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The international Working Group of the Signal Summit is a consortium of experts in the field of cardiac electrophysiology dedicated to advancing knowledge on understanding and clinical application of signal recording and processing techniques. In 2023, the working group met in Reykjavik, Iceland, and laid the foundation for this manuscript. Atrial fibrillation (AF) is the most common arrhythmia in adults, with a rapidly increasing prevalence worldwide. Despite substantial research efforts, advancements in elucidating the underlying mechanisms of AF have been relatively modest. Since the discovery of pulmonary veins as a frequent trigger region for AF initiation more than 2½ decades ago, advancements in patient care have primarily focused on technologic innovations to improve the safety and efficacy of pulmonary vein isolation (PVI). Several factors may explain the limited scientific progress made. First, whereas AF initiation usually begins with an ectopic beat, the mechanisms of initiation, maintenance, and electrical propagation have not been fully elucidated in humans, largely owing to suboptimal spatiotemporal mapping. Second, underlying structural changes have not been clarified and may involve different types of reentry. Third, inconsistent definitions and terminology regarding fibrillatory characteristics contribute to the challenges of comparing results between studies. Fourth, a growing appreciation for phenotypical differences probably explains the wide range of clinical outcomes to catheter ablation in patients with seemingly similar AF types. Last, restoring sinus rhythm in advanced phenotypic forms of AF is often not feasible or may require extensive ablation with minimal or no positive impact on quality of life. The aims of this international position paper are to provide practical definitions as a foundation for discussing potential mechanisms and mapping results and to propose pathways toward meaningful advancements in AF research, ultimately leading to improved therapies for AF., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Heterogeneities in ventricular repolarization contribute significantly to the genesis of ventricular fibrillation (VF). Although clinical arrhythmias are spontaneously triggered by premature ventricular complexes, these triggers are difficult to document and little is known about their site of origin., Objectives: The purpose of this study was to characterize spontaneous VF initiation in an experimental model of repolarization heterogeneity and to identify the origin of triggers in relation to the spatial dispersion of repolarization., Methods: Spatially limited repolarization heterogeneity was created in isolated perfused porcine right ventricles (N = 16) by local administration of pinacidil (20 μM) in a terminal branch of the right coronary artery. High-resolution optical mapping and pseudo-electrocardiography were performed under control conditions and after pinacidil perfusion., Results: No arrhythmia occurred at baseline, but 74 VF episodes were observed in 13 hearts (82%) after pinacidil perfusion and were most often initiated by a ventricular trigger with a short coupling interval (297 ± 66 ms). Sixteen VF initiations were optically mapped in 4 hearts. Mapping showed triggers originating in all cases from the border zone between altered and normal repolarization areas where local action potential duration and repolarization time gradients were steep (15.9 and 15.8 ms/mm vs 1.5 and 3.0 ms/mm at nontrigger sites). Optical action potential traces were compatible with a phase 2 reexcitation mechanism. The subsequent VF cycles were driven by activities located in the same region., Conclusion: This model of localized repolarization heterogeneity is able to produce spontaneous VF initiation. Our study demonstrates that VF triggers originate consistently from the border zone of repolarization dispersion., Competing Interests: Disclosures The authors have no conflict of interest to declare., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Sodium channel blocker (SCB) infusion is used to unmask the electrocardiographic pattern of Brugada syndrome. The test may also induce premature ventricular complexes (PVCs) in individuals without Brugada pattern, the clinical relevance of which is little known., Objective: The purpose of this study was to describe the prevalence of short-coupled (Sc) PVCs induced by ajmaline or flecainide in patients with suspected or documented severe ventricular arrhythmias., Methods: We reviewed the SCB tests performed in 335 patients with suspected ventricular arrhythmias and structurally normal hearts in 9 centers. ScPVCs were defined as frequent and repetitive PVCs with an R-on-T pattern on SCB tests. Repeated SCB tests were performed in 7 patients and electrophysiological mapping of ScPVCs in 9., Results: Sixteen patients (8 men; mean age 36 ± 11 years) showed ScPVCs and were included. ScPVCs appeared 229 ± 118 seconds after the initiation of infusion and displayed coupling intervals of 288 ± 28 ms. ScPVC patterns were monomorphic in 12 patients, originating from the Purkinje system in mapped patients. Repetitive PVCs were induced in 15 patients (94%) including polymorphic ventricular tachycardias in 9 (56%). SCB infusion was repeated 45 (interquartile range 0.6-46) months later and induced identical ScPVC in all. SCB test was the only mean to reveal the malignant arrhythmia in 6 patients. Catheter ablation was performed in 9 patients, resulting in arrhythmia elimination in 8 with a follow-up of 6 (interquartile range 2-9) years., Conclusion: SCB can induce ScPVC, mostly from Purkinje tissue, in a small subset of patients with idiopathic ventricular arrhythmias. Its high reproducibility suggests a distinct individual mechanism., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The Brugada pattern manifests as a spontaneous variability of the electrocardiographic marker, suggesting a variability of the underlying electrical substrate., Objective: The purpose of this study was to investigate the response of the epicardial substrate of Brugada syndrome (BrS) to programmed ventricular stimulation and to Na blocker infusion., Methods: We investigated 6 patients (all male; mean age 54 ± 14 years) with BrS and recurrent ventricular fibrillation. Five had no type 1 BrS electrocardiogram pattern at admission. They underwent combined epicardial-endocardial mapping using multielectrode catheters. Changes in epicardial electrograms were evaluated during single endocardial extrastimulation and after low-dose ajmaline infusion (0.5 mg/kg in 5 minutes)., Results: All patients had a region in the anterior epicardial right ventricle with prolonged multicomponent electrograms. Single extrastimulation prolonged late epicardial components by 59 ± 31 ms and in 4 patients abolished epicardial components at some sites, without reactivation by surrounding activated sites. These localized blocks occurred at an initial coupling interval of 335 ± 58 ms and then expanded to other sites, being observed in up to 40% of epicardial sites. Ajmaline infusion prolonged electrogram duration in all and produced localized blocks in 62% of sites in the same patients as during extrastimulation. Epicardial conduction recovery after ajmaline occurred intermittently and at discontinuous sites and produced beat-to-beat changes in local repolarization, resulting in an area of marked electrical disparity. These changes were consistent with models based on microstructural alterations under critical propagation conditions., Conclusion: In BrS, localized functional conduction blocks occur at multiple epicardial sites and with variable patterns, without being reactivated from the surrounding sites., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Strong electric shocks are the gold standard for ventricular defibrillation but are associated with pain and tissue damage. We hypothesized that targeting the excitable gap (EG) of reentry with low-energy surface stimulation is a less damaging and painless alternative for ventricular defibrillation., Objective: The purpose of this study was to determine the conditions under which low-energy surface stimulation defibrillates large mammalian ventricles., Methods: Low-energy surface stimulation was delivered with five electrodes that were 7 cm long and placed 1-2 cm apart on the endocardial and epicardial surfaces of perfused pig left ventricle (LV). Rapid pacing (>4 Hz) was used to induce reentry from a single electrode. A 2 ms defibrillation pulse ≤0.5 A was delivered from all electrodes with a varied time delay from the end of the induction protocol (0.1-5 seconds). Optical mapping was performed and arrhythmia dynamics analyzed. For mechanistic insight, simulations of the VF induction and defibrillation protocols were performed in silico with an LV model emulating the experimental conditions and electrodes placed 0.25-2 cm apart., Results: In living LV, reentry was induced with varying complexity and dominant frequencies ranging between 3.5 to 6.2 Hz over 8 seconds postinitiation. Low-energy defibrillation was achieved with energy <60 mJ and electrode separations up to 2 cm for less complex arrhythmia. In simulations, defibrillation consistently occurred when stimulation captured >75% of the EG, which blocked reentry <2.9 mm in front of the leading reentrant wavefront., Conclusion: Defibrillation with low-energy, single-pulse surface stimulation is feasible with energies below the human pain threshold (100 mJ). Optimal defibrillation occurs when arrhythmia complexity is minimal and electrodes capture >75% of the EG., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Purkinje ectopics (PurkEs) are major triggers of idiopathic ventricular fibrillation (VF). Identifying clinical factors associated with specific PurkE characteristics could yield insights into the mechanisms of Purkinje-mediated arrhythmogenicity., Objective: The purpose of this study was to examine the associations of clinical, environmental, and genetic factors with PurkE origin in patients with PurkE-initiated idiopathic VF., Methods: Consecutive patients with PurkE-initiated idiopathic VF from 4 arrhythmia referral centers were included. We evaluated demographic characteristics, medical history, clinical circumstances associated with index VF events, and electrophysiological characteristics of PurkEs. An electrophysiology study was performed in most patients to confirm the Purkinje origin., Results: Eighty-three patients were included (mean age 38 ± 14 years; 44 [53%] women), of whom 32 had a history of syncope. Forty-four patients had VF at rest. PurkEs originated from the right ventricle (RV) in 41 patients (49%), from the left ventricle (LV) in 36 (44%), and from both ventricles in 6 (7%). Seasonal and circadian distributions of VF episodes were similar according to PurkE origin. The clinical characteristics of patients with RV vs LV PurkE origins were similar, except for sex. RV PurkEs were more frequent in men than in women (76% vs 24%), whereas LV and biventricular PurkEs were more frequent in women (81% vs 19% and 83% vs 17%, respectively) (P < .0001)., Conclusion: PurkEs triggering idiopathic VF originate dominantly from the RV in men and from the LV or both ventricles in women, adding to other sex-related arrhythmias such as Brugada syndrome or long QT syndrome. Sex-based factors influencing Purkinje arrhythmogenicity warrant investigation., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Early repolarization indicates a distinct electrocardiographic phenotype affecting the junction between the QRS complex and the ST segment in inferolateral leads (inferolateral J-wave syndromes). It has been considered a benign electrocardiographic variant for decades, but recent clinical studies have demonstrated its arrhythmogenicity in a small subset, supported by experimental studies showing transmural dispersion of repolarization. Here we review the current knowledge and the issues of risk stratification that limit clinical management. In addition, we report on new mapping data of patients refractory to pharmacologic treatment using high-density electrogram mapping at the time of inscription of J wave. These data demonstrate that distinct substrates, delayed depolarization, and abnormal early repolarization underlie inferolateral J-wave syndromes, with significant implications. Finally, based on these data, we propose a new simplified mechanistic classification of sudden cardiac deaths without apparent structural heart disease., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Activation mapping using noninvasive electrocardiographic imaging (ECGi) has recently been used to describe the physiology of different cardiac abnormalities. These descriptions differ from prior invasive studies, and both methods have not been thoroughly confronted in a clinical setting., Objective: The goal of the present study was to provide validation of noninvasive activation mapping in a clinical setting through direct confrontation with invasive epicardial contact measures., Methods: Fifty-nine maps were obtained in 55 patients and aligned on a common geometry. Nearest-neighbor interpolation was used to avoid map smoothing. Quantitative comparison was performed by computing between-map correlation coefficients and absolute activation time errors., Results: The mean activation time error was 20.4 ± 8.6 ms, and the between-map correlation was poor (0.03 ± 0.43). The results suggested high interpatient variability (correlation -0.68 to 0.82), wide QRS patterns, and paced rhythms demonstrating significantly better mean correlation (0.68 ± 0.17). Errors were greater in scarred regions (21.9 ± 10.8 ms vs 17.5 ± 6.7 ms; P < .01). Fewer epicardial breakthroughs were imaged using noninvasive mapping (1.3 ± 0.5 vs 2.3 ± 0.7; P < .01). Primary breakthrough locations were imaged 75.7 ± 38.1 mm apart. Lines of conduction block (jumps of ≥50 ms between contiguous points) due to structural anomalies were recorded in 27 of 59 contact maps and were not visualized at these same sites noninvasively. Instead, artificial lines appeared in 33 of 59 noninvasive maps in regions of reduced bipolar voltage amplitudes (P = .03). An in silico model confirms these artificial constructs., Conclusion: Overall, agreement of ECGi activation mapping and contact mapping is poor and heterogeneous. The between-map correlation is good for wide QRS patterns. Lines of block and epicardial breakthrough sites imaged using ECGi are inaccurate. Further work is required to improve the accuracy of the technique., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Poor identification of electrical dyssynchrony is postulated to be a major factor contributing to the low success rate for cardiac resynchronization therapy., Objective: The purpose of this study was to evaluate the sensitivity of body surface mapping and electrocardiographic imaging (ECGi) to detect electrical dyssynchrony noninvasively., Methods: Langendorff-perfused pig hearts (n = 11) were suspended in a human torso-shaped tank, with left bundle branch block (LBBB) induced through ablation. Recordings were taken simultaneously from a 108-electrode epicardial sock and 128 electrodes embedded in the tank surface during sinus rhythm and ventricular pacing. Computed tomography provided electrode and heart positions in the tank. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGi. Dyssynchrony markers from torso potentials (eg, QRS duration) or ECGi (total activation time, interventricular delay [D-LR], and intraventricular markers) were correlated with those recorded from the sock., Results: LBBB was induced (n = 8), and sock-derived activation maps demonstrated interventricular dyssynchrony (D-LR and total activation time) in all cases (P < .05) and intraventricular dyssynchrony for complete LBBB (P < .05) compared to normal sinus rhythm. Only D-LR returned to normal with biventricular pacing (P = .1). Torso markers increased with large degrees of dyssynchrony, and no reduction was seen during biventricular pacing (P > .05). Although ECGi-derived markers were significantly lower than recorded (P < .05), there was a significant strong linear relationship between ECGi and recorded values. ECGi correctly diagnosed electrical dyssynchrony and interventricular resynchronization in all cases. The latest site of activation was identified to 9.1 ± 0.6 mm by ECGi., Conclusion: ECGi reliably and accurately detects electrical dyssynchrony, resynchronization by biventricular pacing, and the site of latest activation, providing more information than do body surface potentials., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Epifluorescence imaging using voltage-sensitive dyes has provided unique insights into cardiac electrical activity and arrhythmias. However, conventional dyes use blue-green excitation light, which has limited depth penetration., Objective: The aim of this study was to demonstrate that combining a short and a long excitation wavelength using near-infrared (NIR) dyes allows for epifluorescence imaging of transmural electrophysiological properties in intact hearts., Methods: Epifluorescence imaging was performed in rat hearts (N = 11) using DI-4-ANEPPS and the NIR dye DI-4-ANBDQBS. Activation and action potential duration (APD) patterns were investigated at 2 excitation wavelengths (530 and 660 nm) after epicardial stimulation at various cycle lengths (160 to 70 ms)., Results: Optical action potential upstrokes acquired with 660-nm excitation of DI-4-ANBDQBS were significantly longer than upstrokes obtained with 530-nm excitation of DI-4-ANEPPS (P < .001). Comparison of activation maps showed counterclockwise rotation of isochrones consistent with a transmural rotation of myofibers. Pronounced APD modulation by the activation sequence was observed at both excitation wavelengths. Significantly prolonged APDs (P = .016) and steeper APD restitution curves were found with DI-4-ANBDQBS (660-nm excitation) when compared with DI-4-ANEPPS (530-nm excitation). Dual excitation wavelength experiments using solely DI-4-ANBDQBS yielded similar results. Monophasic action potential recordings showed prolonged APD and steeper APD restitution curves in the endocardium, indicating that 660-nm excitation provides a significant endocardial contribution to the signal. Three-dimensional computer simulations confirmed our findings., Conclusion: Dual excitation wavelength epifluorescence allows detecting transmural heterogeneity in intact hearts. It therefore has the potential to become an important tool in experimental cardiac electrophysiology., (Copyright © 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)