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Principal Factor Waveforms of the Thoracic QRS Complex By Leo G. Horan, M.D., Nancy C. Flowers, M.D., and Daniel A. Brody, M.D. Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 • Concern has been expressed repeatedly in the electrocardiographic literature as to whether the three leads of a spatial vectorcardiogram contain more or less information than that found in the standard twelve-lead electrocardiogram.1"4 Frequently the adequacy of the report of the twelve-lead electrocardiogram has also been questioned and addition of one or more exploratory leads has been recommended.5"7 These questions are two aspects of the more fundamental problem: What is the minimum number of leads which can contain all of the electrocardiographic information available on the body surface? A theoretical approach to the answer would be to determine the minimum number of unique building blocks capable of synthesizing any waveform detectable on the body surface. For example, by means of principal factor analysis Scher et al. derived a minimum number of mathematically uncorrelated QRS waveforms found in an assortment of electrocardiographic leads varying from 8 to 32 in number.8 A practical answer would be to find those body sites especially sensitive to these elemental waveforms so that placement of leads would insure adequate acquisition of information. In the present study we have extended the use of factor analysis to between 150 and 180 exploratory leads systematically spaced over the thoracic surface. This was done in the hope both of deriving a clearer appreciation for the total scope of informaFrom the Section of Cardiology, Department of Medicine, University of Tennessee, Memphis, Tennessee. Supported by Grants HE-D1362-11 and 5-K6-HE14, 032-02 from the National Institutes of Health, U. S. Public Health Service, and by a grant from the Tennessee Heart Association. Received for publication January 20, 1964. Circulation Research, Vol. XV, August 1964 tion available and of obtaining indications as to whether the topography of lead sensitivity is ascertainable in individual subjects. Factor analysis was chosen as a mathematical means of comparing each QRS complex with all the others. This permitted first the removal, from the entire population of QRS waveforms, of the most common basic QRS pattern. Then similarly, the second most frequently appearing pattern was removed and the process was repeated until all of the distinctive waveform information was accounted for. The net result was a consolidation of the information in the large number of QRS complexes into a considerably smaller number of individually dissimilar waveforms. Methods Two subjects were chosen for study. Systematic spacing of 153 unipolar leads over the surface of the chest of a dog for equipotential mapping has been previously described.9 A 17-kg male dog was placed in normal standing position in a Pavlov stand, was supported by straps under the trunk, and was anesthetized with sodium pentobarbital (30 mgAg I V )- A Crass kymograph C4J camera was employed to photograph the oscilloscopic display of four simultaneous leads on film moving at the rate of 250 mm/sec. A similar set of QRS waveforms was measured from the recordings of 180 electrode sites (with 5.0 rather than 3.0 cm spacing and with eight simultaneous channels *) for a normal healthy 37-year-old man in the sitting position (fig. 1A). For both subjects attention was given to the phase of respiration; records were obtained between the end of expiratory movement and the beginning of inspiration. All records were examined carefully to ascertain the time of earliest departure from the base line of any QRS complex with regard to the control lead. This instant was marked on a * Tektronix 565 oscilloscope with two 3A74 fourtrace amplifier plug-in units and eight 122 low-level preamplifiers. 131 132 HORAN, FLOWERS, BRODY * 12 tit * 13 25 FIGURE 1A Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 A representative set of simultaneously recorded QRS waveforms from a normal human subject and a computer plot of their digitized representations. Original waveforms were recorded on film moving at 250 mm/sec. The plot was made by machine interpolation at 2-msec intervals between the 10-msec data points obtained by direct measurement of an enlarged image from the original film. A loss of precision to one significant figure has occurred in the plot because in this figure the vertical scale has been kept small to make the plot visually comparable to the original record. In subsequent illustrations the vertical scale has been increased so that the curves are smoother and approach clinically familiar configurations. permanent tracing of the control lead Vf on crosssection paper as time zero or the onset of ventricular depolarization. Optically enlarged images of the constant control lead (Vf) were successively superimposed onto the permanent tracing of the control lead. In this way the entire set of QRS waveforms for each subject was matched temporally. Measurements of potential were then made of all QRS complexes at five-msec intervals for the dog and ten-msec intervals for the man. The total duration of QRS complex was about 36 msec in the canine subject and about 87 msec in the human. (About indicates difficulty in measuring the exact duration of the QRS complex because very gentle terminal slopes of the QRS and slight displacement of the ST-segment combined to obscure the exact endpoint in the critical anterior midchest leads.) From the measurements at five- or ten-msec intervals, maps of instantaneous isopotential distribution were constructed by bilinear interpolation and plotting with the aid of a digital computer (fig. 2). 9 Because of the multipolar patterns in evidence on these maps (as will be discussed later) we turned to principal factor analysis to determine if more components than those necessary to describe a dipole were easily detectable. The general plan for processing the data is indicated in the flow chart (fig. IB). Digitized forms of each QRS complex at each electrode site were constructed by interpolation between the measured time values (fig. 1A). For each four successive points a third degree curve was fitted and the central interval retained for calculation of interpolated points (to each msec in the dog and to every second msec in the man). This interpolative procedure permitted the development of digitized QRS waveforms from seven to eight measured points. Representative interpolated waveforms were superimposable upon those digitized at 1-msec intervals from the original with less than 1% error. These surface potential data were organized as a large matrix consisting of 153 or 180 leads (rows) with 40 or 45 successive potential values in time (columns). Such a matrix of data of potential values was designated matrix V. In terms of matrix algebra the equation (180X180) (180X45) (180x45) (1) A X = V states that the potential values throughout the QRS and over the surface of the body may be resynthesized as the product of a set of factors, X, and their distributive coefficients, A. If each of these factors is unique in that none contains information found in the others, the equation represents an orthogonal transformation and the factors may be designated as principal.10 The CircmUtion Ruurcb, Vol. XV, August 1964 133 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 B FIGURE IB A flow-chart presenting diagrammatically the Iwndling of data in the study of principal factor waveforms of the QRS complex in a human subject. The boxes containing labels in capital letters indicate major processes done by the digital computer. From 180 systematically spaced points on the thoracic surface (a) high-fidelity recordings of the QRS complex (b) were obtained and, after time-justification, were measured at 10-msec intervals. These digital measurements (c) were fed into the digital computer which fitted third degree curves between the data points so that the digitized representation of the QRS complex (d) closely simulated one obtained by sampling at 2-msec intervals. All 180 digitized QRS waveforms were then factored by the method of principal factor analysis. Eight component waveforms or principal factors (e) were found. Each digitized QRS waveform was then re-examined for its content of each of the principal factors. From this assay it was possible to determine the degree to which successive addition of factors satisfactorily reproduced the original waveform at any site (f) and to determine the distribution over the subject's chest of each of the principal factors (g). principal factors to be determined are at the outset represented as an unknown number of waveforms (rows) with successive temporal variation in amplitude (columns). The coefficients for 180 electrode sites (rows) will specify the proportions contributed by the respective principal factors to each waveform at each site (columns). Details are provided in the Appendix. Upon diagonalization, the effective size of the transforming or eigenvector matrix, A"1, and consequently the number of significant principal factors may be greatly reduced. In this instance because the eigenvalues beyond the eighth approach zero, only the first eight rows of A-1 need be considered. Therefore, (8X180) (180X45) ( 3 X 4 5 ) (2) V = X A-1 (In actual practice the size of the memory of Circulation Rtiurcb, Vol. XV, A*g*u 1964 the digital computer was limiting. Therefore, factoring was done in successive stages, i.e., 20 waveforms at a time. Subsequently these factors were factored by combining sets of 8 factors into a group of 16 and so on pyramidally until the final factors obtained represented the principal factors of the whole original matrix.) Thus, as indicated in the Appendix, the eigenvector matrix is the inverse of the matrix of coefficients for each principal factor necessary to resynthesize the recorded waveform found at each electrode site. The resynthesis was then performed by substitution into equation 1 in a stepwise fashion in order to examine the contribution of each factor as it was added. The root mean square of the deviation of the original waveform from the base line was accepted as an estimate of total amount of information present in the waveform, and the root mean HORAN, FLOWERS, BRODY 134 .-175 •._ HUUAN gu -100.".,. -1BO I- 075 OS FIGURE 2 An isopotential map of the chest of a normal human subject at 40 msec after the onset of ventricular depolarization. Original electrode sites are indicated by intersection of grid-lines. The isopotential contour lines are spaced at intervals of 025 mv. Note region of positioity over the left anterior and lateral chest where the maximum divides at times into two submaxima. Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 square (RMS) of the deviation of a resynthesized waveform from the original was accepted as an estimate of the error or remainder, after any given number of factors made their contribution to the resynthesis. Thus the appraisal of the relative inadequacy of resynthesis was developed by using a ratio of these HMS values (deviation of resynthesized from original/original's deviation from base line) and converting to percentage. The difference between per cent of error and 100X was used as a convenient, though mathematically imprecise, index of the adequacy of resynthesis (fig. 3 ) . Results COMPARISON BETWEEN MAN AND DOG OF THE SURFACE DISTRIBUTION OF POTENTIAL DURING VENTRICULAR DEPOLARIZATION Information = error = \JId % r.jynihesls = '"formation-error Information x 1 O Q FIGURE 3 Diagrammatic representation of estimate of error in the process of resynthesis of waveforms. The solid-line curve represents the original or known waveform to be resynthesized. The broken line represents an attempted resynthesis. The deviation d between the real and calculated curves for a given interval of observation (2 msec) is the instantaneous error, and the deviation D from the base line represents the instantaneous information in the original recording. The relative error Figure 2 presents a map of potential distribution of the thoracic surface of a man at 40 msec after the onset of ventricular depolarization. The extremes of intensity of surface potential were more limited for the man than for the dog, varying between ±2.5 mv in the man as compared to ± 4 mv in the dog.9 Duration of the QRS complex in the for the whole waveform may be estimated by the ratio of root sum squares, i.e., per cent error = y ~%&*/ X 100. Similarly, the adequacy of resynthesis V in per cent may be estimated by dividing the difference between "information" and "error" by the desired "information" and multiplying the result by 100. CircmUtion Ristxrch, Vol. XV, Amgmst 1964 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX 135 human subject was slightly greater than twice that in the dog. The principal evidence of multipolar activity occurred between 40 and 50 msec after onset in the man as seen in figure 2 with again strong suggestion of multiple islands of activity late in the QRS complex at about the time of the right precordial R prime. THE PRINCIPAL FACTORS AND THE PROBLEM OF RESYNTHESIS PRINCIPAL FACTORS OF QRS WAVEFORMS Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 FIGURE 4 Digital computer plot of the configuration of the eight principal factors derived by factor analysis of 180 QRS waveforms systematically spaced over the thoracic surface of a normal man. The digits of the plot have been joined by a bold black line. Note the relatively greater magnitude of factors one and two as compared with the remainder and the resemblance of factor one to the common configuration of lead Ve. See text for details. Circulstion Rtjurcb, Vol. XV, August 1964 Figure 4 shows the eight final principal factors for the human subject and figure 5 illustrates the role of each in the progressive resynthesis of a selected set of QRS complexes recorded from the anterior chest. The effect of reconstructing the original pattern of surface distribution for given instants after the onset of ventricular depolarization by successive addition of the contributions of each of the principal factors was also examined. Gross distinctions between stages of resynthesis were less obvious than with individual waveforms. Usually upon addition of the third principal factor, very close resemblance to the original waveform became apparent. However, a substantial percentage of information found in the final waveform remained in factors four through seven in the dog and four through eight in man (fig. 5). The eigenvalues corresponding to the principal factors tapered very sharply with an almost abrupt cutoff or diminution in value on the order of 10"3 between seven and eight in the dog. In the man, an abrupt diminution on the order of 10"4 occurred after the eighth eigenvalue. The abrupt cutoff very probably reflected a limitation by the number of raw data points obtained for each set of QRS waveforms. For example, five sets of eight simultaneous leads (I, Vf, and Vi through Vo) for different human subjects were digitized at 2.5-msec intervals. Principal factors for each of these sets were determined and showed heavier concentration of information in factors one and two. Then the points intervening between the 10-msec intervals were discarded and new points at 2-msec intervals were determined by interpolation, i.e., there were now eight original data points. The resulting interpolated waveforms were factored. The contribution of the respective eigenvalues did HORAN, FLOWERS, BRODY 136 D5 E 12 2 5 msec Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 FIGURE 5 F 17 not vary more than 2%. When interpolation was made from only six points (using a 12.5msec sampling interval) there was little difference in eigenvalues until after the sixth when again an abrupt cutoff appeared. Because eigenvalues are estimates of variance these findings indicate that in these normal subjects evidence was not exaggerated or suppressed by interpolation. Similarly, the number of sampling points was limiting only in that it did not permit the detection of effect of principal factors of higher order than the number of sampling points. As noted in table Digital computer plots of the resynthesis of three QRS waveforms showing the effect of successive addition of the contributions of the eight •principal factors. For orientation it may be noted that familiar clinical leads which are near the thoracic sites from which the waveforms were detected are respectively (a) Vr, (b) V3, and (c) Ve. The number of each 2-msec interval represents the cumulative effect of all factors up to and including the numbered factor. Thus, the ones show only the effect of principal factor one, but the threes report the resynthesized waveform after addition of principal factors one, two, and three. Complete resynthesis of the original wave is achieved on each line after addition of factor eight (solid line). Whenever the effect of two or more factors resulted in a coincident point the computer was instructed to report only the final number. Thus in many instances, for example, an eight may have replaced a preceding six and seven. 1, the rough estimate of the adequacy of resynthesis obtained by subtracting the more precise estimate of error from 10035 (fig. 3) was well predicted by the square root of the appropriate eigenvalue. SURFACE DISTRIBUTION OF THE PRINCIPAL FACTORS Certain regions of the thorax showed a relatively high percentage of contribution to the waveform from one or more principal factors as compared with the others. Figure 6 shows the surface distribution of three of the eight principal factors for the man. Note the inCircmUtiou Rtsttrcb, Vol. XV, August 1964 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 tensity of factors one and two over the anterior chest and their resemblance to the patterns of distribution of two orthogonally oriented vectors.9 The distribution of intensity of the third factor and the remaining factors cannot be so simply described but the pattern demonstrated by the third factor is typical in that each of the later factors showed many roughly symmetrical small whorls and islands. Similar maps showing the degree to which successive addition of the factors reproduced all of the information available were of interest. Figure 7 presents a synopsis of a series of maps representing the degree of reproduction of information on the chest of the man. It can be seen that the first principal factor accounts in high degree for much of the information present in the region of maximum excursion in potential values. By the time factor three was incorporated, a majority of waveforms in the region of large amplitude had been satisfied but there were distinctive holdouts of information which were accounted for gradually by the successive addition of factors through eight (or, in a similar analysis of data from the dog, seven). Discussion LIMITATIONS OF THE METHOD This work must be considered merely as preliminary to the task of systematic, compre- 137 hensive acquisition of surface electrocardiographic information, its subsequent reduction to nonredundant form, and, finally, its evaluation for physiological and clinical significance. Only limited conclusions can be drawn from observations, however extensive, from just two subjects, each of a different species. The following discussion relates to difficulties in the successive stages of instrumentation, observation, measurement, and computation that have been encountered and to the obstacles that need to be overcome as this method is extended both to other normal and to abnormal subjects. As previously indicated,9 reconstruction of maps of distribution of surface potential from multiple records is plagued by the possible introduction of artifacts from nonsimultaneous sampling. This is particularly important during the early and late phases of the QRS complex when regions of low potential gradient exhibit islands or small local variations which may arise either from multipolar behavior of the cardiac generator, from noise, or from an error in matching introduced by movement of the animal between samples. We have taken great pains to reduce somatic tremor, to record during the resting postexpiratory phase of breathing, and to match the waveforms to a common timebase by superimposing the constant con- TABLE l Adequacy of Resynthesis Principal factor Eigenvalue Square root of eigenvalue Dog 1 2 3 4 5 6 7 6891.56 543.07 90.66 8.43 5.57 3.07 1.05 83.0 23.3 9.5 2.9 2.4 1.8 1.0 Man 1 2 3 4 5 6 7 8 832.34 170.07 9.53 3.35 2.05 1.23 .76 .50 28.8 13.0 3.1 1.8 1.4 1.1 .9 .7 CirctUlion Resttrcb, Vol. XV, Ant*" 1964 Average error in % of total Information % Rciynthwis (100*/«-average error) 67.0 85.8 93.5 95.9 97.8 99.2 100.0 47.0 26.9 7.2 5.3 4.0 2.3 .7 53.0 73.1 92.8 94.7 96.0 97.7 99.3 56.6 82.3 88.3 91.9 94.7 96.9 98.6 100.0 46.8 20.6 14.6 11.9 9.1 6.9 3.6 .3 53.2 80.4 85.4 88.1 90.0 93.1 96.4 99.7 Cumulative % of square root of eigenvalue 138 HORAN, FLOWERS, BRODY trol lead when each set of measurements was made. The decision to utilize the time of earliest departure from the base line of the midsternal leads as time zero was arbitrary but was consistendy adhered to throughout. Two precautions are suggested concerning die fu- 1HTENSITT Of PRINCIPAL MCTOA MO. 1 Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 FIGURE 6 Contour maps of the distribution of the first three of the eight principal factors in terms of their strength of contribution to the local configuration of the QRS waoeform. Note that maps for factor one and factor two resemble the patterns of distribution of effect of a simple vector3 but that the third factor cannot be so simply described. See text for discussion. CircuUsion Resetrcb, Vol. XV, August 1964 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX ture development of techniques to settle this question about possible multipolar effects in the regions of low gradient. First, there must be widespread multichannel recording over large areas of the chest so that simultaneity is guaranteed. Second, serious consideration should be given to averaging techniques using long magnetic tape recordings. Repetitive summing of waveforms by such methods would allow for the cancellation of both random PER CENT ERROR NRESVNTHES1S_ .•WI-EN ONLY TACTOR ONE APPLIED Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 FIGURE 7 a. An equipercentile contour map of the chest demonstrating the error remaining after attempting resynthesis of the QRS waveforms with principal factor one alone. For example, within the boundary marked "10%" the error was 10% or less, i.e., the resynthesized waves very closely approached the original configuration; however, within the region enclosed by the "90%" line there was an error of 90% or greater and the resynthesized waveform very poorly resembled the recorded QRS complex. b. Composite map of such 10% equipercentile lines from the successive addition of the effect of each principal factor. The black area (1) indicates the region within which factor one brought the resynthesized waveform close to the original, i.e., with less than 10% error. The slant-lined regions (2) indicate the extension of the boundary of close approximation by the addition of the contribution of factor two to the resynthesized waveform and similarly the dotted regions (3) for factor three. A bold black line demarcates the area of over 90% restoration produced by the first three factors alone from those remaining areas which required factors four through eight. CircuUaion Ktsctrch, Vol. XV, Amgmii 1964 140 Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 noise and unrelated cyclic phenomenaX1 thus bringing out only distinctive and real differences in potential gradient. The significance of respiratory changes and the effect of averaging on such variation would have to be experimentally assessed. A limitation imposed by economy and time is the sampling interval of 5 msec in the dog and 10 msec in man. These intervals produced effective sampling rates of 200/sec and 100/sec respectively. Such sampling rates are perfectly satisfactory as long as there are no portions of the QRS waveform of higher frequency than 100 cycles/sec in the dog and 50 cycles/sec in man. Comparison of original and reconstructed waveforms, after the computer filled in the interval between samples, indicated to us that there was no significant information above this level in these normal subjects. When study is extended, however, to abnormal subjects, it will be necessary to prepare for the known occurrence of such phenomena as the high frequency components in the electrocardiogram associated with myocardial infarction.12 The use of magnetic tape recordings with automatic analog-to-digital conversion at sampling rates of 1,000/sec or higher should effectively remove this Limitation and have the additional advantages of removing observer error in measurement and speeding up acquisition of data. There remains one serious impediment to extending this study to a wider spectrum of subjects: the time required for electronic data processing on the digital computer is long. After the computer program was fully developed and ran smoothly, it required about 90 minutes to factor 20 leads. Thus the total computer time needed to obtain eight principal factors from 180 leads (including intermediate steps in the pyramid) for the data from the human subject was about 24 hours. According to the availability of the digital computer, this processing was done at the rate of one and a half to three hours per day. An equal amount of time was required for the resynthesis of these waveforms. The fact that only seven or eight data points were measured per waveform accounts for little or no saving of computation time. In- HORAN, FLOWERS, BRODY deed, the interpolative procedure was employed to simulate the introduction to the computer of data directly digitized at 2-msec intervals. This limitation of sampling points however, does restrict the interpretation to be placed on the cutoffs of factors after the seventh and eighth. Interpolation by fitting with curves of third degree equations instead of simple linear interpolation caused the waveforms to approach more nearly the original in configuration but the theoretical expectation of more final principal factors than seven (in the dog) and eight (in the man) was not seen. Sampling with a greater number of points per curve may allow more factors to be detected but is not Likely to extend the number of significant factors all the way to the new number of samples per curve. Thus, the number of factors found in these two subjects is probably somewhat less than if sampling were carried out to 1-msec intervals. The greater the number of sampling points the greater the degree to which individual variation in waveform is conserved. The crucial point is whether this individual variation in waveform results from noise (including observer error) or significant signal. If noise, then the limiting of the number of samples has reduced the degree to which we have been deceived by spurious variation in contour; if signal, then limiting of the number of samples has made our estimate of the quantity of waveform information, that is present, conservative. We expect that improvement in instrumentation, which will tend to eliminate both noise and observer error, may reduce the number of significant principal factors. On the other hand, in the abnormal population high frequency components, as noted in subjects with myocardial infarction, and local irregularities of contour, as noted in subjects with conducton defects, may be expected to increase the number of factors. Our tentative conclusion is that within the limits of our experimental design there were at least seven significant principal factor waveforms in the dog and eight in the man. INTERPRETATION OF MULTIPOLAR PATTERNS OF SURFACE POTENTIAL DISTRIBUTION The presence of multipolar patterns of Circmltsion Research, Vol. XV, Angmlt 1964 141 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 surface potential distribution at various instants during ventricular depolarization is now well documented both for man and dog.9'18'14 It is possible that an occasional finding of more than one positive maximum or more than one negative maximum of potential may be arrifactual, especially when found in a region of low gradient where the signal has fallen close to the noise level. However, with this exception, multipolar patterns have been demonstrated on repeated examination of individual subjects and during comparable times in the QRS complex in many subjects.9'18 It is important to consider the various possible causes of instantaneous surface "multipolarity." The biophysical possibilities are (1) the formation of reflections or images at each interface between intrathoracic regions of differing resistivity, e.g., between blood and myocardium or between myocardium and lung; (2) conductive focussing of the effect of the wave of activation in selected portions of the myocardium; (3) proximity effects, i.e., where a small fragment of the wave of activation in a portion of the myocardium very close to the chest wall is oriented differently from the large remainder elsewhere; (4) qualitative differences in portions of the wavefronts of myocardial activation. Failure to elicit distinctive multipolar patterns upon implantation of artificial dipolar (bipolar) current sources in the canine myocardium suggested to us that the first of the aforementioned possibilities is unlikely.0 As to the second, the theoretical possibilities of conductive focussing as a contributor are good both because of the theoretical effect of the blood mass on the electrocardiogram16-17 and because of experimental evidence supporting the concept of focussing of the septal contribution.18 Pure proximity effects also seem likely, first because the demonstration of instantaneous surface multipolarity is more striking in the dog than in man, and second because of the appearance of multipolar patterns during the time of the right precordial R prime when it is suspected that the right aspect of the interventricular septum or the right free wall near the pulmonary valve is activated. Finally, we do not know that the wave of activation sweeping through the Circulation Rurtrcb, Vol. XV, A*gnit 1964 myocardium remains uniform in density of charge either over its surface or in time; we think, however, it is reasonable to assume uniformity until experimental evidence suggests otherwise. We agree with Taccardi that the evolution of the surface pattern should be related if possible to the underlying events in the heart.14 We therefore suspect that the appearance of the markedly multipolar pattern which reached its peak between 40 and 50 msec in the human subject may well relate to the separation of components of the wave of activation in the right free wall and interventricular septum from the left free wall by epicardial breakthrough at the apex. Similarly, we suspect that the appearance of a multipolar pattern in the terminal portion of the QRS complex or of the reappearance of a small island of positivity on the anterior precordium late in ventricular depolarization relates to the firing of basilar portions of the right ventricle or interventricular septum. INTERPRETATION OF PRINCIPAL FACTORS By derivation the principal factors are expressions of the limits of information contained in the entire population of waveforms about the chest. As Scher et al. have pointed out,8 finding no more than three principal factors of significance—from which all the information from the body surface could be reproduced— would be compatible with the reduction of the cardiac generator to an equivalent dipole. They, of course, made the proviso that the discovery of three factors was not proof of dipolar equivalence but that any number of three-factor generators were possible, among them a dipole. Because the principal factors are mathematically uncorrelated or orthogonal in terms of signal space, if only three were significant one could consider them also orthogonal in three-dimensional space and merely determine the proper rotational transformation of axes to find the XYZ components of the equivalent dipole or vector. However, more than three significant principal factors were observed. In fact, there appeared to be at least seven and eight (the upper limit set by the number of sampling points). The attempt to translate the information contained in the HORAN, FLOWERS, BRODY 142 principal factors into biologically useful terms should begin with careful reconsideration of the conceptual tools by which we relate surface potential to the interplay between the real or an equivalent cardiac generator and the conductive characteristics of the body. The relationship between current and voltage along a line conductor (or in a network of lines) is described by Ohm's law, E = IR or RI. Potential drop E along the line is the algebraic product of the current I and the resistance of the conductor R. In a volume conductor the relationship is more complex; in the case where the current source is a dipole, surface potentials may be described by a series of expressions similar to those employed by Burger et al.:20 V! = auXi + a12x2 + a13xH Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 t> 3 = (3) + as2x2 + The relationship between the potential v1 across a given lead and the spatially orthogonal components of the heart vector or dipole {xu x-2, xs) at a specified instant is defined in terms of the orthogonal components of the lead vector (aii,a]2,fiis) of the lead. This algebraic expression can be stated more briefly in vector form: V = A-X (4) In a very rough way equation 4 is analogous to Ohm's law in that it states that lead potential (mv) is the scalar product of the lead vector (mv/ma • cm) and the heart vector (ma • cm). The lead vector has been sometimes treated as a statement of the impedance characteristics of the conducting medium for the given lead and called transfer impedance.19 Viewed in the latter way the units of the lead vector may be simplified to ohm/cm. Now the relationship for any number of leads to the heart vector and their respective lead vectors may be stated in matrix form ( n x l ) (nX3) (3X1) VA X (5) in which V represents a column of individual lead voltages, (vuv2, v3 . . . vn), X represents a column describing the three spatial or Carte- sian components of the instantaneous heart vector, and A is a matrix of an appropriate number of sets of lead vectors (each with three coefficients). This instantaneous relationship can be expanded for the time-varying dipole by replacing the units in the matrix dimensions by a given number of consecutive instants in time thus converting V and X respectively from single columns into rectangular matrices. RELATIONSHIP BETWEEN PRINCIPAL FACTORS AND THE EQUIVALENT CARDIAC GENERATOR Because the simplification of the cardiac generator into a dipole of fixed location but varying orientation and intensity is not sufficient to explain the surface potentials found in the living subject a more complex equivalent generator must be considered. Two of the alternative physical models proposed are (1) the dipole with a shifting locus21 or (2) an instantaneous multipolar equivalent generator.22' 2!t In the first instance quadripolar or octapolar components may arise as harmonic additions to the suspected potential at a given surface point because of proximity effect or the effect of changing relative distance from the moving dipole. Now that we know that there are not only proximity effects but also instantaneous multipolar surface potential patterns, the shifting dipole has ceased to be a satisfactory equivalent cardiac generator. However, there are practical as well as conceptual difficulties in substituting a three-dimensional model of an equivalent cardiac multipole as X and a set of lead tensors as A in equation 5. 22 ' 23 We can employ an equivalent generator from whose components the surface leads can be satisfactorily constructed, a mathematical model composed of principal factors. Unfortunately, this turns out to be an unvisualisable eight-dimensional "model" in signal space instead of a three-dimensional model in the everyday Cartesian space of sensory perception.24 Increase of data relating to lead parameters 25 and exploration of the constancy of factors between individual subjects and among normal and abnormal populations may eventually lead to a suitable transformation of Circulation Research, Vol. XV, Angut 1964 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 the eight-dimensional provisional generator into a three-dimensional model directly relevant to the actual electrophysiologic process in the heart. In extending the analogy from the lead vector concept to the present findings it is pertinent to note that just as the principal factors resemble the components of the heart vector, their coefficients of distribution resemble the components of the lead vector. We may then look upon these coefficients as descriptions of the resistive or impedance characteristics of the volume conductor with respect to the various principal factors. Indeed, if the major significant component of the equivalent generator is a tensor of first rank, i.e., a dipole or vector, and if the successive orientations in time of the surface distribution of heart vector all lie within a plane, then it is possible that the surface distribution of factors one and two (fig. 7) describes the two axes of the plane of the vector loop. In such event, the major dipolar component is described by factors one and two,20 and the remaining factors may describe (1) any departures from the plane of the loop, and (2) any contributions to the equivalent generator from higher order components. Thus, knowledge of the relative strength of the distributive coefficients over the body surface may be expected to furnish a very meaningful guide to the choice of leads so that all the factors or components of information will be well represented in the body surface electrocardiogram. In terms of anatomic distribution, the lesser factors played a relatively greater role in accounting for the waveforms in the regions of the low right chest and over the left shoulder. If one views the distribution of factors one and two as describing an ecliptic for the major or dipolar component then those regions are the regions off the ecliptic (i.e., farthest from the plane of the vector loop) and therefore, where noise or somatic tremor would be expected to reach a relative maximum and signal to reach a relative minimum. Here again is the problem discussed under limitations: the region where multipolar effects should be detectable by virtue of not being swamped by CircnUiioH Rtsunch, Vol. XV, August 1964 143 the first order (dipolar) signal is also the region of low gradient where one has to be extremely careful not to read noise and artifact as information. However, careful examination of data exemplified in figure 5 showed symmetric, progressive development of the pattern of distribution. For example, the effect exerted by factor 5 (figs. 5a, b, and 7b) strongly suggested to us the detection of significant information from a higher order component. Summary High-speed, high-fidelity recordings from 150 to 180 systematically spaced points over the thoracic surface of both a dog and a man have yielded detailed maps of QRS waveforms. With the aid of digital computer analysis, these waveforms have been resolved into the minimum number of mathematically uncorrelated waveforms necessary for adequate resynthesis of all the original QRS complexes. Under the conditions imposed by the experimental design, seven (in the dog) and eight (in the man) such waveforms, or principal factors, were found. Maps were constructed for both the contribution of each principal factor to the various regions of the chest and also for the degree of reproducibility of the original waveforms by successive addition of the principal factors. The first three factors accounted for an average of 92.8% of the available information on the chest in the dog and 85.4% in the man. A resynthesis of over 99% of the information was achieved for both subjects when all remaining principal factors were also employed. This necessity for more than three factors or generating functions for reproduction of all the known surface potentials was interpreted as strong support to the equivalent multipole concept of the electrocardiographic generator. In addition, the reduction of total surface information into a compact set of waveforms of specified distribution opens an experimental avenue to the examination of such concepts in living subjects. Acknowledgment We are indebted to Mr. Wallace Marquardt and Mr. Irvin Jaynes of the Department of Medical Illus- 144 HORAN, FLOWERS, BRODY tration for excellent photographic reproduction of the maps and charts, to Miss Martha Hutchison for technical assistance, and to Dr. Charles Sheppard for the use of the facilities of the University Computer Service (supported by U. S. Public Health Service Grant FR 0001). References 1. ABILDSKOV, J. A.: The relation of precordial and orthogonal leads. Circulation 27: 58, 1963. 2. 4a. HUCENHOLTZ, P. G., WHJPPLE, G. H., AND Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 LEVINE, H. D.: A clinical appraisal of the vectorcardiogram in myocardial infarction. I. The cube system. Circulation 24: 808, 1961. HUCENHOLTZ, P. G., FORKNER, C. E., JR., AND LEVINE, H. D.: A clinical appraisal of the vectorcardiogram in myocardial infarction. II. The Frank system. Circulation 24: 825, 1961. 5. COELHO, E . , AArRAN, S. S., E S A , A. B . , MENDES, J. C. F., AND TAVARES, V.: Electrocardiograph- ic and vectorcardiographic alterations in chronic cor pulmonale. Am. J. Cardiol. 10: 20, 1962. 6. HOLZMANN, M.: Clinical Electrocardiography, chapt. 5. London, Staples Press, 1952. 7. MYERS, G. B., KLEIN, H. A., AND STOFER, B. E.: Correlation of electrocardiographic and pathologic findings in lateral infarction. Am. Heart J. 37: 374, 1949. 8. SCHEH, A. M., YOUNG, A. C , AND MEREDITH, W. M.: Factor analysis of the electrocardiogram. Test of electrocardiographic theory: normal hearts. Circulation Res. 8: 519, 1960. 9. HORAN, L. G., FLOWERS, N. C , 12. 17. HORAN, L. C , ANDREAE, R. L., AND YOFFEE, H. L.: The effect of intracavitary carbon dioxide on surface potentials in the intact canine chest. Am. Heart J. 61: 504, 1961. 18. HORAN, L. G., HANSEN, F. L., AND BOUSQUET, R. M.: Relationship between the anatomical orientation of the interventricular septum and the manifest orientation of ventricular depolarization in dogs. Circulation Res. 10: 859, 1962. 19. SCHMITT, O. H.: Lead vectors and transfer impedance. In Electrophysiology of the Heart. N. Y. Acad. Sci. 65: 1092, 1957. 20. BURGER, H. C , AND VAN MILAAN, J. B.: Heart vector and leads. Part I. Brit. Heart J. 8: 157, 1946. 21. PIPBERCER, H. V.: Application of corrected electrocardiographic lead systems in man. Am. J. Med. 25: 539, 1958. 22. BRODY, D. A., BRADSHAW, J. C , AND EVANS, J. W.: A theoretical basis for determining heart-lead relationships of the equivalent cardiac multipole. IRE Trans. Bio-Med. Electron. 8: 139, 1961. 23. CESELOWITZ, D. B.: Multipole representation for an equivalent cardiac generator. Proc. IRE 48: 75, 1960. 24. YOUNG, T. Y., AND HUGCINS, VV. H.: The intrin- sic component theory of electrocardiography. IRE Trans. Bio-Med. Electron. 9: 214, 1962. AND BRODY, D. A.: Body surface potential distribution: Comparison of naturally and artificially produced signals as analyzed by the digital computer. Circulation Res. 12: 373, 1963. 10. HARMAN, H.: Modern Factor Analysis. Chicago, University of Chicago Press, 1960. 11. DAWSON, C. D.: A summation technique for detecting small signals in a large irregular background. J. Physiol. 115: 2, 1951. NELSON, C. V., CHATTERJEE, M., AND ANGELAKOS, E. T.: Further studies on the effect of the intracavitary blood on the electrocardiogram. Proc. New Engl. Cardiovascular Soc. 16: 20, 1957-58. PIPBERGER, H. V., FREIS, E. D., TABACK, L., AND MASON, H. L.: Correlation of the clinical information in the standard 12-lead ECC and in a corrected orthogonal 3-lead ECG. Am. Heart J. 61: 34, 1961. 4b. 16. BURCH, G. E., HORAN, L. C , ZISKIND, J., AND CRONVICH, J. A.: A correlative study of postmortem electrocardiographic and spatial vectorcaxdiographic data in myocardial infarction. Circulation 18: 325, 1958. 3. 13. TACCARDI, B.: Distribution of heart potentials on dog's thoracic surface. Circulation Res. 11: 862, 1962. 14. TACCARDI, B.: Distribution of heart potential on the thoracic surface of normal human subjects. Circulation Res. 12: 341, 1963. 15. BRODY, D. A.: A theoretical analysis of intracavitary blood mass influence on the heart-lead relationship. Circulation Res. 4: 731, 1956. 25. ARZBAECHER, R. C , AND BRODY, D. A.: Electro- cardiographic lead tensor measuring system. Proc. Sixteenth Ann. Conf. Eng. Med. Biol. 5: 34, 1963. 26. HORAN, L. G., FLOWERS, N. C , AND BRODY, D. A.: The limits of information of the vectorcardiogram: Comparative resynthesis of body surface potentials with different lead systems. Am. Heart J. In press. GESELOWITZ, D. B., LANCNER, P. H., AND MAN- SURE, F. T.: Further studies on the first derivative of the electrocardiogram, including instruments available for clinical use. Am. Heart J. 64: 805, 1962. Appendix FACTOR ANALYSIS OF ELECTROCARDIOGRAPHIC WAVEFORMS Principal factor analysis as applied to waveform CircmUtion Rtsetrcb, Vol. XV, August 1964 PRINCIPAL FACTOR WAVEFORMS: QRS COMPLEX analysis is a method of examining the degree of correlation between all the members of a given population of waveforms. Correlation between any two members of the set may be estimated by summing the products of their amplitudes for a series of instantaneous measurements. Stated more intuitively, two waveforms correlate highly if the result of multiplying amplitudes instant-by-instant and totalling the result yields a large number and poorly if the result approaches zero. (Obviously, if the amplitudes of waveforms are referred to a common size the number is more meaningful.) When each member of the population is thus compared with every member (including itself) a family or matrix of numbers results which describes the correlations throughout the population in detail. Principal factor analysis involves what may be appreciated in a geometric and intuitive fashion as rotating the matrix of numbers until most of the information lies on the fewest number of reference axes, i.e., until the correlations between all the waveforms may now be described by how much each contains of a small number of reference waveforms. Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 Oscillographic tracings of QRS complexes are analog displays of electrocardiographic potentials as continuous functions of time, v^t), where the subscript, i, indicates reference to a given member of a set of leads. The initial goal of factor analysis as employed in this study is to derive from the experimentally observed set of leads, vt(t), another set of time functions, Xj(t), whose individual waveforms are uncorrelated with each other. Not only are the uncorrelated waveforms to be determined, but also the distributive coefficients, Oy, which satisfy the transformation relationship vl(t)=a(} x,(t) (1) The correlation coefficient between any two leads, v( and Vj, of the entire set of waveforms V, is defined as h*t — - vt(t) vAt) dt (2) where htj is the correlation coefficient and T is the interval of time occupied by the deflections. If a given htj is zero the two waveforms are said to be orthogonal in time, and therefore uncorrelated. Factor analysis of the experimentally derived leads is accomplished by determining a set of distributive coefficients such that each of the Xj(t) in equation 1 is orthogonal with respect to all other members. In digitized form the <th lead of the original leads becomes the set, c,(f): t ; , ^ ) , v{(t2), ©,((3), v t i( m)- Tn^ can be expressed more como((tt), pactly as the row matrix, vli)k, where the parentheses about first subscript indicate that our attention is focussed for the moment on a set of values which represent a single given lead. Upon removing the parentheses the entire set of digitized lead dpta assumes the matric form, V =: v(k. CircuUtion Rtsurcb, Vol. XV, Auguil 1964 145 If the ith row of V is postmultiplied by the /th column of its transpose we obtain k— m fc=l which is approximately equal to the correlation coefficient given in equation 2. Upon removing the particularizing parentheses we obtain H — VVT (3) where V is the transpose of V, and H is the set of all correlation coefficients in matric form. With the lead data cast into digitized, matric form equation 1 becomes V = A X, from which equation 3 becomes H = WT = A(XXJ)AT (4) Since both H and XXT are necessarily square symmetric matrices it follows that A is a rotatory matrix with its transpose identical to its inverse, that is, AT = A-1. Therefore premultiplying the members of equation 4 by AT and postmultiplying by A gives XXT — A-iHA. The major objective of factor analysis is to determine a transformation such that the individual waveforms of the derived leads are uncorrelated with each other. In other words a rotatory transformation matrix, A, is sought such that A-iHA = A (5) where A is a diagonal matrix. After the required matrix diagonalization has been accomplished, the elements of the derived, uncorrelated waveforms are determined from the relationship X = A-W. Diagonalization as employed here is essentially a rotatory transformation of axes in multidimensional signal space. The amount by which the axes are rotated is specified by A or A-1, which is commonly referred to as an eigenvector matrix. The individual diagonal elements of A are known as eigenvalues. The magnitude of each eigenvalue is a measure of the mean square deflection of the corresponding principal factor waveform. When the number of leads analyzed exceeds the number of principal factor waveforms some of the eigenvalue magnitudes are essentially zero. It is in this way that redundancy of pattern is recognized in the analysis of numerous leads. It is the number of non-zero eigenvalues which specifies the number of principal factor waveforms. In computer applications diagonalization is accomplished by a series of plane rotations in multidimensional signal space. Each rotation is designed to reduce the maximum absolute valued off-diagonal element of the correlation matrix to zero (Jacobi's method). Although this element does not remain zero with succeeding rotations the process is a convergent one, and eventually all off-diagonals can be reduced to or below a specified level of acceptable near-zero values. The eigenvector matrix is simultaneously built up during the computational process by cumulative multiplication of a unit or identity matrix by the plane rotatory matrices. Downloaded from http://circres.ahajournals.org/ by guest on June 11, 2017 Principal Factor Waveforms of the Thoracic QRS Complex LEO G. HORAN, NANCY C. FLOWERS and DANIEL A. BRODY Circ Res. 1964;15:131-145 doi: 10.1161/01.RES.15.2.131 Circulation Research is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1964 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7330. Online ISSN: 1524-4571 The online version of this article, along with updated information and services, is located on the World Wide Web at: http://circres.ahajournals.org/content/15/2/131 Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation Research can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in thePermissions and Rights Question and Answer document. 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