Whole heart action potential duration restitution properties in cardiac patients: a combined clinical and modelling study

Abstract

Steep action potential duration (APD) restitution has been shown to facilitate wavebreak and ventricular fibrillation. The global APD restitution properties in cardiac patients are unknown. We report a combined clinical electrophysiology and computer modelling study to: (1) determine global APD restitution properties in cardiac patients; and (2) examine the interaction of the observed APD restitution with known arrhythmia mechanisms. In 14 patients aged 52-85 years undergoing routine cardiac surgery, 256 electrode epicardial mapping was performed. Activation-recovery intervals (ARI; a surrogate for APD) were recorded over the entire ventricular surface. Mono-exponential restitution curves were constructed for each electrode site using a standard S1-S2 pacing protocol. The median maximum restitution slope was 0.91, with 27% of all electrode sites with slopes < 0.5, 29% between 0.5 and 1.0, and 20% between 1.0 and 1.5. Eleven per cent of restitution curves maintained slope > 1 over a range of diastolic intervals of at least 30 ms; and 0.3% for at least 50 ms. Activation-recovery interval restitution was spatially heterogeneous, showing regional organization with multiple discrete areas of steep and shallow slope. We used a simplified computer model of 2-D cardiac tissue to investigate how heterogeneous APD restitution can influence vulnerability to, and stability of re-entry. Our model showed that heterogeneity of restitution can act as a potent arrhythmogenic substrate, as well as influencing the stability of re-entrant arrhythmias. Global epicardial mapping in humans showed that APD restitution slopes were organized into regions of shallow and steep slopes. This heterogeneous organization of restitution may provide a substrate for arrhythmia.

Techniques for Ventricular Repolarization Instability Assessment From the ECG

“…13 left panel, express the APD as a function of the RR interval (inverse of HR) for different regions within the myocardium. In experimental, clinical and computational studies, it has been shown that an increase in APDR dispersion is associated with greater propensity to suffer from VT/VF, the most common sequence to SCD [25], [26]. Other studies have reported differences in transmural heterogeneity at different cycle lengths between end-stage failing and non-failing human ventricles [27].…”

“…13), therefore providing potentially relevant information for ventricular arrhythmic risk stratification [25], [115]. Heterogeneities in the ventricle lead to non-uniform restitution properties, which makes APDR curves present spatial variations [116].…”

Verification of cardiac tissue electrophysiology simulators using an N -version benchmark

“…To characterize the convergence in space and time of each of the simulation codes, the benchmark problem was solved using combinations of discretizations of the order of those used in the literature. The problem was solved at three spatial (Dx = 0.5, 0.2 and 0.1 mm [33][34][35][36]) resolutions, and each spatial resolution was then solved with three different partial differential equation (PDE) time steps (Dt = 0.05, 0.01 and 0.005 ms [33,34,36,37]), resulting in nine simulation results in total per simulation code applied to the benchmark problem.…”

FPGA in-the-loop simulations of cardiac excitation model under voltage clamp conditions

“…The LR-I is an established mathematical model for cardiac excitation generation in mammalian ventricular cell. This model is chosen because it well described the six ionic currents that retain enough structure of basic currents involved in cardiac excitation to reproduce exact AP morphologies [11] and the model is flexible enough that the parameters can be fitted to replicate accurately the properties and dynamics of other complex ionic models as well as experimental data [12][13] such as action potential duration (APD), thresholds for excitation, upstroke velocities, minimum APD before reaching conduction block, and phase-locking response characteristics to current stimulations. The FPGA implementation in the simulation cardiac excitation model under the voltage clamp is conducted by using the MATLAB Simulink through HDL Coder that gives an opportunity in obtaining Hardware Description Language (HDL) code by using an automatic code generation process without traditionally coding of the HDL code [9].…”