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      Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study

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          Abstract

          Background

          Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model.

          Methods

          Langendorff-perfused pig hearts ( N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (T PEAK-T END) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area ( Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites.

          Results

          After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, T PEAK-T END was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components.

          Conclusion

          Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.

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          Most cited references47

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          Prolonged QTc interval and risk of sudden cardiac death in a population of older adults.

          This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. This study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3). Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.
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            Does Tpeak-Tend provide an index of transmural dispersion of repolarization?

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              Dispersion of repolarization in canine ventricle and the electrocardiographic T wave: Tp-e interval does not reflect transmural dispersion.

              The concept that the interval between the peak (T(peak)) and the end (T(end)) of the T wave (T(p-e)) is a measure of transmural dispersion of repolarization time is widely accepted but has not been tested rigorously by transmural mapping of the intact heart. The purpose of this study was to test the relationship of T(p-e) to transmural dispersion of repolarization by correlating local repolarization times at endocardial, midmural, and epicardial sites in the left and right ventricles with the T wave of the ECG. Local activation times, activation-recovery intervals, and repolarization times were measured at 98 epicardial sites and up to 120 midmural and endocardial sites in eight open-chest dogs. In four of the dogs, long-term cardiac memory was induced by 3 weeks of ventricular pacing at 130 bpm because previous data suggest that, in this setting, delayed epicardial repolarization increases transmural dispersion. The other four dogs were sham operated. In sham dogs, T(p-e) was 41 +/- 2.2 ms (X +/- SEM), whereas the transmural dispersion of repolarization time was 2.7 +/- 4.2 ms (not significant between endocardium and epicardium). Cardiac memory was associated with evolution of a transmural gradient of 14.5 +/- 1.9 ms (P <.02), with epicardium repolarizing later than endocardium. The corresponding T(p-e) was 43 +/- 2.3 ms (not different from sham). In combined sham and memory dogs, T(p-e) intervals did not correlate with transmural dispersion of repolarization times. In contrast, dispersion of repolarization of the whole heart (measured as the difference between the earliest and the latest moment of repolarization from all left and right ventricular, endocardial, intramural, and epicardial recording sites) did correlate with T(p-e) (P <.0005, r = 0.98), although the latter underestimated total repolarization time by approximately 35%. The explanation for this finding is that parts of the heart fully repolarize before the moment of T(peak). T(p-e) does not correlate with transmural dispersion of repolarization but is an index of total dispersion of repolarization.
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                Author and article information

                Contributors
                Journal
                Front Physiol
                Front Physiol
                Front. Physiol.
                Frontiers in Physiology
                Frontiers Media S.A.
                1664-042X
                13 August 2020
                2020
                : 11
                : 933
                Affiliations
                [1] 1Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University , Pessac-Bordeaux, France
                [2] 2University of Bordeaux, CRCTB , Bordeaux, France
                [3] 3INSERM, CRCTB, U1045 , Bordeaux, France
                [4] 4Department of Data Science and Knowledge Engineering, Maastricht University , Maastricht, Netherlands
                [5] 5Department of Cardiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center , Maastricht, Netherlands
                [6] 6Bordeaux University Hospital (CHU), Electrophysiology and Ablation Unit , Pessac, France
                Author notes

                Edited by: Marek Malik, Imperial College London, United Kingdom

                Reviewed by: Pablo Laguna, University of Zaragoza, Spain; Gary Tse, Second Hospital of Tianjin Medical University, China

                This article was submitted to Cardiac Electrophysiology, a section of the journal Frontiers in Physiology

                Article
                10.3389/fphys.2020.00933
                7438571
                609cc4dd-76a7-4a95-a8c1-91c1238b65ee
                Copyright © 2020 Meo, Bonizzi, Bear, Cluitmans, Abell, Haïssaguerre, Bernus and Dubois.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 May 2020
                : 10 July 2020
                Page count
                Figures: 5, Tables: 1, Equations: 8, References: 61, Pages: 16, Words: 0
                Funding
                Funded by: Agence Nationale de la Recherche 10.13039/501100001665
                Funded by: Fondation Leducq 10.13039/501100001674
                Categories
                Physiology
                Original Research

                Anatomy & Physiology
                sudden cardiac death,ventricular repolarization heterogeneity,body surface potential mapping,t-wave,electrocardiology

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