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. RMS curves were derived from 4 lead sets: epicardial, body surface, precordial, and a 6-lead optimal set. Repolarization was altered by changing cycle length, temperature, and activation sequence. Rd, calculated directly from recovery times of the 64 epicardial potentials, was then compared with the width of the T wave of the RMS curve and with QTd for each of these 4 lead sets. The correlation between T-wave width and Rd for each lead set, respectively, was epicardium, 0.91; body surface, 0.84; precordial, 0.72; and optimal leads, 0.81. The correlation between QTd and Rd for each lead set was epicardium, 0.46; body surface, 0.47; precordial, 0.17; and optimal leads, 0.11. CONCLUSIONS: RMS curve analysis provides an accurate method of estimating Rd from the body surface. In contrast, QTd analysis provides a poor estimate of Rd.

Assessment of spatial resolution of pace mapping when using body surface potentials.

Using computer simulations and statistical methods, the resolution of pace mapping when used in combination with body surface potentials was systematically investigated. In an anatomical model of the human ventricular myocardium, pre-excitation sequences were initiated at 69 sites positioned along the atrioventricular (AV) ring and corresponding body surface potential maps (BSPMs) were calculated at 32 leads placed on the anterior torso. For each time after the onset of pre-excitation (every 4 ms to 40 ms) and each root-mean-square (RMS) noise level (5, 10, 20 and 50 microV), BSPMs were cros-correlated and the spatial resolution defined as the largest pacing site separation at which the differences in correlation coefficients were not statistically significant (level p > or = 0.05). The findings indicate that when random RMS noise of 5 microV was added to the simulated BSPMs, average spatial resolution over all 60 sites was at 20 ms after the onset of pre-excitation within 3.5 +/- 0.9 mm. The results provide theoretical evidence that statistical analysis of BSPMs obtained during pace mapping can offer improved means for subcentimetre identification of accessory pathways located along the AV ring.

Methods for accurate measures of total ventricular activation time.

The purpose of this study was to determine improved measures of total ventricular activation time for the diagnosis and treatment of patients undergoing cardiac resynchronization therapy (CRT). This work investigates the accuracy of a root mean square (RMS) based QRS width computed from unipolar electrograms (EGs) measured in heart for representing true total ventricular activation time (TVAT). The study also investigated the use subsets of EGs obtained from the endocardial and epicardial surfaces as indicators of TVAT. Transmural needle electrodes (96) were used to obtain 960 EGs from six normal isolated canine hearts. RMS-based QRS-widths from the endocardial and epicardial surfaces and volume were compared to the TVAT measured from all 960 EGs. No statistically significant differences were found in RMS-based QRS-widths obtained from all three sets of electrograms when compared with true TVAT. Activation times obtained from endocardial and epicardial surfaces were found to be poor indicators of true TVAT. The results support the use of RMS techniques for providing more accurate measures of TVAT.

A comparison of simulated QRS isointegral maps resulting from pacing at adjacent sites: implications for the spatial resolution of pace mapping using body surface potentials.

The precise localization of ventricular tachycardia (VT) foci is a prerequisite for the successful radiofrequency catheter ablation in patients. The purpose of this study was to systematically quantify over what distance adjacent sites in the right ventricular (RV) and left ventricular (LV) epicardium and LV endocardium could be distinguished by inspecting morphological features of QRS isointegral maps using statistical methods. We investigated the spatial resolution of QRS isointegral maps by means of an anatomically accurate computer model of the human ventricular myocardium that incorporates a bidomain model for simulating the realistic activation sequences and the oblique dipole model in combination with the boundary element method for calculating extracardiac potentials. In this model, we initiated activation sequences at a total of 183 epicardial and 75 LV endocardial pacing sites, positioned in three levels (basal, middle, and apical). For each of the 258 pacing sites, we calculated a set of 10 QRS isointegral maps with added Gaussian noise at 117 leads (covering the anterior and posterior torso) and at 32 leads (covering only the anterior torso), respectively. Sets of maps were then cross correlated and root-mean-square (RMS) values of difference maps were calculated for all possible pairs of pacing sites on the same level. We applied the nonparametric unpaired Kolmogorov-Smirnov test and defined the spatial resolution as the pacing site separation at which the differences in correlation coefficients and RMS differences were significant (level P < .05). We observed significant differences in maps when the distances between pacing sites were on average (+/- SD) greater than 4.3 +/- 1.0 mm. In more than 90% of pacing sites, the significant differences in maps were observed within 4 mm even when using a 32-lead mapping system. The findings of our study provide theoretical evidence that QRS isointegral maps may offer noninvasive means for preinterventional planning of the ablative treatment in localizing both endocardial and epicardial sites of origin of VT.

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. METHODS AND RESULTS: The catheter is 3 mm (9 French) in diameter and carries 96 electrodes. Reconstruction accuracy is evaluated through direct comparison with endocardial data measured with 95 needle electrodes. Results show that endocardial potentials, electrograms, and isochrones are reconstructed with good accuracy during pacing from single or multiple sites (simulating ectopic activity). Pacing sites can be located to within 5 mm of their actual position, and intersite distances of 17 mm can be resolved during dual pacing. The reconstructed potential pattern reflects the intramural depth of pacing. The reconstructions are robust in the presence of geometric errors, and the accuracy is minimally reduced when only 62 catheter electrodes are used (32 are sufficient for pacing site localization). CONCLUSION: The study demonstrates that simultaneous endocardial mapping can be accomplished during a single beat from a spiral-shaped noncontact catheter with good accuracy.

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. We developed both simulation and experimental studies based on a realistic shaped torso phantom containing an isolated, perfused dog heart. Interventions included atrial pacing, single pacing and simultaneously pacing at multiple locations on the ventricles. Simulated torso volume potentials closely matched measured potentials in the torso-tank preparation (mean correlation coefficients of 0.95). Simulation further provided a means of estimating the current field in the torso from the computed torso volume potentials and the local geometric and conductive properties of the medium. Applying these techniques to the torso electric fields under a variety of pacing conditions, we have further demonstrated that thoracic current can provide many insights into the relationship between heart surface potential and body surface potentials. Specifically, we have shown that geometric factors including cardiac source configuration and location play an important role in determining to what extent electric activity in the heart is directly visible on the body surface electrocardiogram. The computation and visualization toolkit we developed in this study to explore current fields associated with cardiac events may provide new insights into electrocardiology.

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. The goal of this study was to investigate specifically the role of geometric factors in altering body surface potentials and the electrocardiogram. For this, we used experiments with an isolated, perfused dog heart suspended in a realistically shaped electrolytic torso tank. The experimental preparation allowed us to measure epicardial and tank surface potentials simultaneously, and then reconstruct the geometry of both surfaces. Our results mimicked some of the features described by previous investigators. However, our results also showed differences that included considerably larger changes in the peak QRS and T-wave amplitudes with heart movement than those reported in human studies. We detected smaller values of root-mean-squared variability from heart movements than those reported in a human study comparing body surface potentials during change in inspiration and body position. There was better agreement with relative variability, which in these studies ranged from 0.11 to 0.42, agreeing well with an estimate from human studies of 0.40. Our results suggest that the isolated heart/torso tank preparation is a valuable tool for investigating the effects of geometric variation. Furthermore, the geometric position of the heart appears to be a large source of variation in body surface potentials. The size of these variations easily exceeded thresholds used to distinguish pathologic conditions and thus such variations could have important implications on the interpretation of the standard electrocardiogram.

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. The prevailing biophysical theory of ischemia suggests that complete occlusion should produce at least transient ST-segment depression, a finding we have neither observed in our own studies nor uncovered in the literature. Our goal with these experiments was to understand the difference between complete occlusion and reduced coronary flow, specifically the behavior at the transition between the two. We have performed experiments by using isolated dog hearts with a cannulated left anterior descending artery suspended in a human shaped electrolytic tank. To create a range of ischemic conditions, we changed coronary flow rates both suddenly and in controlled sequences and varied the heart rate of the isolated heart. The main finding was that in the isolated heart preparation, epicardial ST-segment depression over the ischemic zone arose only under conditions of combined restricted flow and elevated heart rate. Reduced coronary flow alone never produced ST-segment depression. These findings suggest that heart rate and probably metabolic work create the conditions necessary for subendocardial ischemia that reduced flow alone cannot provoke. They furthermore suggest that the degree of ST-segment depression for a given restriction in coronary flow may depend on heart rate, which supports the notion of rate correction for clinical stress electrocardiogram testing.

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. Initial results indicate that the conduction velocity is strain dependent in such a manner that several components contribute to establish this relationship. Further studies will help to quantify the relationship and importance of the components.

Quantitative characterization of epicardial wave fronts during regional ischemia and elevated extracellular potassium ion concentration.

This study applied zero-delay wave number spectral estimation as a means of quantifying the changes in activation and recovery sequences of propagating plane waves on the epicardial surface of in situ porcine hearts during regional hyperkalemia and ischemia. Unipolar electrograms (104) were recorded from the left ventricular surface of nine hearts using a plaque electrode array with 1 mm spatial sampling intervals. The objectives were (1) to define a set of parameters capable of quantifying the spatial and temporal changes in measured extracellular potentials associated with localized ischemia prior to the onset of conduction block; (2) to elevate regional levels of extracellular potassium ion concentration and quantify potential changes due to this known physiologic manipulation; and (3) to use quantitative parameters to make statistical comparisons in order to distinguish wave fronts during normal, ischemic and hyperkalemic conditions. Results showed that the parameters of wave number and average temporal frequency and the associated power, as determined from the wave number spectrum, provided statistically significant (p<0.05) quantification of changes in wave front features during normal and ischemic or hyperkalemic conditions. The results were consistent with results obtained from conventional time-space domain methods like isochronal mapping and electrograms, with the advantage of a quantitative result enabling simple comparisons and trend analysis for large numbers of heart beats.

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.

Useful lessons from body surface mapping.

Useful Lessons from Body Surface Mapping. Body surface potential maps (BSMs) depict the time varying distribution of cardiac potentials on the entire surface of the torso. Hundreds of studies have shown that BSMs contain more diagnostic and prognostic information than can be elicited from the 12-lead ECG. Despite these advantages, body surface mapping has not become a routinely used clinical method. One reason is that visual examination and sophisticated analysis of BSMs do not permit inferring the sequence of excitation and repolarization in the heart with a sufficient degree of certainty and detail. These limitations can be partially overcome by implementing inverse procedures that reconstruct epicardial potentials, isochrones, and ECGs from body surface measurements. Furthermore, ongoing experimental work and simulation studies show that a great deal of information about intramural events can be elicited from measured or reconstructed epicardial potential distributions. Interpreting epicardial data in terms of deep activity requires extensive knowledge of the architecture of myocardial fibers, their anisotropic properties, and the role of rotational anisotropy in affecting propagation and the associated potential fields.

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.

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. METHODS AND RESULTS: High-resolution spatial distributions of QTI and potentials were determined on the body surface of human subjects and on the surface of a torso-shaped tank containing an isolated canine heart. Additionally, spatial distributions of QTI, recovery times, and STT areas were determined on the surface of exposed canine hearts. Unipolar electrograms were recorded during atrial and ventricular pacing for normal hearts and cases of myocardial infarction. Regions of shortest QTI always coincided with the location of the zero potential line on the cardiac and body surfaces. On the cardiac surface, in regions away from the zero line, similarities were observed between the patterns of QTI and the sequence of recovery. STT areas and recovery times were highly correlated on the cardiac surface. CONCLUSION: QTI is not a robust index of local recovery time on the cardiac surface. QTI distributions were affected by the position of the zero potential line, which is unrelated to local recovery times. However, similarities in the patterns of QTI and recovery times in some regions may help explain the frequently reported predictive value of QT dispersion. Preliminary results indicate STT area may be a better index of recovery time and recovery time dispersion on the epicardium than QTI.