Willem Einthoven and the Electrocardiogram

Sukaman Lecture delivered at the 14th ASEAN Congress of Cardiology, Kuala Lumpur, Malaysia, July 19, 2002

By Homobono Calleja, MD

It gives me unparalleled pleasure to deliver a lecture in memory of a very good friend and golfmate. Dr. Sukaman fathered the ASEAN Federation of Cardiology. If he were alive today I am sure he would be proud and most pleased to see that the Federation is robust, vibrant, and healthy.

    My lecture is entitled Willem Einthoven and the Electrocardiogram. The rationale for this title arises from two interconnecting events more than a century apart:

    First, Willem Einthoven had his placental roots in the Dutch East Indies, now Indonesia, an original member of the Association of Southeast Asian Nations (ASEAN).

    Second, by 2003 the electrocardiogram will be 100 years old since its introduction by Einthoven.

    Another reason is the reality that the development and benefits of electrocardiography crossed national borders. In the words of the German poet and novelist Goethe, "science and art belong to the world and before them vanish the borders of nationality." Truly, medicine is science and art, and the string galvanometer discovered by Willem Einthoven in 1900 serves all of mankind without boundaries.

From Electricity to Electrocardiography1-4

    It may be said that without electricity there can be no electrocardiography. Hence, the discovery of electricity by no less than three physicians during the Renaissance led to electrocardiography.

• William Gilbert (1540-1603), English physician, discovers static electricity. Electricity comes from the Greek word elektron.

• Sir Thomas Browne (1605-1682), English physician, uses the word electricity for the first time.

• Luigi Galvani (1786), Italian physician- anatomist, experiments with current electricity. In 1791 he proposes the theory that animal tissues generate electricity. The galvanometer that measures the strength of small electric currents is named after him.

• Alessandro Volta (1800), Italian physicist, builds the first battery from a stack of copper and zinc plates separated by paper or cloth moistened with salt solution. He calls it the voltaic pile. The volt, a unit of electrical potential difference is named after him.

• Carlo Matteucci (1842), Italian physicist, observes electrical conduction on nerves and muscles in a frog nerve-muscle preparation.

• Albert von Kolliker and Muller (1856) discover that an exposed frog's heart produces electric current with each beat.

• Gabriel Lippmann (1872) introduces the capillary electrometer to record potential variations.

• John Sanderson and FJ Page (1878) using capillary electrometer record for the first time currents from the heart.

• Augustus Desire Waller (1887), English physiologist, records the first electrocardiogram (ECG) from a human heart with the capillary electrometer. He introduces the term "electrocardiogram."

• Willem Einthoven records the ECG from a Lippmann's capillary electrometer in 1895 and later develops the string galvanometer in 1900. He describes the human ECG recorded from his string galvanometer in 1903. Einthoven receives the Nobel prize for physiology in 1924.

Einthoven and His Electrocardiograph1,3-9

"Honors were to him a smaller recompense

than was the knowledge of the benefits which

his long and arduous work had conferred upon

his fellowmen."

- Sir Thomas Lewis

Willem Einthoven was born in May 1860 in Semarang, Java. Ten years later, his family moved to the Netherlands; he studied at the University of Utrecht where he received his doctor's degree in 1885 at the age of 25. In 1886 he was appointed Professor of Physiology at the University of Leiden. He developed the string galvanometer and gave a preliminary report in 1901 describing the new machine. In 1903, his paper "The galvanometric registration of the human electrocardiogram, likewise a review of the use of the capillary electrometer in physiology" was published. The first paragraph reads: "Up to present, the human electrocardiogram discovered by Augustus D. Waller could be recorded only by the capillary electrometer. Simple inspection of the curve by this instrument results in an entirely fallacious representation of the variation of the potential. If one desires accurate values of the latter, the form of the registered curve must be corrected for the size of the capillary tube, the degree of magnification and the speed of the photosensitive plate. By this method one arrives at the construction of a new curve, the outline of which actually represents the variations of the potential."

    He presents a recording of lead I by the capillary electrometer from patient vdW and the corrected curve. He describes 6 tracings recorded by his string galvanometer and cites the advantages of the new instrument (Table 1). The photographic plate moves at 25 mm/sec equivalent to an abscissa of 1 mm or 0.04 sec and the tension of the filament is adjusted to give a deflection of 1 mm to 10-4 volt of electromotive force. The original string galvanometer recording machine weighed 600 lbs and needed 5 men to operate it, while current editions of portable electrocardiograph weigh 5-8 lbs.

    Einthoven used the ECG not only to study cardiac physiology but saw with a vision of Jules Verne its wide application in clinical cardiology. The galvanometer located in his laboratory at Leiden was connected by telephone to the clinic at the Academic Hospital, which was more than a mile away, enabled him to transmit excellent ECG tracings. In the early 1920s his laboratory at Leiden was closed on Fridays because of experimental wireless transmissions from Dutch East Indies by his son. Einthoven studied other physiologic parameters by correlating ECG with pulse tracings and records of cardiac sounds and murmurs.

    The original letters used by Einthoven of the ECG taken with a refined Lippmann capillary electrometer were ABCD for four deflections designated as follows: A indicated atrial activity, B for first downward deflection of the ventricles, C for upward deflection of the ventricles and D for ventricular repolarization. Einthoven used a mathematically derived formula to correct the deflections and substituted the letters PQRST and later in 1912 he added letter U as we know them today. Obviously, Einthoven adapted the system of Descartes, French philosopher, mathematician, and scientist (1596-1620), who developed analytical geometry and used P and Q to indicate points on the curves.

    In 1913 Einthoven, Fahr, and de Waart devised the equilateral triangle to study the electromotive forces of the heart. The apices of the triangle are at the acromial processes of the scapulae and at the pubic region. The triangle lies in the frontal plane of the body. The electromotive force of the heart is mathematically equivalent to a single dipole, which lies at the center of the triangle. The apices of the triangle are equidistant from the dipole.

    The following Einthoven postulates are basic assumptions of the equilateral triangle hypothesis:9

• The dipole-the heart is a single dipole at any given moment of the cardiac cycle representing the electromotive force generated by the heart.

• The electrical center-the electrical center of the heart is at the center of the dipole which coincides with the center of the triangle.

• The conducting medium-from the electrical standpoint the triangle may be conceived as a homogeneous plane of conducting materials-bones, muscles, etc.

    Einthoven arranged the bipolar connections for leads I, II, III so that all the deflections are positive.9 Hence lead I is positive in the left arm (LA) and negative in the right arm (RA); lead II is positive in the left leg (LL) and negative in the right arm (RA); lead III is positive in the left leg (LL) and negative in the left arm (LA). This lead arrangement results in lead II being equal to the sum of leads I and III. The electrical axis of the QRS was plotted as the resultant vector from leads I and III. The following equation shows lead I plus lead III equals lead II:

Lead I + Lead III = Lead II

substitute: (LA - RA) + (LL - LA) = LL - RA

cancel : (LA - RA) + (LL - LA) = LL - RA

therefore : LL - RA = LL - RA

Anatomy of Impulse Generation and Conduction10

    The introduction of the electrocardiogram was accompanied by discoveries of the components of the human impulse generator and conduction system by multinational investigators. It is interesting to note that the discovery dates of the various parts of the system are in reverse sequence of the normal generation and conduction of the electrical impulse of the heart (Table 2).

    As early as 1839 Jan Evangelista Purkinje (Czech) described the muscle fibers connecting the His bundle with the ventricular musculature now known as the Purkinje fibers. Wilhelm His the Younger (Swiss) described the muscular connection between the atria and ventricles in 1893. Tawara (Japanese) working with Aschoff in Germany identified the A-V node, His bundle and Purkinje fibers in 1906. Keith and Flack (English) in 1907 followed with their description of the sinus node. Finally in 1910 Sir Thomas Lewis identified the sinus node as the pacemaker of the heart in mammalian hearts.11,12

    The atrial internodal pathways of the human heart were identified by Wenckebach (1907), Thorel (1909) and James (1963) separately. In 1907 Wenckebach described the myocardial bundle leaving the sinus node and curving behind the superior vena cava to descend to the A-V node. This is designated as the middle internodal tract. Thorel in 1909 described a posterior pathway arising from the sinus node proceeding to the crista terminalis to enter the Eustachian valve and cross the coronary sinus to reach the A-V node. In 1916 Bachmann described the interatrial bundle that delivers the impulse from the sinus node to the left atrium without being aware of a branch going to the A-V node. Finally, James in 1963 discovered a branch of the Bachmann bundle descending back and down the interatrial septum to reach the crest of the A-V node. He called this the anterior internodal tract while the tracts of Thorel and Wenckebach are designated the posterior and middle internodal tract respectively (Table 3).

Transmembrane Action Potential and Clinical Electrocardiogram9

    In 1945 Wilson and in 1968 Hecht separately suggested that the ECG can be considered as the second derivative curve of the transmembrane action potential (TAP)9. Even earlier than Hecht, Hoffman and Cranefield13 in 1960 has already correlated the consecutive phases of TAP to QRS, R-ST and T of the ECG. Similarly Ashman and Hull14 suggested V5 or V6 as the algebraic sum of the TAP of subendocardium minus that of the subepicardium in 1941. The corresponding events in the TAP and the V5 or V6 ECG are as follows: phase O of TAP is R of ECG, 1 is J, 2 is RS-T segment, 3 is T wave and duration of TAP is QT interval respectively (Table 4). Sodi-Pallares et al.15 using this correspondence of TAP with left sided precordial ECG introduced polyparametric intepretation of the ECG in 1970.

Eponyms in Clinical Electrocardiography

    Wenckebach KF (1899,1906)16 describes type I second degree A-V block with gradual prolongation of the a-c interval of the jugular pulse followed by loss of arterial pulse and type II second degree heart block where ventricular beats are dropped without preceding a-c interval prolongation. In 1906 he identifies these heart blocks in the ECG record.

    Lewis T (1910)11,12 identifies the SA node as the site of origin of the heart beat and describes the ECG of atrial fibrillation. In 1912 he introduces the Lewis Index to diagnose left and right ventricular hypertrophy.

Einthoven used the ECG not only to study cardiac physiology but saw with a vision of Jules Verne its wide application in clinical cardiology. The galvanometer located in his laboratory at Leiden was connected by telephone to the clinic at the Academic Hospital, which was more than a mile away, enable him to transmit excellent ECG tracings.

    Wilson FN (1920) establishes the scientific basis of the ECG and identifies abnormalities in the ECG waveforms. In 1932 he introduces the unipolar (v) limb leads using a central terminal with resistance of 5000 ohms in each limb connection and in 1934 the unipolar precordial leads. In 1942 Wilson corrects the error in designating RBBB and LBBB.5,17,18

• Oppenheimer BS, Rothschild MA (1917) describe the electrocardiographic changes in myocardial infarction.19

• Mobitz W (1924) describes type I and type II second degree heart block.16

• Craib WH (1927) introduces the "doublet" hypothesis or dipole theory of depolarization.20

• Wolff L, Parkinson J, White PD (1930) describe the WPW syndrome as "bundle branch block with short P-R interval in healthy young people prone to paroxysmal tachycardia."21

• Master AM (1935) introduces the two step test to diagnose coronary insufficiency.22

• Katz LN, Wachtel H (1937) identify the large biphasic RS in V2-4 in ventricular septal defect.23

• Bayley RH (1939) introduces the triaxial reference system by transposing the sides of the Einthoven's triangle to bisect each other at the center.9

• Goldberger E (1942) modifies Wilson's central terminal by removing the resistances and detaching the connection between the central terminal and the extremity explored hence augmenting (a) the deflection.24

• Ohnell RF (1944) introduces the term "preexcitation" to include all cases of short P-R interval, anomalous QRS complex and/or their anatomic substrates.25

• Sokolow M, Lyon TP (1949) introduce the Sokolow-Lyon Index for left ventricular hypertrophy.26

• Lown B, Ganong WF, Levine SA (1952) describe the syndrome of short P-R interval, normal QRS and paroxysmal tachycardia (Lown-Ganong-Levine syndrome).27

• Cabrera E., Monroy Jr (1952) introduce the physiologic, clinical and electrocardiographic data for systolic and diastolic overloading.28

• Macruz R (1957) introduces the Macruz Index for diagnosis of atrial enlargement.29

• Jervell A, Lange-Nielsen F (1957) describe prolonged QT interval, congenital deafness and syncope (Jervell-Lange-Nielsen syndrome).30 Romano C, Ward OC (1963) separately describe prolonged QT interval and syncope without deafness (Romano-Ward syndrome).31,32

• Rosenbaum M (1968) describes the ECG diagnosis of anterior and posterior hemiblocks.33

• Romhilt DW, Estes EH (1968) introduce a point system (Romhilt-Estes Score) for diagnosis of left ventricular hypertrophy.34

• Brugada P, Brugada J (1992) describes RBBB with ST elevation in V1-3 with no demonstrable structural defect as high risk for sudden death (Brugada syndrome).35

Epilogue

    The standard 12 lead electrocardiogram is the product of the 20th century. As a single diagnostic tool it has brought cardiology to what it is today. The importance of the portable electrocardiograph in office, hospital and home consultation is only next to the stethoscope in clinical settings. As the stethoscope is to the practicing physician in the 19th century so is the electrocardiograph to the cardiologist in our century.

    The evolution of the scientific basis of the ECG waveforms was made possible by the contributions of many investigators that pried into the generation, conduction and propagation of the electrical activity of the heart from dipole theory to lead systems and electrode placements in animal models and clinical studies. The Einthoven equilateral triangle and its standard bipolar leads I, II, III survived other proposed triangles like Burger's obtuse triangle (1946), Wilson's equilateral tetrahedron (1932), Grant isoseles tetrahedron (1950) and Arrighi's sagittal triangle (1938) to represent the cardiac vector.36-40 Even the introduction of the unipolar limb leads (V for voltage) by Wilson in 1932 did not supplant the standard bipolar limb leads. In 1934 6 unipolar chest leads from V1 to V5 and VE for ensiform cartilage placement were introduced by Wilson to replace the bipolar chest leads of earlier investigators. The electrode placements suggested by Wilson from V1 to V5 across the precordium were retained while VE was replaced by V6 at the anterior axillary line on line with V5 and these changes were included in the supplementary report written exclusively by the Committee on Precordial Leads of the American Heart Association in 1938, barely one month after the initial report of the combined panel of 6 cardiologists from Great Britain and Ireland and 5 from the United States.40 Subsequently, Goldberger in 1942 modified the Wilson central terminal by augmenting the unipolar limb leads.24 The resultant product of all these changes is the standard 12 lead ECG with the 3 bipolar limb leads of Einthoven, the 3 unipolar augmented leads of Wilson and Goldberger and the 6 unipolar chest leads of Wilson.

    Today the ECG rests on firm scientific data with important diagnostic, therapeutic and prognostic indicators. Indeed, it has no equal in the bedside diagnosis of arrhythmias. Historically, the "negativity hypothesis" of electrical phenomena in tissues of the old physiologists40 formed the basis of earlier recordings and interpretations of upright deflections as electronegative and downward deflections electropositive, hence Q and S were peaks and R nadir. With the introduction of unipolar precordial leads by Wilson18 in 1934 and Craib's dipole theory20 in 1927 the activation wave was conceived as a dipole moving through the tissues undergoing excitation with the positive pole in front and the negative pole behind, the electrically positive deflection became R and the negative deflection Q and S. At this juncture it is apropos to state a basic clinical principle that an abnormal ECG does not necessarily mean heart disease nor a normal ECG a normal heart. The ultimate test of a clinical decision is the thoroughness of evaluation of the patient's condition taking the ECG record as an integral part of decision making.

    Einthoven on the occasion of his being awarded the Nobel Prize award in 1924 paid tribute to the many investigators worldwide with special mention of the work of Sir Thomas Lewis. He said thus, "Thomas Lewis who has played a great part in the development of electrocardiography- I doubt that without his valuable contributions, I should have the privilege of standing before you today-a new chapter has been opened in the study of heart disease, not by the work of a single investigator, but of many talented men."

    Of the many talented men, Frank N. Wilson of Michigan, a student of Lewis, did much to bring the ECG to its present stature in clinical cardiology. His electrocardiographic investigations over 40 years covered a wide range of ECG subjects from theory to arrhythmias. Indeed, 90 of his publications dating from 1915 to 1954 were cited by Sodi-Pallares in his book on "New Bases of Electrocardiography" in 1956. Symbolically, Einthoven, Lewis, and Wilson make up the "equilateral triangle" who labored devotedly in times of peace and through two world wars building the massive pillars of electrocardiography. In them we take pride for telescoping in sharp focus the universality of medicine and cardiology.

    During World War II and thereafter in the fourth and fifth decades of the 20th century the Mexican Institute of Cardiology under the leadership of Sodi-Pallares in collaboration with several South American cardiologists from Argentina, Brazil, Cuba, Peru and Mexico pursued experimental and clinical investigations infusing into clinical cardiology the concepts of atrial and ventricular overload patterns, hemiblocks and polyparametric electrocardiography. To them and many more not mentioned for obvious limitations of time and space, a million thanks.