Bonnie B. Punske

Spatial Methods of Epicardial Activation Time Determination in Normal Hearts

AbstractThe 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. When comparing activation times from the time derivative for the case of epicardial pacing, spatial gradient and Laplacian methods with the standard for EGs without fractionation, correlations were high (R2=0.98, 0.98, 0.97, respectively). Similar comparisons using results from only fractionated EGs (R2=0.85,0.97,0.95) showed a lower correlation between times from the time derivative method and the standard. The results suggest an advantage of spatial methods over the time derivative method only for the case of epicardial pacing where large numbers of fractionated electrograms are found.

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. In this study, we investigated those mechanisms experimentally. Under pentobarbital anesthesia, epicardial and intramural excitation isochrone and potential maps have been recorded from 22 exposed or isolated dog hearts, by means of epicardial electrode arrays and transmural plunge electrodes. In five experiments, a ventricular cavity was perfused with diluted Lugol solution. The epicardial bulges result from electrotonic attraction from the helically shaped subepicardial portions of the wave front. The high-velocity patterns and the associated multiple breakthroughs are due to involvement of the Purkinje network. The low velocity at the septum crossing is due to the missing Purkinje involvement in that area. The asymmetric magnitude of the epicardial potential maxima and the shift of the breakthrough sites provoked by deep stimulation are a consequence of the epi-endocardial obliqueness of the intramural fibers. These results improve our understanding of intramural and epicardial propagation during premature ventricular contractions and paced beats. This can be useful for interpreting epicardial maps recorded at surgery or inversely computed from body surface ECGs.

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

Electrophysiologic Noncontact Endocardial Mapping. Introduction: The need for high‐resulution simultaneous mapping of cardiac excitation and arrhythmias on a heat‐hy‐heat 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 chamher.

Integrin Activation in the Heart A Link Between Electrical and Contractile Dysfunction

Integrins mechanically link the cytoskeleton to the extracellular matrix in cardiac myocytes and are thereby involved in mechanotransduction. Integrins appear to be necessary for cardiac myocyte hypertrophy. To determine the effect of increased integrin ligation and signaling on adult cardiac function, a heart-specific truncated α5 integrin (gain of function) was conditionally expressed in mice. Four days later, we observed an 80% reduction in amplitude of the QRS complex, profound systolic dysfunction, decreased connexin43, loss of gap junctions, and abnormal intercalated discs. Surprisingly, isolated left ventricular myocytes contracted normally and exhibited normal Ca2+ transients. This suggested that cell/cell electrical and/or mechanical coupling was disrupted. To distinguish electrical from mechanical coupling deficits, we compared the papillary muscle force generated by electrically stimulated versus rapid cooling contractions in which intracellular Ca2+ is released without electrical depolarization. Both were decreased in the transgenic muscle. However, electrically stimulated contractions were more significantly reduced than rapid cooling contractures. This suggests a component of cell/cell electrical uncoupling. Optical mapping revealed a loss of the normal elliptical isochronal activation pattern implying a loss of preferential conduction through gap junctions. For the first time, we have shown that integrins can regulate both mechanical and electrical coupling in the adult heart, even in the absence of primary hemodynamic alterations. Furthermore, we demonstrated that unregulated integrin activation leads to both contractile dysfunction and arrhythmias.

Body Surface Potential Mapping

Body surface potential maps (BSPMs) depict the spatial distribution of heart potentials on the surface of the torso. They are obtained by recording a number of unipolar electrocardiograms (ECGs) from the surface of the torso. 1 2 The amplitude of every ECG is measured at a given time instant during the PQRSTU interval. The values are converted into millivolts and plotted on a chart representing the torso surface. Equipotential lines are then drawn on the map, generally by using linear interpolation. The same procedure is repeated for every time instant during one or more heart beats. The time interval between successive instantaneous maps (frames) is generally 1 or 2 msec. A sequence of 400 to 800 frames shows the evolution of the potential pattern during the PQRSTU interval. Often, 20 to 50 properly selected maps are sufficient to show the essential features of the time-varying surface field.

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. Mean and dispersion of activation and recovery times, and activation-recovery interval (ARI) were calculated for each beat. The waveform was then calculated from all leads. Estimates of mean and dispersion of activation and recovery times and mean ARI were derived using only inflection points from the RMS waveform. QT intervals were also measured and QT dispersion was determined. Estimates determined from the RMS waveform provided accurate estimates of repolarization and were, in particular, a better measure of repolarization dispersion than QT dispersion.

Mechanisms of the Spatial Distribution of QT Intervals on the Epicardial and Body Surfaces

Spatial Distribution of the QT Interval. Introduction: The role of QT dispersion as a predictor of arrhythmia vulnerability has not been consistently confirmed in the literature. Therefore, it is important to identify the electrophysiologic mechanisms that affect QT duration and distribution. We compared the spatial distributions of QT intervals (QTI) with potential distributions on cardiac and body surfaces and with recovery times on the cardiac surface. We hypothesized that the measure of QTI is affected by the presence of the zero potential line in the potential distribution, as well as the sequence of recovery. We also investigated use of the STT area as a possible indicator of recovery times on the cardiac surface.

Noninvasive Indices of Repolarization and Its Dispersion

In experimental studies using Langendorff perfused, isolated canine hearts immersed in a torso-shaped electrolytic tank we studied repolarization and its dispersion using direct epicardial measurements and newly derived, noninvasive body surface indices. Activation recovery intervals (ARIs) measured from 64 epicardial sites based on differences between activation times (ATs) and recovery times (RTs) provided direct measures of repolarization. The indirect, torso surface indices were derived from inflections of the root-mean-square (RMS) voltage of the torso tank surface electrocardiograms recorded simultaneously with the epicardial data. For cycle lengths ranging from 300 to 900 ms, and electrolyte temperatures ranging from 32 degrees C to 40 degrees C we calculated mean, variance, and range of ATs, RTs, and ARIs from the epicardium. From epicardial and torso surface RMS waveforms, we used times of R and T peaks and their differences to estimate mean ATs, RTs, and ARIs, respectively. The RMS T wave width as determined from the second derivative inflections on either side of the T peak served as an estimate of the dispersion of RTs. In parallel studies, we showed that the direct measures of repolarization and its dispersion were reflected in RMS waveforms generated from the epicardial electrograms themselves. In this study, we confirm that the torso and epicardial RMS waveforms reflect comparable information for estimating repolarization and its dispersion. Furthermore, the derived measures provide a method to assess mean ARIs and dispersion of RTs on a beat-to-beat basis and during abnormal (ectopic ventricular) activation sequences.

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. We have developed a statistical approach by which to estimate high-resolution maps of epicardial activation from very low-resolution multi-electrode venous catheter measurements. A training set of previously recorded maps is necessary for this technique so that composition of the database becomes an important determinant of accuracy. The specific hypothesis of the study was that estimation accuracy would be best when the training data set matches that of the test beat(s), whereby the matching was according to the site of initiation of the beats. This hypothesis suggests approaches to optimized selection of the training set, three of which we have developed and evaluated. One of these methods, the high-CC refinement method, was able to estimate the earliest activation site of left ventricularly paced maps within an average of 4.67 mm of the true site; in 89% of the cases (a total of 231 cases) the error was smaller than 10 mm. In another method, MHC-Spatial activation, right ventricularly paced maps (239 maps) were estimated with an error of 7.15 mm. The average correlation coefficient between the original and the estimated maps was also very high (0.97), which shows the ability of the training data set refinement methods to estimate the epicardial activation sequence. The results of these tests support the hypothesis and, moreover, suggest that such an approach is feasible for providing accurate reconstruction of complete epicardial activation-time maps in a clinical setting.

Experimental measures of ventricular activation and synchrony.

Background: A widened QRS complex as a primary indication for cardiac resynchronization therapy (CRT) for heart failure patients has been reported to be an inconsistent indicator for dyssynchronous ventricular activation. The purpose of this study was to conduct a detailed experimental investigation of total ventricular activation time (TVAT), determine how to measure it accurately, and compare it to the commonly used measure of QRS width. In addition, we investigated a measure of electrical synchrony and determined its relationship to the duration of ventricular activation.