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      Optimization of anti-tachycardia pacing efficacy through scar-specific delivery and minimization of re-initiation: a virtual study on a cohort of infarcted porcine hearts

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          Abstract

          Aims

          Anti-tachycardia pacing (ATP) is a reliable electrotherapy to painlessly terminate ventricular tachycardia (VT). However, ATP is often ineffective, particularly for fast VTs. The efficacy may be enhanced by optimized delivery closer to the re-entrant circuit driving the VT. This study aims to compare ATP efficacy for different delivery locations with respect to the re-entrant circuit, and further optimize ATP by minimizing failure through re-initiation.

          Methods and results

          Seventy-three sustained VTs were induced in a cohort of seven infarcted porcine ventricular computational models, largely dominated by a single re-entrant pathway. The efficacy of burst ATP delivered from three locations proximal to the re-entrant circuit (septum) and three distal locations (lateral/posterior left ventricle) was compared. Re-initiation episodes were used to develop an algorithm utilizing correlations between successive sensed electrogram morphologies to automatically truncate ATP pulse delivery. Anti-tachycardia pacing was more efficacious at terminating slow compared with fast VTs (65 vs. 46%, P = 0.000039). A separate analysis of slow VTs showed that the efficacy was significantly higher when delivered from distal compared with proximal locations (distal 72%, proximal 59%), being reversed for fast VTs (distal 41%, proximal 51%). Application of our early termination detection algorithm (ETDA) accurately detected VT termination in 79% of re-initiated cases, improving the overall efficacy for proximal delivery with delivery inside the critical isthmus (CI) itself being overall most effective.

          Conclusion

          Anti-tachycardia pacing delivery proximal to the re-entrant circuit is more effective at terminating fast VTs, but less so slow VTs, due to frequent re-initiation. Attenuating re-initiation, through ETDA, increases the efficacy of delivery within the CI for all VTs.

          Graphical Abstract

          Graphical Abstract

          ATP efficacy with respect to VT rates and delivery locations from the re-entrant circuit and ETDA for attenuating re-initiation and improving efficacy. ATP, anti-tachycardia pacing; ETDA, early termination detection algorithm; VT, ventricular tachycardia.

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          Most cited references20

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          Alternans and spiral breakup in a human ventricular tissue model.

          Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.
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            Basic mechanisms of cardiac impulse propagation and associated arrhythmias.

            Propagation of excitation in the heart involves action potential (AP) generation by cardiac cells and its propagation in the multicellular tissue. AP conduction is the outcome of complex interactions between cellular electrical activity, electrical cell-to-cell communication, and the cardiac tissue structure. As shown in this review, strong interactions occur among these determinants of electrical impulse propagation. A special form of conduction that underlies many cardiac arrhythmias involves circulating excitation. In this situation, the curvature of the propagating excitation wavefront and the interaction of the wavefront with the repolarization tail of the preceding wave are additional important determinants of impulse propagation. This review attempts to synthesize results from computer simulations and experimental preparations to define mechanisms and biophysical principles that govern normal and abnormal conduction in the heart.
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              • Record: found
              • Abstract: found
              • Article: not found

              Differences in effects of electrical therapy type for ventricular arrhythmias on mortality in implantable cardioverter-defibrillator patients.

              Implantable cardioverter-defibrillator (ICD) shocks have been associated with an increased risk of death. It is unknown whether this is due to the ventricular arrhythmia (VA) or shocks and whether antitachycardia pacing (ATP) termination can reduce this risk.
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                Author and article information

                Contributors
                Journal
                Europace
                Europace
                europace
                Europace
                Oxford University Press (US )
                1099-5129
                1532-2092
                February 2023
                05 October 2022
                05 October 2022
                : 25
                : 2
                : 716-725
                Affiliations
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Invicro , London, UK
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Department of Cardiology, Guy’s and St Thomas’ Hospital , London, UK
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Department of Cardiology, Guy’s and St Thomas’ Hospital , London, UK
                Department of Biomedical Engineering, School of Imaging Sciences and Biomedical Engineering, Kings College London , London, UK
                Author notes
                Corresponding author. Tel: +44 (0) 740 458 6951. E-mail address: shuang.qian@ 123456kcl.ac.uk

                Conflict of interest: None declared.

                Author information
                https://orcid.org/0000-0002-2313-0268
                https://orcid.org/0000-0002-7682-0094
                https://orcid.org/0000-0001-7921-7840
                https://orcid.org/0000-0002-5361-5725
                https://orcid.org/0000-0002-3930-1957
                https://orcid.org/0000-0002-6237-1902
                Article
                euac165
                10.1093/europace/euac165
                9935023
                36197749
                5a3ddec3-ef94-4cb1-bce8-ce42b890e743
                © The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 March 2022
                : 31 August 2022
                Page count
                Pages: 10
                Funding
                Funded by: Medical Research Council, doi 10.13039/501100000265;
                Award ID: MR/N011007/1
                Funded by: NIHR Biomedical Research Centre;
                Funded by: NHS Foundation Trust, doi 10.13039/100009745;
                Funded by: British Heart Foundation, doi 10.13039/501100000274;
                Award ID: PG/18/74/34077
                Funded by: Welcome EPSRC Centre for Medical Engineering, doi 10.13039/501100003921;
                Funded by: King’s College London, doi 10.13039/501100000764;
                Award ID: WT 203148/Z/16/Z
                Funded by: Welcome Trust;
                Award ID: 213342/Z/18/Z
                Funded by: European Union’s Horizon 2020 Research;
                Award ID: 764738
                Categories
                Basic Science
                AcademicSubjects/MED00200

                Cardiovascular Medicine
                ȃanti-tachycardia pacing,cardiac resynchronization therapy,implantable cardioverter defibrillator,patient-specific modelling,ventricular tachycardia

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