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Introduction: Ventricular tachycardia (VT) in patients with structural heart disease can be life-threatening and may persist despite antiarrhythmic therapy and catheter ablation. When standard treatments are ineffective or contraindicated, stereotactic arrhythmia radioablation (STAR) has emerged as a non-invasive salvage option.

Methods: This prospective, single-center study included 19 patients with structural heart disease and recurrent VT unresponsive to conventional therapy and who were ineligible for ablation. Patients were selected by a multidisciplinary team and underwent cardiac CT and electroanatomic mapping for substrate characterization. STAR was delivered in a single 25Gy fraction using volumetric modulated arc therapy. Primary endpoints included safety (adverse events within 12 months) and efficacy (reduction in VT burden, assessed by ICD-recorded anti-tachycardia pacing [ATP] and shocks).

Results: During a median follow-up of 14 months [IQR 9-15], STAR was associated with a significant reduction in ICD therapies, with an average decrease of 81%. Mean ATP interventions/month dropped from 4.5±6.5 to 0.8±2.3 (p=0.029), and total ICD therapies/month decreased from 4.8±7.0 to 0.9±2.5 (p=0.032). Mild pulmonary injury and pericardial effusion occurred in 22.2% of patients. Most cases were asymptomatic; one patient (5.5%) required non-urgent pericardiocentesis. No significant changes in left ventricular function, valvular status, or coronary artery disease progression (assessed by CAD-RADS and PCAT analysis) were observed. One-year mortality was 33.3%; no deaths were directly attributable to STAR.

Conclusion: STAR shows promise as a safe, noninvasive option for patients with refractory VT and advanced cardiomyopathy. Larger multicenter studies are needed to confirm long-term outcomes and better define its clinical role.

The KCNH2 (hERG) gene encodes the Kv11.1 protein, the pore-forming subunit of the rapid delayed rectifier potassium channel, which plays a key role in cardiac repolarization. We aimed to investigate the function of two Kv11.1 variants in trans, S1021Qfs*98 and A228V, identified in a patient suffering from idiopathic ventricular fibrillation (VF). A detailed clinical and genetic investigation was followed by functional analysis using the whole-cell patch clamp technique, western blot, and mathematical simulations in a human ventricular cell model. In comparison with WT, the current was decreased by 69.5 and 69.2 % in S1021Qfs*98 and S1021Qfs*98/A228V, respectively, which agreed well with a significant decrease in the expression of S1021Qfs*98 channels, but no differences were observed in A228V. The voltage dependence of activation and inactivation and the time course of activation and deactivation remained unchanged. Minor changes were observed in the time course of inactivation and recovery from inactivation in S1021Qfs*98 and S1021Qfs*98/A228V. Arrhythmogenesis based on early afterdepolarizations (EADs) at rest, provoked by hypokalemia, and during β-adrenergic stimulation was suggested by simulations in a human ventricular cell model. To conclude, A228V is a benign variant, whereas S1021Qfs*98 exhibits a loss-of-function defect and dominant negativity. EADs-related arrhythmogenesis was predicted, which explains the pathogenic phenotype of the proband carrying both these variants and experiencing repetitive VF episodes. Based on the findings, we reclassify S1021Qfs*98 as a pathogenic, LQT2-associated variant. The data highlight the importance of functional analysis for the correct management of patients with idiopathic VF and genetic variants.

Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain major contributors to sudden cardiac death, with current therapies limited by our incomplete understanding of the arrhythmogenic substrate. This narrative review explores recent developments in computer-aided techniques for characterizing the arrhythmogenic substrate, focusing on post-myocardial infarction VT. High-resolution cardiac imaging now enables detailed visualization of structural abnormalities, including heterogeneous scar architecture and fatty infiltration. Sophisticated invasive mapping techniques provide insights into local electrophysiological properties, while novel noninvasive mapping approaches offer complementary views of global electrical patterns. Integration of these modalities through computational simulations allows for mechanistic insights into arrhythmia initiation and maintenance, particularly in post-myocardial infarction VT where structural and functional substrates interact in complex ways. Emerging artificial intelligence applications enhance substrate analysis through automated feature extraction and pattern recognition, enabling more sophisticated risk stratification. These computer-aided approaches are advancing from research tools to clinical applications, with early evidence suggesting improved ablation outcomes and better risk prediction. However, significant challenges remain in validation, standardization, and clinical implementation of these innovations. This narrative review highlights recent methodological advances and clinical applications of computer-aided substrate characterization, and conceptualizes future directions toward personalized arrhythmia management, also beyond post-infarction VTs.

Aimes: Cardioneuroablation (CNA) is a catheter-based intervention for reflex syncope and functional bradyarrhythmias that consists in the modulation of the parasympathetic cardiac autonomic nervous by targeting ganglionated plexi (GPs).To compare an ablation strategy of selective GP targeting based on clinical phenotype (tailored approach) versus the standard approach of targeting all GPs (standard approach).

Methods and results: This is a prospective, multicenter European study (ELEGANCE), including 123 patients who underwent CNA (73 men; median age 50 years). Among them 54 (44%) were treated with a tailored approach, targeting the SPSGP for sinus node dysfunction and the IPSGP for AV block symptoms. Procedural data and clinical outcomes were compared with the remaining 69 patients treated using a standard approach.Clinical phenotypes included isolated functional sinus node dysfunction (43.1%), isolated functional AV block (9.8%), and dual presentations (47.2%). In the tailored group 1.6 ± 0.7 GP were targeted per patient. Compared to the standard approach, the tailored group had significantly shorter procedure times (63 vs 85 minutes, p=0.005) and reduced RF time (5.4 vs. 10.4 minutes, p < 0.001). Acute procedural success (tailored: 93% vs. standard: 90%, p = 0.98) and the increase in heart rate (tailored: 40 ± 30.7% vs standard: 40 ± 31.4%, p = 0.96) were similar between groups. During a median 15.9 months [IQR: 9.8, 24.6] follow-up, there were no differences in syncope recurrence rate (log-rank p = 0.96). Inappropriate sinus tachycardia occurred in 8.1% of patients, (tailored 8.6% vs standard 7.4%; p = 0.79).

Conclusions: An individualized CNA strategy, simplified by targeting specific GPs according to patient's pathophysiology, achieved outcomes equivalent to the standard approach while improving procedural efficiency through reduced RF delivery, shorter procedure duration, and limited ablation extent.

Inherited mutations in the KCNH2 gene, which encodes the cardiac hERG potassium channel, are major contributors to arrhythmogenic syndromes such as Long QT and Short QT syndromes. However, clinical interpretation of the growing number of missense variants - many of which are classified as variants of uncertain significance (VUS) - remains a pressing challenge. Here, we present a semi-automated in silico pipeline for predicting hERG variant pathogenicity, acting as a binary classifier and integrating five structural metrics - residue volume, hydrophobicity, charge, steric clashes, and proximity to pathogenic hotspots - into a composite structural pathogenicity score (SPS) scaled from 1 to 5. Applied to 1727 hERG variants from ClinVar and from a French nationwide cohort, this binary classifier, termed SPARC, identified 260 variants as high risk of pathogenicity with SPS ≥ 3.25, of which a representative subset from the French cohort was functionally validated using high-throughput automated patch clamp. Functional phenotyping confirmed the structural predictions, including for several VUS, demonstrating that comprehensive structural scoring can reliably stratify variant pathogenicity. This approach, benchmarked with Alpha Missense and Revel, offers a superior scalable, cost-effective pre-screening tool to guide clinical variant interpretation and prioritization for experimental validation.

Background and aims: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation, but recurrences are frequent. Ablating AF sources beyond PVI may prevent re-initiations. This proof-of-principle in silico study compares a novel source-based ablation approach to conventional strategies in preventing AF re-initiation.

Methods: We compared two conventional ablation strategies (PVI and PVI + posterior wall isolation [box ablation]) with our source-based approach. After PVI, a high-density mapping catheter was guided sequentially upstream of local repetitive conduction patterns until a source was identified. Located targets were ablated, connecting them to non-conducting boundaries. Strategies were compared based on their AF re-initiation rates after incremental pacing, and ablated and electrically isolated areas. Analyses were performed in 7 different scenarios with atria of different sizes, without (n=3) and with fibrosis (n=4) to assess different AF progression stages.

Results: Compared to no ablation, PVI reduced initiation rates in non-fibrotic atria (23±8% control vs. 15±0% PVI) but was less effective with fibrosis (60±4% vs. 53±10%). Box ablation was not superior to PVI while isolating more of the left atrium (isolated area in PVI: 31.5±0.7% vs. box: 43.6±0.5%). Conversely, source ablation completely prevented AF initiation in all scenarios, achieving comparable left atrial isolation with box ablation (isolated area without fibrosis: 36.3±1.4%; with fibrosis: 43.2±2.6%) and including right atrial lesions. Although macro-reentrant tachycardias occurred frequently after source ablation, they were terminated with minimal lesions.

Conclusion: Ablating AF sources using our high-density mapping approach was more efficient in preventing AF re-initiation in silico than anatomy-based strategies.

Aims: To explore the prevalence and incidence of paediatric implantable cardioverter defibrillator (ICD) patients in Sweden and identify risk factors associated with appropriate shocks and adverse events.

Methods and results: We performed a nationwide, retrospective cohort study of ICD-use in paediatric patients (<19 years) between 1995 and 2017; 120 patients underwent ICD implantation at median age 14.7 (range:1.1-18.9) years and were followed for 7.1 (0.3-20.4) years. Fifty-four patients (45%) received a primary preventive ICD. Forty-six percent had cardiomyopathy and 41% had primary electrical disease.The estimated 5-year survival without appropriate shocks was 68% (CI 59-78). Secondary preventive ICDs, and lower weight (<30 kg), at implantation were associated with a higher rate of appropriate shocks, respectively. Lower weight at implantation was not a risk factor for adverse events. Inadequate medication or insufficient compliance were common in patients who experienced shocks. Less than half (46%) of the cases with inappropriate shocks were adequately medicated with good compliance. Secondly, an incidence and prevalence study of all paediatric and adult patients who had an ICD implanted in Sweden was analyzed in four-year periods between 2002 to 2021. The incidence of paediatric ICD-implantations in Sweden peaked at 0.56 per 100,000 person-years in 2010-2013, decreasing to 0.45 per 100,000 person-years in the last study period (2018-2021).

Conclusions: Appropriate shocks were more than twice as common in the youngest patient group, whereas adverse events were not more frequent than in the older patient group. Inadequate medication or lack of compliance were common in connection with ICD-shocks.

Atrial fibrillation (AF) is a growing unmet medical need. To reduce its impact on patients' lives, improvements in stroke prevention therapy, treatment of concomitant conditions, and rhythm control therapy are actively developed: Innovations in anti-thrombotic agents, new anti-arrhythmic drugs (AADs), and novel interventional rhythm control therapies emerge alongside AF-reducing effects of general cardiometabolic therapies. Simple risk scores are slowly replaced by personalized AF risk estimation using quantifiable features. These developments were discussed by over 80 experts from academia and industry during the 10th Atrial Fibrillation NETwork /European Heart Rhythm Association consensus conference from 5 to 7 May 2025. The emerging consensus, described here, is multi-domain therapy combining stroke prevention, rhythm control, and therapy of concomitant cardiovascular conditions. This combines anti-coagulants, AADs, and AF ablation with old and new cardiometabolic drugs that can reduce AF risk, AF burden, and AF-related complications at scale. The paper furthermore describes quantitative traits that may enable a shift towards risk-driven therapy based on AF phenotypes. These can enable adjusted therapy strategies that are safe, accessible, and patient-centred. Applying modern data science and artificial intelligence methods to quantitative phenotypic and genetic features can further improve risk estimation and personalized therapy selection. At the same time, translational and clinical research into reversing the drivers of AF and into improved stroke prevention through new drugs and through combination therapies is needed. Together, these efforts offer pathways towards personalized, patient-centred, multi-modal, and accessible AF management that integrates rhythm control, stroke prevention, and therapy of concomitant conditions to bridge today's practical needs with tomorrow's therapeutic innovation.

Aims: A personalized pulmonary vein isolation (PVI) approach aimed at ablation index (AI) titration according to multidetector computed tomography-derived left atrial wall thickness (LAWT) maps reported high effectiveness and efficiency outcomes for persistent atrial fibrillation (PeAF) ablation. To date, no randomized trials have compared this approach with the standard CLOSE protocol. This non-inferiority randomized controlled trial sought to compare a LAWT-guided PVI with CLOSE protocol-based for PeAF (NCT05396534).

Methods and results: Consecutive patients referred for first-time PeAF ablation were randomized on a 1:1 basis. In the by-LAWT arm, the AI was titrated according to local LAWT, and the ablation line was personalized to avoid the thickest regions at the pulmonary vein antrum. In the CLOSE arm, LAWT information was not available to the operator; the ablation was performed according to the CLOSE study settings: AI is ≥400 at the posterior wall and ≥550 at the anterior wall. Primary endpoint was freedom from atrial arrhythmias recurrence. Secondary endpoints were the major complication rate, procedure time, radiofrequency time, and first-pass PVI rate. One hundred fifty-six patients were included. At 12 month follow-up, no significant difference occurred in atrial arrhythmia-free survival between groups (P = 0.50). In the by-LAWT group, a significant reduction in procedure time (60.5 vs. 80.0 min; P < 0.01) and RF time (14.4 vs. 28.6 min; P < 0.01) was observed. No difference was observed regarding first-pass PVI (P = 0.72) and the major complication rate (P = 0.99).

Conclusions: The PeAF-by-LAWT trial is the first prospective randomized study to demonstrate that a personalized LAWT-guided PVI for PeAF ablation is non-inferior to the standard CLOSE protocol in terms of arrhythmia-free survival while significantly improving procedural efficiency. The study was not powered to detect differences in safety outcomes.