Download The Anatomical Substrates of Wolff-Parkinson-White

870
CIRCULATION
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
16. Moore EN, Hoffman BF, Patterson DF, Stuckey JH: Electrocardiographic changes due to delayed activation of the wall of the right ventricle. Am Heart J 68: 347, 1964
17. Rosenbaum MB, Corrado G, Oliveri R, Castellanos A Jr, Elizari MV:
Right bundle branch block with left anterior hemiblock surgically induced in tetralogy of Fallot. Am J Cardiol 26: 12, 1970
18. Bocala RR, Guller B, Danielson GK, Feldt RH: Left anterior hemiblock
and complete repair of tetralogy of Fallot. (abstr) Pediatr Res 8: 347,
1974
19. Sonheimer HM, Izukawa T, Olley PM, Trusler GA, Mustard WT: Conduction disturbances after total correction of tetralogy of Fallot. Am
Heart J 92: 278, 1976
20. Yabek SM, Jarmakani JM, Roberts N: Postoperative trifascicular block
complicating tetralogy of Fallot repair. Pediatrics 58: 236, 1976
21. Boxer R, Krongrad E, Bowman FO Jr, Malm JR, Gersony WM: Conduction defects following ventricular septal defect closure with and
without a right ventriculotomy. Pediatr Res 11: 386, 1977
22. Okoroma EO, Guller B, Maloney JD, Weidman WH: Etiology of right
bundle branch block pattern after surgical closure of ventricular septal
defects. Am Heart J 90: 14, 1975
23. Antar RA, Krongrad E, Bowman FO Jr, Malm JR: Etiology of right
bundle branch block pattern following surgical repair of A-V cushion
defects. Pediatr Res 10: 310, 1976
24. Kittle CF, Santos EM, Dimond EG: Persistent right bundle branch block
due to pulmonic valvotomy and infundibulectomy. Am Surg 22: 80, 1956
25. Downing JW, Kaplan S, Bore KE: Post surgical left anterior hemiblock
and right bundle branch block. Br Heart J 34: 263, 1972
26. Watt TB, Pruitt RD: Focal lesions in the canine bundle of His: Their
effects on ventricular excitation. Circ Res 31: 351, 1972
VOL 57, No
5, MAY 1978
27. Krongrad E, Rosen MR, Merker C, Hoffman BF: Creation of
counterclockwise superiorly oriented frontal plane loops in isolated blood
perfused canine hearts. Pediatr Res 7: 300, 1973
28. Sugiura M, Okada R, Keisuke H, Shinichiro 0: Histological studies on
the conduction system in 14 cases of right bundle branch block associated
with left axis deviation. Jap Heart J 10: 121, 1969
29. Squarcia U, Merideth J, McGoon DC, Weidman WH: Prognosis of transient atrioventricular conduction disturbances complicating open heart
surgery for congenital heart defects. Am J Cardiol 28: 648, 1971
30. Krongrad E, Rosen MR, Merker C, Fenoglio J, Hoffman BF: Creation
of trifascicular block in isolated blood perfused canine hearts. (abstr) Circulation 48 (suppl IV): IV-21, 1973
31. El-Said G, Rosenberg HS, Mullins CE, Hallman GL, Cooley DA,
McNamara DG: Dysrhythmias after Mustard's operation for transposition of the great arteries. Am J Cardiol 30: 526, 1972
32. Waldo AL, Krongrad E, Bowman FO Jr, Kaiser GA, Husson GS, Malm
JR: Electrophysiological considerations during total repair of transposition of the great vessels. Circulation 45 & 46 (suppl II): 11-34, 1972
33. Clarkson PM, Barratt-Boyes BG, Neutze JM: Late dysrhythmias and
disturbances of conduction following Mustard operation for complete
transposition of the great arteries. Circulation 53: 519, 1976
34. Stanton RE, Lindesmith GG, Meyer BW: Arrhythmias following the
Mustard operation for transposition of the great vessels. (abstr) Circulation 45 & 46 (suppl II): 11-225, 1972
35. James FW, Kaplan S, Chou T-C: Unexpected cardiac arrest in patients
after surgical correction of tetralogy of Fallot. Circulation 52: 691, 1975
36. James FW, Kaplan S, Schwartz DC, Chou T-C, Sandker ET, Naylor V:
Response to exercise in patients after total surgical correction of
tetralogy of Fallot. Circulation 54: 671, 1976
The Anatomical Substrates
of Wolff-Parkinson-White Syndrome
A Clinicopathologic Correlation in Seven Patients
ANTON E. BECKER, M.D., ROBERT H. ANDERSON, M.D., M.R.C. PATH.,
DIRK DURRER, M.D., AND HEIN J. J. WELLENS, M.D.
SUMMARY Clinicopathological correlations were made on the
hearts from seven patients known to have exhibited electrocardiographic evidence of the Wolff-Parkinson-White syndrome. In each
case, clinical and pathological investigations were conducted independently, neither group of investigators having knowledge of the
other's results. In all seven hearts, the entire atrioventricular junctions were serially sectioned. Accessory atrioventricular connections
were predicted in all seven cases following electrocardiographic investigation. Connections were identified histopathologically in four
hearts in the predicted site. In another case two connections were
identified, one being considered responsible for the pre-excitation. In
the sixth case a right lateral connection was anticipated, but only
accessory nodo-ventricular fibers were identified following histopathologic studies. In the final case, a posterior septal connection was
predicted but the entire septum had fibrosed following previous operation. These findings are discussed in the light of the investigative
techniques used, the theories of pre-excitation and the embryogenetic
mechanisms producing accessory atrioventricular connections.
MANY CLINICAL AND ELECTROPHYSIOLOGICAL STUDIES of the Wolff-Parkinson-White (WPW)
syndrome exist; in comparison, relatively little is known of
the underlying pathology. Indeed at present there is still a
dispute regarding the precise anatomy that underlies the abnormal ventricular activation pattern found in this syndrome. Paladino' and Kent2 had described myocardial fibers
in normal hearts that connected atrial and ventricular myocardium which they considered to be responsible for normal
atrioventricular conduction. However, these findings could
not be considered to represent normality when Tawara3
demonstrated the existence of the atrioventricular node and
its connection with the atrioventricular bundle,4 and then
Hering' demonstrated experimentally that in the dog heart
this bundle was the only conducting connection between
atria and ventricles. In their classic study on the WPW syndrome Holzmann and Scherf 6 suggested two possible
mechanisms, one of which assumed the existence of conducting muscular bridges between atrial and ventricular
myocardia. Considerable time elapsed before such accessory
pathways were actually demonstrated in a patient with
WPW by Wood, Wolferth and Geckeler.7 Since then the
number of cases in which these accessory connections have
From the Departments of Pathology and Cardiology and Clinical
Physiology, Wilhelmina Gasthuis, University of Amsterdam, Amsterdam,
The Netherlands.
Dr. Anderson is a British Heart Foundation Senior Research Fellow. His
present address is Department of Pediatrics, Brompton Hospital, London,
England.
Address for reprints: Dr. Anton E. Becker, Department of Pathology,
Wilhelmina Gasthuis, Eerste Helmersstraat 104, Amsterdam, The
Netherlands.
Received October 26, 1977; revision accepted November 28, 1977.
ANATOMICAL SUBSTRATES OF WPW/Becker et al.
871
TABLE 1. Clinical and Electrophysiological Data of the Patients Studied
Patient
Age (yr)
Sex
1
31
F
2
3
19
55
M
M
4
45
M
Mode of death
Type of arrhythmia
During surgery
Atrial fibrillation,
circus movement,
tachycardia
Syncopal attacks
Atrial fibrillation,
circus movement,
tachyeardia
Atrial fibrillation,
circus movement,
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
34
60
F
M
Atrial fibrillation
Atrial fibrillation
7
61
F
Atrial fibrillation,
circus movement,
tachyeardia
been identified has considerably increased, so that at present approximately 25 well-documented cases have been
reported.8 This still remains a small number when compared
to the vast clinical experience of the syndrome. Precise
knowledge concerning the anatomic substrates of the syndrome is desirable, because apart from the concept of an
accessory pathway as an explanation of the abnormal ventricular activation pattern, many alternative mechanisms
have been postulated, one of the most interesting of which is
synchronized sino-ventricular conduction.9-"
In view of this problem it seemed appropriate to report
our study of a series of patients with WPW who died and in
whom a morphologic study of the heart was undertaken.
Suddenly
2 weeks post
surgery
Sudden
Cardiogenic shock
following anteroseptal MI
Suddenly 3 yr after
ligation of bundle
of His
I
1
2
3
4
5
6
7
I
III
TABLE 2. Predicted Localization of Accessory Pathway on
ECG and Anatomic Localization
ECG localization
III
Anatomic localization
Anterior paraseptal 1. Left posterior (working
myocardium)
2. Right anterior paraseptal
(specialized)
Left posterior
Left posterior close
to septum
Left posterior
Left posterior close
to septum
Right posterior septal
Right septal
?
Right lateral
Left lateral
Left lateral
?
Left septal
AVR
lmv
FIGURE 1. ECG from patient 1. On the basis of the criteria
described by Frank"2 and Tonkin et al.13 the pre-excitation in this
patient was predicted to be due to an accessory atrioventricular connection in right paraseptal position. The morphologicalfindings are
illustrated in figures 7 and 8.
Aortic incompetence,
Ebstein's disease
Hypertension
(ECG) showing pre-excitation were available (figs. 1-5).
Based upon the ECG the most likely site of the accessory
pathway was predicted without knowledge of the anatomic
findings, using the criteria of Frank12 and Tonkin et al.'3
(table 2). In a similar fashion, the histopathological studies
in each case were conducted without prior knowledge of the
results of clinical investigation.
Materials and Methods
Seven hearts from patients suffering from the WPW syndrome were studied. Clinical and electrocardiographic data
are given in table 1. From all patients electrocardiograms
Patient
Ebstein's disease
Sudden
Sudden
tachycardia
5
6
Additional abnormalities
IAF
200msec
VI
VOL
CIRCULATION
872
I
-J.--
VIi
V,
,-i
I
57, No 5, MAY 1978
v2-w
a
A
I
III
A
AVR
AVL
AVF
-
1
V2
V2
V3
V3
III
V3
V54
AVR
V4
V5'
AVL
v4JV-.
AVR
V5A
AVL
V6
AVF
JL
_>,V^
V2
4
V5
AVF I
1
fs
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
200 msec
Patient 2
Patient 3
Patient 4
FIGURE 2. ECGs from patients 2, 3 and 4. In patient 2, using the criteria of Frank12 and Tonkin et al.,'3 an accessory
connection was predicted to exist in left posterior position. Morphologicfindings in this patient are illustrated in figures 7
and 9A. In patient 3, an accessory connection was again anticipated in left posterior position, and the bundle thus identified is illustrated in figure 10. A right septal accessory connection was predicted to exist in patient 4; the morphology of
the connection discovered in this site is illustrated in figure 11.
In all cases, both right and left atrioventricular (A-V)
rings, together with the A-V septal area containing the A-V
specialized conducting tissues were studied. The junctional
regions were separated into multiple blocks, each of which
was embedded for histologic serial sectioning. In each heart
the number of blocks cut varied from 14 to 20 (fig. 6). The
blocks were embedded in paraffin and serially sectioned at
7,u thickness in a plane at right angles to the atrioventricular junction. All the sections were retained in trays. As a
routine, every fiftieth section was mounted; the remaining
sections were studied, when deemed necessary, after examination of the initially mounted series. The sections were
stained with hematoxylin and eosin, an elastic tissue stain
counterstained with the van Gieson stain or with Masson's
trichrome stain.
Case Reports
Patient 1. A 3 1-year-old woman was investigated because
of atrial fibrillation and circus movement tachycardia. Study
of the ECG suggested presence of a right, probably anterior
septal accessory connection (fig. 1). At operation, the patient's penetrating atrioventricular (His) bundle was ligated,
but she died during this procedure.
The autopsy demonstrated the presence of Ebstein's
malformation of the tricuspid valve. Histologic examination
showed a marked deficiency of the atrioventricular fibrous
anulus both in the septal area and posteriorly to the right.
However, atrial and ventricular myocardium remained
separated by adipose tissue throughout the whole area. The
I
II
-
t
1
V2
V3
III
AVR
V4
AVL
V5_
AVF
VeJ
FIGURE 3. ECG from patient 5. A right lateral accessory connection was anticipated (fig. 7). No such connection was identified
following morphological studies.
V,
200 msec
tv
ANATOMICAL SUBSTRATES OF WPW/Becker et al.
I
873
AVR
AVR_v
I
AVL
II
11
AVF
III
AVF
III
V3
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
V1
, 4
i'
V4
V2
V5
V2 a
V
FIGURE 4. ECG from patient 6. A left lateral connection was
predicted (fig. 7). The connection identified in this site is illustrated
in figure 9B.
FIGURE 5. ECG from patient 7. A septal connection on the left
side was expected. Morphological studies revealed that the entire
septal area had fibrosed following operation (fig. 7).
mv
v
Epi
FIGURE 6. Plane view of the atrioventricular junctional region viewed from above showing how the entire atrioventricular junction was divided into a series of blocks. The septal area, containing the specialized atrioventricularjunctional area (dotted tissue) was removed in three blocks. A typical section of this area is shown in the middle inset. The
right and left parietal junctions were then divided into 5 10 blocks on each side depending upon the size of the heart.
Sample sections of the parietal junctions are shown in the insets. AM = atrial myocardium; VM = ventricular myocardium; MV = mitral valve; TV = tricuspid valve; Epi = epicardium; PA = pulmonary artery. The anulusfibrosus is the
cross-hatched tissue.
-
VOL 57, No 5, MAY 1978
CI RCULATION
874
7 Cases - Accessory Connections
Casel
ECG Right Septal
Case 2 ECG Left Posterior
Case 3 ECG Left Posterior
Ant
L
Post
Case4 ECG Right Septal
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
Case 5 ECG Right Lateral
Case 6 ECG Left Lateral
Case 7 ECG Left Septal
FIGURE 7. Diagram showing the correlation between electrocardiographic and morphologic findings in each of the
seven patients studied. The meaning of the symbols is given in the key (A VA C = atrioventricular accessory connection).
The ECG of patient I is shown in figure 1, the histological findings in figure 8. The ECGs of patients 2, 3 and 4 are illustrated in figure 2, and those of patients 5, 6 and 7 in figures 3, 4 and 5, respectively. The histological findings from
patient 2 are illustrated in figure 9A, patient 3 in figure 10; patient 4 in figure 11 and patient 6 in figure 9B.
A-V node and penetrating bundle were extensively
traumatized, their normal architecture being completely
obliterated. Examination of the parietal junctional tissues
revealed presence of two accessory atrioventricular connections (figs. 7 and 8). One of these was composed of working
myocardium and was located in a left posterior site close to
the crux of the heart. This bundle ran through the epicardial
fat, close to a well formed fibrous anulus (fig. 8A). The bundle had an overall length of 10 mm with a maximal diameter of I mm. At its ventricular side it divided into smaller
W-1
.- -I-,
-6. 1,
FIGIURE 8. Morphological findings in patient /. A shows the left sided accessory connection (A C), which had not been
anticipatedfrom the ECG. Note that the connection is on the epicardial aspect of a wellformed anulusfibrosus (A F), and
joins atrial (AM) and ventricular (VM) myocardium by traversing the epicardial fat rather than by passing through a defect in the anulus. Note also the hemorrhage (H) following surgical intervention in the case. Figures 8B-D illustrate the
second accessory connection, which was composed ofspecialized tissue. Figure 8B illu-strates the anterior node-like structure (in box) situated at the insertion of the atrial myocardium into the tricuspid valve (TV). A section further anterior
(fig. 8C) at higher magnification shows that the anterior node (A N) is composed of a basket-like collection ofspecialized
cells, and that the accessory connection (A C) originates from the node, the connection itself also being composed of
specialized tissue. Figure 8D shows the course of the bundle in the tricuspid valve, lying alongside and ramifying into the
ventricular myocardium in anterior paraseptal position. Note the lack of a discrete anulus fibrosus in this heart.
ANATOMICAL SUBSTRATES OF WPW/Becker et al.
IA
I
II
aI
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
FIGURE 9. Histological findings in patients 2 (fig. 9A) and 6 (fig.
9B). In patient 2, the accessory connection (arrows) was in the left
posterior position; in patient 6, the connection (arrows) was in left
lateral position. Note that in both cases the connections skirt a well
formed an ulus fibros us (AIF) and course through the epicardial fat
(EF) to join atrial (AM) and ventricular (VM) myocardia. Note
also the bridging of the coronary artery (CA) in patient 6.
MV mitral valve.
bundles which became continuous with ventricular myocardium. The second connection was located in a right anterolateral position (fig. 7). A node-like structure was found at
the insertion of atrial myocardium into the anulus (fig. 8B),
being composed of cells typical of those found in the
specialized atrioventricular junctional area (fig. 8C). They
formed an interweaving, basket-like structure reminiscent of
the normal compact atrioventricular node (fig. 8C). From
this node-like structure a bundle originated composed of
specialized cells, which coursed caudally toward the anterior
tricuspid valve leaflet (fig. 81D). The latter exhibited
dysplastic features, as commonly encountered in Ebstein's
malformation, having myocardium present on its ventricular
aspect. The ventricular extension of the specialized
875
accessory connection became continuous with the myocardium in the valve leaflet (fig. 8D). The overall length of the
connection was 10 mm, with a maximal width of 1 mm.
Patient 2. A 19-year-old man was first seen because of
syncopal attacks. The site of the anticipated accessory atrioventricular connection was predicted to be left sided and
posterior, close to the crux of the heart (fig. 2). The patient
died suddenly at home. There were no abnormal findings
during gross examination of the heart. Histopathological
studies revealed an accessory atrioventricular connection
located at the anticipated site (fig. 7). The bundle was composed of working myocardium. At its atrial end the bundle
was well delineated with a width of slightly less than 1 mm.
The bundle ran through epicardial adipose tissue, skirting a
well formed fibrous anulus at its epicardial aspect (fig. 9A).
Close to the ventricular myocardium, on its epicardial
aspect, the bundle ramified into smaller bundles. The
smaller bundles connected directly to the ventricular
myocardium like the roots of a tree. The overall length of
the connection was estimated at approximately 6 mm. There
was deficiency of the fibrous anulus posteriorly in the septum, but no atrioventricular connection could be established
at that site. The specialized atrioventricular junctional area
was considered normal.
Patient 3. A 55-year-old man first presented with signs
and symptoms of a circus movement tachyeardia and atrial
fibrillation. Following examination of the ECG, it was considered that an accessory atrioventricular connection would
be present in a left posterior position, close to the crux of the
heart (fig. 2). The patient died suddenly. Gross examination
of the heart revealed normal anatomy. Histological studies
demonstrated the presence of a connection at the anticipated
site (fig. 7). The bundle was composed of working myocardium. At its atrial side the bundle was approximately 1
mm in width. It ran through epicardial adipose tissue, skirting the fibrous anulus (fig. 10). The latter was well formed.
During its course the bundle was accompanied by a small
artery and vein and a small nerve trunk (fig. 1OC). On reaching the ventricular myocardium the bundle ramified into
K
jk.
. I.
1;
j,.
A
q'i
.
I$
XfI'
FIGURE 1 0. Series ofphotographs illustrating the left posterior connection identified in patient 3. Figure I OA illustrates
the origin of the accessory connection (arrow) from the atrial myocardium. Note that it originates very close to a well
formed anulusfibrosus and "points'" into the epicardial fat (A F). Figure lOB shows a section across the bundle (arrow) as
it courses through the epicardialfat, skirting the anulus. The area within the box is shown in higher magnification infigure
JOC. The accessory connection is a small bundle (B) of working myocardial cells, and is accompanied by a nerve (N),
artery (A ) and vein ( V). Figure IOD shows the insertion of one "root" of the connection (arrow) into the ventricular myocardium (VM) some appreciable distance outside the well-formed anulus fibrosus.
876
CIRCULATION
VOL 57, No 5, MAY 1978
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
FIGURE 1 1. Serial photographs of the septal accessory connection identified in patient 4. A is a posterior section showing the origin of the accessory connection (solid arrow) from the distal point of the right side of the interatrial septal
myocardium (IAS). Note that the interatrial and interventricular septal (IVS) myocardia are separated only by epicardial
fat (open arrows), the anulusfibrosus being deficient in this area. B, taken more anteriorly to A, illustrates the connection
as afree running strand in the atrioventricular sulcus (solid arrow). C, again more anterior, shows the insertion of the connection into the ventricular mvocardium (solid arrow).
several smaller bundles each of which anchored itself into
ventricular myocardium (fig. lOD). The area of insertion
had an approximate diameter of 1 mm. The overall length of
the bundle was 10 mm. No other accessory connections were
found; the A-V node and penetrating bundle were considered
normal.
Patient 4. A 45-year-old man with aortic insufficiency was
investigated because of tachycardia. He was shown to have a
circus movement tachycardia and atrial fibrillation. The
findings were considered to indicate the presence of a right
septal accessory atrioventricular connection (fig. 2). The patient's aortic valve was replaced by a ball valve prosthesis
and at the same procedure the penetrating atrioventricular
(His) bundle was ligated. The patient died suddenly two
weeks after operation, following a previously uneventful
postoperative period. At gross examination of the heart, the
tricuspid valve was found to exhibit Ebstein's malformation.
The anulus fibrosus in the septal area was highly deficient.
Histopathological studies revealed the presence of an
accessory atrioventricular connection, which was right sided
and posterior to the orifice of the coronary sinus (fig. 7). The
bundle was composed of working myocardium. At its atrial
side it had a width of approximately 3 mm (fig. 1 IA). It
coursed anteriorly from atrium to ventricle tapering down to
a diameter of approximately 1.5 mm (fig. 1 B). Close to its
ventricular insertion the bundle broke up into a number of
small branches. The total length of the bundle was estimated
at 5 mm. Throughout its course the bundle ran in subendocardial position, and passed through an area in which the
fibrous anulus was completely deficient. Atrial and ventricular myocardium in this position were separated by only
adipose tissue (fig. 11). Examination of the remaining junctional tissues failed to demonstrate any further connections.
The area of the A-V node and penetrating bundle had been
extensively traumatized by sutures.
Patient 5. A 34-year-old woman had been known to have
hypertension for many years. When first seen her electrocar-
diogram revealed atrial fibrillation and a pattern typical for
the WPW syndrome (fig. 3). The ECG was interpreted as being compatible with presence of an accessory atrioventricular connection in a right lateral position. The patient died suddenly at home before any further investigations
could be undertaken.
At autopsy, there were no abnormalities detected during
gross examination of the heart. Histopathological studies
revealed that the connections between atrial transitional
cells and the compact node were normal. The penetrating
bundle was normally formed, but there were extensive
accessory nodo-ventricular connections.14 These were the
only accessory connections found. The right and left parietal atrioventricular junctions exhibited the anticipated
architecture with the right fibrous ring being deficient at
many sites. Continuity between atrial and ventricular
myocardium was never established. Because of the electrocardiographic interpretations the right lateral region was
further studied by mounting all sections taken from that
area. It still proved impossible to demonstrate any accessory
connections.
Patient 6. A 60-year-old man had been known to have
atrial fibrillation for a prolonged time. The ECG was considered suggestive of a left lateral accessory atrioventricular
connection (fig. 4). He also suffered from angina pectoris.
As a consequence of his atherosclerotic disease acute
anteroseptal myocardial infarction occurred and he died
suddenly one week following onset of infarction.
Gross examination of the heart confirmed the diagnosis of
anteroseptal transmural myocardial infarction. Two vessel
coronary artery disease was identified with multiple stenoses
of more than 75% in the dominant right coronary artery.
The left anterior descending coronary artery showed total
occlusion in its proximal segment. Serial sectioning of the
right and left atrioventricular rings revealed an accessory
atrioventricular connection at the predicted left lateral position (fig. 7). The left circumflex artery, positioned in the
ANATOMICAL SUBSTRATES OF WPW/Becker et al.
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
atrioventricular sulcus, was extensively bridged at that site
by atrial myocardium. From this bridging myocardium an
accessory bundle of 1 mm diameter took origin (fig. 9B). It
skirted the anulus fibrosus on its epicardial aspect and, just
prior to its insertion into the ventricular myocardium,
divided into two smaller bundles. The overall length of the
connection was 3 mm. No other connections were found and
the A-V node and penetrating bundle were considered normal.
Patient 7. A 61-year old woman was known to have coronary artery disease. She also suffered from a circus movement tachycardia. Following study of the ECG, an accessory
atrioventricular connection was predicted to be present
posteriorly in the left side of the septum (fig. 5). At operation, her penetrating atrioventricular (His) bundle was
ligated. Her postoperative electrocardiogram showed conduction over the anomalous pathway. She recovered uneventfully but died suddenly three years after the operation.
Gross examination revealed considerable fibrosis of the
septal junctional area. Histopathology revealed that the
fibrosis had obliterated both the specialized junctional area
and the posterior part of the septum. No accessory connections were identified (fig. 8).
Discussion
It is important to stress that the histopathological findings presently reported in each patient were derived without
prior knowledge of the clinical and electrocardiographic
data from that patient. Similarly, the interpretation of the
electrocardiogram, using the criteria of Frank12 and Tonkin
et al.,13 was made without any knowledge of the
histopathological results. Bearing in mind this approach it is
therefore of considerable significance that accessory
atrioventricular connections were identified in five of seven
hearts (fig. 7). A connection was considered to be present
when atrial and ventricular myocardia became continuous
with each other due to the interposition of a strand of muscle
cells. In patients 2, 3, 4 and 6 a positive correlation was obtained with the ECG findings. In patient 1 the accessory connection was predicted to be in the anterior paraseptal region.
The anatomical study revealed the presence of two connections, neither being in the precise situation. However, the
specialized bundle originating from the anterior node-like
structure in this patient coursed toward the anterior septum.
This case is of considerable significance and will be discussed
separately below.
In the two remaining patients, our studies failed to
demonstrate the presence of an accessory connection,
although such connections had been anticipated following
study of the ECG. In patient 5 the accessory connections
had been predicted to be in a right lateral position. Even
following retrospective study, we failed to demonstrate any
connection at that site. Our retrospective study included the
mounting of all sections from the different blocks covering
the area. It must be realized, however, that this failure could
easily be a consequence of the necessity to cut the specimen
prior to histological sectioning. This immediately introduces
the danger of cutting through a connection or destroying it
by the proximity of the incision. This possibility was increased in our cases since the pathologist cutting the
specimen was unaware of the predicted site of the connec-
877
tion. This could be regretted in retrospect but we remain
convinced that our elaborate methodology has led to an unbiased interpretation of the histology. The heart of this patient did show extensive accessory nodo-ventricular
(Mahaim) connections but the ECG was atypical for preexcitation of this type. It should therefore be questioned
whether these connections in this particular case had any
functional significance. In our experience such connections
are frequently encountered in hearts of patients without
signs of pre-excitation,15 although it must be emphasized
that they have been directly implicated in another case
following histopathological correlation.'6 In this latter instance, however, the ECG was not as expected for classical
WPW pre-excitation. The final patient in whom we failed to
demonstrate a connection had undergone surgery, ligation
of the penetrating bundle having been performed (patient 7).
In this case the predicted site of the connection had been the
posterior left septal area. The operative procedure had led to
fibrosis of the specialized junctional area, which extended
posteriorly into the posterior part of the septum. It is surprising, therefore, that the electrocardiogram had shown
conduction over the anomalous pathway, although we may
speculate about progressive fibrosis eventually affecting the
pathway itself and hampering the microscopic investigations.
In summary, we strongly feel that failure to demonstrate
an abnormal atrioventricular connection at the anticipated
sites in these two hearts relates to the method of cutting
blocks "in the blind" rather than to the existence of other
mechanisms eliciting pre-excitation. It is important in this
respect that no anatomical substrate could be detected to
accept a phenomenon of synchronized sino-ventricular con-
duction.9-"1
As indicated above, our case with dual accessory connections (patient 1) is of particular significance. In this heart,
one of the connections was situated in the left posterior wall,
being composed of ordinary working myocardium. The second connection was located in the anterolateral margin of
the tricuspid orifice, and was composed of specialized cells.
This connection took origin from an anteriorly located A-V
node-like structure, which we believe represents a vestige of
the anterior expansion of the specialized ring tissue present
in the embryonic heart.17 Indeed, this node is remarkably
similar to that described in a human heart as contacting the
ventricular myocardium by Kent in 1914,1' although Kent
did not describe a bundle originating from the node as in the
present case. Furthermore, the node in this case is similar to
those recently described in congenitally malformed hearts,
notably corrected transposition19 and univentricular
hearts.2'-22 The diameters of the cells composing the bundle
which took origin from the ant r node were smaller than
those of working myocardium and strikingly similar to those
cells which make up a sizable portion of the A-V junctional
specialized tissues." It must remain speculative as to
whether this node and bundle could have displayed functional acteristics of specialized tissues. To the best of our
knowledge only two previous connections have been
reported to resemble specialized tissue. One of the connections reported by Verduyn Lunel was stated to be composed
of Purkinje cells.22asecond case was reported by James et al.
and a left lateral connection was said to be composed of p
cells.24 It is significant, however, that the occurrence of a
878
CIRCULATION
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
specialized connection such as that presently described had
been predicted on the basis of previous morphological
studies in embryos and adult human hearts.'7 The present
case is of further interest, since in addition to the presence of
dual accessory connections it also exhibited a deficient
anulus fibrosus as a consequence of Ebstein's anomaly.
Multiple accessory connections have previously been
reported, both anatomically25 and clinically,26 and it has
been indicated how this feature may hamper the electrocardiographic interpretation.28 In this case, we would suggest
that the specialized connection was responsible for the preexcitation, since the distribution of the descending bundle
would have involved the anterior segment of the right ventricular myocardium.
It has previously been postulated that the accessory
atrioventricular connections present in the WPW syndrome
are the result of an embryologic fault in the formation of
fibrous tissue separating both structures.23 This supposition
has not been borne out by our data. Of the five hearts with
identified connections there were four with a left-sided bundle. Each of these four left-sided connections occurred in the
presence of a well formed fibrous anulus. Indeed the fibrous
ring was in no way different from that encountered in the
normal heart. The bundle in each instance skirted the anulus
on its epicardial aspect, albeit that the bundle spatially was
more closely related to the inner surface of the heart rather
than the epicardial surface (fig. 12). It is significant that
careful review of the cases reported in the literature similarly
demonstrates that the majority of described left sided connections skirt a well formed fibrous anulus. These findings
indicate that the presence of left-sided bundles cannot
simply be explained on the basis of faulty development of the
fibrous ring. An alternative explanation for their existence is
thus far lacking.
In contrast to left-sided bridges, the single heart in our
series with a right-sided septal connection exhibited this connection in subendocardial position. The heart also displayed
an Ebstein's malformation and therefore does not
necessarily reflect the usual configuration in the case of a
right-sided connection. Careful review of the cases reporting
this morphology of WPW cases with right-sided connections
demonstrates that the majority of these connections had a
subendocardial course. This should not be surprising, since
the normal anatomy of the right atrioventricular fibrous
anulus is quite different from the left. The left sided anulus is
usually well formed, and nearly always complete. The rightsided anulus, on the other hand, is poorly formed and
deficient at many sites (Becker AE, Anderson RH, unpublished observations). From this anatomy one may anticipate the existence of right-sided accessory connections
which indeed pass through an area of incomplete development.
In conclusion, our study demonstrates that the electrocardiogram can be a good indicator of the site of the accessory
connection when employing the criteria of Frank22 and the
Duke University investigators,13 and when the accessory
connection contributes significantly to ventricular activation." However, we would hesitate to use the predicted
sites as a basis for surgery without having the facility for
further electrophysiological studies before and during operation. It is noteworthy that the incision suggested by Sealy et
al.28 to sever left-sided accessory connections probably
VOL 57, No 5, MAY 1978
ANULUS
'CONNECTION
FIGURE 12. Diagrammatic representation of left-sided accessory
atrioventricular connections, based on our four identified connections (patients 1, 2, 3 and 6) and others reported in literature. It is
important to note that the connections skirt through the epicardial
fat, being outside a well formed anulus fibrosus. However, being
close to the anulus they are still closer to the endocardial rather than
the epicardial surfaces of the heart. It is also important to appreciate that, owing to the proximity of connection to anulus, the
surgical incision advocated by Sealy et al.28 probably divides only
the atrial input to the connection. As recently suggested by Sealy et
al.29 in order to divide the connection itself, it will be necessary to
scrape away the fat from the epicardial aspect of the anulus, removing the connection at the same time.
divides the atrial input to the connection rather than the connection itself (fig. 12). This fact and the possibility of multiple pathways has led Sealy et al.28 to advocate an extensive
incision. Moreover, in order to divide the ventricular connection itself, Sealy and co-workers29 recently proposed dissecting all fat tissue and vessels away from the ventricular
surface. Our observations, which revealed atrioventricular
connections skirting the anulus fibrosus, endorse the need
for such a meticulous method (fig. 12). Finally, it should be
emphasized that in two of our cases, Ebstein's malformation
was discovered only at autopsy, and the failure of its earlier
demonstration may well have contributed to the dismal outcome in these patients. We would therefore advocate rightsided angiography as a preoperative study in all patients
scheduled for the WPW syndrome.
Acknowledgment
We are indebted to Miss H.J. Dijk and Messrs E.M.E. Heeren and M.J.
Klaver for their technical assistance; to Mr. R.H. Verhoeven for
photographic assistance and to Miss M.I. Schenker for secretarial assistance.
References
1. Paladino G: Contribuzione all'anatomia, istologia e fisiologia del cuore.
Mov Med-Chir (Napoli) 8: 428, 1876
2. Kent AFS: Researches on the structure and function of the mammalian
heart. J Physiol 14: 233, 1893
3. Tawara S: Das Reizleitungssystem des Sauigetierherzens. Eine
anatomischhistologische Studie fiber das Atrioventrikularbiundel und die
Purkinjeschen Faden. Gustav Fisher, Jena, 1906
4. His W Jr: Die Thatigkeit des embryonalen Herzens und deren Bedeutung
ANATOMICAL SUBSTRATES OF WPW/Becker et al.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
14.
15.
16.
fur die Lehre von Herzbewegung beim Erwachsenen. Arbeit aus der
medicin Klinik zu Leipzig: 14, 1893
Hering HE: Nachweis dass die Verzogerung der Erregungsulberleitung
zwischen Vorhof und kammer des Sauigetierherzens im Tawara, schen
Knoten erfolgt. Pfluger Arch Ges Physiol 131: 572, 1910
Holzmann M, Scherf D: Ueber Elektrocardiogramme mit verkurzter
Vorhof-Kammer-Distanz und positiven P-Zacken. Z Klin Med 121: 404,
1932
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 25: 454,
1943
Frank R, Brechenmacher C, Fontaine G: Apport de l'histologie dans
l'etude des syndromes de pre-excitation ventriculaire. Coeur Med Int 15:
337, 1976
James TN: The Wolff-Parkinson-White syndrome: Evolving concepts of
its pathogenesis. Prog Cardiovasc Dis 13: 159, 1970
Sherf L, James TN: A new electrocardiographic concept: Synchronized
sinoventricular conduction. Dis Chest 55: 127, 1969
Sherf L: The atrial conduction system: Clinical implications. Am J Cardiol 37: 814, 1976
Frank R: Apport des investigations endocaitaires et des cartographies
epicardiques dans l'etude des syndrome de pre-excitation ventriculaire.
Thesis, Paris, 1974
Tonkin AM, Wagner GS, Gallagher JJ, Cope GD, Kasell J, Wallace AG:
Initial forces of ventricular depolarization in the Wolff-Parkinson-White
syndrome. Circulation 52: 1030, 1975
Anderson RH, Becker AE, Brechenmacher C, Davies MJ, Rossi L: Ventricular pre-excitation. A proposed nomenclature for its substrates. Eur J
Cardiol 3: 27, 1975
Becker AE, Anderson RH: Morphology of the human atrioventricular
junctional area. In The Conduction System of the Heart, edited by
Wellens HJJ, Lie KI, Janse MJ. Leiden, HE Stenfert Kroese BV, 1976,
chapter 15
Lev M, Fox SM, Bharati S, Greenfield JC, Rosen KM, Pick A: Mahaim
and James fibers as a basis for a unique variety of ventricular preexcitation. Am J Cardiol 36: 880, 1975
879
17. Anderson RH, Davies MJ, Becker AE: Atrioventricular ring specialized
tissue in the normal heart. Eur J Cardiol 2: 219, 1974
18. Kent AFS: The right lateral auriculo-ventricular junction of the heart. J
Physiol 48: 22, 1914
19. Anderson RH, Becker AE, Arnold R, Wilkinson JL: The conducting
tissues in congenitally corrected transposition. Circulation 50: 911, 1974
20. Anderson RH, Arnold R, Thapar MK, Jones R, Hamilton DI: Cardiac
specialized tissue in hearts with an apparently single ventricular chamber
(double inlet left ventricle). Am J Cardiol 33: 95, 1974
21. Bharati S, Lev M: The course of the conduction system in single ventricle with inverted (L-) loop and inverted (L-) transposition. Circulation
51: 723, 1975
22. Wilkinson JL, Anderson RH, Arnold R, Hamilton DI, Smith A: The
conducting tissues in primitive ventricular hearts without an outlet
chamber. Circulation 53: 930, 1976
23. Verduyn Lunel AA: Significance of annulus fibrosus of heart in relation
to AV conduction and ventricular activation in cases of Wolff-ParkinsonWhite syndrome. Br Heart J 34: 1263, 1972
24. James TN, Puech P: De subitaneis mortibus IX. Type A WolffParkinson-White syndrome. Circulation 50: 1264, 1974
25. Deerhake HG, Kimball JL, Burch GE, Henthorne JC: Wolff-ParkinsonWhite syndrome: Histologic study of the cardiac septum and atrioventricular groove in one case. Quoted by Kimball JL, Burch GE: Ann
Intern Med 27: 239, 1947
26. Denes P, Amat-y-Leon F, Wyndham C, Wu D, Levitsky S, Rosen K:
Electrophysiological demonstration of bilateral anomalous pathways in a
patient with Wolff-Parkinson-White syndrome (Type B pre-excitation).
Am J Cardiol 37: 93, 1976
27. Wellens HJJ: Contribution of cardiac pacing to our understanding of the
Wolff-Parkinson-White syndrome. Br Heart J 37: 231, 1975
28. Sealy WC, Wallace AG, Ramming KP, Gallagher JJ, Svenson RH: An
improved operation for the definitive treatment of the Wolff-ParkinsonWhite syndrome. Ann Thorac Surg 17: 107, 1974
29. Sealy WC, Gallagher JJ, Wallace AG: The surgical treatment of WolffParkinson-White syndrome: Evolution of improved methods for identification and interruption of the Kent bundle. Ann Thorac Surg 22: 443,
1976
The anatomical substrates of wolff-parkinson-white syndrome. A clinicopathologic
correlation in seven patients.
A E Becker, R H Anderson, D Durrer and H J Wellens
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
Circulation. 1978;57:870-879
doi: 10.1161/01.CIR.57.5.870
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1978 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on
the World Wide Web at:
http://circ.ahajournals.org/content/57/5/870
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally
published in Circulation can be obtained via RightsLink, a service of the Copyright Clearance Center, not the
Editorial Office. Once the online version of the published article for which permission is being requested is
located, click Request Permissions in the middle column of the Web page under Services. Further
information about this process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Circulation is online at:
http://circ.ahajournals.org//subscriptions/