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Europace (2005) 7, 28e33
REVIEW ARTICLE
Early history of the pre-excitation syndrome
Sam Hanon, Michael Shapiro, Paul Schweitzer)
Submitted 16 July 2003, and accepted after revision 15 September 2004
KEYWORDS
WPW syndrome;
pre-excitation
syndrome;
early history;
accessory connections
Abstract This brief review discusses the interesting early history of the preexcitation syndrome. In 1913 Cohn and Fraser published the first patient with
a short P-R interval, wide QRS complexes, and paroxysmal tachycardia. This was
followed by other cases of pre-excitation syndrome, all of which were considered
to be due to bundle branch blocks. In 1930 Wolff, Parkinson, and White reported 11
patients with the syndrome, which came to bear their name. Two years later,
Holzmann and Scherf suggested bypass tracts as the most likely mechanism of preexcitation syndrome. In 1942, Wood et al. documented the first accessory
connection at autopsy. Despite these early studies supporting the bypass theory,
the quest for alternative mechanisms continued until the 1970s when electrophysiological studies and surgical therapy confirmed accessory connections as the
mechanism of pre-excitation syndrome.
ª 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights
reserved.
Introduction
Pre-excitation syndrome has an interesting and
remarkable history. Early descriptions of this phenomenon date back more than 80 years to the first
isolated cases reported by Wilson [1], Wedd [2],
and Hamburger [3]. The more comprehensive description by Wolff, Parkinson, and White in 1930
brought this syndrome to prominence. Wolff and
coworkers [4] reported 11 mostly young, healthy
) Corresponding author. Tel.: C1 212 420 2416; fax: C1 212
420 2406.
E-mail address: [email protected] (P. Schweitzer).
subjects with a short P-R interval, wide QRS
complexes, and paroxysms of tachycardia. This
pattern, which later came to be known as the
WolffeParkinsoneWhite (WPW) syndrome, was the
first characterized pre-excitation syndrome.
In 1944, Ohnell [5] introduced the term preexcitation syndrome for an electrocardiogram
(ECG) manifested by a short P-R interval and a wide
QRS complex, regardless of the presence or absence of tachycardia. That same year, Segers and
coworkers proposed the term delta wave for the
initial slurred component of the QRS complex [6].
The aim of this review is to discuss some of
the notable historical aspects of pre-excitation
1099-5129/$30 ª 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.eupc.2004.09.005
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The Heart Institute, Beth Israel Medical Center, University Hospital and Manhattan
Campus for the Albert Einstein College of Medicine, Department of Cardiology,
1st Avenue at 16th Street, Dazian Building, 11th Floor, NY 10003, USA
Early history of the pre-excitation syndrome
syndrome, specifically the early misconceptions
regarding the basis of the electrocardiographic
abnormalities and arrhythmias associated with this
condition [1,2,7,8].
Early reports of pre-excitation
syndrome
Anatomical substrate of pre-excitation
syndrome
Kent dramatically advanced the understanding of
intracardiac conduction with his study of auriculoventricular (A-V) muscular connections. Kent proposed that there were multiple muscular links,
which crossed the A-V groove. Specifically, he
focused attention on a muscular connection between the right auricle and right ventricle at the
lateral right border of the heart [9]. Thomas Lewis,
who in 1925 did not find adequate anatomical or
physiological evidence to support this hypothesis
[10], questioned the role of ‘‘Kent’s bundle’’ in A-V
conduction. Despite this scepticism, the notion
that these bundles might play a role in A-V
conduction continued to be studied [11,12]. Fifty
years after Kent’s first work on the subject was
published, Mahaim stated, ‘‘If conduction by
Kent’s fibres is accepted (and it has still not been
proved that these fibres regularly exist, and one
can even doubt it), it should be regarded as an
accessory form of conduction: para-specific conduction’’ [13].
A significant development occurred in 1942
when Wood and coworkers [14] reported the first
histological proof of muscular connections between the right auricle and the right ventricle in
a human autopsy specimen. The patient was a 16year-old boy with episodes of paroxysmal tachycardia. Three years after the initial presentation,
he presented with palpitations, severe substernal
distress, and a heart rate over 150 beats per
minute (bpm). The patient died 2 h later after
drinking cold water. Autopsy revealed a normal
heart with three muscular A-V connections between the right atrium and ventricle.
In the subsequent years, accessory connections
were documented in series of patients with preexcitation syndromes [15e18]. Despite these findings, Lev [15] in 1966 stated, ‘‘the anatomical base
of the WPW syndrome is today unknown’’ and seven
years later, ‘‘one must not overlook, however, the
concept of Sherf and James of a physiological
bypass within the conduction system’’ [16]. In
other words, according to Lev, accessory connections were not the only means of pre-excitation.
The mechanism of pre-excitation
syndrome
Interestingly, two groups working independently in
the early 1930s proposed that the muscular connections described by Kent might be used to
conduct an auricular impulse to the ventricle.
Holzmann and Scherf [11], in 1932, were the first
Figure 1 Rhythm strip showing three pre-excited beats followed by a ventricular premature, which initiates a run of
narrow complex tachycardia (from Cohn and Fraser [7] with permission).
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Cohn and Fraser [7] in essence reported the first
case of pre-excitation syndrome in 1913. These
authors presented two patients with paroxysmal
tachycardia, terminated by vagal stimulation. In
the first patient, the resting ECG showed right
bundle branch block (RBBB) and the second patient’s ECG revealed a slurring of the initial portion
of the QRS complex (Fig. 1). In 1915, Wilson [1]
published a patient with pre-excitation and episodes of supraventricular tachycardia, which were
terminated by the Valsalva manoeuver. This patient also had spontaneous and atropine induced
AV junctional rhythm. These two reports [1,7]
were followed by additional cases of pre-excitation syndrome in 1921 and 1926, all of which were
classified as bundle branch block (BBB) [2,8].
29
30
Figure 2 Early, accurate hypothesis on the mechanism
of pre-excitation (from Wolferth and Wood [12] with
permission).
Holzmann and Scherf, in addition to their
pioneering theory on the mechanism of pre-excitation, also discussed the possibility of an ‘‘excitable centre’’ [11]. A properly timed atrial
contraction could initiate a ventricular impulse
from an excitable ventricular centre, thereby
causing a short P-R interval and a delta wave.
Sodi-Palares offered a similar mechanism in which
electrotonus from the depolarized atrium triggers
a ventricular impulse [20]. Further, according to
Prinzmetal et al., a short P-R interval and a delta
wave could be due to an accelerated atrial impulse
stimulating the summit of the intraventricular
septum [21]. The initial slurring of the QRS complex during stimulation of the intraventricular
septum in patients undergoing right heart catheterization supported this concept [22]. Finally
Sherf and James developed the ‘‘synchronized
sino-ventricular conduction’’ theory [23]. According to these authors, an impulse originating in the
posterior intranodal bundle preferentially activates the ventricle and causes pre-excitation.
Substantial support for the accessory pathway
theorists arrived in 1942 when Butterworth and
Poindexter published the first experimental animal
study using an ‘‘electric bypass between the
atrium and ventricle’’ [24]. The investigators were
able experimentally to generate tracings similar to
the previously described WPW syndrome.
Thus, A-V bypass tracts as the mechanism of
pre-excitation was not generally accepted until
the 1970s. A major advance was achieved when
Durrer and Roos performed epicardial excitation
mapping on a patient with the WPW syndrome
[25]. Mapping was performed on a 21-year-old
woman during surgery for a large atrial septal
defect. The right ventricle was activated earliest
as a result of conduction of the atrial impulse
through a connection near the right lateral atrioventricular sulcus. This finding laid the foundation
for later invasive electrophysiological studies
[26e29], which not only clarified the underlying abnormality but also confirmed reentry as the
mechanism of paroxysmal tachycardias in the WPW
syndrome. These studies also became the basis for
the surgical and catheter ablation therapy of the
pre-excitation syndrome. It is most likely that
James, in 1976, more than 80 years after Kent’s
original publications, wrote the last article challenging accessory connection as the mechanism of
pre-excitation syndrome [30].
Another interesting aspect of the history of preexcitation syndrome is the role of accessory connections within the specialized conduction system
(nodoventricular, nodofascicular, and fasciculoventricular connections). According to Ferrer,
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to publish this theory. They expounded on the
likelihood that an accessory A-V connection was
the most likely mechanism of pre-excitation in the
syndrome described by Wolff, Parkinson, and
White. Wolferth and Wood [12], whose article
was in press at the time of the Holzmann and
Scherf publication, also put forward this theory
and further, speculated that the electrocardiographic findings were due to conduction over the
‘‘bundle of Kent’’ as well as the bundle of His
(Fig. 2). Wolferth and Wood further detailed the
abnormal ECG features of this syndrome. They
pointed out that the interval from the beginning of
the P wave to the end of the QRS was within
normal limits. Thus, though the P-R interval was
shortened, the QRS was widened to a degree that
allows the total P-QRS segment to remain of
normal duration. Moreover, if the P-R lengthens,
the QRS can be expected to shorten to the same
extent. For this reason, the authors disputed the
idea that the QRS abnormality represented a bundle branch block. They stated that ‘‘the abnormality of the QRS complex consists, not of a block
or delay, but of an actual early arrival in the
ventricular muscle of the impulse from the auricle’’ [12].
Despite anatomical and electrophysiological evidence of accessory connections, search for alternative mechanisms continued. In 1964, Scherf and
Cohen [19] reviewed the literature and found more
than 60 possible mechanisms of pre-excitation
‘‘most of [which] have no support and some are
fantastic’’. In addition to the BBB mechanism
initially suspected by Wolff, Parkinson, and White
and challenged from the beginning, the more
common suggestions were the ‘‘excitable centre’’
theory and the concept of accelerated conduction [19].
S. Hanon et al.
Early history of the pre-excitation syndrome
WPW syndrome could either be due to a Kent
bundle or a combination of James’ posterior intranodal tract with Mahaim fibres [31]. Lev et al.
documented this combination in a patient with
pre-excitation syndrome who subsequently developed complete A-V block [32]. The role of the
Mahaim fibres was also considered in patients with
accessory pathways and decremental conduction
properties. However, electrophysiological studies
and surgical results in the 1980s and 1990s challenged the participation of Mahaim fibres in the
pre-excitation syndrome [33,34].
Wide QRS complex tachycardia in
WolffeParkinsoneWhite syndrome
case was of a 4-year-old boy with palpitations and
difficulty breathing. The electrocardiogram revealed paroxysms of wide QRS complex tachycardia with a short P-R interval. Dr. Hamburger made
a presumptive diagnosis of auricular tachycardia
with right bundle branch block due to a respiratory
infection [3].
In 1941, Levine and Beeson reported three
patients with paroxysms of tachycardia classified
by the authors as ‘‘ventricular tachycardia’’ [35].
All of their patients had pre-excitation and irregular wide QRS complex tachycardia, most likely
due to atrial fibrillation. The most notable patient
was a 36-year-old steamfitter who ‘‘while lifting
a heavy box, suddenly became conscious of
a ‘‘knock’’ in the centre of his chest’’. The initial
ECG showed ‘‘ventricular tachycardia,’’ which was
treated with 0.8 mg of oral digitalis (Fig. 3). After
restoration of sinus rhythm the ECG showed a short
P-R interval and bundle branch block, with an
infarct pattern. The patient was hospitalized for
six weeks with the diagnosis of acute myocardial
infarction. However, according to Levine, who saw
the patient two months later, the diagnosis of
Figure 3 Four leads showing irregular rhythm with wide and narrow QRS complexes classified as ‘‘ventricular
tachycardia’’ and inferior pseudoinfarct (from Levine and Beeson [35] with permission).
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Studies have repeatedly shown that wide QRS
tachycardias are seen in patients with the WPW
syndrome. Early reports diagnosed these rhythms
as ventricular tachycardia.
In 1929, Hamburger reviewed four cases of
‘‘Intraventricular block showing some interesting
and unusual features’’ [3]. The ‘‘most interesting’’
31
32
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
Conclusion
In summary, pre-excitation syndrome has a long
and interesting history. This ECG abnormality was
originally classified as BBB. Two years after Wolff
and coworker’s classic article, Holzmann and
Scherf and then Wolferth and Wood suggested
accessory connection as its cause. In 1942, Wood
et al. first reported the human anatomical substrate of the pre-excitation syndrome. However,
even after documentation of accessory pathways, the search for alternative mechanisms
continued. Finally, electrophysiological studies
and ablative surgical therapy confirmed accessory
A-V connections as the underlying mechanism of
pre-excitation syndrome and put the debate to
rest.
[15]
[16]
[17]
[18]
[19]
[20]
[21]
References
[22]
[1] Wilson FN. A case in which the vagus influenced the form of
the ventricular complex of the electrocardiogram. Arch
Intern Med 1915;16:1008e27.
[2] Wedd AM. Paroxysmal tachycardia with reference to
nomotopic tachycardia and the role of the extrinsic
cardiac nerves. Arch Intern Med 1921;27:571e90.
[3] Hamburger WW. Bundle branch block. Four cases of
intraventricular block showing some interesting and unusual clinical features. Med Clin North Am 1929;13:
343e62.
[4] Wolff L, Parkinson J, White PD. Bundle-branch block with
short P-R interval in healthy young people prone to
paroxysmal tachycardia. Am Heart J 1930;5:685e704.
[5] Ohnell RF. Pre-excitation, a cardiac abnormality. Acta Med
Scand 1944;52(Suppl.):1e167.
[6] Segers M, Lequime J, Denolin H. L’activation ventriculaire
precoce de certain coeurs hyperexcitables. Etude de
[23]
[24]
[25]
[26]
[27]
l’onde de l’electrocardiogramme. Cardiologia 1944;8:
113e67.
Cohn AE, Fraser FR. Paroxysmal tachycardia and the effect
of stimulation of the vagus nerve by pressure. Heart
1913e14;5:93e105.
Curtis CW, Hamilton CK. Electrocardiographic changes in
rheumatic fever. Lancet 1926;807e9.
Kent AFS. Researches on the structure and function of the
mammalian heart. J Physiol 1893;14:233e54.
Lewis T. The mechanism and graphic registration of
the heart beat. London: Shaw and Sons Ltd; 1925.
p. 13.
Holzmann M, Scherf D. Uber Elektrokardiogramme mit
verkurzter Vorhof-Kammerdiztanz und positiven P-Zacken.
Z Klin Med 1932;121:404e23.
Wolferth CC, Wood FC. The mechanism of production of
short P-R interval and prolonged QRS complexes in
patients with presumably undamaged hearts; hypothesis
of an accessory pathway of auriculo-ventricular conduction (bundle of Kent). Am Heart J 1933;8:297e311.
Mahaim I. Kent’s fibers and the A-V paraspecific conduction through the upper connections of the bundle of HisTawara. Am Heart J 1947;33:651e3.
Wood FC, Wolferth CC, Geckeler GD. Histologic demonstration of accessory muscular connections between
auricle and ventricle in a case of short P-R interval
and prolonged QRS complex. Am Heart J 1943;25:454e62.
Lev M. Anatomic consideration of anomalous AV pathways.
In: Dreifus LS, Likoff W, editors. Mechanisms and therapy
of cardiac arrhythmias. New York: Grune & Stratton; 1966.
p. 665e70.
Lev M. Anatomic considerations of anomalous AV pathways. In: Dreyfus LS, Likoff W, editors. Cardiac arrhythmias. New York: Grune & Stratton; 1973. p. 417e9.
Becker AE. Morphologic characteristics of arrhythmias. In:
Brugada P, Wellens HJJ, editors. Cardiac arrhythmias.
Where to go from here? Futura Publishing Co: Mount Kisco;
1987. p. 1e26.
James TN. Morphology of the human atrioventricular node
with remarks pertinent to its electrophysiology. Am Heart
J 1961;62:756e71.
Scherf D, Cohen J. The atrioventricular node and selected
cardiac arrhythmias. New York: Grune & Stratton; 1964. p.
372e447.
Sodi-Palares D, Calder RM. New bases of electrocardiography. St Louis: Mosby; 1956. p. 596e616.
Prinzmetal M, Kennamer R, Corday E, et al. Accelerated
conduction. The WolffeParkinsoneWhite syndrome and
related conditions. New York: Grune & Stratton; 1952.
Kossman C, Berger AR, Rader B, et al. Anomalous
atrioventricular excitation produced by catheterization
of normal human hearts. Circulation 1950;1:902e9.
Sherf L, James TN. New electrocardiographic concept:
synchronized sinoventricular conduction. Chest 1969;55:
127e40.
Butterworth JS, Poindexter CA. Short P-R interval associated with a prolonged QRS complex. A clinical and
experimental study. Arch Intern Med 69:437e45.
Durrer D, Roos JP. Epicardial excitation of the ventricles in
a patient with the WolffeParkinsoneWhite Syndrome
(type B). Circulation 1967;35:15e21.
Durrer D, Schuilenburg RM, Wellens HJJ. Pre-excitation
revisited. Am J Cardiol 1970;25:690e7.
Burchell HB, Frye RL, Anderson MW, et al. Atrioventricular
and ventriculo-atrial excitation in WolffeParkinsoneWhite
syndrome (type B): temporary ablation at surgery. Circulation 1967;36:663e72.
Downloaded from http://europace.oxfordjournals.org/ by guest on April 16, 2014
myocardial infarction was erroneous. He still
believed however, that the clinical syndrome could
be attributed to ‘‘an attack of ventricular tachycardia’’ [35]. The case was recognized for its
similarity to those described by Wolff, Parkinson,
and White, in that the young steamfitter was free
of organic heart disease, yet a ventricular origin
for the arrhythmias was assumed.
These wide complex rhythms initially thought to
be ventricular in origin are in fact, the result of
a supraventricular rhythm inducing a ventricular
complex that is broad and slurred. Additional
reports detailing ventricular tachycardia and fibrillation in WPW syndrome abound [3,35e41]. However, as understanding of the condition advanced,
retrospective review of the rhythms reported as
ventricular in origin called these diagnoses into
question [42].
S. Hanon et al.
Early history of the pre-excitation syndrome
[35] Levine SA, Beeson PB. The WolffeParkinsoneWhite syndrome with paroxysms of ventricular tachycardia. Am
Heart J 1941;22:401e9.
[36] Gilchrist AR. Paroxysmal ventricular tachycardia. A report
of five cases. Am Heart J 1926;1:546e63.
[37] Schiebler GL, Wood RS, Johnson WS. Paroxysmal pseudoventricular tachycardia in an infant with the Wolff
Parkinson White syndrome. J Florida Med Ass 1963;49:805.
[38] Yahini JH, Zahavi I, Neufeld HN. Paroxysmal atrial
fibrillation in the Wolff Parkinson White syndrome simulating ventricular tachycardia. Am J Cardiol 1964;14:248.
[39] Herrmann GR, Aotes JR, Runge TM, Hejtmancik MR.
Paroxysmal pseudoventricular tachycardia and pseudoventricular fibrillation in patients with accelerated A-V
conduction. Am Heart J 1957;53:254.
[40] Lown B, Ganong WF, Levine SA. The syndrome of short P-R
interval, normal QRS complexes and paroxysmal rapid
heart action. Circulation 1952;5:693.
[41] Hejtmancik MR, Herrmann GR. The electrocardiographic
syndrome of short P-R interval and broad QRS complexes.
Am Heart J 1957;54:708e21.
[42] Langendorf R, Lev M, Pick R. Auricular fibrillation with
anomalous A-V excitation (WPW syndrome) imitating
ventricular paroxysmal tachycardia. Acta Cardiol 1952;
7:241.
Downloaded from http://europace.oxfordjournals.org/ by guest on April 16, 2014
[28] Cobb FR, Blumenschein SD, Sealy WC, Boineau JP,
Wagner GS, Wallace AG. Successful surgical interruption
of the bundle of Kent in a patient with WolffeParkinsone
White syndrome type A. Circulation 1968;38:1018e29.
[29] Castellanos Jr A, Agha AS, Castillo CS, et al. Ventricular
activation in the presence of WolffeParkinsoneWhite
syndrome. In: Dreifus LS, Likoff, editors. Cardiac arrhythmias. New York: Grune & Stratton; 1973. p. 457e74.
[30] James TN. Heuristic thoughts on the WolffeParkinsone
White syndrome. In: Schlant RC, Hurst JW, editors.
Advances in electrocardiography. New York: Grune &
Stratton; 1976. p. 199e217.
[31] Ferrer IM. New concept relating to pre-excitation. JAMA
1967;201:162e3.
[32] Lev M, Leffler WB, Langendorf R, et al. Anatomic finding in
a case of ventricular pre-excitation (WePeW). Circulation
1966;34:718e33.
[33] Tchou P, Lehmann MH, Jazayeri M, et al. Atriofascicular
connection or a nodoventricular Mahaim fiber? Electrophysiologic elucidation of the pathway and associated
reentrant circuit. Circulation 1988;77:837e48.
[34] Klein GJ, Guiraudon GM, Kerr CR, et al. Nodoventricular
accessory pathway: evidence for a distinct accessory
atrioventricular pathway with atrioventricular node-like
properties. J Am Coll Cardiol 1988;11:1035e40.
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