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Background: Though pulsed-field ablation (PFA) has demonstrated an excellent safety profile in reducing collateral injury to the esophagus and phrenic nerve, it is still associated with specific effects, including electrode heating, hemolysis, and electrolysis due to excessive energy dispersion. Whether saline irrigation during PFA application could mitigate these risks remains unclear.

Methods: To comprehensively evaluate the effect of irrigation with the variable-loop circular catheter (VLCC), the following experiments were performed: a) ex-vivo potato model: to evaluate the lesion depth, bubble formation, and thermal effects in different irrigation regimens; b) in vitro blood pool and cardiac ablation: to determine the hemolysis status and tissue temperature change after PFA; c) in vivo swine ablation (n=8), and d) clinical randomized trial (n=25): to compare the efficacy and safety profile between low (4 ml/min) and high (30 ml/min) flow irrigation using the VLCC.

Results: Though peak core temperatures at 5 mm depth were all < 50℃ under low- and high- irrigation, high irrigation significantly mitigated the instant electrode and deep tissue heating both in the potato and isolated cardiac models. Ex vivo potato slices showed that high-flow irrigation produced the deepest lesion sets when compared to low-flow irrigation (5.94±0.29 mm vs. 5.36±0.33 mm, P=0.043). Assessment from a high-speed camera and bubble detector demonstrated that high-flow irrigation significantly reduced the total number of gaseous bubbles (54.50 IQR 53.00-56.75 vs. 82.00 IQR 72.00-83.00, P<0.001) and eliminated the occurrence of larger bubbles. The high-flow irrigation group showed a smaller increase in the level of free hemoglobin immediately after the procedure across the blood pool, swine, and clinical models. Haptoglobin and lactate dehydrogenase levels were also attenuated by high irrigation in the in-vivo swine model and clinical trial. One swine in the low-irrigation group developed an acute cerebral lesion (3 mm). The clinical trial confirmed that the incidence of silent cerebral lesions was significantly lower in the high-flow irrigation group (16.7% vs. 66.7%, P=0.036).

Conclusion: Proper saline irrigation during PFA with VLCC may mitigate electrode-associated hemolysis, reduce electrode and tissue temperature, limit bubble aggregation, and be associated with a lower incidence of silent cerebral lesions, the clinical significance of which remains unclear.

Novel technologies and ablation techniques for identification of atrial fibrillation (AF) sources and personalized substrate modification may be required to improve outcomes for persistent AF. We hypothesize that a unison of electrophysiologic phase and optical flow mapping could be used to selectively prioritize ablation targets and optimize patient outcome while minimizing the tissue ablated. We aim to evaluate the efficacy of a novel electro-optic flow (EOF)-based ablation strategy for persistent AF patients using a virtual cohort of bi-atrial digital twins (DTs). A patient cohort (n=250) from a bi-atrial in silico population with different atrial fibrosis distributions was utilized to simulate five AF episodes per case. Phase singularity (PS) and average optical flow maps were computed for post-pulmonary vein isolation (PVI) sustained AF. Concordant regions, overlapping in at least three binarized PS maps were used to define regions to search for the highest optical curl cluster centroids as candidate EOF targets. Using optical curl as the weight, the centroid of five candidate EOF targets were computed and selected as an ablation target inside each concordant boundary. Six clinical ablation strategies were simulated. An inducibility-to-ablated tissue area metric was calculated to evaluate the efficacy of the tested ablation strategies. The pipeline automatically identified extra-PV targets and generated patient-specific EOF ablation plans. Electro-optic flow-guided ablations resulted in an average 32±2% AF inducibility, outperforming PVI (90±5%), and PVI+empiric (87±6%). Consensus-EOF further reduced inducibility to 20±5% while sparing 28±2% tissue as compared to PVI+PS ablation. Consensus mapping provides a novel method for assessing the dynamic nature of AF, while EOF offers a promising multimodal metric for identifying critical ablation targets outside of PVI. These findings underscore the potential of EOF-guided ablation planning in advancing the clinical translation of DT-based personalized therapy for PeAF patients.

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.