Abstract
BackgroundIncreased 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.MethodsLangendorff-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 (TPEAK-TEND) 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.ResultsAfter drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, TPEAK-TEND 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.ConclusionRepolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.
Highlights
Abnormal heterogeneity of ventricular repolarization predisposes to the development of life−threatening ventricular arrhythmias and it is associated with increased mortality in the general population (Antzelevitch, 2007; Prenner et al, 2016).Global ventricular repolarization dispersion is mainly determined by the heterogeneity of action potential durations (APDs) between different myocardial regions, which can be apical-basal, transmural and/or interventricular, and affects T-wave properties from surface electrocardiogram (ECG) (Merri et al, 1989; Vinzio Maggio et al, 2012)
Pinacidil injection is responsible for a marked increase in EGM interventricular repolarization time (RT) dispersion repolarization time gradient (RTG)(LV/right ventricle (RV))GLOBAL in experiments #1 and #2 (Figure 2A, middle), whereas RTs become more similar with time in experiment #3
Regarding experiment #3, T-wave peak (TPEAK)-TEND prolongation is more pronounced when pinacidil injection has started, and a drop in the index can be observed, with a time evolution resembling more that of global invasive markers of repolarization dispersion (RTGGLOBAL and RTG(LV/RV)GLOBAL) rather than regional measures (RTGLOCAL)
Summary
Abnormal heterogeneity of ventricular repolarization predisposes to the development of life−threatening ventricular arrhythmias and it is associated with increased mortality in the general population (Antzelevitch, 2007; Prenner et al, 2016).Global ventricular repolarization dispersion is mainly determined by the heterogeneity of action potential durations (APDs) between different myocardial regions, which can be apical-basal (from apex to base of ventricles), transmural (from endocardium to epicardium) and/or interventricular (left vs. right ventricle), and affects T-wave properties from surface electrocardiogram (ECG) (Merri et al, 1989; Vinzio Maggio et al, 2012). Global ventricular repolarization dispersion is mainly determined by the heterogeneity of action potential durations (APDs) between different myocardial regions, which can be apical-basal (from apex to base of ventricles), transmural (from endocardium to epicardium) and/or interventricular (left vs right ventricle), and affects T-wave properties from surface electrocardiogram (ECG) (Merri et al, 1989; Vinzio Maggio et al, 2012). Regional dispersion of repolarization strongly affects T-wave profile as well, measures of local inhomogeneity have been introduced to take into account spatial distribution of RTs and their variations across adjacent tissue sites. In Brugada syndrome, sharp local gradients of repolarization and slow conduction areas can both contribute to increased susceptibility to sustained reentrant excitation and are accompanied by T-wave inversion on the body surface (Zhang et al, 2015). 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
Published Version (Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have