 0.019) or LVZ% > 43.4% (AUC 0.681; p = 0.008) at 300 ms were associated with a higher risk of recurrence. CONCLUSION:Rapid pacing at 300 ms reveals latent bi-atrial substrate occult during SR and may improve risk stratification.

BACKGROUND: Predictive models for recurrence following atrial fibrillation (AF) radiofrequency catheter ablation (RFCA) have potential value in minimizing the risk of recurrent atrial tachyarrhythmias (ATAs). This study aims to develop and validate models to optimize patient selection and post-ablation management. METHODS: A retrospective analysis of consecutive AF patients undergoing RFCA from January 2021 to August 2023 identified risk factors for ATAs recurrence through regression analysis, leading to the development of two predictive models, HWARNER 1 and HWARNER 2, which were preliminarily externally validated. RESULTS: Seven risk factors were identified: Weight > 77.5 kg, HbA1c > 5.75%, RA (dimension / > 46.5 mm), NT-proBNP > 650.18 pg/ml, Early AF recurrence, Redo procedures, and Height > 171.5 cm. Based on these factors, the HWARNER models showed high predictive accuracy with AUCs of 0.775 and 0.773, outperforming established models. Kaplan–Meier analysis revealed significant differences in ATAs recurrence between low- and high-risk groups (HWARNER 1: 93.0% vs. 59.1%, P < 0.001; HWARNER 2: 94.5% vs. 67.9%, P < 0.001) with an median follow-up of one year. In subgroup analysis, HbA1c showed stronger predictive value in patients with BMI > 26.7 (OR = 7.191, 95% CI: 1.375–37.594, P = 0.019). In paroxysmal AF (PAF) patients, the pulmonary vein isolation plus low voltage zones-stepwise (PVI + LVZs-Stepwise) protocol showed no benefit over PVI alone. CONCLUSION: The HWARNER models have the potential to predict ATAs recurrence after RFCA, providing a valuable tool for patient selection and management. HbA1c is an important independent risk factor.

Catheter ablation of premature ventricular contractions (PVCs) arising from the parahisian region poses considerable technical challenges due to the proximity of the His bundle, increasing the risk of atrioventricular (AV) block. We report the case of a 69-year-old woman with symptomatic, high-burden parahisian PVCs refractory to beta-blocker therapy. After structural heart disease was excluded through standard clinical evaluations, a combined approach using high-density mapping and cryoablation was adopted. Using an HD Grid multipolar mapping catheter, the earliest ventricular activation site was precisely identified near the His bundle, with a local activation time of -26 ms. After confirming safety with a test freeze, cryoablation was performed at -75°C for 480 seconds. The PVCs were successfully eliminated without any AV conduction disturbances. At the 12-month follow-up, the patient remained asymptomatic, and the PVC burden had decreased by more than 95%. This case demonstrates the safety and efficacy of combining HD Grid mapping with cryoablation for treating parahisian PVCs.

Introduction: EDIL3 has been identified as an endogenous inhibitor of neutrophil adhesion, playing a critical role in the regulation of inflammation. Despite its known functions, its potential involvement in the pathogenesis of atherosclerosis remains largely unexplored. This study aims to investigate the relationship between EDIL3 and atherosclerosis, with the goal of uncovering new insights that could enhance our understanding and inform the treatment of atherosclerotic diseases. Methods: We crossbred Edil3 -/- mice with Apoe -/- mice to generate Apoe/Edil3 -/- mice. To induce atherosclerosis, we utilized Edil3 knockout combined with a high-fat diet (HFD). We then compared the progression of atherosclerosis between Apoe/Edil3 -/- mice and Apoe -/- mice to investigate the role of EDIL3 in the disease. The severity of atherosclerotic changes, neutrophil infiltration, and efferocytosis were assessed using oil red O staining and immunofluorescence staining. Additionally, RNA sequencing was performed to elucidate the downstream mechanisms through which Edil3 influences the pathogenesis of atherosclerosis. Results: We observed that, compared to Apoe -/- mice, the aorta of Apoe/Edil3 -/- mice displayed a greater number of atherosclerotic plaques, with lesions more widely distributed at both 10 weeks (0.12 vs. 0.33, P = 0.0105) and 22 weeks (0.28 vs. 0.51, P = 0.0122) following the initiation of HFD. Additionally, Apoe/Edil3 -/- mice developed more severe necrotic cores within the lesions, as well as a higher ratio of necrotic area to total lesion area after 10 weeks (44,003 µm 2 vs. 12,055 µm 2 , P < 0.0001; 11.31% vs. 5.02%, P = 0.0011) and 22 weeks (117,644 µm 2 vs. 31,542 µm 2 , P = 0.0013; 13.10% vs. 5.95%, P = 0.0220) of HFD. Further analysis revealed that the ratio of free apoptotic cells to apoptotic cells engulfed by lesional macrophages was significantly higher in Apoe/Edil3 -/- mice (2.375 vs. 0.3575, P = 0.0040). Moreover, RNA sequencing demonstrated that genes associated with efferocytosis, including Pparg , Cd36 , and Abca1 , were downregulated in Apoe/Edil3 -/- mice compared to Apoe -/- mice. Conclusion: EDIL3 may exert a protective role in the pathological mechanism of atherosclerosis by promoting the efferocytosis of macrophages within atherosclerotic plaques.

Most studies have followed patients with persistent atrial fibrillation (PeAF) using 12-lead or 24-h Holter electrocardiography, but this may overestimate the effectiveness of pulsed field ablation (PFA) in the treatment of PeAF. This study aimed to investigate the feasibility of PFA in patients with PeAF and follow-up using insertable cardiac monitoring that can provide information on the actual status of atrial arrhythmia (AA) recurrence after PFA. We prospectively enrolled 49 patients with PeAF who underwent PFA strategy comprising superior vena cava isolation, pulmonary vein isolation, and posterior wall box isolation between December 2022 and January 2024. After median follow-up of 14.1 months, 30 patients (61.22%) had zero AA burden. Kaplan-Meier analysis show that the freedom from recurrence increased with arrhythmia duration thresholds, from 59.54% to 80.50% (duration < 2 min vs. duration > 48 h, p = 0.040). Safety events occurred in two patients (one transient ischemic attack and one pseudoaneurysm). PFA is an effective modality for the treatment of patients with PeAF.

BackgroundCryoballoon ablation (CBA) is extensively utilized to treat paroxysmal atrial fibrillation (PAF). The IceMagicTM Cardiac CryoAblation System (CryoMST, MicroPort EP MedTech CO., Ltd, Shanghai, China) has recently been introduced.ObjectivesTo evaluate the clinical efficiency and potential benefits of CryoMST in PAF.MethodsA propensity-score matched study compared 16 patients with PAF undergoing initial CBA with CryoMST against cohorts treated with Arctic Front Advance™ (n = 48), radiofrequency ablation (RFA, n = 48), and pulsed-field ablation (PFA, n = 16). Peri-procedural and 12-month outcome data were compared among the four groups to assess the efficacy and safety of the CryoMST.ResultsThe CryoMST cohort showed significant reductions in total procedure time [83.00 (Q1, Q3: 75.00, 89.25) vs. 102.00 (Q1, Q3: 85.00, 127.75) min], ablation time [20.00 (Q1, Q3: 18.74, 21.00) vs. 46.00 (Q1, Q3: 38.00, 55.75) min], fluoroscopy time [12.93 (Q1, Q3: 11.15, 16.96) vs. 17.85 (Q1, Q3: 12.35, 23.38) min], fluoroscopy dose [81.80 (Q1, Q3: 69.93, 96.03) vs. 200.00 (Q1, Q3: 134.75, 311.50) mGy], and contrast agent volume [16.00 (Q1, Q3: 11.00, 22.00) vs. 52.50 (Q1, Q3: 45.00, 57.00) mL] compared to the Arctic Front Advance™ group (P < 0.05). CryoMST accurately predicted pulmonary vein occlusion, showing high concordance with pulmonary vein angiograph (sensitivity 89.3%, specificity 100.0%, Kappa value = 0.87, p < 0.001). At 12-month follow-up, rates of arrhythmia recurrence and complications did not differ among the groups.ConclusionsThe CryoMST system demonstrates excellent diagnostic accuracy for pulmonary vein occlusion, obviating the need for routine venography. It significantly reduces procedure time, radiation exposure, and contrast use compared to conventional CBA, while maintaining comparable 12-month efficacy and safety to established ablation modalities for PAF.

INTRODUCTION:The optimized ablation index (AI) value for catheter ablation of atrial fibrillation (AF) remains to be defined. We aimed to compare the efficacy and safety of CLOSE protocol and lower AI protocol in paroxysmal AF. METHODS AND RESULTS:Patients with symptomatic, drug-resistant paroxysmal AF for first ablation were prospectively enrolled from September 2020 to January 2022. The patients were randomly divided into CLOSE group (AI ≥ 550 for anterior/roof segments and ≥400 for posterior/inferior segments) and lower AI group (AI ≥ 450 for anterior/roof segments and ≥350 for posterior/inferior segments). First-pass isolation, acute pulmonary vein (PV) reconnections, 1-year arrhythmia recurrence, and major complications were assessed. Of the 270 enrolled patients, 238 completed 1-year follow-up (118 in CLOSE group and 120 in lower AI group). First-pass isolation in left PVs was higher in CLOSE group (71.2% vs. 53.3%, p = .005). Acute PV reconnections were comparable between groups (9.3% vs. 14.2%, p = .246). At 1 year, 86.4% in CLOSE group versus 81.7% in lower AI group were free from atrial arrhythmia (log rank p = .334). The proportion difference was -4.8% (95% CI: -14.1% to 4.6%), and p = .475 for noninferiority. Stroke occurred in four patients of lower AI group, and no cardiac tamponade, atrioesophageal fistula, major bleeding or death occurred post procedure. CONCLUSION:For patients with paroxysmal AF and treated by AI-guided PV ablation, lower AI is not noninferior to CLOSE protocol.

BACKGROUND:Pulsed field ablation (PFA) has gained attention in cardiac electrophysiology, but data on its application to paroxysmal supraventricular tachycardia are limited. This study aimed to assess the feasibility and safety of PFA and its combination with radiofrequency ablation for treating paroxysmal supraventricular tachycardia.METHODS:A prospective, multicenter, single-arm study was conducted across 8 centers in China. Patients with atrioventricular nodal reentrant tachycardia, atrioventricular reentrant tachycardia, or Wolff-Parkinson-White syndrome underwent ablation using a focal point dual-mode PFA/radiofrequency ablation catheter. PFA was used to achieve acute ablation success, with consolidation using PFA for atrioventricular nodal reentrant tachycardia or near-His accessory pathways and radiofrequency ablation for far-His accessory pathways. Primary and secondary end points were acute ablation success and 180-day follow-up success, respectively.RESULTS:A total of 158 patients (77 with atrioventricular nodal reentrant tachycardia, 63 with atrioventricular reentrant tachycardia, 16 with Wolff-Parkinson-White, and 2 with both atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia) completed the trial. Acute ablation was successful in 157 patients (99.37%). The skin-to-skin procedure time was 89.9 +/- 35.5 min. The median number of PFA discharges was 12 (8-19) with a median effective PFA discharge time of 4.6 (3.2-6.4) ms. Five patients (4 with atrioventricular reentrant tachycardia and 1 with Wolff-Parkinson-White syndrome) experienced paroxysmal supraventricular tachycardia recurrence during the 180-day follow-up period. One patient had a transient first-degree atrioventricular block resolving in 12 hours, and one patient had a transient third-degree atrioventricular block resolving in 24 hours. No permanent atrioventricular block or other adverse events occurred during the ablation procedure or 180-day follow-up period.CONCLUSIONS:PFA demonstrated the feasibility of the treatment of SVT. Reversible first- and third-degree atrioventricular blocks were observed following ablation in one patient each. The preliminary results indicated the safety and feasibility of a combination of PFA and radiofrequency ablation treatment for atrioventricular accessory pathways although it is impossible to determine the relative contribution of PFA.

Background:Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods:We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings:Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation:The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding:SyMap Medical (Suzhou), LTD, Suzhou, China.

We present the case of an elderly woman with congenital dextrocardia who experienced severe palpitations. An electrocardiogram revealed paroxysmal atrial fibrillation, and her medical history unveiled cerebral infarction and renal failure. In the treatment of paroxysmal atrial fibrillation, anticoagulation is a key requirement. Although non-vitamin K antagonist oral anticoagulants are recommended by guidelines, their efficacy is compromised in patients undergoing dialysis due to renal metabolism. In addition, warfarin may cause fluctuations in international normalized ratio, which is not conducive to controlling symptoms of cerebral infarction. To improve the patient's quality of life, we focused on addressing the unique challenges posed by dextrocardia in a one-stop procedure.

Atopic dermatitis (AD) is a common inflammation skin disease that involves dysregulated interplay between immune cells and keratinocytes. Interleukin-38 (IL-38), a poorly characterized IL-1 family cytokine, its role and mechanism in the pathogenesis of AD is elusive. Here, we show that IL-38 is mainly secreted by epidermal keratinocytes and highly expressed in the skin and downregulated in AD lesions. We generated IL-38 keratinocyte-specific knockout mice ( K14 Cre/ + -IL-38 f/f ) and induced AD models by 2,4-dinitrofluorobenzene (DNFB). Unexpectedly, after treatment with DNFB, K14 Cre/ + -IL-38 f/f mice were less susceptible to cutaneous inflammation of AD. Moreover, keratinocyte-specific deletion of IL-38 suppressed the migration of Langerhans cells (LCs) into lymph nodes which results in disturbed differentiation of CD4 + T cells and decreased the infiltration of immune cells into AD lesions. LCs are a type of dendritic cell that reside specifically in the epidermis and regulate immune responses. We developed LC-like cells in vitro from mouse bone marrow (BM) and treated with recombined IL-38. The results show that IL-38 depended on IL-36R, activated the phosphorylated expression of IRAK4 and NF- kappa B P65 and upregulated the expression of CCR7 to promoting the migration of LCs, nevertheless, the upregulation disappeared with the addition of IL-36 receptor antagonist (IL-36RA), IRAK4 or NF- kappa B P65 inhibitor. Furthermore, after treatment with IRAK4 inhibitors, the experimental AD phenotypes were alleviated and so IRAK4 is considered a promising target for the treatment of inflammatory diseases. Overall, our findings indicated a potential pathway that IL-38 depends on IL-36R, leading to LCs migration to promote AD by upregulating CCR7 via IRAK4/NF- kappa B and implied the prevention and treatment of AD, supporting potential clinical utilization of IRAK4 inhibitors in AD treatment.

Psoriatic arthritis (PsA) is an immune-mediated, chronic inflammatory joint disease that commonly occurs as a complication of psoriasis. EGF-like repeats and discoidal I-like domain 3 (EDIL3) is a secreted protein with multiple structural domains and associated with various physiological functions. In this study, we employed a mannan-induced psoriatic arthritis model to investigate the impact of EDIL3 on PsA pathogenesis. Notably, a downregulation of EDIL3 expression was observed in the PsA model, which correlated with increased disease severity. EDIL3 knockout mice exhibited a more severe phenotype of PsA, which was ameliorated upon re-infusion of recombinant EDIL3 protein. The mitigation effect of EDIL3 on PsA depends on its regulation of the activation of monocyte-derived DCs (MoDCs) and T-help 17 cells (Th17). After inhibiting the function of MoDCs and Th17 cells with neutralizing antibodies, the beneficial effects of EDIL3 on PsA were lost. By inducing adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation and suppressing protein kinase B (AKT) phosphorylation, EDIL3 attenuates intracellular glycolysis in MoDCs stimulated by glucose, thereby impeding their maturation and differentiation. Moreover, it diminishes the differentiation of Th17 cells and decelerates the progression of PsA. In conclusion, our findings elucidate the role and mechanism of EDIL3 in the development of PsA, providing a new target for clinical diagnosis and treatment.

Background: A novel visualized steerable sheath, referred to as the Vizigo sheath, has been utilized in clinical interventions. The objective of this study was to evaluate and contrast the efficacy and safety of the Vizigo sheath with other sheaths in the catheter ablation (CA) for focal atrial tachycardia (FAT). Methods: A retrospective cohort study was conducted on consecutive patients with CA for FAT from March 2019 to February 2022. Objectives were to assess the impact of the Vizigo sheath on acute and longterm ablation success rates, procedural and fluoroscopy times, and contact force (CF). Results: A total of 164 patients, mean age 50 +/- 15 years, 97 (59.1%) women, underwent CA of FAT using the Vizigo sheath (N=42), non-visualized steerable sheath (N=36), or other conventional sheath (N=86). Age, sex, body mass index (BMI), presence of hypertension, heart failure, and diabetes mellitus were not significantly different among the three groups. The acute success rate of 94.0% was similar among the three groups. Over a follow-up of 14 +/- 2 months, the Vizigo sheath was associated with superior arrhythmia-free survival (88.1%) when compared to non-visualized steerable (69.4%; P=0.04) and other conventional (72.1%, P=0.046) sheaths. Procedural duration, number of ablation lesions, and ablation times were similar among the three groups. However, the Vizigo sheath was associated with lower fluoroscopy times (e.g., 145 vs. 250 s with Vizigo versus non-visualized steerable sheaths, P=0.03) and higher CF (e.g., average CF 12.0 versus 8.0 g with Vizigo versus non-visualized steerable sheaths, P=0.003). Conclusions: The application of Vizigo sheath can improve the long-term success rate of FAT and reduce the radiation exposure of patients and medical staff in our single-center limited sample study. More research may be needed in the future to confirm our findings.