A reliability analysis of cardiac repolarization time markers.

Only a limited number of studies have addressed the reliability of extracellular markers of cardiac repolarization time, such as the classical marker RT(eg) defined as the time of maximum upslope of the electrogram T wave. This work presents an extensive three-dimensional simulation study of cardiac repolarization time, extending the previous one-dimensional simulation study of a myocardial strand by Steinhaus [B.M.

Modeling ventricular repolarization: effects of transmural and apex-to-base heterogeneities in action potential durations.

Heterogeneities in the densities of membrane ionic currents of myocytes cause regional variations in action potential duration (APD) at various intramural depths and along the apico-basal and circumferential directions in the left ventricle. This work extends our previous study of cartesian slabs to ventricular walls shaped as an ellipsoidal volume and including both transmural and apex-to-base APD heterogeneities. Our 3D simulation study investigates the combined effect on repolarization sequences and APD distributions of: (a) the intrinsic APD heterogeneity across the wall and along the apex-to-base direction, and (b) the electrotonic currents that modulate the APDs when myocytes are embedded in a ventricular wall with fiber rotation and orthotropic anisotropy.

Experimental and computational studies of strain-conduction velocity relationships in cardiac tissue.

Velocity of electrical conduction in cardiac tissue is a function of mechanical strain. Although strain-modulated velocity is a well established finding in experimental cardiology, its underlying mechanisms are not well understood. In this work, we summarized potential factors contributing to strain-velocity relationships and reviewed related experimental and computational studies.

Epicardial and intramural excitation during ventricular pacing: effect of myocardial structure.

Published studies show that ventricular pacing in canine hearts produces three distinct patterns of epicardial excitation: elliptical isochrones near an epicardial pacing site, with asymmetric bulges; areas with high propagation velocity, up to 2 or 3 m/s and numerous breakthrough sites; and lower velocity areas (<1 m/s), where excitation moves across the epicardial projection of the septum. With increasing pacing depth, the magnitude of epicardial potential maxima becomes asymmetric. The electrophysiological mechanisms that generate the distinct patterns have not been fully elucidated.

Monophasic action potentials generated by bidomain modeling as a tool for detecting cardiac repolarization times.

Unipolar electrograms (EGs) and hybrid (or unorthodox or unipolar) monophasic action potentials (HMAPs) are currently the only proposed extracellular electrical recording techniques for obtaining cardiac recovery maps with high spatial resolution in exposed and isolated hearts. Estimates of the repolarization times from the HMAP downstroke phase have been the subject of recent controversies. The goal of this paper is to computationally address the controversies concerning the HMAP information content, in particular the reliability of estimating the repolarization time from the HMAP downstroke phase.

Visualization of electrical current flow with a new streamline technique: application in mono- and bidomain simulations of cardiac tissue.

Mathematical modeling and computer-based simulation of electrical fields in the heart provide important insights into the cardiac electrophysiological behavior. Streamline based techniques are frequently applied for visualization of these electrical fields. In this work we present a new automated technique for placement of seed points of streamlines.

Conduction velocity in myocardium modulated by strain: measurement instrumentation and initial results.

Quantification of the relationship between strain and excitation velocity in cardiac muscle gives important insights into the significance and contribution of microstructure and several transmembrane proteins to cardiac electrophysiology. In this study we introduce a measurement and analysis system for quantification of the relationship in papillary muscle of small mammals, superfused and kept in a physiological environment. A novelty of the approach is the extensive automation and computerization of the measurement and analysis procedure.

Effects of transmural electrical heterogeneities and electrotonic interactions on the dispersion of cardiac repolarization and action potential duration: A simulation study.

It has been shown in the literature that myocytes isolated from the ventricular walls at various intramural depths have different action potential durations (APDs). When these myocytes are embedded in the ventricular wall, their inhomogeneous properties affect the sequence of repolarization and the actual distribution of the APDs in the entire wall. In this article, we implement a mathematical model to simulate the combined effect of (a) the non-homogeneous intrinsic membrane properties (in particular the non-homogeneous APDs) and (b) the electrotonic currents that modulate the APDs when the myocytes are embedded in the ventricular myocardium.

Venous catheter based mapping of ectopic epicardial activation: training data set selection for statistical estimation.

A source of error in most of the existing catheter cardiac mapping approaches is that they are not capable of acquiring epicardial potentials even though arrhythmic substrates involving epicardial and subepicardial layers account for about 15% of the ventricular tachycardias. In this subgroup of patients, mapping techniques that are limited to the endocardium result in localization errors and failure in subsequent ablation procedures. In addition, catheter-based electrophysiological studies of the epicardium are limited to regions near the coronary vessels or require transthoracic access.

Intramural activation and repolarization sequences in canine ventricles. Experimental and simulation studies.

Background: There are no published data showing the three-dimensional sequence of repolarization and the associated potential fields in the ventricles. Knowledge of the sequence of repolarization has medical relevance because high spatial dispersion of recovery times and action potential durations favors cardiac arrhythmias. In this study we describe measured and simulated 3-D excitation and recovery sequences and activation-recovery intervals (ARIs) (measured) or action potential durations (APDs) (simulated) in the ventricular walls.

Effect of fiber orientation on propagation: electrical mapping of genetically altered mouse hearts.

Background: Epicardial potentials reveal the strong effects of fiber anisotropy, rotation, imbrication, and coupling on propagation in the intact heart. From the patterns of the surface potentials, we can obtain information about the local fiber orientation, anisotropy, the transmural fiber rotation, and which direction the wave front is traveling through the wall. In this study, lessons learned from epicardial potential mapping of large hearts were applied to studies conducted in genetically altered mouse hearts.

Simulating patterns of excitation, repolarization and action potential duration with cardiac Bidomain and Monodomain models.

Parallel numerical simulations of excitation and recovery in three-dimensional myocardial domains are presented. The simulations are based on the anisotropic Bidomain and Monodomain models, including intramural fiber rotation and orthotropic or axisymmetric anisotropy of the intra- and extra-cellular conductivity tensors. The Bidomain model consist of a system of two reaction-diffusion equations, while the Monodomain model consists of one reaction-diffusion equation.

Modeling ventricular excitation: axial and orthotropic anisotropy effects on wavefronts and potentials.

By applying the eikonal approximation to the bidomain model of the cardiac tissue we investigate the influence of the axially isotropic and orthotropic conductivity tensors on the propagation of the excitation wavefronts and on the associated potential distribution and electrograms.

Spatial methods of epicardial activation time determination in normal hearts.

The purpose of this study was to demonstrate errors in activation time maps created using the time derivative method on fractionated unipolar electrograms, to characterize the epicardial distribution of those fractionated electrograms, and to investigate spatial methods of activation time determination. Electrograms (EGs) were recorded using uniform grids of electrodes (1 or 2 mm spacing) on the epicardial surface of six normal canine hearts. Activation times were estimated using the time of the minimum time derivative, maximum spatial gradient, and zero Laplacian and compared with the time of arrival of the activation wave front as assessed from a time series of potential maps as the standard.

Endocardial mapping of electrophysiologically abnormal substrates and cardiac arrhythmias using a noncontact nonexpandable catheter.

Introduction: In previous studies, we established methodology for reconstructing endocardial potential maps, electrograms, and isochrones from a noncontact intracavitary catheter during a single beat. Recently, we evaluated this approach using a 9-French (3-mm) spiral catheter in a normal heart preparation. Here we extend the approach to hearts with structural disease and examine its ability to detect and characterize abnormal electrophysiologic (EP) substrates and to map ventricular arrhythmias on a beat-by-beat basis.

The role of heart rate in myocardial ischemia from restricted coronary perfusion.

Despite many years of study, certain aspects of myocardial ischemia remain incompletely understood. One observation that motivated this study is that acute, complete occlusion produces elevations but never depression of the ST-segment potentials in electrocardiographic leads over the ischemic zone. Limited flow, on the other hand, leads to ST-segment depression, both in in situ experiments and during clinical stress tests.

Noninvasive electrocardiogram imaging of substrate and intramural ventricular tachycardia in infarcted hearts.

Objectives: The goal of this study was to experimentally evaluate a novel noninvasive electrocardiographic imaging modality during intramural reentrant ventricular tachycardia (VT).

Background: Myocardial infarction and subsequent remodeling produce abnormal electrophysiologic substrates capable of initiating and maintaining reentrant arrhythmias. Existing noninvasive electrocardiographic methods cannot characterize abnormal electrophysiologic substrates in the heart or the details of associated arrhythmias.

Effects of heart position on the body-surface electrocardiogram.

Previous studies have examined the influence of body position, respiration, and habitus on body surface potentials. However, the authors could only estimate the sources of the effects they documented. Among the proposed origin of changes in body surface potentials from those studies were the position of the heart, alterations in autonomic tone, differences in ventricular blood volume, and variations in torso resistivity.

Computing and visualizing electric potentials and current pathways in the thorax.

The long-term goal of electrocardiography is to relate electric potentials on the body surface with activities in the heart. Many previously reported studies have focused on direct links between heart and body surface potentials. The goals of this study were first to validate computational methods of determining volume potentials and currents with high-resolution experimental measurements and then to use interactive visualization of thoracic currents to understand features of the electrocardiographic fields from measured cardiac sources.

Anisotropic mechanisms for multiphasic unipolar electrograms: simulation studies and experimental recordings.

The origin of the multiple, complex morphologies observed in unipolar epicardial electrograms, and their relationships with myocardial architecture, have not been fully elucidated. To clarify this problem we simulated electrograms (EGs) with a model representing the heart as an anisotropic bidomain with unequal anisotropy ratio, ellipsoidal ventricular geometry, transmural fiber rotation, epi-endocardial obliqueness of fiber direction and a simplified Purkinje network. The EGs were compared with those directly recorded from isolated dog hearts immersed in a conducting medium during ventricular excitation initiated by epicardial stimulation.

Electrophysiologic endocardial mapping from a noncontact nonexpandable catheter: a validation study of a geometry-based concept.

Introduction: The need for high-resolution simultaneous mapping of cardiac excitation and arrhythmias on a beat-by-beat basis is widely recognized. Here we validate a noncontact mapping approach that combines a spiral catheter design with mathematical reconstruction to generate potential maps, electrograms, and activation maps (isochrones) on the entire left ventricular endocardial surface during a single beat. The approach is applicable to any heart chamber.

A noninvasive imaging modality for cardiac arrhythmias.

Background: The last decade witnessed an explosion of information regarding the genetic, molecular, and mechanistic basis of heart disease. Translating this information into clinical practice requires the development of novel functional imaging modalities for diagnosis, localization, and guided intervention. A noninvasive modality for imaging cardiac arrhythmias is not yet available.

Estimates of repolarization dispersion from electrocardiographic measurements.

Background: Repolarization dispersion (Rd) is frequently mentioned as a predictor of cardiac abnormalities. We present a new measure of Rd based on the root-mean-square (RMS) curve of an ECG lead set and compare its performance with that of the commonly used QT dispersion (QTd) measure with the use of recovery times measured from directly recorded canine electrograms.

Methods And Results: Using isolated, perfused canine hearts suspended in a torso-shaped electrolytic tank, we simultaneously recorded electrograms from 64 epicardial sites and ECGs from 192 "body surface" sites.

Estimates of repolarization and its dispersion from electrocardiographic measurements: direct epicardial assessment in the canine heart.

This study investigates a technique to estimate dispersion based on the root mean square (RMS) signal of multiple electrocardiographic leads. Activation and recovery times were measured from 64 sites on the epicardium of canine hearts using acute in situ or Langendorff perfused isolated heart preparations. Repolarization and its dispersion were altered by varying cycle length, myocardial temperature, or ventricular pacing site.