Robert L. Lux

Correlation between in vivo transmembrane action potential durations and activation-recovery intervals from electrograms. Effects of interventions that alter repolarization time.

Classic cable theory was used to analyze the relation between the activation-recovery interval measured from unipolar electrograms and transmembrane action potential duration. Theoretic analysis demonstrated that the temporal derivative of the extracellular potential is proportional to a spatial weighting of the third temporal derivative of the transmembrane action potentials along a cable with uniform propagation in a homogeneous medium. Thus, the activation-recovery interval, measured as the interval between times of minimum derivative (Vmin) of the QRS and maximum derivative (Vmax) of the T wave, should be related to action potential duration, measured as the interval between times of Vmax of the upstroke and Vmin of the downstroke of the transmembrane action potential. This relation was examined experimentally in 12 anesthetized dogs. Unipolar electrograms and transmembrane action potentials were recorded simultaneously from sites within 2 mm of each other during control states, cardiac sympathetic nerve stimulation, localized epicardial warming, and graded reductions in myocardial perfusion. The heart was paced from several sites. There was close correlation between activation-recovery interval and action potential duration measurements taken during cardiac sympathetic nerve stimulation and local epicardial warming (r = 0.96 and 0.99 for cardiac sympathetic nerve stimulation and warming, respectively). In five animals in which coronary perfusion pressure was gradually lowered, the variables correlated closely over a range of values from 62 to 212 msec (r = 0.98). However, although the overall correlation was good and mean differences between activation-recovery interval and action potential duration were small, in individual cases there were differences up to 24 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Noninvasive Electrocardiographic Imaging Reconstruction of Epicardial Potentials, Electrograms, and Isochrones and Localization of Single and Multiple Electrocardiac Events

BACKGROUND The goal of noninvasive electrocardiographic imaging (ECGI) is to determine electric activity of the heart by reconstructing maps of epicardial potentials, excitation times (isochrones), and electrograms from data measured on the body surface. METHODS AND RESULTS Local electrocardiac events were initiated by pacing a dog heart in a human torso-shaped tank. Body surface potential measurements (384 electrodes) were used to compute epicardial potentials noninvasively. The accuracy of reconstructed epicardial potentials was evaluated by direct comparison to measured ones (134 electrodes). Protocols included pacing from single sites and simultaneously from two sites with various intersite distances. Body surface potentials showed a single minimum for both single- and double-site pacing (intersite distances of 52, 35, and 17 mm). Noninvasively reconstructed epicardial electrograms, potentials, and isochrones closely approximated the measured ones. Single pacing sites were reconstructed to within < or = 10 mm of their measured positions. Dual sites were located accurately and resolved for the above intersite distances. Regions of sparse and crowded isochrones, indicating spatial nonuniformities of epicardial activation spread, were also reconstructed. CONCLUSIONS The study demonstrates that ECGI can reconstruct epicardial potentials, electrograms, and isochrones over the entire epicardial surface during the cardiac cycle. It can provide detailed information on local activation of the heart noninvasively. Its uses could include localization of cardiac electric events (eg, ectopic foci), characterization of nonuniformities of conduction, characterization of repolarization properties (eg, dispersion), and mapping of dynamically changing arrhythmias (eg, polymorphic VT) on a beat-by-beat basis.

Limited Lead Selection for Estimation of Body Surface Potential Maps in Electrocardiography

Body surface potential mapping has shown promise as a technique to improve the resolution and accuracy of diagnostic electrocardiography, but the cost and effort required to obtain maps have made wide spread use impractical. As a step toward a practical system, the problems of redundancy and uniqueness of electrocardiographic signal information contained in large numbers of leads were investigated. An algorithm for optimal selection of a limited number of leads was developed. Data obtained from 132 human subjects including some with normal electrocardiograms (ECG) as well as some with abnormal ECGs, were used in the study. Estimation of body surface potentials from limited leads was evaluated using three criteria, including rms error, mean correlation coefficient between limited lead and total lead maps, and error to signal power ratio. Using 30 leads the average rms error was 32 ¿V, average correlation coefficient was .983 and noise to signal power was 3.5% in the presence of 20 ¿V rms noise. Another finding was that optimal sites are not unique, i.e., different sets of optimal sites may be found which perform equally well. This result has practical implications for the design of lead systems for estimating maps on the critically ill and on patients undergoing stress tests.

Effect of myocardial fiber direction on epicardial potentials.

BackgroundUnderstanding the relations between the architecture of myocardial fibers, the spread of excitation, and the associated ECG signals is necessary for addressing the forward problem of electrocardiography, that is, predicting intracardiac and extracardiac ECGs from known intracardiac activity. So far, these relations have been studied experimentally only in small myocardial areas. In this study, we tested the hypothesis that potential distributions measured over extensive epicardial regions during paced beats reflect the direction of superficial and intramural fibers through which excitation is spreading in both the initial and later stages of ventricular excitation. We also tried to establish whether the features of the epicardial potential distribution that correlate with fiber direction vary as a function of pacing site, intramural pacing depth, and time elapsed after the stimulus. An additional purpose was to compare measured epicardial potentials with recently published numerical simulations depicting the three-dimensional spread of excitation in the heart muscle and the associated potential fields. Methods and ResultsThe hearts of 18 mongrel dogs were exposed and 182 to 744 unipolar electrograms were recorded from epicardial electrode arrays (2.3 × 3.0 to 6.5 × 6.5 cm). Hearts were paced at various intramural depths through an intramural needle. The overall number of pacing sites in 18 dogs was 241. Epicardial potential distributions, electrographic waveforms, and excitation time maps were displayed, and fiber directions in the ventricular wall underlying the electrodes were determined histologically. During the early stages of ventricular excitation, the position of the epicardial maxima and minima revealed the orientation of myocardial fibers near the pacing site in all cases of epicardial and intramural pacing and in 60% of cases of endocardial or subendocardial pacing. During later stages of propagation, the rotation and expansion of the positive areas correlated with the helical spread of excitation through intramurally rotating fibers. Marked asymmetry of potential patterns probably reflected epicardial-endocardial obliqueness of intramural fibers. Multiple maxima appeared in the expanding positive areas. ConclusionsFor 93% of pacing sites, results verified our hypothesis that epicardial potential patterns elicited by ventricular pacing reflect the direction of fibers through which excitation is spreading during both the initial and later stages of propagation. Epicardial potential distributions provided information on the site of origin and subsequent helical spread of excitation in an epicardial-endocardial, endocardial-epicardial, or double direction. Results were in agreement with previously published numerical simulations except for the asymmetry and fragmentation of the positive areas.

Electrocardiographic Imaging Noninvasive Characterization of Intramural Myocardial Activation From Inverse-Reconstructed Epicardial Potentials and Electrograms

BACKGROUND A recent study demonstrated the ability of electrocardiographic imaging (ECGI) to reconstruct, noninvasively, epicardial potentials, electrograms, and activation sequences (isochrones) generated by epicardial activation. The current study expands the earlier work to the three-dimensional myocardium and investigates the ability of ECGI to characterize intramural myocardial activation noninvasively and to relate it to the underlying fiber structure of the myocardium. This objective is motivated by the fact that cardiac excitation and arrhythmogenesis involve the three-dimensional ventricular wall and its anisotropic structure. METHODS AND RESULTS Intramural activation was initiated by pacing a dog heart in a human torso tank. Body surface potentials (384 electrodes) were used to compute epicardial potentials noninvasively. Accuracy of reconstructed epicardial potentials was evaluated by direct comparison to measured ones (134 electrodes). Protocols included pacing from five intramural depths. Epicardial potentials showed characteristic patterns (1) early in activation, central negative region with two flanking maxima aligned with the orientation of fibers at the depth of pacing; (2) counterclockwise rotation of positive potentials with time for epicardial pacing, clockwise rotation for subendocardial pacing, and dual rotation for midmyocardial pacing; and (3) central positive region for endocardial pacing. Noninvasively reconstructed potentials closely approximated these patterns. Reconstructed epicardial electrograms and epicardial breakthrough times closely resembled measured ones, demonstrating progressively later epicardial activation with deeper pacing. CONCLUSIONS ECGI can noninvasively estimate the depth of intramyocardial electrophysiological events and provides information on the spread of excitation in the three-dimensional anisotropic myocardium on a beat-by-beat basis.

Clinically practical lead systems for improved electrocardiography: comparison with precordial grids and conventional lead systems.

The use of limited leads for estimating total body surface potential distributions was investigated as a practical solution to the problem associated with extensive electrocardiographic sampling used in surface potential mapping. Two practical, limited lead sets of 32 leads each were derived and contrasted to a set of 30 precordial leads similar to those used in ST-segment and QRS mapping for estimating infarct size, and to a set of nine leads simulating those used in conventional 12-lead examinations. The two arrays, one of which excluded posterior sites for use in recumbent patients, showed little difference in ability to estimate 192 lead measured maps (average rms voltage error of 35,V and average correlation coefficient of 0.97). The 30- and 9-lead arrays consistently showed twice the voltage (72,uV) and poorer pattern estimation (average correlation coefficient of 0.91) than either of the 32 lead arrays. These findings indicate the need for 20-35 properly located electrodes for accurate total body surface potential estimation. They also show that there is no difference in the abilities of a 30-lead precordial array and conventional leads to estimate maps

Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo.

The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use-dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals.

Diagnosis of old inferior myocardial infarction by body surface isopotential mapping

Body surface isopotential maps obtained from 28 patients with old inferior wall myocardial infarction were compared with maps from 120 normal subjects. The 12 lead electrocardiogram of 8 of the 28 patients (29 percent) with inferior wall infarction was normal or showed only nondiagnostic ST-T wave abnormalities at the time the isopotential maps were obtained. In all patients with inferior wall infarction the isopotential map showed a minimum (area of negative potentials) on the inferior or right thoracic surface during the early portions of the QRS complex. This finding was observed in patients with normal or nonspecific abnormalities in the 12 lead electrocardiogram as well as those with QRS abnormalities. By contrast, the minimum during the early QRS complex in normal subjects was located on the right upper back and shoulder region...

The unidentified information content of the electrocardiogram.

DEVELOPMENT of practical recording methods for the human electrocardiogram was rapidly followed by important medical applications. Electrocardiography was established as the major means of classifying disturbances of cardiac rhythm and an important aid in the recognition of myocardial disease including infarction. Applications have been sufficiently significant to result in widespread use of the method and there have been continuing technological improvements and extensions of the methods utility. At the present time and as presently used, electrocardiography is one of the major medical diagnostic methods. Despite considerable utility, it is unlikely that the full medical significance of electrocardiographic examination has been achieved. A variety of theoretic considerations together with supporting experimental and clinical observations suggest that the record may contain information of equal or even greater medical significance than that now obtained. This communication will review some of these considerations and observations. Material will be presented under the headings of regional cardiac examination, prognostic utility, and extended diagnostic applications. None of these represent totally new objectives for electrocardiographic examination but each offers substantial possibilities for improved use of the technique. The material reviewed does not include all areas in which improvements of electrocardiography are likely and should be viewed only as selected examples. Much of the material is necessarily speculative although some theoretic and/or clinical and experimental support for the speculations in each area will be furnished.

Experimental evidence for regional cardiac influence in body surface isopotential maps of dogs.

Isopotential maps based on 192–200 body surface electrocardiograms were obtained for 20 dogs during multiple patterns of ventricular activation. The purposes of the study were to determine whether the cardiac location of events responsible for surface potentials had a recognizable influence on surface potential patterns and to examine the influence of electrical events occurring simultaneously in multiple cardiac regions. Substantially different effects of electrical activity in various cardiac regions on body surface potentials were evidenced by the body surface location of potential maxima and minima and by patterns of isopotential lines during early portions of ventricular excitation initiated at different ventricular sites. Simultaneous stimulation at some sites gave surface potential distributions with multiple extrema. These were demonstrated to be due to effects of the different cardiac regions, because addition of potentials due to stimulation of the individual sites duplicated those associated with simultaneous stimulation of the same sites. It was also shown that body surface locations of maxima and minima are not related in the same manner to the cardiac location of the responsible events when these events are present in single and multiple regions. Slopes of potentials due to events in single cardiac regions were shown to combine with slopes produced by events in other regions to yield maxima or minima at new body surface locations. Results of the study support the possibility of regional cardiac examination by electrocardiograph) but suggest that this will require quantitative descriptions of the details of potential patterns in addition to the location of potential peaks.