the electrocardiogram today: a symposium discussion

Conference on Electrocardiography

The Electrocardiogg-am Todav

A Symposium Discussion*

ROBERT P. GRANT, M.D., F..A.c.c.,t hloderator

Washington, D. C.

Participants

J. A. Abildskov, M.D., Syracuse, X. Y. S. Abraham, Washington, D. C. F. H. Adams, M.D., F.A.c.c., Los Angeles. C. A. Bachrach, M.D., Washington, D. C. A. Berson, Washington, D. C. H. Blackburn, M.D., F.A.c.c., Minneapolis E. R. Borun, M.D., F.A.c.c., Los Angeles D. A. Brody, M.D., Nashville, Tenn. C. A. Caceres, M.D., Washington, D. C. I,. D. Cady, M.D., Houston, Texas J. B. Calatayud, M.D., Washington, D. C. T. Dublin, M.D., Washington, D. C. S. M. Fox III, M.D., F.A.c.c., Washington,

D. C.

A. Grishman, M.D., F.A.c.c., New York H. Hellerstein, M.D., F.A.c.c., Cleveland L. C. Hinkle, M.D., New York C. A. Imboden, Jr., M.D., F.A.c.c., Bethesda, Md. T. W. Mattingly, M.D., F.A.c.c., Washington,

D. C. A. Pick, M.D., F.A.G.c., Chicago H. V. Pipberger, M.D., F.A.c.c., Washington,

D. C. E. Simonson, M.D., Minneapolis R. Smith, M.D., Minneapolis Anna Lea Weihrer, Washington, D. C. G. H. Whipple, M.D., ~.~.~.~.,Boston H. F. Zinsser, M.D., F.A.c.c., Philadelphia

FOREWORD

A SYMPOSIUM was held in Washington, D. C., in January 1965, to provide guidelines for

future development of the multiscience that underlies electrocardiography. Dr. Robert P. Grant moderated the final symposium session.

Dr. Grant had been a long-time friend and adviser of the Heart Disease Control Program and its Instrumentation Field Station (U. S. Public Health Service), which coordinated the symposiuln. To a great extent he had been responsible for the formulation of the initial ideas and planning for the Field Station’s work in automation of electrocardiographic analysis. It was only one of the areas in which, in his quiet

manner, he had been a dominant beneficial influence. In innumerable other areas he stimu- lated students, associates, and friends to become creative or to attempt research. He was suc- cessful because of keen insight to comprehend real meanings. In his own words, “Under- standing is a relative matter. It is not a tally card or a receptacle to be filled, it is an equi- librium between outer, always incomplete information and inner need .” (Grant, R. P. Foreword. In : Biomedical Telemetry. New York, 1965. Academic Press.)

In the early sixties Dr. Grant retired from electrocardiographic work and undertook stltdies

* This study was sponsored by the Heart Disease Control Program, Division Iof Chronic Diseases, U. S. Public IIealth Service, Department of Health, Education and Welfare, The American Heart Association Computer Committee and the George \Vashington University School of Engineering and Applied Sciences. This discussion was prepared for publication by Dr. James K. Cooper, Mr. Mort Gilbert and Dr. Cesar .4. Caceres, of the Heart Disease Control Program’s Instrumentation Field Station.

t Deceased.

VOL.UME 19, MARCH 1967 401

402 Gram

in embryology. He was persuaded to return to The entire symposium is being prepared for electrocardiography, and particularly to this later publication. The editors believe that the symposium, to point out areas in which, from his final session, guided and moderated by Dr. Grant “retirement” vantage point, he could see the 18 months before his untimely death, reflects his need for creative work. The final session, de- personality and philosophy and gives insight into voted to the future of electrocardiography, en- his realm of understanding. In addition to compasses reflections on the current status of the providing guidance and direction to electro- field, emphasizes areas in critical need of devel- cardiography, the final session serves as a most opment and suggests paths for future creativity suitable tribute to Dr. Grant and to his and research. work.

SYMPOSIUM DISCUSSION

DR. GRANT. I have been away from electro- The search for a balance between clinical cardiography for some time. To prepare for application and basic study of the electrocardio- this conference, I sampled some of the 600 arti- gram for its own sake is illustrated in our sym- cles per year about the subject. It was not an posium. Take, for example, the problem of altogether enjoyable excursion. I was im- electrocardiographic nomenclature, for which pressed by the overwhelming preponderance of Dr. Caceres hopes to develop a committee. clinical or “applied” articles. No field of medi- Why have previous committees been unsuccess- cine is more dominated by clinical application. ful in standardizing nomenclature? Primarily Any new idea is instantly swept into studies de- because the members cannot agree among them- signed to test its usefulness in clinical interpreta- selves, or, if they do, their clinical colleagues will tion, and its intrinsic scientific interest is rapidly disagree. Disagreement occurs because the lost from sight. data are ambiguous, inadequate and unreliable.

The man with the new idea is often eager to have this happen. Scientists in electrocardiography are few; the clinician audience is much larger. Electrocardiography is in a curious position : It is of interest to almost no other field of science. New scientific ideas in electrocardiography are practically meaningless to anyone except the clinician with problems of interpretation.

This dominance of electrocardiographic research by considerations of clinical application suffocates the scientific aspects of electrocardiography, as the history of electrocardiography shows. The older ones among us can remember some of the spectacular debates of the past, the voices and challenges ringing in the auditoriums of Haddon Hall. These debates nearly always arose because some aspect of standard electrocardiographic practice was being threatened by a new idea. Typical was the controversy over the use of the precordial lead, the arguments over the introduction of V or unipolar leads, the debates about vector methods. All these were ideas caught in controversy about clinical application before they had a fair chance to be developed for their own intrinsic interest. As Dr. Peterson has pointed out, electrocardiography grows from two sources, clinical application and fundamental studies, and each is important.

This is the trouble, at present, with the ST-T segment, which is important to the clinician (especially in exercise tests) and therefore ur- gently in need of standardization. Rut our information of its mechanism does not permit standardization, except on purely empirical bases, for few people are working on its basic physiology. About 5 per cent of electrocardiographic literature is on ST-T, primarily on such clinical problems as the peculiar ST-T changes produced by this or that disease or drug. The experimental paths which have been so fruitful in QRS research have never been applied to the ST-T segment.

When a committee is set up, I always hope that each member agrees that one condition for being on the committee is that he will work on the problem. This is the way that science agencies like the National Institutes of Health work in the smaller countries of Europe. The committee does not simply identify the gaps in knowledge. It agrees to devote its own separate en- ergies to fill these gaps. I recommend this as the basis for organizing an ST-T committee.

Before this meeting I asked each of you to sub- mit what you believe to be the two most important questions in electrocardiography today. Now I want to turn to some of the questions re- sulting from our poll.

THE AMERICAN JOURNAL OF CARDIOLOGY

Conference on Electrocardiography 40.3

UNDERSTANDING THE T WAVE

Several of you see as the most important question, “What is happening between the generator and the body surface?” What happens to the signal the heart generates in its transmission to the body surface electrode? Dr. Brody, since there are bigger gap areas in connection with ST-T than with QRS, would you tell us whether present models, designed for QRS, are also optimal for ST-T in man.

DH. BRODY. Little is known about the basic process of repolarization. During QRS, we are dealing with a propagated impulse that more or less hangs together. We can think in approximately correct terms of a double-layer (dipole) behavior. If we know what the double layer is, and particularly what the rim configuration is, it is not too difficult to come up with various order components, beginning with the first order of approximation of the dipolar component and then going to quadripolar and octopolar components. We owe this knowledge to such people as Scher, Durrer and the Mexico City group. When that has been attempted for the T wave, we ha\:e drawn a blank. During repolarization we are apparently dealing with an electrical swanip. Studies on repolarization of the rat atrium, for instance, show that the density of re- charge is only a statistical phenomenon. Since we have been taught that depolarization is pre- dominantly from endocardium toward epicardium, we tend to think of repolarization proceed- ing oppositely, from epicardium toward endocardium. But is that just statistical?

We need a new basic experimental approach to this problem. Dr. Grant spoke of the need for more information about the basic physiologic process in the heart during inscription of the S-T and T complex. I certainly would agree. During the last few years three groups with which I a111 familiar have done fine work on the properties of the body as a volume conductor. The influence of these properties on the form of the surface electrocardiogram is limited to QRS. The three groups, which have all developed a yearning to get closer to the problem, want to get inside the cell; and they have spent a great deal of time developing technics for registration of transmembrane potential. Yet this has not been highly rewarding. They have developed the necessary technic, but they have not been able to develop a productive investigative program. We need a set of new concepts upon which to base further investigations in this particular area of repolarization.

VOLUME 19, MARCH 1967

DR. GRANT. \Vould the 111odel for tl1c ‘1‘ wa1.e br the same as for the QRS co~nplcx?

DR. ABILDSKOV. One of the classic contribu- tions to electrocardiography is .‘.\n .-\nalysis of the T wave,” by A. G. MacIJeod. \Vl1ilc this analysis preceded any records of the action potential, in effect it postulated the for111 of the intercellular cardiac action potential and 11sed that postulated form as the basis for a conceptual model of the T wave. I am not pessimistic about the possibility of achieving, fair]?. soon, a working conceptual model of the T wave. Since MacLeod’s time, the general form of the action potential has been partialI)-, tho11gh not adequately, defined. It has not been s)-stenlati- tally defined for all areas of normal 111yocardiu111 or for all individI1al abnormalities. \c’cx also know so111ething about the variations in dluration of action potential by both direct and indirect measurement of the refractory period. It is not too great a step to combine AlacLcod’s co11cept of the T wave with modern information on the action potential.

Information has also beco1nc a\,aila ble on the sequence in which the heart is excited. When the problem of the QRS and ST-T is considered from the standpoint of the shape of the. action potential, and depolarization is recog11ized as simply the first phase of that action potential. the problem should be solvable. _4t the present time Dr. Harumi and Dr. Rr1rger in our laboratory are attempting to combine these itc.ms, namely, the seq11ence of ventricular activation and MacLcod’s concept of the shape of the action potential, as a basis for explaining the polarity and for1n of the T wave.

DR. GRANT. Do lead systems optimal for the T differ from those optimal for the QRS?

DR. PIPBERGER. On the same subjects, agreement between lead systenls is always easiest to get for the T and S-T and n1ost difficult for the QRS.

DR. GRANT. Could this be due to the effect of a greater body capacitance on T events than on QRS events, a blunting or reducing of SOIIIF of the electrical properties of T events so that their variabilitv is eliminated at the body sllrface?

DR. P~PBERKER. The T has a relatively- simple configuration, compared to the QRS, and thus the agreement is much closer. Another aspect that we explored has no bearing on lrad systems. We used sets of points for QRS and for S-T and T to discriminate between various diagnostic entities. Results were expressed as per- centages of the total number of cases classified correctly.

404 Grant

With the QRS, a little more than 90 per cent of the cases can be classified correctly, and with the S-T and T, more than 80 per cent. The percentage levels need to be considered in relative but not absolute terms. Information in the S-T and T allows discrimination between, let us say, a lateral infarct and a diaphragmatic infarct, even in older patients with histories of infarcts for several years. When the S-T and T of such patients are examined, no difference is discernible “by eye.” But the information has to be in there. It has never been used because we have to define it first.

DR. ABILDSKOV : Understanding in this area is handicapped by a number of items that have been mentioned, such as variability, but it is handicapped also by an aura of pessimism and by irrelevant questions, such as whether repolarization represents a propagated phenomenon. This is not an appropriate question, since we all seemed to agree earlier that the recovery process begins immediately on the completion of the excitation process but that recovery requires considerable time for completion. Although a given stage of recovery, such as a moment 0.10 second after excitation, can be treated as a propagated event, the term propagation is not applicable to the entire process.

The important thing is that more than one moment has to be considered in relating the action potential to the form of the T wave. To speak of recovery as one entity is incorrect, and to ask whether that entity is a propagated process is an irrelevant question and a handicap in attempts to understand the process.

DR. PICK: I would not say it is a handicap. That has to be proved. It is just one more difficulty. I would like to continue from where Dr. Abildskov stopped in reviewing the fundamen- tals. We have always treated the whole repolarization process as a secondary event. The primary event is the depolarization. In recent years physiologists have raised the possibility of propagated repolarization, and there is some evidence for it. If that is true, then here is an area that can be explored and perhaps may provide the basis for a model for primary variations of the T wave.

DR. PIPBERGER : There is one additional reason why the QRS has been explored on the basic physiologic level much more than the T and S-T. Everybody working on S-T and T in animals will experience the same thing. Durrer said he would never work with T waves because they behave like women ; they change all the time.

When you open a dog’s chest and look closely at the heart, the T may go down or up though you have not even touched the heart. It changes rapidly and unpredictably. Even with accurate temperature control inside and outside, the T changes with or without any temperature change. Durrer came to the same frustrating point.

DR. GRANT. Dr. Mattingly, are you satisfied with the explanations of T abnormalities? Is this a problem area to a clinician?

DR. MATTINGLY. Yes, in the sense that usually the answers are purely empiric. Very little has been written about what the T wave is. Interpretation of the T wave would fill more volumes than what is written about QRS, because with less knowledge, the field is more subject to opinion and comment.

Perhaps the best known information about the T wave is the serial change that has been observed in known, recognized myocardial infarction. But there are many areas of speculation: The so-called hyperacute or the large T, the tall, symmetrical T over the anterior leads in posterior wall ischemia, etc. With true posterior wall ischemia, the T wave may be the only indicator. Aside from basic electrophysiology, surprisingly little empiric observation of value has been made regarding the T wave.

DR. GRANT. The present situation in ST-T reminds me of an early stage in the history of mathematics, when Riemann decided to con- struct a geometry based upon the assumption that Euclidean geometry was wrong. From this effort evolved another, new geometry and ultimately, the theory of relativity, one of the most forward steps in the history of mathematics.

I wish someone would assume that all previous knowledge of ST-T is probably wrong and explore completely new possibilities: For example, that T inversions are not due to biochemical effects of ischemia, that S-T shifts in man have nothing to do with injury current.

DR. PIPBERGER. The linkage between electrophysiology of the heart, particularly on the cellular level, and what we record on the body surface is so weak for QRS and for T that we have no valid concept of how to link the two. Isn’t that why so many people have been dis- appointed when they go into cellular electrophysiology? We know something about the propagation of activation in the heart. But a composite recording at the body surface from thousands of cells is a completely different thing.

DR. SMITH. May I ask Dr. Abildskov about


(Conference on Electrocardioqaph>~ 10.5

sin~lliatiol~ of the genesis of the T wave? YOU

ha1.c taken into account some obvious things, the length of time of potential in the myocardial cell and the scqucnce of depolarization. Do stretch potentials entrr into your simulation?

Drz. ABILDSKOV. No. So far the only con- sideratiorr in the silnltlation is the approximate shape of the action potential. In the very first simulation, for example, it was assulned that all action potentials had the same duration and CornI. That, of course, had to be Inodified. But all the conventional assumptions about the hod\, as a volrme conductor are inherent in the simulation.

DR. BROD~.. If you end up with a series of little nnit-model generatcrs, what would the out- pllt of each generator resemble as a function in tinlc’?

DR. ABILDSKOV. In the studies we have done and in those by Sylvester and others, the essence of the simulation of the QRS complex is that the distance between the broken ends of this excitation front defines a vector which has some repre- sentation on a body surface electrocardiogram.

If t!;at excitation moment represents the first phase cf the action potential, the rest of the shape of the action potential might be simulated with the same basic kind of model. The effect of repolarization at many moments at each of the points represented by the activation front is modulated by the length of the vector which has bee11 used to represent excitation. In other words, the effect of the recovery of one area of luyocardium on the body surface electrocardio- grain receives less weight than the effect of re- covrry of another portion of the myocardium whose whole activation must be represented by a larger vector.

DR. GRANT. Dr. Durrer in Amsterdam has been conducting some experiments in which he is, in effect, “exploding” the heart electrically, firing all parts at once so that there is no propagation problem for QRS or T. The experiments are not very far along, and there are many technical difficulties, but Ee has demonstrated \irtllally the same body surface T as when there is a propagated QRS.

VECXORCARDIOGRAPHIC LEADS

DR. GRAKT. Dr. Grishman, vectorcardio- graphic nlethods are now used a great deal in pediatrics. Is that a valid use? Is the body of an infant geometrically suited to the use of vector principles?

DR. GRISHMAN. I don’t see much of a prob-


leni. It,jlist depends 011 the traillino of tht. loch- . .

I:lcla:l.

CR. GRAIVT. You believe that SIIC~ problenls as electrode placement are the sanlc for the infant and the adult?

DR. GRISHMAN. You are talkinS now about two different things, recording technic and validity. We ha1.e to discuss technic and the assumptions we make that th? technic is valid. When you transfer criteria front adults to infants or children you r’rquire t\vo srts of rcferrnces. I>et’s tackle that problem first.

There is a clinical reference which helps differentiate a normal or clinically well child from a sick child. Application of technic dcprnds on how criteria are developed. “l’nsophisticatcd” technic and so-called “sophisticated” technic have been developed on adults. Both technics of course, should be tested on infants as well. The bipolar lead system has simple assumptions which allow you to get a computed phase relation out of a vectorcardiogram (if you allow the term “computed”). The most important clinical information that we want at the present time is the phase relation between leads, which ).ou place in an assumed geometric relationship.

That is useful information because. for instance, yo11 can clearly delineate the nortnal infant above the agl: of two nlonths from the abnormal one havinjg right ventricular prcponder- ante. Of course, the same inforlnation can often be obtained from the electrocardiogram, provided your technic is correct. 1Vhen taken in proper combination, simultaneo~ls leads can give information on counterclockwise or clock- wise rotation.

With the bipolar or “unsophisticated” technic, by just placing three bipolar leads appropri- ately there is little opportunitv to add to the error inherent in the technic. i‘he sophisticated or so-called “corrected technics” have evolved from studies of chest models of young adlIlts. It is not possible to apply networks deri\,rd from these studies to all individuals without introduc- ing error. The unsophisticated technics need improvement, but they should be improved or replaced by something equally reliable or better.

DR. GRANT. Your liew, then, is that if the vectorcardiogram is used solely as a Inethod for data reduction, the question of physiologic validity does not arise.

DR. GRISHMAN. That is in part correct. The most important clinical information w-hich we try to get from the so-called vector presentation is the phase relation. This is reliably pre-

406 Grant

sented by the unsophisticated technics. For the From a strictly technical point of view, there bipolar leads, it is impossible to get reversal of may be some advantages. If there is somatic polarity, and, therefore, misleading information tremor, compound lead arrangements tend to on phase relation. However, in the Frank and cancel it. If a synthetic lead is compounded at, the Schmitt technic, we have encountered nlore say, half a dozen electrodes, the manifestations of than 5 per cent misleading or incorrect phase muscle tremor under one electrode are reduced relation. to approximately a sixth.

These technics have their problems: The combination of various leads-horizontal, verti- cal and sagittal---as they evolve out of the net- work and are again combined into vectorial presentation, may look quite different from what they looked like individually. In part, they differ because lead-system networks in conjunc- tion with electrodes have a very tricky electrical behavior. Dr. Burger, for instance, uses a pre- amplifier for each of his electrodes. The solution which Schmitt proposed, using cathode- follower electrodes, is a technical makeshift but is practical.

DR. GRANT. Are there aspects of pediatric electrocardiography that are troublesome because of body size?

DR. ADAMS. I am not aware of any. We have been interested most in the constantly changing hemodynamics during the first few hours and days of life-in pulmonary vascular resistance and cardiac output; I don’t know what the impact of these changes would be on the electrocardiogram.

Adapting the model to encompass such situations as hypertrophy or hypertrophy and dilatation certainly is a difficult matter. In our own

work, we use a “cardiac region” which, at present, is spherical. We analyze lead behavior over this entire region, which we try to make large enough to include all active myocardium, not only in normality but in most pathologic states. I will agree that some huge hearts will not fit into this spherical region that we are obli- gated to use because of the mathematics of the situation. As an expedient to analysis, we rely heavily on spherical harmonics or terrestrial harmonics. Within certain limits we do not have to adjust our model for hypertrophy, because we deal with a large region to begin with. The only adjustment that we would envision is not in the model itself; it’s simply that the equivalent generators would be of greater intensity.

DR. GRANT. Are accurate three-dimensional studies of the ST-T possible during exercise?

DR. BLACKBURN. Yes, it is possible to record instantaneous S-T vectors. It is a problem to attempt to relate them to QRS, but it is possible to identify these vectors in space.

DR. GRANT. How do you handle electrode placement? Can you satisfy corrected and orthogonal lead relations in the exercise test?

DR. BLACKBURN. None of the present systems are that elegant, except in concept. One can take orthogonal leads, but the electrode itself has limitations.

Perhaps later on, as we get more sophisticated, we will be able to use a different type of analysis, maybe ellipsoidal harmonics which will be Inuch more efficient than a sphere enclosing a cardiac region. Ultimately we will be limited. We are dealing with body surface potentials, and the pick-up sites are removed from the origin or formation of the impulse. The body surface signal contains only a limited amount of intrinsic information. Our particular task is to decide how much basic intrinsic information we can squeeze out regarding the true nature of the electrocardiographic generator, and there we have to stop.

DR. GRANT. What about the accuracy of mathematical models of the electrical field for changes in the geometry of the heart in disease? In other words, what are the effects of variations in the size or shape of the heart? When the model was made from measurements of a normal young man, what kind of corrections are needed to make it valid for the same young man when he has cardiac hypertrophy or dilatation?

DR. BRODY. It is entirely feasible to use so- called “corrected” lead systems in exercise. I am surprised that more has not been done.

If I can get back to T waves for a moment, there is a lot more to be done. Langer did some work several years ago on cancellation of T waves. He showed that T waves can be well cancelled over many locations of search electrodes. Many of the technics to analyze the body surface characteristics of QRS have not yet been applied to ST-T; it is quite feasible that they should be. Models can be made to simu- late body surface potentials very well. Physical phenomena can be interpreted in almost an in- finite number of ways. The farther you are removed from the source of these phenomena, the less certain is the interpretation.

DR. GRANT. Do you think that the geometry


Conference on Electrocardiograplly 407

of the heart corlld he an important variable in, sa).. interpreting the exercise electrocardiogram?

DR. BRODY. It must be an important con- tributor to the nature of the body surface tracing. Phase inhomogeneities, including the geometr) of thy heart, ulrlst bc important determinants.

KEl_A.rioN OF EI.EC.TROCARDIOGRAM TO CELLULAR EVENTS

DR. GRANT. Dr. Hellerstein, as one who has been deeply interested in relating the body surface electrocardiogram to cellular events, who will do the necessary research? Probably not the cellular biologists; they are faced in another direction in their research. Clinical investigators will ha1.e to do the work. What are the prolilising lines of attack? We know a good deal abollt the cellular events and the body surface deflections separately. How are we going to relate these two?

DR. HEI.I.ERS.rEIN. We are still living with the empiric utilization of the surface electro- cardioqraln. We went through a state of self- c!eiltsioll believing that by using the geometric lnethod of al;alysis, we could be “scientific.” I,ater, \Vilson llsed mathematics, and those who didn’t tinderstand mathematics were over- whehned by the concept that he was reall) scientific. In tile final analysis and despite the recent ad\-antes, basic concepts of interpreting an electrocardiogram are still empiric; we know the asslmlptions arc not tenable beyond a certain per cent.

The heart is not an equivalent, single dipole. Some believe it likely that the multiple component is very significant in disease, more so than in health. The models using the dipole have not been good models. They have been based on an assuilled homogeneity which really did not exist, particlllarly in disease states such as lung dis- case. emphysema, etc. Since our interpreta- tions now are empiric, it is necessary for the clinicians or people interested in this from the clinical standpoint to go back to the laboratory to find out what is the common pathway by which, say, the ST-T or the recovery process is modified. The fact that effort, food, tobacco, exposure to cold, and emotional stress can produce electrocardiographic changes that are in- distinguishable from one another means one co~nmon pathway or close to one common pathway of modification of the signal.

That does not say how the clinician can get more information. He has to acknowledge that this too is purely empiric, that the same changes

“OI.UME 19 MARCH 1967

can be produced in the ST-T coiilples by lo- calized effect, by differences of endo-epicardial localization of the repolarization or reco\-er)- processes. \Ye must accept the idea that we will get only a limited a tnount of additional illforrna- tion on the obser\.ed effect ; but the C~IIIIIIO~ pathway will be found in the research laborator)- at the cellular level, and electrocardiography will have made a step towards a scientific basis.

Let us not fool ourselves: There is no such thing as a sophisticated lead or an unsophisticated lead. In the final analysis, the heart is not a siiigle dipole, the body is not horuogeneotls, and the self-deception that we have gone through in medicine is not justified. We have better systems now than before, meaning that nlorc people will get similar results with siinilar sit\lations. But the newer lead systems cannot be considered to be truly scientific, because the)- are based upon assumptions that are not tenable at the 95 per cent confidence level.

I had the opportunity of being exposed to Katz, Wilson, and others; they were sincere people, and each literally thought he was right. The same diagnosis came from their laboratories. but by different n.,ental processes and methods. One was geometric and one was analytical, but in the final analysis they still made the sanlc diagnosis.

DR. GRANT. Dr. Smith, earlier York ques- tioned the usefulness of the exercise test, particularly for large population studies. FVhat do yo11 suggest \ve do about that? How are we going to improve our understanding of ST-T ; what is the responsibility of the clinical investigator in trying to convert cellular information into clinical meaning?

DR. SMITH. With exercise there are niank simultaneously occurring events: changes in pC02, glucose, potassiunl, and in the autonomic nervous system. These events should be sepa- rated from changes that occur with ischemia. We must attempt to separate what appear to be identical changes and determine those caused b) ischemia.

DR. GRANT. Dr. Zinsser, do you have ideas about the role of the clinical investigator in closing the gap between biophysics and clinical practice3

DR. ZINSSER. I have about the same approach that Dr. Smith and Dr. Hellerstein expressed. For example, one could list numerous things affecting this particular segment of the electrocardiogram, such as electrolytes, digitalis, catecholamines and oxygenation and metabo-

408 Grant

lism. There must be some common denomina- tor. If you would work at these variables and changes, perhaps the computer system could de- cipher it.

DR. GRANT. Dr. Pipberger, were Dr. Paul Langner’s studies of high-frequency components in the electrocardiogram useful in separating out different causes of S-T segment deviation or T inversion? blight the ST-T area have quali- tively different information from what he found in the QRS.

DR. PIPBERGER. Langner and his co-workers never found high-frequency components outside of QRS, neither in the T nor in the ST-T. The frequencies of the S-T and T are generally below 20 c.p.s.

THE ELECTROCARDIOGRAM AND MECHANICAL FUNCTION OF HEART (HEMODYNAMICS)

DR. CALATAYUD. Panel members have suggested relating the electrocardiogram to electrolytes, glucose, and so on; yet no one relates T wave changes with the hemodynamic phenomena in the ventricles. When changes appear in the surface electrocardiogram, almost certainly changes, maybe very minute and difficult to define, are occurring in the pressure inside the heart and in the intracavitary electrocardiogram. I propose that when we are doing all these studies involving monitoring electrocardiograms, we monitor with catheters in the right or left atrium to obtain intracavitary cardiograms and pressures.

DR. HELLERSTEIN. Most of us are very skep- tical about trying to relate electrical and mechanical events insthe heart. Sodi-Pollares, for example, no longer believes in the pattern of systolic and diastolic overload for hypertrophy. Further, one can certainly see significant cardiographic changes in a heart that has been given something that binds calcium. The changes in the electrocardiogram can occur with no changes in the action of the heart.

DR. PIPBERGER. We tried to derive electrical changes from mechanical changes by lowering blood pressure in hypertensive patients or increasing blood pressure over a span of 80 to 100 mm. Hg. The electrocardiogram changed little or not at all. But the electrocardiographic changes associated with cardiac filling is something we studied more recently with the Valsalva maneuver. With the release of the Valsalva maneuver, in most patients there is an increased cardiac filling on the right side and a classic pattern of right ventricular hypertrophy for two or

three heartbeats. This cannot be due to hypcr- trophy ; it has to he due to cardiac filling. Cardiac fillin seems to influence the electrocardiogram considerably for very short periods of time.

DR. MATTIKGLY. Dr. Grant, for some years you have studied the relation of potassiutn and the ST-T changes. Have you any theoretic basis or bases for concepts of the passage of so- dium and potassium as being the prime factors in producing ST-T changes?

DR. GRANT. I agree wholeheartedly that the T probably contains a great deal more information about the function of the heart than we have yet learned how to derive from it. My experience concerned the use of digitalis as a way of augmenting T responsiveness t3 hemodynaniic changes. Just a small amount, not even enough to produce a significant change in ST-T morphology at rest, permits a remarkable change in T morphology on hemodynamic alterations- standing up, lying down-and so there is a gold mine in the study of the relation between heart mechanical function and the T wave.

DR. PICK. I would suggest a study of the relation of hemodynamics and infarction T waves- but starting with the dog, not with 1xu1.

DR. GRANT. But, for studying T waves, the dog is one of the worst animals.

DR. PICK. One can produce infarction in a dog and T wave changes, which are very similar to human changes, and at the same time study the dynamics. So it is worthwhile to start in an animal instead of in man.

DR. GRANT. For one thing, when experimental hypertension is produced in a dog and then is relieved, marked T wave changes occur, much more marked than in man.

DR. GRISHMAN. In recent years myocardial infarctions were produced in primates just by feeding them so-called human diets. These animals develop true coronary disease, myocardial infarction and heart failure. Here is a wonderful opportunity to study these problems in primates with a tendency to coronary disease similar to that in man. I agree with Dr. Pick, one does not have to jump to the human for research.

You asked whether something in the frequency of a QRS complex could possibly help us understand the ST-T segment or the high and low T take-off. I think there is. All of you who have watched the electrocardiograms being scanned on a Z-axis modulated oscilloscope have seen in certain cases like those with hypertrophies that the latter part of the QRS complex is, time-wise,


C:onference on Electrocardiography 409

condensed and sl,urred. This you do not see in so-called injury deviations, which will exhibit a sharp linkage to the T wave. There is an avenue which one certainly can well explore, particularly with the more sophisticated parametric anlplifiers which we can more easily handle in differentiation. The parametric amplifier was originally developed for military purposes, such as radar. It uses “nonlinear” components and offers high amplification with minimal inter- ference or noise.

DR. GRANT. Your discussion about what llliyht be called experimental electrocardiograplly is very timely. We do not have nearly so milch animal experimentation in electrocardiography as we find in other areas of medicine. The theoretic research in electrocardiography, with its mathematical studies, with all due respect to the brilliance behind it, is static. This is because most electrocardiographic research is QRS oriented. Our attitude toward the QRS is that it is not particularly related to physiologic function of the heart and therefore does not lend itself to the experimental approach. The ST-T is quite different. This is an area where the ex- perinlental approach and use of experimental anilnals would pay off in the study of hemodynamics, electrolyte and metabolic changes, or even in exercise studies.

DR. SIMONSON. We can vary the workload of subjects in wide limits, and the electrocardiogram does not change. It is not a sensitive indicator of hemodynamic changes.

DR. WHIPPLE. The question of the non- specificity of the ST-T changes has another aspect. Dr. Smith said that perhaps we should look more closely at the ST-T for further information. I am sure it is there. Dr. Pipberger has shown that he can profitably look further into the ST-T. With a relatively few points he can make a separation between different diagnostic categories. But one can’t look for much help in this direction, because in most instances he is making a discrimination between a relatively few selected entities. And it was suggested perhaps we should correlate it with the hemodynamic events. Dr. Simonson and Dr. Calatayud had different views about this.

The solution to the problem of what the clinicians should do, at least until we get better basic electrophysiologic models-the so-called model T’s-is to take the little bit of information that is present in eac.h of these approaches where it can be obtained readily (including certainly the clinical information), enter the significance of

VoI.“ME 19, MARCH 1967

the observed data by row into an appropriate additive weighting matrix, and add up how much is contributed to each diagnosis (column). I have expressed this in a digital computer-like format, but the experienced electrocardiog- rapher probably does something analogous to it in his brain.

For some time yet, we are going to ha1.e to make multivariate analyses, using information from all sources and not necessarily excluding hemodynamics or any of the other factors that have been mentioned.

HYPOXIA vs EXERCISE TESTS

DR. GRANT. Earlier I made the point that electrocardiographic research tends often to be smothered by the requirements of clinical application, which searches always for causal one-to- one concordance. The clinician wants a specified electrocardiographic deviation, always to be “due to” a specified clinical event, and he resists any more complicated relations. That is certainly one of the difficulties today in the interpretation of ST-T shifts after exercise. The clinician wants to separate all other “causes” of ST-T shift on exercise from those due to ischemia. The probability, however, is that coronary flow is but one of a number of participating factors, and perhaps not often the most important one. He must come to learn that A + B + C: + D = S-T shift, and that ischemia is only a D: perhaps, in this equation.

What we must do, then, is try to quantita- tively identify the A, B, and C: of the equation. It may prove, finally, that if we want to isolate the D part of the equation, exercise is not the best way. For example, there is hypoxia. Dr. Zinsser has described some of the S-T shifts which accompan)r anesthesia. These must bear on the hypoxia problem. Dr. Simonson has had some experience with hypoxia.

DR. SIMONSON. Hypoxia tests were used a great deal about 20 years ago. Now few use them here, although they arc still used on a large scale in Sweden, where they are sometimes associated with exercise tests. Quite a few subjects have an abnormal response to hypoxia with a normal response on exercise. Pharmacologic agents can be used for additional inforrrlation.

Master has tried to use hypoxia to differentiate the response of normal activity from that of injury, which is difficult to differentiate. B) correlation between responses to both csercise and hypoxia, we might arrive at a definition of so-called “ischemia responses.”

410 Grant

DR. GRANT. The hypoxia approach lends itself more readily to experimental animal technic than does exercise. Have there been animal studies of the hypoxia test?

DR. SIMONSON. Hopkins did a great deal of work approximately 15 years ago. One difi- culty with the hypoxia test is that, given, let us say, a 10 per cent oxygen mixture, the changes in the arterial saturation are quite different. They may range from a drop of 5 to 20 per cent. For a simple clinical application, I would just use the 10 per cent mixture for approximately 10 minutes.

The exercise test has one disadvantage. If one gets an undesirable response, e.g., one of severe coronary insufficiency, it is difficult to re- vert. In the hypoxia test, changes in percentage of oxygen can rapidly be effected-say, half a minute to get back to a 98 per cent saturation.

DR. Fox. What would be the comparative risks of (1) the hypoxia test at 10 per cent inhala- tion with a variability of ~02 in the arterial blood as monitored to a certain level by an ex- ternal sensor, (2) the Master two-step or bicycle ergometric test with a pulse rate of 150, such as Hellerstein has proposed, and (3) the self-im- posed maximal exercise test of Balke, Bruce, and others?

DR. SIMONSON. That is a very good question and a very hard one to answer, because the proponents of each type of test claim that their test is safe and that the others might not be. No large scale study has been made to compare the risk, but it is small in any case. I would not consider a test undesirable if one subject in a thou- sand has a reaction.

A large number of subjects would be needed to compare the risk. I believe that the risk in the hypoxia test is not any greater than in the exercise test. The hypoxia test has an advantage, when monitored consistently, in that it can be stopped earlier than the exercise test if changes occur.

DR. MATTINGLY. In Robb’s study, there were more individuals with good clear-cut changes with hypoxia which did not appear on exercise. For disabled persons, such as those with arthritis, amputees, and many others, the hypoxia test is of course more satisfactory. Although I have not worked with hypoxia, I believe a psychologic effect is produced with the hypoxia test, especially if the subjects know that less oxygen than normal is to be given. For some reason this affects people. Fear is a minor problem with the exercise test.

DR. GRANT. Do you think you could give such a person a mask just with room air?

DR. PICK. Nordenfeld in Norway gave exercise tests after application of ergotamine and found a difference. He could abolish sym- pathomimetic effects and separate them from hypoxic ones. Perhaps with the new beta-re- ceptor blocking agents, we may have another chance to separate autonomic and emotional changes from pathologic ones.

DR. SIMONSON. In hypoxia and exercise tests, I question whether it is possible to differentiate these changes.

DR. GRANT. Nevertheless, something can be said for searching for pharmacologic agents that will influence the susceptibility of ST-T to altera- tion. Potassium, for example, alters the ST-T effects of standing. Are there other methods for challenging the cardiovascular system which might help in identifying coronary diseases?

DR. ZINSSER. When the hypoxia test is done as we do it, it has certain advantages in that the patient does not know what is happening to him. He has a mask consistently, he is lying down, and he is relaxed. Then he can be switched by valves from room-air to 100 per cent oxygen or to a 10 per cent composition, and he does not know which it is. He is told to raise his hand if he gets pain. This is helpful, because some patients consistently will raise their hand each time they are at the lo-per cent level and never raise it at another level; someone who for some reason really wants to have pain, for example, he is suing, he can be wrong and quite erratic as to when he gets pain. He will often get it during the oxygen-breathing periods rather than during the deprivation.

DR. GRANT. Dr. Dublin, in conducting epidemiologic studies, what problems are posed by using these additional tests? If exercise tests are not totally discriminatory, what problems in cost accounting would this present in large epidemiologic studies? What order of certitude do you demand before you incorporate a new test in a large epidemiologic survey?

DR. DUBLIN : One of the things that epide- miologists ask initially is whether the sensitivity and selectivity of a test are known. What variables with the test itself enter into the experi- ment? Is the instrument one that has a highly discriminating value, that is, is it highly specific, or can it be used only in a screening sense in that it includes a large number of false positives as well as positives?

In some of our population studies m:e were in-


Conference on Electrocardiography 411

tercstcd in the variability in the distribution of the biologic phenomenon. For example, do we see a lot of changes in the S-T segment or the T wax.<.? Are these definitely related to coronary discasc, ischemic disease, or myocardial infarction? Or does this variation in the S-T complex relate nlore to an age factor? Coronary disease SCUILS to occur with greater frequency in a given age period.

I \vouid like to know whether there are data to help IIS discriminate shall we say, in using an electrocardiogram in a large population survey. 1Yhen \ve find a number of individuals with changes in the S-T complex, is this really associated with ischemic heart disease, or is it related more to changes in aging or to other biologic phrnomcna?

~I.~C.TRO(:ARDIOGRAPHY IN EPIDEMIOLOGIC STUDIES

DR. GRANT. A number of you have questions about the use of electrocardiography in epidemiologic studies. You wonder if electrocardiographic criteria and technology presently available are adequate, or if today there are reasons for incorporating the more advanced lead-design systems and display methods, and so on, for screening large populations.

DR. IRISHMAN. The present programs for computer application in electrocardiography are a good a\.enue to a final solution. The program undertaken by Dr. Caceres and his group, for example, is a very solid one, in that it starts off with something which we all accept, the routine clinical electrocardiogram, and it tries to handle this sub_ject in a mechanical fashion. The machine seems to be doing a very good job: and I an1 sure with more education the machine can do a better job. We should exploit this avenue first. because it would immediately link a broader technical program to what all of us are doing in clinical and hospital practice. The potential of this development is great. Of course, it is limited in the sense it does not explore new electrophysiologic concepts and avenues. Dr. Pipbergcr does that, and there are other groups around the world with similar ideas.

\l’hat do we as clinicians, not machine opera- tors, learn from this? We have to view electrocardiograms in a somewhat different fashion. The descriptive approach requires updating. i\‘e have to learn to translate the naked eye technic into clinically and physically measurable dimensions. Unless we do so, there is no way of instructing the lnachine. This process is going

V"I.IiME 19, MARCH 1967

to be instructive, as vectorial thinkinq has been.

Of course, it is to be hoped that the lnachine can furnish a better diagnosis and a colclposite analysis of the electrocardiogran~~ a composite of the best visual electrocardiographic analysis in the United States or in the world.

DR. SMITH. The computer really shollld have value in clinical situations when the electrocardiogram is abnormal. And it is here that the computer gap exists, as mentioned before, and 1 would like to see this gap closed.

DR. BLACKBURN. As to specificity or non- specificity of ST-T changes, sollleone mentioned that during exercise they were more conlmon in women than in men. It has also been fotmd in other studies, such as in the Tccumseh Co~nmu- nity Study in Michigan, that negative T wa.\‘es were more common among women in a population. This seems to indicate there is sotnething mysteriously different about women other thall the obvious things. It might represent a difference in the coronary fatality rate. It rniqht represent the same thing in women that it represents in men, except that when men ha\:e coronary disease they die at a higher mortality rate. This leaves behind in the population wolnen with coronary disease, because it is less rapidly fatal i:t them. It does not mean women in general ha\.e more coronary disease or that something mysteri- ous is going on in women. It tna)- simply indicate a difference in coronary fatality rate among men and women.

DR. SMITH. But what about the Lepeschkin studies of young women aged 20 to 40 with all these ST-T changes?

DR. HINKLE. I have seen the remarkable variability and prompt responsiveness of the cardiovascular system of young persons, both male and female, to changing situations, whether in digestion, the alnbient telnperature, or in response of the central nervous system to something that is going on around them.

This remarkable and rapid responsi\.eness seems to involve such things as marked shifts in rhythmicity of the heartbeat, in the heart rate and in the configuration complex. To a certain extent it seems to be even more nlarked in children. It may be that healthier people ha\,? vigorous responses of many kinds.

Among other things, a rapid adaptability of the cardiovascular system to the dnnands upon the organism may be reflected in changes in the electrical pattern of the heart. Sometimes WC have had impressions that it has been the people

412 Grant

with the least reactive cardiovascular systems, i.e., the ones whose rates are maintained more steadily and who respond less to what is going on around them, who may be subject to sudden and fatal crises.

We ought not to limit ourselves to thinking in terms of a scale with final levels of deviation from normal. I think we have a tremendously responsive cardiovascular system attached to another tremendously responsive system-the nervous system. I am not at all surprised to see that the reflection of the electrical events, especially through this single-lead peephole through which we are looking at it, looks so many different ways. Every other body function we have ever studied in the active individual has behaved like this.

MR. ABRAHAM. Dr. Grant, I believe that your original question was not answered. This pertained to the use of methods or tools in the epidemiology of cardiovascular disease. In a recent review of 57 study groups, Weinstein and Epstein pointed out the variability of methods. Perhaps Dr. Calatayud can elaborate.

DR. CAL ATAYUD. Among the 57 studies re- viewed, it is very interesting that in 39 of them the scalar 12-lead recording was still being used and in 30 studies, other leads.

DR. GRANT. Dr. Imboden, you must have put considerable thought into this problem in order to justify the program that you are father- ing. Could y-011 reassure Dr. Dublin about the reasons for deciding to go into it?

DR. IMBODEN. No, I am afraid we can’t reassure him in any way. We have about the same list of questions. We have asked whether a study of this sort is feasible, and whether useful information can be developed that will guide future service programs.

We wish to determine whether the recording of the electrocardiogram during extended periods of physical activity is a more sensitive diagnostic tool than the brief exercise tests now in broader use. If more sensitivity is demonstrated, how much specificity has been lost, again compared to measures in more common use? If there is an increased yield, is it of a sufficient order to warrant more extensive trials? We want to know the comparative value of different methods with respect to finding new cases of ischemic heart disease and in evaluating myocardial status in follow-up studies during various forms of therapy. What are their value in determining the functional status of patients?

DR. GRANT. Is it your plan to take popula-

tions generally without discrimination as to age, sex, or health, or will you start with a selected population?

DR. IMBODEN. The study should include a broad segment of the population with balanced groups in the adult age range, including both sexes, and with and without known heart disease. Of course, the characteristics of each individual studied would be defined. If the extent and limitations of the method are to be determined, the electrocardiogram would have to be analyzed without preconceived notions of what part of the complex is significant or what portion of the population will exhibit a certain change.

DR. DUBLIN. We are currently surveying, in Israel, some 10,000 men over the age of 40, from whom all the electrocardiographic information has been recorded on Dr. Caceres’ data acquisition systems. Unquestionably we are going to benefit greatly both in discritninating, on the basis of current knowledge, how many of these individuals by different categories-age, ethnic origin, educational level, dietary patterns, and a host of other variables-have ischernic heart disease, and in being able to calculate the comparative prevalence of ischemic heart disease in various populations.

We are looking forward to the advantage of computer analysis to help us arrive at “clinical” diagnoses. We have a lot of additional information, and we are going to use whatever diagnoses and clinical judgments the current status of knowledge of electrocardiography can give us. I would like to know from this group what other kinds of analysis can be made with this mass of data which would be helpful to the fields of electrocardiography and medicine in general.

Incidentally, we are about to begin a second series on these individuals. We hope in another two year interval to do a third series on these same individuals. How can these data be made maximally useful to the science of electrocardiography, medicine in general, and epidemiology as well?

DR. CALATAYUD. From the epidemiologic point of view, we must analyze the electrocardiogram to try to determine which parameters are the most valuable and which ones yield the maximal amount of information. Our studies indicate that the mean QRS axis, for example, is very sensitive in differentiating disease or the individual with heart disease from the so-called normal.

Of course, we would not be able to go any farther in classifying the type of disease with that


C:onference on Electrocardiograph) 413

alo~lc, but in a grot~p of 200 subjects carefully r~latchcd, we found a significant statistical differ- encc in QRS axis between the so-called coronary and the noncoronary group.

1)~. PIPBERGER. This is actually what we did I~I~II\. years ago when we tested the various para;netcrs that were measurable from the elec- trccardiogralns to see which ones would discriminate best. One of the first things we found, in 1961 or so, was that the mean QRS axis will separate the normal from the abnormal but will not tell you what the patient has. For a separa- ticn of normal from abnormal, it is a reasonable measure, but it is by far not discriminating enough to allow specific diagnostic conclllsions to be drawn fro111 it.

EXERCISE AND STRESS TESTS IN POPUI.ATION

STLiI)[ES

I)rt. HELLERSTEIN. What is the relation of coronary arteriosclerosis, overt or silent, to the electrocardiographic changes with exercise? What is the relation of fitness to age, fitness to arteriosclerosis, or fitness to the cardiographic changes in exercise? Although obvious, these are critical questions that require an answer. Certainly in the epidemiologic studies that are beinli dolie, it would be possible by proper selection of subjects or by taking a M hole population, as is being done, to try to answer these questions in reference to at least these four L ariables. L\:e really have gra1.e doubt as to ~1 hich is the crucial factor--age per se, corcnar) arteriosclerosis, or the cardiographic changes.

In ctlr lvork-classification experience, the cardiographic response to exercise in persons with rheumatic heart disease or syphilitic heart disease has had the same prognostic significance as Mattingly and Robb found in coronar)- patients. After 8 years, 56 per cent with an ab- norlnal response (1.5 mm. or more S-T segment displacement, premature beats, and other criteria) were dead. So there is prognostic significance.

Studies in process by Dr. Blackburn and at Tecumseh and Fralningham should provide an answer to Dr. Dublin’s question by including just two or three niore measurements.

MR. ABRAHAM. It is erroneous to inject a new hy-pothesis and then evaluate the data to ansM er the hypothesis. I prefer to start a study with a hypothesis, pretest the questions in terms of the hypothesis, and then collect the data. For example, if you want to answer a q,lestion abotlt physical fitness after the study has started

VOLI:MI; 19, MARCH 1967

and )our data do not adequatel!- dcscribr this variable, the usual approach is to LISC SOIW crude measure such as occupation status. I \\,ould hesitate to requesl. a study grotlp to answer this question (Inless there was specific accounting for the variable at the start. 71’011 tllay cet a partial answer or a hunch.

DR. HELLERSIXIN. As I lmdcrstand it: these studies are in perpetuum, isn’t that correct? In the Scandinavian and other litcraturc, the ability to perform muscular work in a steady state is studied in a multilevel program: de- pending on the physical fitness of the sub_jcct.

MR. ABRAHAM: Are there any- studies, such as the Framingham Heart Study, that describe the index of physical fitness? The investigation in the Albany, Kew York, Civil Service Stud)- does not evaluate physical fitness of the stltdl- population.

DR. HELLERSTEIN. You already answered Dr. Dublin’s question. In a large population, one can ask, “What is the relation of age to fitness, of age to coronary arteriosclerosis, and the relation of cardiographic changes to clinic,all\- apparent coronary arteriosclerosis?” You certainly know that of those who are stricken with overt coronary disease, maybe 40 per cent will have an abnormal cardiographic response, dc- pending upon the test that is done. YOII can answer the question even from taking a study in progress and sampling it at ol?e @\-en time to assess it.

MR. ABRAHAh1. You can answer this question, bllt I repeat, we dor_‘t know what fitness means in the data that have been gathered in the existing studies.

DR. HELLERSTEJN. The methods of most investigators are comparable in that they can categorize the spectrum of fitness to perform muscular work. In Montreal the results are quite similar to those in Cleveland, Stockholnl, and to those of Robert Bruce, Robello, Hoh- gren and others. It is a remarkable coincidence. A fit person can be fit in Sweden as well as in Washington or Cleveland. I am referring to ability to perform steady work.

MR. ABRAHAM. You are getting involved in specifics. I do not know what fitness means. I would not want to compare the physical fitness of lumberjacks in the Finnish studies with the physical fitness of the study popltlation in the Cleveland YMCA study.

DR. HELLERSTIXN. I am talking abollt the ability to perform so much work per kilogram of body weight.

414 Grant

MR. ABRAIIAM. This appears to he rather a semantic problem. The main tFing that I wanted to bring out is the difficulties that arise if someone asks a question after the study had started ; you usually cannot insert a hypothesis and hope for appropriate data on a study already under way.

DR. GRANT. On the other hand, it is also likely that Dr. Dublin would not have become involved in his study if these questions were already answered. One of his goals has been to shed light on these very questions.

DR. MATTINGLY. One method someone might be interested in following is the measurement of ventricular work during the Valsalva maneuver. A few );ears ago Dr. Baldwin showed that one can give a good stress test of the left arterial circulation by the Valsalva maneuver. I saw at least a few of the patients who had the same changes in the Valsalva maneuver as in exercise tests. I do not know whether this hemodynamic procedure is worth exploring further.

DR. GRANT. I agree; furthermore, the Val- salva test is as good as the exercise test, which in the digitalized person produces S-T shifts.

DR. PIPBERGER. When we did a few, the changes I mentioned before were found in normal subjects. The drastic changes of QRS following a Valsalva maneuver are not seen in patients in cardiac failure. We have studied this in 5 or 6 cases. I don’t know whether this is useful, since there are other ways to determine whether a patient is in failure.

DR. GRANT. Anybody planning to launch a large epidemiologic study of coronary disease in which the cost factor is significant should hesitate before he employs an exercise test. On the other hand, such a test would be indicated for a large general study of an entire population, including women and all age groups, so that one could focus on the problem of S-T physiology in general rather than coronary disease alone.

DR. BLACKBURN. Are you concerned with technical difficulty or cost, or with just what we are or are not going to learn from exercise testing? For most of the tools that we would like to add to such studies, one tries them to see if they fit the time schedule in the field. Added expenses are usually insignificant in comparison with the over-all time and energy spent in mobilizing the populations for study. The problem really is in not having enough good tools or enough facilities to try out new things.

In many cases we are doing research on these

tools in the field, rather than back in the laboratory where they might he evaluated. Bllt there are advantages here, too. In total population samples you may come up with better ideas about how valuable a tool is than if you try it in a small, well-defined group back home.

The problem with the maximal performance tests is that there may not be as many lnen to see when we come back for follow-up. Either they are discouraged from the stress wc have given them or something more serious has happened to them. Dr. Bruce has not had this experience. Because of this concern about the future, some of us want to try multistage tests in other areas and have not been able to. Potentially, maximal lead tests with orthogonal leads and computer analysis would be the “ideal” standardization.

DR. HELLERSTEIN. We have used a test that we called the ECG Flack test. It is based upon a Valsalva maneuver electrocardiogram that is taken before and during the time the subject used an ergometer. The subject strained for 15 to 20 seconds. This has been amply described by one of the workers in Katz’s laboratory some years ago. Our correlation of this test of 2,996 people in the work-classification clinic led us to consider it as a satisfactory measure of “fitness.” Those who failed to have a slowing of the heartbeat within the ninth to eleventh beats after the cessation of the procedure were Jlot "fit."

Subjects with car pulmonale, restriction of the flow of blood through the mitral or tricuspid valve, or congestive failure had a delayed response of the slowing of the rapid heart rate to this effort. We did not consider this test at all indicative of coronary disease, of the ability of the heart to increase cardiac output after the post-straining period. We have gone back to more implicitly accepting the idea that these abnormal responses are indicative of coronary diseases and coronary insufficiency, but that has yet to be proved.

I would like to mention the last simple test- that of hyperventilation. Any exercise tests must incorporate hyperventilation because there are many false positives which are definitely not related to increase in heart work or to increase in total body oxygen consumption, which are associated with significant electrocardiographic changes. I would add hyperventilation to the Valsalva maneuver, if possible, using that as a measure of function but not of struc- tural change.


C:onference on Electrocardiograpll) -11 5

Da. i’I(:K. What is the diagnostic significance of prenlature beats appearing under stress, without any contour changes of the electrocar- ciio:gran?

DR. h I ATTINGLY. What significance does it ha1.r in a11 individual in a resting position?

DR. PICK: Premature beats normally have a tendency to disappear during stress. But they ma)’ dexlop in the abnorlllal patient. Is that right?

DR. HINKLE. During cardiac acceleration, for whatever reason, premature contraction is more likely to appear, although when a more rapid rate is established there may be fewer instances. Also, men who have more than 50 prelnature contractions per hour are likely to have clinical evidence of coronary heart disease, but this observation is not definite.

So premature beats may ha\-e some meaning. But, for Dr. Dublin, if these tests are included in an epidemiologic study, the justification is to find whether the tests have any diagnostic meaning. If they are included, I would strongly large that we include population groups of all types, of all ages, and an electrocardiographic data pool.

ELECTROCARDIOGRAlM REFERENCE LIBR./\RY

DR. GRANT. A major need in electrocardiography is a reference library. Of course, Dr. Caceres is already well on the way toward this in the Instrumentation Field Station. The 10,000 tracings from Dr. Dublin’s study and additional thousands from other sources will be permanently retrievable. But what should be the function of such a reference library? Many aspects of clinical interpretation could be clari- fied if a large number of “before and after” tracings in the same subject were available. It lllight be useful to have a national repository of srlch tracings.

DR. GRISHMAN. To cope with the flood of information in cardiology, as new information is developed, it should be immediately available. The cataloging and the ready availability of this information should be organized. The information should be made available in a center for cardiology literature and, specifically also for electrocardiography, with teleprinters and other automated devices.

DR. BORUN. A center or central effort might be extremely helpful in answering some questions that have arisen here, such as, what are diagnostic changes? What changes discriminate diseases? What lead systems are most useful?

VOLIJME 19. MARCH 1967

One reason we do Ilot agree is that \\f ai-v iiot looking at the same data. \Ve are also not using sinlilar methods. Some centralization. at least coordination in looking at problcblls that arc under acti1.e consideration hv differcllt investigators, could give answers ra;idl>T, although it is not feasible to tape-record and anal).ze this information by computer.

DR. CADY. This is necessary, but, as Dr. Grishman said, it relates not only to clcctro- cardiograms, but to all of medicinee the ill- dexed literature, the “Medlars” progralll, heart and brain wave references, and n.agnetic tapes for conjparative computer studies and r<xsidcnc>- training. It should be considered in contest with what is happening to storage and retricl-al in medicine and society in general. All lliajor medical centers would be important locations for this information.

DR. GRANT. k’ou have in mind a repositor) that will be kept updated, even in research?

DR. CADY. We might well have a center for cardiographic recordings in the Heart Disease Control Program. Whatever it is decided to make truly available must go through decen- tralized units in the larger urban centers. As- pects of the research service which are still experimental would be kept in the central office. When data are removed from the area of doubt and further investigation, they would be useful for comparative purposes. An in\:estigator would then be able, in a day’s time, to retrieve cardiographic reference tapes and other conl- parative data.

DR. GRISH~~AN. That is most important, In addition, to make sure that the material which enters such a reference library or m~lscu~n is acceptable to the scientific community. once or twice a year a group of experts should review each case, give opinions on it, and classify it as a grade 1 acceptable case, grade 2 acceptable case, etc.

My large file and a good memory allowed me to remember two unusual published cases of corrected transposition. Another case! not published, was once flashed on a screen for mv interpretation and reminded me of the brie; ab- stract which we had published on the subject. Two cases are still a curiosity, bllt there are probably many such cases. As soon as you have 20, they become solid diagnostic information. With a Ixluseum, a casual observation can be transferred rapidly for immediate diagnostic availability. Periodically, subcenters lrhich are interested in Isimilar lesions could Set frown

416 Grant

the museum the latest information from the survey of the electrocardiograms or of corrective measures.

DR. PIPBERGER. I would agree. As we go into multivariate analysis of the electrocardiogram by computer means, it becomes absolutely necessary. The samples have to become larger and larger to yield significant results. When you use 20 points or so from each tracing, and the samples are small, the results are almost always 100 per cent correct. But this is due only to the small number of cases and to the larger number of points. The more information we try to get from the electrocardiogram, the larger the samples have to become. Nobody is going to live long enough to get sufficient data in one hospital or medical school. Something has to be organized to get samples of adequate sizes to arrive at stable statistical boundaries which would not fluctuate when new cases are added.

The results of multivariate analysis in small samples are completely unreliable. The more we automate, the more we use multiple points, the larger the samples have to become. Who can gtt the samples?

DR. PICK. Do you store everything? If not, how would you make a selection?

DR. PIPBERGER. At the Veterans Adminis- tration we are collecting strictly electrocardiographic data, plus a prescribed form with clinical information, from 10 hospitals.

DR. PICK. Under certain conditions, broader sampling could be started. How many possibilities are there that some time in the future somebody will be interested in some aspect that appears trivial to us today? How can one store the next 10 years’ information from all over the country, or what selection should be made?

DR. PIPBERGER. If you organize a coopera- tive study, and you put everything on tape, it is fairly simple. We have 10,000 electrocardiograms on tape right now which we can use again and again.

DR. GRANT. But the difference is that yours is not a reference library but a selective collection for a particular purpose.

DR. PIPBERGER. Yes, but one has to think of data collections in a completely different frame- work for the future.

DR. GRISHMAN. That is perfectly correct. Off the cuff, I do not want to say how it should be organized. Certainly one should have an organization containing a proved diagnostic reference file. As we get more sophisticated, we can narrow it down. From patterns we

can become more specific in deflections. If we are intelligent about this, design it well, with the help of computer and retrieval experts, we can store it as Dr. Pipberger does, for instance, on tapes, so that we can retrieve it and reshuffle it at any time as we please.

Dr. PIPBERCER. We have all been brought up on the idea that autopsy information is the only valid confirmation of what we find in the electrocardiogram or in the clinical data. The more autopsy material we get-and we have more than 400 cases by now-the more frustrating it becomes. Usually there are multiple or combinations of infarcts. The patient usually does not die from one infarct.

Cases with one isolated infarct are desirable as reference material. These cases are not as frequent as one might think. No hospital in the world can get enough such cases.

DR. GRANT. Dr. Caceres, what can and should be retrieved from electrocardiograms?

DR. CACERES. Probably the most important items are the numerical values of electrocardiographic parameters. We need to know the distributions of these values in various types of populations. For example, we should have a storehouse of data on each electrocardiographic wave on, let us say, 46 year old males 5 feet 8.5 inches tal!. with a weight of 175 pounds. Had we distributions of values found in those sub- groups, given an unknown subject of those characteristics, we could readily define his placement and determine that he was in the upper 5 percentile, at the median point, and so on.

Subsequently distributions can be made up of values of physical as well as disease characteristics. We would then be able to determine that a subject within a disease distribution, by going toward the upper percentile, for example, might be leaving the specific disease distribution, i.e., getting better. It might be possible to do away with the current necessity of using a subject as his own control in comparing tracings.

So we need to store and retrieve electrocardiographic values; i.e., measurements of amplitude and durations of existing waves and some related subject and patient data. We have been organizing our own data in that fashion and heartily agree with what is being said-that it would be of national value. As Dr. Pipberger points out, getting enough clear-cut cases of anything is difficult. The approach being suggested can help solve that problem.

We are currently categorizing the Israeli population study that Dr. Dublin has conceived


Conference on Electrocardiography 417

into various electrocardiographic groupings. Dr. Bachrach, who engaged in this study, might wish to comment.

DR. BACHRACH. With the criteria that we established, the number with evidence of infarcts was quite high-5 per cent of the population with a probable infarct and another 10 per cent with a postinfarction configuration. We are not completely happy with the results from the criteria, but at least they have the great virtue of apparently being very sensitive. We do know that anybody that was called normal has a very low probability of really having an infarct.

DR. CACERES. These are electrocardiographic categories. We have not yet obtained the data to correlate the electrocardiograms to specific diseases and people.

DR. BACHRACH. It will be advantageous to consider the possibilities of these categorizations as diagnostic groups. What is the probability, in two, four, or six years, of persons with a particular configuration or measure of an electrocardiographic parameter developing a clinical infarct or meeting sudden death, irrespective of whether they now have electrocardiographi- cally a tentative postinfarct configuration?

MRS. WEIHRER. The advantage of computers and appropriate storage of numerical data is that it can satisfy Dr. Bachrach within a few minutes. If Dr. Dublin restructures the hypothesis it could also satisfy him. We can conclude that research can be speeded to allow time for more creative and imaginative use of data.

We have the ability to go back to the same initial data, regardless of how they are stored, and to put in instructions if an area becomes important. Then we can play the same things again. It is important to do that and to save enough information to be able to go back to the data with new criteria.

DR. GRANT. One hopes that the next time somebody is interested, for example, in the electrocardiogram in infancy, or rheumatic heart disease or heart surgery, a request to Dr. Caceres’ group to do the electrocardiography will help this reference library grow. Whether the library would be adequate for a need such as Dr. Grishtnan mentioned is hard to say. Of course, it might never be totally comprehensive and able to provide data for all possible questions which workers later might want to ask, but it could answer many current questions. For example, one thing that has troubled me in clinical electrocardiography is incomplete bun-


dle branch block. I belong to the school that believes it does not exist. Nevertheless, this type of block is still to be found in the literature. The only way the question can be settled is by having a collection of tracings of patients who acquired complete left bundle branch block--- after left incomplete block-for whom there are data to show what they looked like beforehand. Only then can one establish whether there is such a thing as incomplete left bundle branch block. A reference library could solve man) other questions like that one.

DR. GRISHMAN. I have the same skepticis about incomplete left bundle branch block that you have, but being on the editorial board of two journals, I ran across a paper about a patient who had started off with a normal electrocardiogram and who now has a transient bundle branch block with all sorts of transitional beats. In the transitional beats, which were all beautifully recorded but mixed up, there were transitional beats which looked like incomplete bundle branch block. This is the only case in the published literature of transitional blmdle branch block with transitional beats.

DR. GRANT. it has been described before as a transient state with one or two beats prior to a complete left bundle block, bnt it has never been described as a stable conduction defect preliminary to complete left block.

DR. GRISHMAN. The transitional beat that I mentioned looked like left ventriclilar hypertrophy, possibly anteroseptal infarction. 1Vhen such a case is in a reference file? it is nationall) available. This one was fortlmately published. Otherwise, in a similar situation2 a case like this would be buried. Somebody in a snlaller community not having the time or the access to a library, might not publish it. The itnpor- tance of making it available is quite considerable.

DR. PICK. In Michael Reese Hospital we have collected and stored all electrocardiograms taken in the past 40 years. We had to devise a specific coding system, which we thought was comprehensive. It has to be enlarged, a tre- mendous job if it is to be detailed in every little aspect. Now, if we study something, we can spend a year jush pulling out records possibl) containing what we are looking for.

To Dr. Grishman I would like to say I am a believer in the concept of incomplete left bundle branch block on the basis of a collection of cases with a gradual evolution of a normal electrocardiogram over typical patterns of left ventricular hypertrophy to progressive degrees of left-

418 Grant

sided conduction defects. Offhand, I think I can provide you with at least five examples frown our collection.

DR. GRISHMAN. But you haven’t published thenl.

DR. PICK. We have not been interested in doing it, but others did.

DR. PIPBERGER. If you have difficulty in storing and filing them, you need an automatic filing system.

DR. PICK. It will not help me if I am interested in a particular type of aspect of the electrocardiogram.

DR. PIPBERGER. Once programmed, an efficient retrieval system would find it for you.

DR. PICK. I have still to go through the records to find it.

DR. PIPBERGER. The machine would do that. DR. PICK. You cannot program arrhyth-

mias, because there is no steady reference point for understanding the mechanisms. To devise a sample program to be fed into the machine, one would have to use relative rates, pacemakers, and functional changes of the refractory period. Arrhythmias are the result of interdevelopmental changes of these two parameters, frequently occurring front beat to beat.

DR. PIPBERGER. If you can analyze it, the machine can do it too.

MR. BERSON. Some physicians have trouble deciding when certain kinds of equipment or technic are technically sound. Researchers in large units, such as the government, who have access to engineers and mathematicians may not have this trouble. The others might have use for, let us say, two things: First, advice as to what equipment is available or what equipment can be modified; second, if they already have equipment and they don’t feel confident about its characteristics, a place where the) might send it to be tested. As possible functions of a reference center, do you people think them necessary?

DR. GRANT. That is an excellent suggestion for important additional functions of a reference library. For another function, there is the gathering of such a meeting as this, for example, and the previous one, which Dr. Caceres’ group has hosted. With its access to engineers and other people serving it as con- sultants, this group becomes a very powerful and useful organization in the field of electrocardiography and certainly in electrocardiographic instrumentation.

DR. BLACKBURN. May I mention a third

possibility. You discussed the possibility of a repository and possibly the Bureau of Standards testing cardiovascular data. Perhaps other data processing centers should be established so that every private hospital will have access to computer data-processing. That is more immediate, and I don’t know of any adequate pro- visions being made.

DR. GRISHMAN. I support this strongly, because I think the tendency will be for us to duplicate centers, like this one, for instance, throughout the nation, which is probably un- necessary. There are 24 hours per day to the completer. Modern technic for transmitting data are suitable for a computer system. The design of a standardized data acquisition unit with three channels and its own tape unit could make the data available to the computer. It could transmit the information from the tape to the central computer at any preselected time, and then the next morning at 8 o’clock or so, you would get the printed diagnostic sheets.

It would be much more sensible to plan for this kind of program than to have 50 different units throughout the United States. I am not talking about research, but about hardware for processing conventional data.

“PROGRAMED RESEARCH"

DR. GRANT. I should like to comment on a new trend today in the form of “consulting committees,” which could be especially important in electrocardiography. A rapidly increasing tendency in this country as well as overseas is toward “programed research.” It often takes the following form: A group of workers in a field of high promise are gathered together to decide what next needs to be done. But one of the conditions for membership on the committee is that one agrees to devote part of the resources of his lab to a project which the committee decides he is best equipped to perform. In other words, each member surrenders a little bit of sovereignty in order to be a part of the team-attack on the problem.

Electrocardiography is not a popular field among the biomedical sciences, and electrocardiographic projects always have hard sledding before granting agencies. But a well designed, team-operated, collaborative approach to an important aspect of electrocardiography would have great appeal before government and vol- untary granting agencies. The ST-T problem would be ideal for this. For example, the committee could get Dr. Brody to work on the


C:onference on Electrocardiograph) 410

capacitance propertics of the body for frequencies in the T range. Dr. Abildskov would work on a T model. Dr. Zinsser and Dr. Slllith collld lrndertake careful experiments on doqs. or other animals perhaps with hypoxia, \vith dener\-ation, and so on.

\\‘hen investigators pool their goals in this way, they will get much better receptivity from the scientific public. Furthermore, the investigators will assume some of the responsibility that important lines of research get done in their held-research which may seem at first perhaps uninteresti~~,~ and dull, however important it is.

This is the only approach, it secnts to IIW, for ever finally finding out the validity and the usefulness of the exercise test: It requires a broadly planned attack on ST-T electrocardiography in general. I doubt if any granting agency today would invest much lnoncy in further studies on epidemiology employing the exercise test. It’s time folks stopped publishing exercise test- epidemiology studies and began the work which will explain the physiology of ST-T wa\res.

I want to thank you all, and tell you how much I have enjoyed this revisit to electrocardiography after so Illany years of absence.


the electrocardiogram today: a symposium discussion

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