INSTRUMENTS AND TECHNIQUES
`
`
`
`New Method for Heart Studies
`Continuous electrocardiography of active subjects
`over long periods is now practical.
`
`Norman J. Holter
`
`Electrocardiography today is an in-
`dispensable
`tool for physiologist and
`physician. Cardiac electrophysiology be-
`gan in 1887 when Ludwig and Waller
`first noted changing chest potentials;
`and practical electrocardiography began
`in 1893 with Einthoven's string galva-
`nometer work. Then followed the body
`of classic work in this field, but the
`electrocardiograph did not find wide
`use until the advent of modern direct-
`writing instruments. Today's' clinical in-
`strument is convenient and dependable
`and will remain an important tool in
`research and in examinations of estab-
`lished heart conditions. It is still only a
`hit-or-miss affair for studying long-peri-
`od , heart action or detecting transient
`heart aberrations.
`Until
`recently, electrocardiography
`required connecting leads from subject
`to instrument. This was no handicap in
`building present-day principles but has
`been a handicap in studying active sub-
`jects. Leads can be detached during
`
`The author is president of the Holier Research
`Foundation, Helena, Montana. This article is
`based on a paper presented 20 July 1961 at the
`4th International Conference on Medical Elec-
`tronics, New York.
`1214
`
`exercise and reconnected later, and with
`special electrodes some exercise is fea-
`sible during recording. However, con-
`siderably more physical freedom is de-
`sirable if one is to learn more about the
`heart under realistic conditions of daily
`life.
`This article reports a series of con-
`cepts and developments concerned with
`obtaining long-period continuous elec-
`trocardiographic records from active
`subjects in order to obtain data which
`constitute a statistically valid sample of
`heart action under conditions that give •
`the subject the greatest possible freedom
`of activity. This goal automatically gen-
`erates the problem of handling, in a
`convenient and practical way, the very
`voluminous data acquired. No one can
`adequately examine 100,000 continuous
`ordinary electrocardiograms
`(24-hour
`recording at a pulse rate ,of 70). A
`number of early ideas have led to the
`concept of breaking away from the
`limitations of orthodox electrocardiog-
`raphy to solve the scientific problem of
`adequate sampling and the medical
`problem of obtaining electrocardiograms
`in situations other than the highly arti-
`
`ficial and unrealistic situation of resting
`quietly on a comfortable pad after a
`good sleep, with no breakfast, and with
`calm confidence in one's physician.
`In 1939 J. A. Gengerelli and I be-
`came interested in remote stimulation
`of physiological systems as; means for
`minimizing interference with the system.
`By modifying a classic experiment, we
`produced contractions of frog muscle
`by stimulating its nerve supply by
`means of a changing electric field
`without electrodes or connecting wires
`(7). This raised the converse question
`of whether an external field is created
`by a nerve impulse. From these two
`basic and converse ideas developed a
`series of studies leading, on the one
`hand, to the remote stimulation of the
`brain 'of the intact animal and a study >
`of corresponding behavior (2, 3) and,
`on the other hand, to the use of radio
`for the accurate transmission of elec-
`troencephalograms and electrocardio-
`grams from freely exercising subjects
`(4, 5). With the electronics of 1942, a
`nerve impulse field was not detected (2),
`but recently we obtained evidence for
`the existence of such a field (6). Radio-
`electrocardiography as a practical and
`convenient technique is now becoming
`relatively routine; its first clinical appli-
`cation was by Maclnnis in 1954 (7).
`
`Steps toward Freedom
`
`Up to this point- there has been de-
`veloped only what-I would call an initial
`step toward freedom—the elimination
`of entangling wires. Moreover, while
`telem.etering per se does provide greater
`freedom of action, it does hot provide
`practical long-period continuous elec-
`trocardiography. It also requires an in-
`SCIENCE, VOL. 134
`
`1 of 7
`
`FITBIT EXHIBIT 1017
`
`

`
`dividual to remain within range of radio
`receiving and electrocardiographic ob-
`serving equipment and has the disad-
`vantage of being subject to occasional
`radio interference. W. R. Glasscock and
`I therefore developed a portable radio-
`receiver tape-recording unit, to be car-
`ried by a subject free to go where he
`wished as long as he took the "ECG
`brief case" and left it in his general
`environment (8). Still needed, however,
`was freedom from such baggage and
`from radio interference, plus means of
`rapidly studying the long magnetic tapes
`obtained. iWe therefore developed the
`"electrocardiocorder," which eliminates
`radio circuits at both ends and, when
`used with
`rapid-analysis
`instruments
`developed for the purpose, achieves
`what I call full freedom (9). This means
`freedom from connecting wires, free-
`dom from the restriction of staying in
`one locality, freedom from the incon-
`venience of carrying electronic baggage,
`and freedom to make records of any
`desired length and still be able to ana-
`lyze them. Thus the sequence of con-
`cepts progressed from remote 'stimu-
`lation of nerves to 'the hardly antici-
`pated stage of our next efforts—the
`study of the heart action of swimmers,
`forest fire fighters, bronco riders, and
`so on.
`Beginning steps are illustrated in Fig.
`1 (top), which shows our current radio-
`electrocardiograph system; the "electro-
`cardiocaster" is held in the hand, and
`the radioelectrocardiograph receiver, de-
`modulator, oscilloscope, and clinical
`electrocardiograph are at the right—a
`useful system when we need to make
`observations at the exact moment of
`the heart beat. The lower part of Fig. 1
`shows our ECG brief case in use; d*
`subject is eating in a restaurant while
`an electrocardiocaster in his upper coat
`pocket sends data to the unit on the
`small table by the wall. This system is
`also one step toward truly long-period
`continuous electrocardiography, because
`magnetic :tape storage in the unit re-
`places spot observation on an oscillo-
`scope or on electrocardiograph paper. I
`define "long-period" as longer than a
`half hour, the usual limit for one roll
`of ordinary electrocardiograph paper.
`The electrocardiocorder is shown in
`Fig. 2. It is a small portable unit con-
`taining voltage amplifier, power am-
`plifier, oscillator, mixer,
`temperature
`compensator, recording heads, motor
`control, drive mechanism, batteries, tape
`and reels, case, switches, and connec-
`tors. It is oval, measures 19.5 by 9.8 by
`4.6 centimeters, weighs 1 kilogram, and
`20 OCTOBER 1961
`
`Ill
`
`Fig. 1. (Top) Laboratory radioelectrocardiograph system; (bottom) portable version in
`use.
`
`model just completed 1000 hours of
`is conveniently carried in a man's coat
`total operation without failure. The
`pocket or a woman's strap-type handbag,
`woman shown in Fig. 3 is walking up-
`or is fastened to the chest during unusual
`hill after working 8 hours. The tape, of
`physical activity. The power supply is
`10-hour capacity, provides a continuous
`adequate
`for 80
`to 100 hours of
`record of all heartbeats from 1 hour be-
`operation, and the tape capacity is 10
`fore to 1 hour after her workday. Chest
`hours; after 10 hours the tape is changed
`leads, approximately Vi leads, are used.
`for longer tests. Our latest
`
`Fig. 2. The recorder-analyzer system for long-period continuous electrocardiograpny of
`active subjects and rapid analysis of the resulting voluminous data.
`'
`
`1215
`
`
`
`2 of 7
`
`

`
`
`
`time;
`to pulse
`is proportional
`length
`compression of the pattern into a small
`space; and the resulting prominence of two
`arrhythmias. (Actually, & premature beat
`results in a short vertical line, and it is the
`long line, representing the compensatory
`pause, that stands out most prominently.)
`In a test on a certain very long ordinary
`paper i record, 2 hours of a technician's time
`were required to establish with confidence
`the existence of 16 premature systoles,
`whereas the same quantitative result was
`obtained
`from
`the corresponding ar-
`rhythmiagram in 6 seconds. Typical ar-
`rhythmiagrams are also shown in Fig. 6 .
`(middle and bottom). Premature systoles
`may be seen; the bottom record is from a
`subject with an extremely heavy work load,
`mental and physical fatigue, and inadequate
`Fig. 3. The electroeardiocorder in use, car-
`sleep, who had drunk a considerable
`ried hi a handbag. The chest leads run
`amount of coffee.
`down the strap.
`
`The arrhythmiagraph part of the
`analysis unit presents rapid, quantita-
`Electrodes ~
`tive, compact information on pulse ir-
`regularities, whereas AVSEP is used to
`There have been occasional innovations
`observe changes of form. (Changes in
`in the design of electrodes for orthodox
`pulse time, the R-R interval, are seen
`electrocardiography—innovations in shape,
`on AVSEP only as a rapidly changing
`size, and material and in holding devices
`tail on the electrocardiogram.) The ar-
`(elastic straps, suction cups, and so on)—but
`rhythmiagraph idea (10), which may
`little attention heretofore has been paid to
`or may not be new with us, is illustrated
`problems that arise with use over long
`schematically in Fig. 6 (top). The dia-
`periods. Such problems are changes in
`gram shows the conversion of each
`impedance, patient comfort, dermatitis,
`R-R interval to a vertical line whose
`effects
`
`Fig. 4. (Top) Normal AVSEP pattern; Fig. 5. Block diagram of the recorder-.
`(bottom) pattern of a bigeminy attack. analyzer system.
`
`SCIENCE, VOL. 134
`
`
`
`112
`AVSEP-Arrhythmiagraph Analyzer
`
`Long records are useless without
`means of rapidly locating parts of in-
`terest; this is accomplished by the analysis
`part of the system. Changes in form are
`detected by "AVSEP" (an abbreviation
`for
`"audio
`visual
`superimposed
`electrocardiogram presentation"); the ar-
`rhythmia detector is described later. A
`crude model of the analyzer described in
`1957 (5), was a floor-rack assembly, but
`the model shown in Fig. 2 is as portable
`as an ordinary electrocardiograph. In
`operation,
`electrocardiocorder
`tapes
`move at relatively high speed and
`present the signals on an oscilloscope,
`each electrocardiogram being rapidly
`superimposed
`upon
`its
`predecessor.
`Electrocardiograms which are continuous
`duplicates of each other thus appear as a
`single,
`relatively
`steady
`electrocardiogram, as shown in Fig. 4
`(top). This is a 1-second photograph of
`the AVSEP screen; during this period,
`80 electrocardiograms were displayed.
`The signals are also presented aurally, as
`a noisy growl in the low audio region;
`and the ear notes any change in the
`nature of this noise, thus adding to the
`over-all sensitivity of the method. If only
`one
`electrocardiogram
`differs
`^significantly, the change will be seen and
`heard. During complicated heart attacks
`the "single" dynamic electrocardiogram
`pattern of AVSEP appears much like a
`snake writhing about, shpwing details of
`the attack and of its 4 approach and
`termination.
`The tape, run at 60 times the record
`ing speed of 7У2 inches per minute,
`provides two signals from the recording
`heads, which are mechanically displaced
`so that AVSEP will begin with the P
`wave rather than the R wave used to
`trigger the sweep. One signal goes
`through an amplifier stage, through an
`integrator (to correct reproducing-head
`distortion), through another amplifier,
`and to the AVSEP speaker and oscillo-
`scope. The alternate signal goes through
`an amplifier stage, a clipper-filter stage,
`and a delay-trigger stage, becoming a
`sawtooth signal for the horizontal
`AVSEP sweep; it goes also to a separate
`oscilloscope (Fig. 5, bottom) to form
`the arrhythmiagram. A 10-hour record
`can be examined in 10 minutes; a syn-
`chronized clock tells the observer the
`time of day for any part of the tape, so
`changes can be correlated with activity.
`Myographic potentials, when present,
`rarely interfere because the AVSEP
`pattern is regular and the unwanted
`signals
`are
`purely
`random.
`
` '
`
`
`
`1216
`
`3 of 7
`
`

`
`of moving wires, and so on. With the
`advent of long-period continuous elec-
`trocardiography, various modifications
`of the usual methods can be introduced,
`although more work remains to be done.
`I do not intend to give a comprehensive
`review, but interested readers can check
`some references (11) and, with a little
`experience, сад readily select some-
`thing suitable for a particular purpose.
`Relatively simple methods will suffice
`in some cases—for example, flat elec-
`trodes with the usual paste, held on
`the chest by small balls of cotton and
`strips of paper masking tape. An Ace
`bandage around the chest provides add-
`ed support. More elaborate methods are
`needed for recording periods of several
`hours to several days; it is my present
`opinion that the best long-period elec-
`trodes will be some form of the so-
`called fluid-type assembly, with elec-
`trodes supported some distance from
`the skin ;in a manner to seal a suitable
`electrolyte between electrode and skin.
`Glasscock proposes carbon electrodes
`in such assemblies; his preliminary tests
`show minimal artifacts from motion.
`
`Medical Uses of the System
`
`The electrocard iocorder-A VSEP-ar-
`rhythmiagraph system may be used
`both in clinical research and in routine
`medical practice. A discussion of med-
`ical uses of necessity includes research
`uses, since routine use of the system at
`this time often uncovers new facts on
`heart action. Many individuals come to
`autopsy without having had either
`symptoms or treatment of what are
`'found to: be heart lesions of a type
`which would have shown on an electro-
`cardiogram. The problem of asympto-
`matic heart disease is intriguing and
`important, both clinically and academ-
`ically (12). As stated in the introduc-
`tion, orthodox electrocardiography will
`always have its uses in the measurement
`of established heart conditions, but it
`does not provide an accurate sampling
`of all-day heart activity any more than
`the analysis of a single rock provides
`an accurate sample of a mountain of
`ore. Through AVSEP and arrhythmia-
`graphic analysis of a long electrocardio-
`corder record, there is a far better
`chance of finding heart difficulties at an
`early stage. According to one authority
`more than half the individuals who have
`serious arrhythmias are not aware of
`them (13), and some sudden deaths
`are deaths from arrhythmia that does
`not result from coronary occlusion. A
`20 OCTOBER 1961
`
`thorough modern physical examination
`takes parts of several days of the pa-
`tient's time, and I suggest that routine
`recording with a electrocardiocorder
`for a suitable interval be included, for
`the possible detection of any subclinical
`angina, potentially serious arrhythmias,
`or other transient heart disorders. A
`large clinic might have a number of
`electrocordiocorders in use and one
`analyzer for examining the results. The
`
`effects of drugs or other therapy on
`electrocardiagraphic form and D'ulse
`anomalies can be followed quantita-
`lively.
`Figure 7 is an electrocardiograph^
`record (of research and clinical interest)
`of one of our laboratory subjects at the
`end of "a long, attack of paroxysmal
`tachycardia. The heart had started beat-
`ing at twice the normal rate 8 hours
`earlier, and the usual medical measures
`
`Fig. 6. (Top) Schematic drawing of the arrhythmiagraph; (middle and bottom; typical
`arrhythmiagrams, showing pulse time variability, including premature systoles.
`
`1217
`
`
`
`4 of 7
`
`

`
`
`
`
`
`1218
`
`had not corrected it. The attack later
`terminated spontaneously, and Fig. 7
`shows the complex details of the transi-
`tion to normal. Figure 8 (top) shows
`the pulse time details.
`I have
`lent
`the recorder-analyzer
`equipment to Dr. John S. Gilson of
`Great Falls, Montana, who has made
`records of some 200 clinical cases (14).
`One interesting case is that of a man
`who, in one occupation, had clinical
`symptoms of angina pectoris, for which
`electrocardiographic confirmation could
`not be obtained. Later, in a different
`occupation, this individual had no sub-
`jective symptoms of angina, but an
`electrocardiocorder record showed def-
`inite anginal changes on AVSEP.
`Figure 4 (bottom) reveals a transient
`attack of bigeminy, a phenomenon in
`which alternate heart beats differ great-
`ly, both in electrocardiographic form
`and pulse time. Figure 4 shows two
`separate electrocardiograms from one
`heart.
`The dynamic nature of the AVSEP
`pattern is shown in Fig. 9, a series of
`moving picture frames showing
`the
`magnitude of the changes in the AVSEP
`pattern of a man during, an angina at-
`tack brought on by lifting heavy boxes
`in his occupation. On AVSEP this is
`seen as a single electrocardiogram
`which begins ' to "writhe about" as
`changes occur. Note the great drop in
`the S-T segment of frame No. 7 as
`compared with frame No. 1. The pa-
`tient felt pain and took nitroglycerine,
`and the electrocardiogram returned to
`what was normal for him. This record
`enabled Gilson to confirm a question-
`able diagnosis.
`Other arrhythmiagrams of clinical
`situations are shown in Fig. 8. In the
`center is the arrhythmiagram of the pa-
`tient having the bigeminy attack of Fig.
`
`Fig. 7 (above). Detail of an electrocardio-
`gram during termination of paroxysmal
`tachycardia. Note the high pulse at left
`and the normal pulse at right. Fig. 8 (left).
`Arrhythmiagrams of
`(top) paroxysmal
`tachycardia at the moment of return to
`normal and (middle and bottom) of other
`hearts, showing bigeminy and multiple
`pulse times.
`
`SCIENCE, VOL. 134
`
`5 of 7
`
`

`
`4. At the bottom, a heart "can't decide"
`what pulse rate to settle down to; there,
`are several fairly regular pulse times
`from the same heart. The acoustic effect
`is interesting in many of these cases; a
`signal which often sounds like a motor
`boat suddenly sounds like an entirely
`different motor boat as anomalies occur.
`Two of Gilson subjects equipped with
`the unit have been
`involved
`in
`automobile accidents; in each case the
`patient and equipment survived, but the
`accident precipitated an angina attack
`in one subject. One of our subjects,
`a nervous individual, accidentally vio-
`lated a traffic law while equipped with
`the unit and was stopped by the police.
`The story has an unhappy ending sci-
`entifically, for the unit had run out of
`tape a few minutes earlier. However,
`this illustrates the kind of real-life situ-
`ations in which heart studies can be
`made.
`
`Research Uses
`
`We need to learn more about heart-
`beat phenomena and the mechanism of
`production of certain types of electro-
`cardiograms, especially under conditions
`not measurable by traditional methods.
`An isolated heart beats very regularly,
`and all pulse times are equal. Dissected-
`out parts of suitable hearts beat by
`themselves at steady rates characteristic
`of the heart region. However, when the
`heart is not isolated, outside influences
`disturb the steadiness seen in the iso-
`lated heart. Thus two individuals may
`each have an average pulse rate of 70
`per minute; then why do the two indi-
`viduals arrive at this average by entirely
`different routes? Are these variations
`truly random? What produces them? Is
`a given variability pattern characteristic
`of one individual, and does its frequen-
`cy distribution pattern change and, if
`so, why? The principle of biological
`variability is well illustrated when an
`ounce of alcohol rapidly eliminates a
`"forest" of premature systoles in the
`arrhythmiagram of one individual and
`increases them in another. The quanti-
`tative effects of nicotine, caffeine, alco-
`hol, fatigue, tension, and so on, have
`been easily measured from arrhythmia-
`grams, hence much new. pharmacolog-
`ical research can be conducted with
`these tools.: What I call pulse micro-
`structure needs detailed exploration and
`statistical analysis, possibly with both
`our recorder-analysis system and a-digi-
`tal computer. We might profitably use
`one data-reduction machine to examine
`20 OCTOBER 1961
`
`the data provided by another data-re-
`duction machine.
`In 1951 (5) I suggested that signifi-
`cant electrocardiographic changes might
`occur during the normal active day of
`a clinically normal individual. We now
`have good reason to feel that changes
`of considerable magnitude do occur in
`normal people, and we propose use of
`the electrocardiocorder to better under-
`stand the correlation of heart activity
`with eating, exercise, sexual and other
`emotional activity, fatigue, sleep, and
`so on.
`The recorder-analyzer combination
`might be adapted for the study of physi-
`ological phenomena other than those of
`the heart. Some physiological tests al-
`ready provide data which have been
`"integrated" over a period of time, so
`that little would be gained by continu-
`ous recording. This is illustrated by a
`single test for sugar in the urine. If
`such a test is negative, one can say with
`reasonable assurance that sugar was not
`produced by
`the kidney during
`the
`several-hour period of filling the blad-
`der. Here one can extrapolate back-
`wards with some safety. On the other
`hand, the usual electrocardiogram or
`electroencephalogram is a statistically
`.insignificant sample of what has oc-
`curred over a period of several hours.
`Hence, I suggest that suitable physiolog-
`ical phenomena be recorded at the site
`of occurrence in such a way as to pro-
`
`vide the physical freedom necessary for
`'normal daily activity. The electrocardio-
`corder can be made into an electroen-
`cephalocorder to free a brain-test subject
`from his radio-receiver environment,
`and it should be possible to design suit-
`able analyzers.
`
`The Future
`
`When I speak of "full freedom"
`through the elimination of wires, re-
`stricted locations, electronic baggage,
`and radio interference I mean freedom
`within the limits of electronic and me-
`chanical performance. Thus, there will
`always be room for improvement of the
`equipment, but, basically, "full free-
`dom" means freedom to make long,
`continuous
`records of physiological
`phenomena as close as possible to the
`geographic site of occurrence. Thus the
`future—and this development may not
`be remote, in view of the present in-
`creasing interest in medical electronics
`—will see human beings and other
`animals of many types "wired for re-
`search," with numerous little boxes pil-
`ing up information about body function.
`Numerous physiological variables will
`be recorded in one over-all portable
`recording system and coded into one
`record for later study by more sophisti-
`cated analyzers than those described
`here.
`
`Fig. 9. Frames from a moving picture of an AVSEP pattern, showing an attack of
`angina pectoris in an individual doing forbidden heavy work.
`
`1219
`
`6 of 7
`
`

`
`116
`Summary
`
`I have proposed that orthodox electro-
`cardiography be implemented, both for
`research and medical purposes, by the
`use of long-period, continuous recording
`of heart potentials with a portable, self-
`contained
`instrument—the electrocar-
`diocorder together with semiautomatic
`methods for the rapid analysis of the
`resulting voluminous data. An electronic
`system to make this concept practical
`has been developed in our laboratory
`and typical results are described in this
`article.
`
`References and Notes
`1. J. A. Gengerelli and N. J. Holter, Proc. Soc.
`Exptl. Biol. Med. 46, 532 (1941); 49, 220
`(1942).
`2. J. A. Gengerelli, ibid. 51, 189 (1942).
`3. ---------, ibid. 52, 189 (1943); -------- and V.
`Kallejian, J. Psychol. 29, 263 (1950); J. A.
`Gengerelli, /. Сотр. and Physiol. Psychol.
`44, 535 (1951); ------— and J. W. Cullen,
`ibid. 47, 204 (1954).
`4. N. J. Holter and J. A. Gengerelli, Rocky
`Mt. Med. J. (Sept. 1949); Proc. AAAS,
`117th Annual Meeting, Cleveland (1950);
`W. R. Glasscock and N. J. Holter, Elec
`tronics (Aug. 1952).
`5. N. J. Holter, Ann. N.Y. Acad. Set. 65, 913
`(1957).
`6. J. A. Gengerelli, N. J. Holter, W. R. Glass-
`cock, J. Psychol. 52, 317 (1961).
`7. H. F. Maclnnis, Can. Med. Assoc. J. 70, 574
`(1954).
`8. N. J. Holter, Progr. Kept., Public Health
`Service research grant No. H-2614(C2) (1959).
`
`9. W. R. Glasscock has made major contribu-
`tions to the mechanical and electronic design
`of these instruments. Electronics technician
`Frank Theobald has given valuable assistance
`in this study. This work was supported, in
`part, b> Public Health Service grant No. H-
`2614. The names Radioelectrocardiograph.
`Electrocardiocaster, Electrocardiocorder, AV~
`SEP, and Arrhythmiagraph are Holter Research
`Foundation trademarks.:
`10. N. J. Holter and W. R. Glasscock, Proc.
`Montana Acad. Sci. 18(1958), 35 (1958).
`11. R. F. Abarquez el al, Circulation 22, 1060
`(1960); C. E. Pruett and J. N. Shellabarger,
`Naval Research Revs. (Feb. 1961); D. A.
`Rowley et al., Am. Heart J. (Aug. 1961);
`J. S. Gilson and R. B. Grifflng, Am. J.
`Cardiol. 8, 212 (1961).
`12. H. A. Lindberg et al., A.M.A. Arch. Intern.
`Med. 106, 628 (1960).
`,
`13. E. Corday, private communication.
`14. J. S. Gilson, N. 3. Holter, W. R. Glasscock,
`Proc. American Heart Association, 34th An
`nual Meeting, Miami Beach (1961).
`
`7 of 7