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ABSTRACT J‐wave syndromes (JWS)—comprising Brugada syndrome (BrS) and early repolarization syndrome (ERS)—are important causes of malignant ventricular arrhythmias and sudden cardiac death in patients whose hearts appear structurally normal. Since the 2016 consensus, advances in genetics, pathophysiology, and therapy have redefined both understanding and management. BrS, once viewed as a purely electrical disorder, is now recognized along a microstructural–electrical continuum, with sodium‐channel dysfunction and subtle epicardial fibrosis of the right ventricular outflow tract as key contributors. Likewise, ERS—historically considered benign—carries significant risk when inferolateral J‐waves coexist with arrhythmic events. Genetically, SCN5A remains the sole gene with definitive disease association, while polygenic susceptibility materially modulates risk, underscoring complex inheritance. Risk stratification remains challenging: patients with prior cardiac arrest or arrhythmic syncope are highest risk, whereas asymptomatic individuals warrant multiparametric assessment integrating clinical features, ECG markers, electrophysiologic studies, and genetics. For decades, treatment centered on implantable cardioverter‐defibrillators and quinidine, both limited by availability, tolerance, and device complications. More recently, epicardial substrate ablation has emerged as a transformative therapy, with large registries and randomized trials demonstrating durable suppression of ventricular fibrillation and acceptable safety. This APHRS‐organized international consensus updates and extends the 2016 Expert Consensus and the 2022 ESC Guidelines, providing contemporary diagnostic frameworks, pragmatic risk‐stratification tools, and treatment algorithms for BrS and ERS. It emphasizes JWS as a microstructural–electrical disease spectrum and elevates substrate ablation as a major therapeutic advance, while outlining priorities for genetics, risk‐stratification and treatment algorithms.

Background Eosinophilic oesophagitis (EoE) is a food allergen-induced inflammatory disorder characterised by interleukin (IL)-13-mediated oesophageal inflammation and epithelial basal cell hyperplasia (BCH). The role of mitochondria in EoE pathogenesis remains elusive. Design Prompted by single cell transcriptomics data, we interrogated the role of mitochondria in EoE pathobiology using patient biopsies, EoE-mouse models and oesophageal epithelial cells grown in monolayer and three-dimensional (3D) organoid cultures treated with EoE-relevant cytokines. 3D organoids and EoE-bearing mice were treated with omeprazole—a proton-pump inhibitor used as first-line EoE therapy. We performed CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) interference in mouse organoids to identify the key mitochondrial regulatory genes whose depletion may lead to BCH. We analysed mitochondrial membrane potential, mass and superoxide production by flow cytometry, cellular oxygen consumption by respirometry, mitochondrial structures and perturbation of cellular energy homeostasis by immunoblotting. Results Mitochondrial dysfunction appeared to be a hallmark of EoE-related BCH where mitochondrial structural damage was associated with impaired oxidative respiratory capacity, elevation of mitochondrial superoxide and decreased adenosine triphosphate (ATP) production, as corroborated by activation of the adenosine monophosphate (AMP) -activated protein kinase and suppression of mammalian target-of-rapamycin signalling. Depletion of PGC1A, the master regulator of mitochondria biogenesis, recapitulated EoE-related BCH, suggesting that mitochondrial dysfunction drives BCH. Further, omeprazole alleviated mitochondrial damage and dysfunction in EoE-related BCH modelled in mice and patient-derived organoids. Conclusion Mitochondrial dysfunction is tightly linked to perturbation of redox homeostasis in EoE-related BCH, which is promoted by IL-13 and reversible with omeprazole treatment.

Introduction: Increasingly, catheter ablation for atrial fibrillation (AF) has been utilized for rhythm control and to improve quality of life (QoL). Data are limited on patient-centered ablation outcomes in individuals with chronic kidney disease (CKD). Objective: To examine clinical outcomes and QoL following AF ablation in CKD patients from a large patient-reported outcomes (PRO) database. Methods: All patients undergoing AF ablation (2013-2016) at our center were enrolled and assessed for outcomes using automated PRO surveys (baseline, 3 and 6 months after ablation, every 6 months thereafter). This analysis captured data at 1- and 3-year follow-up. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min using the 2021 CKD-EPI equation. The atrial fibrillation symptom severity scale (AFSSS) was used as the main measure for QoL assessment. In addition, data were collected on clinical improvement by patient report, AF burden, and healthcare utilization. Results: A total of 488 patients were identified (66% male, mean age 68.5, 56.2% persistent AF). QoL was significantly improved from baseline median (IQR) AFSSS of 14 (6-19.5) to 3 (0-9) at 1-year and 4 (0-9.5) at 3-year; P≤0.0001 for both. About 90% of patients reported improvement in their overall AF-related symptoms both at 1- and 3-year follow up. The proportion of patients in AF at the time of completion of the baseline survey was 51.2%, and this decreased to 6.2% at 1-year and 9.7% at 3-year follow up (P<0.0001 for both). AF burden was significantly reduced at 1-year and 3-year including frequency and duration of episodes (P<0.05 for both), with associated decrease in ER visits and hospitalizations; P<0.0001 for all comparisons. The proportion of patients on antiarrhythmics decreased from 61.8% at baseline to 35.6% and 22.7% at 1-year and 3-year, respectively (P<0.0001 for both). Conclusions: In a large AF-specific PRO system, catheter ablation for AF was associated with a significant improvement of QoL in most patients with CKD; with a decrease in AF burden and healthcare utilization.

AbstractBackgroundEosinophilic esophagitis (EoE) is a chronic allergic disease associated with type 2 inflammation and epithelial barrier dysfunction. The etiology is unknown, however, genetic heritability studies suggest environmental factors play a key role in pathogenesis. Detergents, such as sodium dodecyl sulfate (SDS), are common ingredients in household products such as dish soap and toothpaste. We hypothesized detergent exposure decreases epithelial barrier function and induces esophageal inflammation.MethodsImmortalized esophageal epithelial cells (EPC2) were cultured in air‐liquid interface (ALI) and exposed to SDS. Barrier function/activity was assessed by transepithelial electrical resistance (TEER), FITC‐dextran flux, and RT‐PCR. Additionally, SDS‐treated mouse esophageal organoids were evaluated for morphology. To investigate the effects of SDS in vivo, mice were treated with 0.5% SDS in drinking water for 14 days. Esophagi were assessed by gross morphology, histopathology, protein expression, and bulk RNA sequencing.ResultsWhen EPC2 cells were exposed to SDS (5 μg/ml) for 96 h, TEER decreased (p = 0.03), and FITC‐dextran flux increased (p = 0.0002). mRNA expression of IL‐33 increased 4.5‐fold (p = 0.02) at 6 h and DSG1 decreased (p < 0.0001) by 72 h. Disrupted epithelial integrity was noted in SDS‐treated esophageal organoids. When mice were exposed to SDS, they showed increased esophageal width, chemokine, and metalloprotease levels. Mice treated with SDS also showed increased IL‐33 protein expression, basal zone hyperplasia, CD4+ cell infiltration, and esophageal eosinophilia. RNA sequencing revealed upregulation of immune response pathway genes.ConclusionExposure to SDS decreases esophageal barrier integrity, stimulates IL‐33 production, and promotes epithelial hyperplasia and tissue eosinophilia. Detergents may be a key environmental trigger in EoE pathogenesis.

Background: Atrial fibrillation (AF) ablation targets improvement in quality of life (QoL). Data is scarce on predictors of QoL improvement following ablation. We aimed to investigate the clinical characteristics underlying differential response in QoL after AF ablation (with or without arrhythmia recurrence). Methods: All patients undergoing AF ablation (2013–2016) at our center were prospectively enrolled in a fully automated patient-reported outcomes registry. A large number of variables were collected including AF symptom severity scale and AF burden (as indicated by AF frequency and duration scores). Patients were divided into 3 groups based on self-report of QoL improvement: remarkable (super responders), mild/moderate, and unchanged or worse (nonresponders). Univariable and multivariable logistic regression models assessed clinical characteristics and QoL outcomes. Results: A total of 956 patients were included (25% females, mean age 63.9). Most patients (≈80%) were super responders (n=761), 138 (14.4%) had mild/moderate improvement, and 57 (5.9%) were nonresponders. The strongest predictors of remarkable QoL improvement were freedom of arrhythmia recurrence (OR, 2.42 [95% CI, 1.27–4.59], P =0.007) and lower AF burden at 12 months. Similarly, higher AF burden was significantly associated with clinical nonresponse. In patients with observed clinical recurrence-QoL mismatch, changes in AF burden at 12 months were the main predictors of QoL outcome, with lower burden predicting higher improvement in QoL and vice versa. Conclusions: Most patients derive significant QoL benefit from AF ablation. Freedom from arrhythmia recurrence and lower AF burden predict remarkable QoL improvement following ablation.