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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 in 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 in 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. Published by Elsevier Inc.)

Ithildin is an open-source library and framework for efficient parallelized simulations of excitable media, written in the C++ programming language. It uses parallelization on multiple CPU processors via the message passing interface (MPI). We demonstrate the library's versatility through a series of simulations in the context of the monodomain description of cardiac electrophysiology, including the S1S2 protocol, spiral break-up, and spiral waves in ventricular geometry. Our work demonstrates the power of Ithildin as a tool for studying complex wave patterns in cardiac tissue and its potential to inform future experimental and theoretical studies. We publish our full code with this paper in the name of open science., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kabus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Idiopathic ventricular fibrillation (IVF) can be associated with undetected distinct conditions such as microstructural cardiomyopathic alterations (MiCM) or Purkinje (Purk) activities with structurally normal hearts., Objectives: This study sought to evaluate the characteristics of recurrent VF recorded on implantable defibrillator electrograms, associated with these substrates., Methods: This was a multicenter collaboration study. At 32 centers, we selected patients with an initial diagnosis of IVF and recurrent arrhythmia at follow-up without antiarrhythmic drugs, in whom mapping demonstrated Purk or MiCM substrate. We analyzed variables related to previous ectopy, sinus rate preceding VF, trigger, and initial VF cycle lengths. Logistic regression with cross validation was used to evaluate the performance of criteria to discriminate Purk or MiCM substrates., Results: Among 95 patients (35 women, age 35 ± 11 years) meeting the inclusion criteria, IVF was associated with MiCM in 41 and Purk in 54 patients. A total of 117 arrhythmia recurrences including 91% VF were recorded on defibrillator. Three variables were mostly discriminant. Sinus tachycardia (≤570 ms) was more frequent in MiCM (35.9% vs 13.4%, P = 0.014) whereas short-coupled (<350 ms) triggers were most frequent in Purk-related VF (95.5% vs 23.1%, P = 0.001), which also had shorter VFCLs (182 ± 15 ms vs 215 ± 24 ms, P < 0.001).The multivariable combination provided the highest prediction (accuracy = 0.93 ± 0.05, range 0.833-1.000), discriminating 81% of IVF substrates with a high probability (>80%). Ectopy were inconsistently present before VF., Conclusions: Characteristics of arrhythmia recurrences on implantable cardioverter- defibrillator provide phenotypic markers of the distinct and hidden substrates underlying IVF. These findings have significant clinical and genetic implications., Competing Interests: Funding Support and Author Disclosures Dr Haissaguerre has received grant support from Biosense Webster. Dr Marijon has received grant support and consulting fees from Medtronic, Boston Scientific, Abbott, Microport, Biotronik, and Zoll. Pr Gandjbakhch has received lecture fees from Biotronik; and consulting fees from Medtronic, Microport, and Abbott. Dr Tilz is a consultant for Boston Scientific, Biotronik, Biosense Webster, and Abbott Medical; has received speaker honoraria from Boston Scientific, Biotronik, Biosense Webster, Abbott Medical, and Lifetech; and has received research grants from Abbott, Biosense Webster, and Lifetech. Dr Roten has received research grants from Medtronic, the Swiss National Foundation, the Swiss Heart Foundation, the Immanuel and Ilse Straub Foundation, and the Sitem Insel Support Fund, all for work outside the submitted study; and has received speaker/consulting honoraria from Abbott and Medtronic. Dr Reichlin has receivedresearch grants from the Swiss National Science Foundation, the Swiss Heart Foundation, the Sitem Insel support funds, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study; and has received speaker/consulting honoraria or travel support from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic, all for work outside the submitted study. Support for his institution’s fellowship program from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific, and Medtronic for work outside the submitted study. Dr Sacher has receivedspeaking honorarium from Abbott, Boston Scientific, and Biosense Webster; and equity from InHeart. Dr Nogami has received lecture fees from Abbott; and endowments from Medtronic. Dr Massoullié has received lecture fees from Boston Scientific, Biosense Webster, and Abbot. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent clinical studies have indicated the presence of localized electrical abnormalities in idiopathic ventricular fibrillation and J-wave syndrome patients., Objectives: This study aims to characterize the specific electrical signatures of localized repolarization and conduction heterogeneities and their respective role in vulnerability to arrhythmias., Methods: Optical mapping was performed in porcine right ventricles with local: 1) repolarization shortening; 2) conduction slowing; or 3) structural heterogeneity induced by locally perfusing: 1) pinacidil (20 μmol/L, n = 13); or 2) flecainide (2 μmol/L, n = 13) via an epicardial catheter; or 3) by local epicardial tissue destruction (9 radiofrequency lesions n = 12). Electrograms were recorded (n = 5 in each group) and spontaneous and induced arrhythmias were quantified and optically mapped., Results: Electrograms were normal in (1) but showed local fragmentation in 40% of preparations in (2) with greater effects observed at high pacing frequencies dependent on the wavefront direction. In (3), the structural substrate alone increased the width and number of peaks in the electrograms, and addition of flecainide induced pronounced fragmentation (≥3 peaks and ≥70 ms) in all cases. Occurrence of spontaneous arrhythmias was significantly increased in (1) and (2) (P < 0.0001 and 0.05, respectively, vs baseline) and were triggered by ectopies. Vulnerability to arrhythmias at high pacing frequencies (≥2 Hz) was the lowest in (1) and greatest in (2)., Conclusions: Microstructural substrates have the most pronounced impact on electrograms, especially when combined with sodium channel blockers, whereas local action potential duration shortening does not lead to electrogram fragmentation even though it is associated with the highest prevalence of spontaneous arrhythmias., Competing Interests: Funding Support and Author Disclosures This study received financial support from the French Government as part of the “Investments of the Future” program managed by the National Research Agency (ANR-10-IAHU04-LIRYC). It was funded by the Leducq-Foundation (RHYTHM network, 16CVD02), the Fondation Coeur et Artères (FC17T2), and the European Research Council (ERC-2021-ADG 101054717). All authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Respiratory rate (RR) is a critical vital sign used to assess pulmonary function. Currently, RR estimating instrumentation is specialized and bulky, therefore unsuitable for remote health monitoring. Previously, RR was estimated using proprietary software that extract surface electrocardiogram (ECG) waveform features obtained at several thoracic locations. However, developing a non-proprietary method that uses minimal ECG leads, generally available from mobile cardiac monitors is highly desirable. Here, we introduce an open-source and well-documented Python-based algorithm that estimates RR requiring only single-stream ECG signals. The algorithm was first developed using ECGs from awake, spontaneously breathing adult human subjects. The algorithm-estimated RRs exhibited close linear correlation to the subjects' true RR values demonstrating an R 2 of 0.9092 and root mean square error of 2.2 bpm. The algorithm robustness was then tested using ECGs generated by the ischemic hearts of anesthetized, mechanically ventilated sheep. Although the ECG waveforms during ischemia exhibited severe morphologic changes, the algorithm-determined RRs exhibited high fidelity with a resolution of 1 bpm, an absolute error of 0.07 ± 0.07 bpm, and a relative error of 0.67 ± 0.64%. This optimized Python-based RR estimation technique will likely be widely adapted for remote lung function assessment in patients with cardiopulmonary disease., (© 2024. The Author(s).)