Interactions between Activation and Repolarization Restitution Properties in the Intact Human Heart: In-Vivo Whole-Heart Data and Mathematical Description

Abstract

BackgroundThe restitution of the action potential duration (APDR) and conduction velocity (CVR) are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood.MethodsThis paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves) undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed.ResultsThis study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was as high as 250 ms. Heterogeneity in conduction velocity restitution can translate into both activation and repolarization dispersion and increase cardiac instability. The proposed mathematical formulation shows an excellent agreement with the experimental data (correlation coefficient r = 0.94) and provides a useful tool for the understanding of the complex interactions between activation and repolarization restitution properties as well as between their measurements.

Spatiotemporal characterization of the transition from sinus rhythm to ventricular fibrillation during an acute ischemic event in the intact human heart by whole-heart sock-mapping

“…Cardiopulmonary bypass was temporarily commenced to allow the surgeon to fit the multielectrode sock over the epicardium of both ventricles as in previous studies 6 . The heart was then refilled and the bypass discontinued in order to allow the study to proceed with a normally beating heart.…”

“…Data were exported and analyzed off-line with bespoke software 6, 7, 8. Local activation time (AT) was measured as the interval between the time of the pacing stimulus and the instant corresponding to the minimum derivative during the local QRS 5 .…”

Novel Repolarisation Metric Predicts Arrhythmia Origin And Clinical Events In ARVC And Brugada Syndrome

“…The non-contact mapping data consisting of 256 unipolar electrograms were collected with a recording bandwidth of 0-300 Hz in all cases and measurements made with a filter band width of 0.1-25 Hz. Electrograms were exported and analysed using semi-automated custom software running in Matlab (The Mathworks Inc., MA, USA) (10,11). During pacing, the time from pacing artefact to the steepest negative deflection (dV/dt min ) was used as the local activation time (AT).…”

A Time-Varying Nonparametric Methodology for Assessing Changes in QT Variability Unrelated to Heart Rate Variability

“…Several studies have suggested that QTV is associated with sympathetic ventricular outflow and susceptibility to malignant ventricular arrhythmias [1], [9]- [13]. However, part of QTV may be explained by RR interval variability (RRV), which is related to QTV through the restitution properties [14]. In fact, QTV can be interpreted as the contribution of two components, one related to RRV (QTVrRRV) and another unrelated to RRV (QTVuRRV) and associated with intrinsic ventricular repolarization dynamics (VRD).…”