Author: David Geselowitz
In the modern world, electrocardiography is a medical technology that is used every day in doctors' offices, clinics, and hospitals around the world. The technology grew out of investigations beginning in the late 18th century of electrical phenomena in living systems. Nerve and muscle are electrically active, and the heart produces currents and voltages that can be recorded in what is called the electrocardiogram (ECG). In the course of the 20th century, scientists and engineers elucidated the medical significance of ECGs, set standards for recording ECGs, and helped make the technology invaluable to medical practitioners.
|1791||Luigi Galvani reports that an electric spark can cause muscle to twitch|
|1853||Hermann von Helmholtz develops the physics of the volume conductor problem|
|1856||R.A. von Kölliker and Heinrich Müller measure electric currents generated by frog heart|
|1887||A.D. Waller records a human electrocardiogram (ECG)|
|1901||Willem Einthoven describes the string galvanometer for recording an ECG|
|1905||Cambridge Scientific Instrument Company sells first commercial string galvanometer|
|1927||William Craib develops the theory of a dipole source in a sphere|
|1933||Frank Wilson relates current sources in the heart to external potentials|
|1938||The first standards for electrocardiographs are published|
|1946||Herman Burger formalizes heart vector and lead vector concepts|
|1949||Norman Holter invents an ambulatory ECG monitor|
|1953||Otto Schmitt, Richard McFee, and Ernest Frank develop vector lead systems|
|1963||G.M. Baule and Richard McFee measure the magnetic field of the heart|
|1984||Adrian van Oosterom and Thom Oostendorp publish the first version of ECGSIM|
Because heart disease, along with cancer, is at the top of the list of public health concerns, electrocardiography, which provides vital information about the functioning of a heart, is one of the most important of all medical technologies. This technology grew out of investigations beginning in the late 18th century of electrical phenomena in living systems.
Galvani to Waller
In 1791 Luigi Galvani reported his observations that an electric spark could cause the muscle of a frog leg to twitch. This report initiated the study of bioelectricity, which made great progress in the 19th century through the efforts of numerous investigators, often with ingenious experiments. It was found that muscle and nerve cells are electrically active and that electric activity propagates along muscle and nerve fibers. In a sense, the electric battery was an off-shoot of bioelectricity: Alessandro Volta suggested that a voltage arose in the path Galvani was studying due to a contact potential between dissimilar metals, and Volta went on to use this idea to invent the battery.
Since body tissues conduct electricity, currents and electric potentials (voltages) are produced in the surrounding medium. In some cases the potentials are large enough to be detected at the body surface. In the case of muscle, signals can be detected for each of the three muscle types—skeletal, smooth, and cardiac. It was realized that these signals could provide important clinical information. The electrogastrogram, for example, reflects electric activity of the stomach; the electromyogram records electric activity of skeletal muscle; and the electroencephalogram records activity of the brain as measured on the scalp. Of greatest clinical significance was the realization that the electrocardiogram provides information about the heart.
It should be pointed out that Galvani’s experiment dealt with electric stimulation of muscle, and stimulation of muscle, especially of the heart, is an important medical topic on its own. This topic, which includes the development of pacemakers and defibrillators, is outside the scope of this article.
The study of the spread of currents in body tissues is called the volume conductor problem. In 1853 Hermann von Helmholtz developed the physics of the volume conductor problem in a remarkable paper, which was later of value in understanding the electrocardiogram.
In 1856 R.A. von Kölliker and Heinrich Müller of the University of Würzburg measured the electric currents generated by a frog heart, and in 1887 Augustus D. Waller of St. Mary’s Hospital, London, was the first to record the human electrocardiogram (ECG). Waller used a sensitive detector of electricity, the Lippmann capillary electrometer. He captured a time record of the voltages by photographing the shadow of the meniscus (the top surface of the liquid in the capillary tube) on moving paper. It was immediately recognized that the ECG could be a powerful tool for learning about the function of the heart.
In 1901 Willem Einthoven, a physician and physiologist at the University of Leiden, developed the string galvanometer. It had a better sensitivity and frequency response than the capillary electrometer and was much sturdier. Using this device, Einthoven made clinical electrocardiography practical. He undertook many clinical studies, which advanced the art of interpretation of the ECG, and he performed animal experiments to aid in this understanding. Finally, he presented a theoretical framework for relating the ECG to sources in the heart, work for which he received a Nobel Prize in 1924.
A lead is a pair of electrodes in which a voltage, as recorded in an electrocardiogram, is developed. In the simplest case a lead involves two electrodes attached to the skin. The leads used by Einthoven, called limb leads, were obtained from pairs of electrodes attached at the left leg (Lead 1), the left arm (Lead 2), and the right arm (Lead 3). Einthoven recognized that these voltages were not independent, but that Lead I + Lead III = Lead II, a relationship today known as Einthoven’s law.
A lead may also involve several electrodes to which resistors are attached. One such lead used in the standard ECG recording is obtained by connecting equal resistors to the three limb electrodes and tying them together. This terminal is referred to as the Wilson central terminal. It was proposed by Frank N. Wilson of the University of Michigan, who made many outstanding contributions to electrocardiography, both clinical and theoretical.
Einthoven proposed that the heart as an electric generator acts approximately as a dipole, that is, as a pair of electrodes (electrical terminals) separated by a short distance. He regarded the electrical action of the heart and other quantities as vectors (quantities consisting of a magnitude and a direction), and proposed an analytic scheme in which three vectors form a triangle, called today the Einthoven triangle.
From Einthoven to Burger
Nerve fibers and muscle fibers are cylindrical in shape. When a fiber is active, an impulse, called the action potential, propagates along the cylinder with a given velocity. The impulse involves the membrane of the cell, which undergoes a rapid depolarization. The action potential produces currents which may be considered to arise from a dipole.
In cardiac muscle, the cells are interconnected in such a way that the muscle can be considered a syncytium (a cell-like structure with many nuclei). As activity propagates through the heart muscle (myocardium), it produces a waveform on the body surface designated the QRS complex. Excitation is followed by recovery (repolarization), which produces a T wave. These characteristic ECG forms were recognized and named by Einthoven.
In the 1920s the South African William H. Craib studied the field of muscle preparations in a spherical conductor. In a famous experiment Craib showed that the potential produced by a strip of muscle was that of a dipole. This helped validate Einthoven's idea that the heart could be regarded as a dipole, with the distance between the pair of electrodes small in comparison with the distance from the heart to the skin. Theoretical work by investigators in various countries advanced the understanding of the biological phenomena behind the ECG. For example, in the United States in 1933 Frank Wilson related current sources in the heart to external potentials, and in the Netherlands Herman C. Burger formalized the concepts of heart vector and lead vector thirteen years later.
Einthoven’s concepts led investigators to consider several problems. First, how can surface potentials be calculated given a current dipole source in a bounded-volume conductor? This is called the forward problem. Second, how can the heart dipole be estimated from skin potentials, which is known as the inverse problem. Third, how accurate is the single dipole approximation?
The investigators named above tried to put the theory on a firm physical basis, with the earliest work being done by Burger. Since there were no digital computers available, the investigators resorted to a physical analog to relate a dipole source (representing the heart) to skin potentials. The analog, called a phantom, was a surface representing the human torso. A dipole source in the heart region was energized, and potentials on the surface were measured. In this way the problem of relating skin potentials to a dipolar cardiac source was solved.
The inverse problem involved determining the characteristics of the heart dipole from voltages measured at the skin. Several investigators came up with schemes for doing this, relating the measurements made at a small number of skin electrodes to the characteristics of the dipole.
The third question is how good an approximation is the heart dipole. A definitive answer was provided in 1956 by Ernest Frank, an electrical engineer at the University of Pennsylvania. Frank built a phantom that was a plaster cast of a particular individual, which he could equip with leads and then measure electrical behavior. He found rather good agreement between the actual behavior of the heart and the behavior of a dipole source, thus validating the approach.
With the advent of electronic digital computers it became possible to solve the forward problem without the use of a phantom. The team of H. Gelernter and J. C. Swihart at IBM, and Roger C. Barr and subsequent investigators elsewhere began pioneering this approach in 1964.
Relation to cellular activity
The forward problem can be solved for a given source distribution. For many years emphasis was on the current dipole as discussed above. At the same time there was interest in relating the source distribution to cardiac cell activity. There was evidence that the wavefront separating resting heart cells from those that had undergone depolarization was a surface dipole layer. This activation layer would move through the heart during the cardiac cycle. So researchers regarded the cardiac activity as the motion of this double layer, which could be approximated as a single dipole.
Investigators studied animal hearts to try to determine the spread of activation. Many electrodes were placed in the heart and the voltage recorded. As activation passed an electrode the recorded voltage changed abruptly. Dirk Durrer of the University of Amsterdam reported results from a resuscitated human heart in 1970. In this way a picture emerged of the spread of activation in the heart. These studies also gave information about the repolarization or recovery phase of the heart, which occurs more gradually.
In 1973 Walter Miller and David Geselowitz published a simulation of the ECG which gave very good results for the normal heart as well as for several examples of infarction and ischemia. Their result has been referred to as the Miller-Geselowitz model. The heart was represented by 23 dipoles. It incorporated reported results of the sequence of activation and the cardiac action potential. A digital computer solution was used for calculating potentials at electrode sites on a realistic torso. Subsequently Adrian van Oosterom and Thom Oostendorp of the Radboud University Medical Center in Nijmegen published a more sophisticated simulation called ECGSIM in 1984.
Standards and safety
An important group advancing the state of electrocardiography was the American Heart Association (AHA) Committee on Electrocardiography. This committee proposed standards for leads, electrode placement, axis conventions, and nomenclature. Three activities of this committee were standards for electrocardiographs, for electric safety, and for computer interpretation of arrhythmias. When Hubert Pipberger, a cardiologist with the Veterans Administration in Washington, D.C., became chairman of the committee in the mid-1960s, he appointed a subcommittee of biomedical engineers to address instrumentation problems. Later engineers became full members of the committee.
The electrocardiograph is powered from the mains. Because impedance (a measure of opposition to current) is relatively small at the electrode skin interface, the electrocardiograph acts a current source driving current into the body. The key to the electric safety standard is to specify the limit on this leakage current, which has a direct path to the heart through the body.
A modest number of experiments had been performed to try to determine the threshold for causing the heart to fibrillate, which is the danger of small currents. These experiments led the committee to adopt a leakage-current limit of 10 microamperes. There had been a study in 1936 to determine safety limits for electric currents with regard to workers in the vicinity of high power lines. These studies identified the important concept of the vulnerable period, an interval during the cardiac cycle when a current pulse could cause fibrillation.
The earliest standards for electrocardiographs were published in 1938. They have been revised several times. Pipberger instituted the policy that no member of the committee could have any connection with industry. The question was raised whether the committee lacked knowledge about the design and engineering of the devices. This contingency was handled by the committee holding periodic open meetings where they presented their current thinking. Manufacturers could then provide feedback.
ECG monitoring and other topics
The ECG is monitored routinely in the operating room. It is monitored on patients in coronary care units, often with a wireless connection to the nurse’s station. With a routine ECG a rhythm strip of the order of ten seconds is recorded to detect arrhythmias. Researchers have found, however, that this duration is often inadequate. Norman Holter developed an ambulatory monitoring device, the Holter monitor, which records the ECG over a period of 24 hours to detect arrhythmias which occur more infrequently.
Systems have been developed to transmit the ECG over a telephone line to a central station where a report will be sent to the physician. If an emergency situation is detected, help can be sent to the patient. At present, the telephone transmission is activated by the patient, but schemes are under development for the patient to be continuously monitored and if a critical event is detected the transmission will be automatic.
In 1963 Gerhardt Baule and Richard McFee measured the external magnetic field resulting from cardiac activity (magnetocardiogram). David Cohen introduced use of a more sensitive magnetometer, called SQUID for Superconducting QUantum Interference Device. David Geselowitz worked out the theory for magnetic fields external to a volume conductor, and several laboratories have been exploring magnetocardiography, but clinical relevance is yet to be established.
Several investigators developed computer programs for interpretation of the ECG, including manufacturers who incorporated these programs in electrocardiographs. Interpretation of cardiac arrhythmia provides a particular challenge. The AHA Committee on Electrocardiography formed a group of experts to come up with a database in which representative ECGs were annotated to indicate the arrhythmia. This database could then be used to evaluate the performance of arrhythmia programs.
Another topic of interest is body surface mapping, where a large number of electrodes are attached to the skin to produce a map of ECG activity instant by instant during the cardiac cycle. Robert Lux used principal component analysis to determine the number of components necessary to extract the information present. A separate but related question is the number of leads necessary to extract the diagnostic information from the ECG.
A final topic is cardiac mapping. An electrode can be inserted into the heart and placed at various locations on the endocardial surface. Techniques are available for tracking the location of the electrode and displaying the electrograms. One very important application involves identifying the site of the origin of an arrhythmia, which can then be treated directly. This technique has proven to be quite successful. Studies have also been performed on the pattern of excitation waves during fibrillation to try to understand the mechanism of this phenomenon.
The development of the field of electrocardiography has been a continual collaboration between cardiologists and engineers. The result has been a painless, noninvasive technology that is today invaluable to medical care throughout the world.
References of Historical Significance
References for Further Reading
About the Author(s)
David B. Geselowitz is Professor Emeritus of Bioengineering and Medicine at the Pennsylvania State University. He is a Fellow of the IEEE, the American College of Cardiology, and the American Association for the Advancement of Science, and he is a Founding Fellow of the American Institute for Medical and Biological Engineering. He served as editor of the IEEE Transactions on Biomedical Engineering. He was elected to the National Academy of Engineering in 1989, and he received the Roger Granit Prize for contributions to bioelectromagnetism.