ci,

Europace (2005) 7, 28e33

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KEYWORDSWPW syndrome;pre-excitation

syndrome;early history;accessory connections

Abstract This brief review discusses the interesting early history of the pre-excitation syndrome. In 1913 Cohn and Fraser published the first patient witha short P-R interval, wide QRS complexes, and paroxysmal tachycardia. This wasfollowed by other cases of pre-excitation syndrome, all of which were consideredto be due to bundle branch blocks. In 1930 Wolff, Parkinson, and White reported 11patients with the syndrome, which came to bear their name. Two years later,Holzmann and Scherf suggested bypass tracts as the most likely mechanism of pre-excitation syndrome. In 1942, Wood et al. documented the first accessoryconnection at autopsy. Despite these early studies supporting the bypass theory,the quest for alternative mechanisms continued until the 1970s when electrophys-iological studies and surgical therapy confirmed accessory connections as themechanism of pre-excitation syndrome. 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rightsreserved.

Introduction

Pre-excitation syndrome has an interesting andremarkable history. Early descriptions of this phe-nomenon date back more than 80 years to the firstisolated cases reported by Wilson [1], Wedd [2],and Hamburger [3]. The more comprehensive de-scription by Wolff, Parkinson, and White in 1930brought this syndrome to prominence. Wolff andcoworkers [4] reported 11 mostly young, healthy

subjects with a short P-R interval, wide QRScomplexes, and paroxysms of tachycardia. Thispattern, which later came to be known as theWolffeParkinsoneWhite (WPW) syndrome, was thefirst characterized pre-excitation syndrome.

In 1944, Ohnell [5] introduced the term pre-excitation syndrome for an electrocardiogram(ECG) manifested by a short P-R interval and a wideQRS complex, regardless of the presence or ab-sence of tachycardia. That same year, Segers andcoworkers proposed the term delta wave for theinitial slurred component of the QRS complex [6].) Corresponding author. Tel.: C1 212 420 2416; fax: C1 212REVIEW ARTICLE

Early history of the pre-e

Sam Hanon, Michael Shapiro, Paul S

The Heart Institute, Beth Israel Medical Center, UnCampus for the Albert Einstein College of Medicine1st Avenue at 16th Street, Dazian Building, 11th Flo420 2406.E-mail address: pschweit@bethisraelny.org (P. Schweitzer).

1099-5129/$30 2004 The European Society of Cardiology. Publisdoi:10.1016/j.eupc.2004.09.005xcitation syndrome

hweitzer)

versity Hospital and ManhattanDepartment of Cardiology,or, NY 10003, USAThe aim of this review is to discuss some ofthe notable historical aspects of pre-excitation

hed by Elsevier Ltd. All rights reserved.

syndrome, specifically the early misconceptions that these bundles might play a role in A-V

a human autopsy specimen. The patient was a 16-

t

Early history of the pre-excitation syndrome 29

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nloaded from the first patient, the resting ECG showed rightbundle branch block (RBBB) and the second pa-tients ECG revealed a slurring of the initial portionof the QRS complex (Fig. 1). In 1915, Wilson [1]published a patient with pre-excitation and epi-sodes of supraventricular tachycardia, which wereterminated by the Valsalva manoeuver. This pa-tient also had spontaneous and atropine inducedAV junctional rhythm. These two reports [1,7]were followed by additional cases of pre-excita-tion syndrome in 1921 and 1926, all of which wereclassified as bundle branch block (BBB) [2,8].

Anatomical substrate of pre-excitationsyndrome

Kent dramatically advanced the understanding ofintracardiac conduction with his study of auriculo-ventricular (A-V) muscular connections. Kent pro-posed that there were multiple muscular links,which crossed the A-V groove. Specifically, hefocused attention on a muscular connection be-tween the right auricle and right ventricle at thelateral right border of the heart [9]. Thomas Lewis,who in 1925 did not find adequate anatomical orphysiological evidence to support this hypothesis[10], questioned the role of Kents bundle in A-Vconduction. Despite this scepticism, the notion

Figure 1 Rhythm strip showing three pre-excited beats fonarrow complex tachycardia (from Cohn and Fraser [7] wiyear-old boy with episodes of paroxysmal tachy-cardia. Three years after the initial presentation,he presented with palpitations, severe substernaldistress, and a heart rate over 150 beats perminute (bpm). The patient died 2 h later afterdrinking cold water. Autopsy revealed a normalheart with three muscular A-V connections be-tween the right atrium and ventricle.

In the subsequent years, accessory connectionswere documented in series of patients with pre-excitation syndromes [15e18]. Despite these find-ings, Lev [15] in 1966 stated, the anatomical baseof the WPW syndrome is today unknown and sevenyears later, one must not overlook, however, theconcept of Sherf and James of a physiologicalbypass within the conduction system [16]. Inother words, according to Lev, accessory connec-tions were not the only means of pre-excitation.

The mechanism of pre-excitationsyndrome

Interestingly, two groups working independently inthe early 1930s proposed that the muscular con-nections described by Kent might be used toconduct an auricular impulse to the ventricle.Holzmann and Scherf [11], in 1932, were the first

llowed by a ventricular premature, which initiates a run ofh permission).regarding the basis of the electrocardiographicabnormalities and arrhythmias associated with thiscondition [1,2,7,8].

Early reports of pre-excitationsyndrome

Cohn and Fraser [7] in essence reported the firstcase of pre-excitation syndrome in 1913. Theseauthors presented two patients with paroxysmaltachycardia, terminated by vagal stimulation. In

conduction continued to be studied [11,12]. Fiftyyears after Kents first work on the subject waspublished, Mahaim stated, If conduction byKents fibres is accepted (and it has still not beenproved that these fibres regularly exist, and onecan even doubt it), it should be regarded as anaccessory form of conduction: para-specific con-duction [13].

A significant development occurred in 1942when Wood and coworkers [14] reported the firsthistological proof of muscular connections be-tween the right auricle and the right ventricle in

30 S. Hanon et al.

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nloaded from to publish this theory. They expounded on thelikelihood that an accessory A-V connection wasthe most likely mechanism of pre-excitation in thesyndrome described by Wolff, Parkinson, andWhite. Wolferth and Wood [12], whose articlewas in press at the time of the Holzmann andScherf publication, also put forward this theoryand further, speculated that the electrocardio-graphic findings were due to conduction over thebundle of Kent as well as the bundle of His(Fig. 2). Wolferth and Wood further detailed theabnormal ECG features of this syndrome. Theypointed out that the interval from the beginning ofthe P wave to the end of the QRS was withinnormal limits. Thus, though the P-R interval wasshortened, the QRS was widened to a degree thatallows the total P-QRS segment to remain ofnormal duration. Moreover, if the P-R lengthens,the QRS can be expected to shorten to the sameextent. For this reason, the authors disputed theidea that the QRS abnormality represented a bun-dle branch block. They stated that the abnor-mality of the QRS complex consists, not of a blockor delay, but of an actual early arrival in theventricular muscle of the impulse from the auri-cle [12].

Despite anatomical and electrophysiological ev-idence of accessory connections, search for alter-native mechanisms continued. In 1964, Scherf andCohen [19] reviewed the literature and found morethan 60 possible mechanisms of pre-excitationmost of [which] have no support and some arefantastic. In addition to the BBB mechanisminitially suspected by Wolff, Parkinson, and Whiteand challenged from the beginning, the morecommon suggestions were the excitable centretheory and the concept of accelerated conduc-tion [19].

Figure 2 Early, accurate hypothesis on the mechanismof pre-excitation (from Wolferth and Wood [12] withpermission).Holzmann and Scherf, in addition to theirpioneering theory on the mechanism of pre-exci-tation, also discussed the possibility of an excit-able centre [11]. A properly timed atrialcontraction could initiate a ventricular impulsefrom an excitable ventricular centre, therebycausing a short P-R interval and a delta wave.Sodi-Palares offered a similar mechanism in whichelectrotonus from the depolarized atrium triggersa ventricular impulse [20]. Further, according toPrinzmetal et al., a short P-R interval and a deltawave could be due to an accelerated atrial impulsestimulating the summit of the intraventricularseptum [21]. The initial slurring of the QRS com-plex during stimulation of the intraventricularseptum in patients undergoing right heart cathe-terization supported this concept [22]. FinallySherf and James developed the synchronizedsino-ventricular conduction theory [23]. Accord-ing to these authors, an impulse originating in theposterior intranodal bundle preferentially acti-vates the ventricle and causes pre-excitation.

Substantial support for the accessory pathwaytheorists arrived in 1942 when Butterworth andPoindexter published the first experimental animalstudy using an electric bypass between theatrium and ventricle [24]. The investigators wereable experimentally to generate tracings similar tothe previously described WPW syndrome.

Thus, A-V bypass tracts as the mechanism ofpre-excitation was not generally accepted untilthe 1970s. A major advance was achieved whenDurrer and Roos performed epicardial excitationmapping on a patient with the WPW syndrome[25]. Mapping was performed on a 21-year-oldwoman during surgery for a large atrial septaldefect. The right ventricle was activated earliestas a result of conduction of the atrial impulsethrough a connection near the right lateral atrio-ventricular sulcus. This finding laid the foundationfor later invasive electrophysiological studies[26e29], which not only clarified the underly-ing abnormality but also confirmed reentry as themechanism of paroxysmal tachycardias in the WPWsyndrome. These studies also became the basis forthe surgical and catheter ablation therapy of thepre-excitation syndrome. It is most likely thatJames, in 1976, more than 80 years after Kentsoriginal publications, wrote the last article chal-lenging accessory connection as the mechanism ofpre-excitation syndrome [30].

Another interesting aspect of the history of pre-excitation syndrome is the role of accessory con-nections within the specialized conduction system(nodoventricular, nodofascicular, and fasciculo-ventricular connections). According to Ferrer,

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nloaded from Figure 3 Four leads showing irregular rhythm with widtachycardia and inferior pseudoinfarct (from Levine ande and narrow QRS complexes classified as ventriculareeson [35] with permission).WPW syndrome could either be due to a Kentbundle or a combination of James posterior intra-nodal tract with Mahaim fibres [31]. Lev et al.documented this combination in a patient withpre-excitation syndrome who subsequently devel-oped complete A-V block [32]. The role of theMahaim fibres was also considered in patients withaccessory pathways and decremental conductionproperties. However, electrophysiological studiesand surgical results in the 1980s and 1990s chal-lenged the participation of Mahaim fibres in thepre-excitation syndrome [33,34].

Wide QRS complex tachycardia inWolffeParkinsoneWhite syndrome

Studies have repeatedly shown that wide QRStachycardias are seen in patients with the WPWsyndrome. Early reports diagnosed these rhythmsas ventricular tachycardia.

In 1929, Hamburger reviewed four cases ofIntraventricular block showing some interestingand unusual features [3]. The most interesting

case was of a 4-year-old boy with palpitations anddifficulty breathing. The electrocardiogram re-vealed paroxysms of wide QRS complex tachycar-dia with a short P-R interval. Dr. Hamburger madea presumptive diagnosis of auricular tachycardiawith right bundle branch block due to a respiratoryinfection [3].

In 1941, Levine and Beeson reported threepatients with paroxysms of tachycardia classifiedby the authors as ventricular tachycardia [35].All of their patients had pre-excitation and irreg-ular wide QRS complex tachycardia, most likelydue to atrial fibrillation. The most notable patientwas a 36-year-old steamfitter who while liftinga heavy box, suddenly became conscious ofa knock in the centre of his chest. The initialECG showed ventricular tachycardia, which wastreated with 0.8 mg of oral digitalis (Fig. 3). Afterrestoration of sinus rhythm the ECG showed a shortP-R interval and bundle branch block, with aninfarct pattern. The patient was hospitalized forsix weeks with the diagnosis of acute myocardialinfarction. However, according to Levine, who sawthe patient two months later, the diagnosis of

myocardial infarction was erroneous. He still londe de lelectrocardiogramme. Cardiologia 1944;8:

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nloaded from believed however, that the clinical syndrome couldbe attributed to an attack of ventricular tachy-cardia [35]. The case was recognized for itssimilarity to those described by Wolff, Parkinson,and White, in that the young steamfitter was freeof organic heart disease, yet a ventricular originfor the arrhythmias was assumed.

These wide complex rhythms initially thought tobe ventricular in origin are in fact, the result ofa supraventricular rhythm inducing a ventricularcomplex that is broad and slurred. Additionalreports detailing ventricular tachycardia and fibril-lation in WPW syndrome abound [3,35e41]. How-ever, as understanding of the condition advanced,retrospective review of the rhythms reported asventricular in origin called these diagnoses intoquestion [42].

Conclusion

In summary, pre-excitation syndrome has a longand interesting history. This ECG abnormality wasoriginally classified as BBB. Two years after Wolffand coworkers classic article, Holzmann andScherf and then Wolferth and Wood suggestedaccessory connection as its cause. In 1942, Woodet al. first reported the human anatomical sub-strate of the pre-excitation syndrome. However,even after documentation of accessory path-ways, the search for alternative mechanismscontinued. Finally, electrophysiological studiesand ablative surgical therapy confirmed accessoryA-V connections as the underlying mechanism ofpre-excitation syndrome and put the debate torest.

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Early history of the pre-excitation syndromeIntroductionEarly reports of pre-excitation syndromeAnatomical substrate of pre-excitation syndromeThe mechanism of pre-excitation syndromeWide QRS complex tachycardia in Wolff-Parkinson-White syndromeConclusionReferences