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

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.

Relation of surface T-wave to vulnerability to ventricular fibrillation in explanted structurally normal hearts

“…Two representative single-lead beats with their fiducial points are displayed before and after drug injection from the same experiment in Figure 1, in conditions of noninducible and inducible VF, respectively. In [7], we demonstrated that increased heterogeneity of repolarization is responsible for severe alterations of T-wave duration and morphology. Moving from this research, the present study investigates whether these T-wave markers may bring additional insights into the propensity to develop trigger-induced arrhythmias in these abnormal substrates.…”

“…The experimental protocol was approved by Directive 2010/63/EU of the European Parliament on the protection of animals used for scientific purposes and the local ethical committee. As in [6,7], N H =7 Langendorff-perfused pig hearts were suspended in a human-shaped torso tank filled with Tyrode's solution. Repolarization gradients were created by separate infusion of pinacidil (30 µM, shortening repolarization duration) and/or dofetilide (250 nM, prolonging repolarization duration) through the left anterior descending (LAD) and non-LAD coronaries, respectively.…”

“…Prior to VF induction, at each experimental step, tank potentials (BioSemi, the Netherlands) were recorded over N b =10 beats in sinus rhythm from L=256 electrodes embedded in the surface at a sampling frequency of 2048 Hz. Noise filtering and detection of QRST fiducial points from torso signals were performed as in [7]. Too noisy or lowvoltage signals were discarded after visual inspection.…”

“…Moving from this research, the present study investigates whether these T-wave markers may bring additional insights into the propensity to develop trigger-induced arrhythmias in these abnormal substrates. Specifically, as in [7], we measured the duration of the peak-to-end interval of the T-wave signal s ,i from each heartbeat i=1, . .…”

“…, L, and its median value over all electrodes was considered as a global metric of T-wave duration (T PEAK -T END ). T-wave morphological aberrations have been associated with abnormal dispersion of electrical recovery [7,9]. As in [7], in each tank electrode = 1, .…”