Download Paroxysmal Supraventricular Tachycardia in Patients

Paroxysmal Supraventricular Tachycardia
in Patients with Mitral Valve Prolapse
MARK E. JOSEPHSON, M.D., LEONARD N. HOROWITZ, M.D.,
AND
JOHN A. KASTOR, M.D.
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SUMMARY The mechanism of supraventricular tachycardia was
evaluated in twelve patients with mitral valve prolapse utilizing standard intracardiac recording and stimulation techniques. Eight
patients had normal electrocardiograms, three had a short PR interval and normal QRS (Lown-Ganong-Levine syndrome) and one had
Wolff-Parkinson-White type A. Six of the eight patients with normal
electrocardiograms were demonstrated to have atrioventricular
bypass tracts. Five patients had A-V nodal re-entrant supraventricular tachycardia. In two patients the bypass tract could be demon-
strated to conduct antegradely when the left atrium was paced via the
coronary sinus, while in four the bypass tract only conducted retrogradely. In all seven patients with atrioventricular bypass tracts, the
accessory pathway was left-sided. We conclude that a) supraventricular tachycardia in the mitral valve prolapse syndrome appears
related to a high frequency of bypass tracts; b) electrophysiological
studies are required to diagnose these bypass tracts; and c) the
atrioventricular bypass tracts may be related to the mitral valve abnormality since they are always left-sided.
MITRAL VALVE PROLAPSE has become recognized as
the most prevalent cardiac valvular abnormality, affecting
perhaps 6% of the population." 2 Arrhythmias are an important complication of this disorder. While ventricular premature depolarizations are most frequently noted, paroxysmal supraventricular tachycardia is probably the most
commonly sustained tachyarrhythmia.3 I The present study
was undertaken to analyze the mechanisms of supraventricular tachycardia that occur with mitral valve prolapse and
compare them to the mechanisms that are responsible for
supraventricular tachycardias in the population at large.
response to atrial and ventricular pacing and extrastimuli
delivered by a custom designed programmable stimulator
using an optically isolated constant current source (Bloom
Associates). Particular attention was paid to the mode of
initiation of supraventricular tachycardia, the atrial activation sequence during the tachycardia, the effects of developing bundle branch block during the tachycardia, and the
effects of stimulation (atrial and ventricular) during the
tachycardia.
The mechanisms suggested by the electrocardiographic
findings included: a) A-V nodal re-entry;4-7 b) A-V nodal
re-entry associated with the Lown-Ganong-Levine syndrome,8"11 and c) atrio-nodal-ventriculo-atrial circus movement re-entry characteristic of the Wolff-Parkinson-White
syndrome.4 12-16 Criteria used to define these mechanisms
were as follows:
Methods and Material
Electrophysiologic studies were performed in twelve
patients with auscultatory and/or echocardiographic findings of mitral valve prolapse in whom paroxysmal supraventricular tachycardia had been documented (table 1).
There were seven women and five men, aged from 17 to 63
years. Their resting electrocardiograms demonstrated a
short PR interval (< .12 sec) with a normal QRS in three,
Wolff-Parkinson-White type A in one, and were normal in
the remaining eight.
Each patient was studied in the postabsorptive nonsedated
state after informed consent was obtained. Antiarrhythmic
agents were discontinued 48 hours prior to study.
Quadripolar electrode catheters were percutaneously inserted through the femoral and/or antecubital veins and
positioned under fluoroscopic control in the right atrium,
right ventricle, and coronary sinus. One pair of electrodes
was used for recording and the other for stimulation. A
tripolar catheter was percutaneously introduced through the
right femoral vein and positioned across the tricuspid valve
to obtain a His bundle electrogram. The intracardiac electrograms were simultaneously recorded with multiple surface electrocardiographic leads, usually I, aVF, and V,, and
displayed on a switch-beam oscilloscope (E for M, DR16).
In each patient the mechanism of the tachycardia was
determined using intracardiac recordings and analyzing the
Re-entry Within the A-V Node
1. Dual A-V nodal pathways.
2. Echo zone and initiation of supraventricular tachycardia dependent upon attaining a critical A-H interval.
3. Normal retrograde atrial activation during supraventricular tachycardia.
4. Recording of retrograde atrial electrogram prior to or
simultaneous with the onset of the QRS.
A trio-Nodal- Ventriculo-A trial Re-entry
(Wolff-Parkinson-
White Syndrome)
1. Supraventricular tachycardia dependent on critical
A-V interval only after antegrade block in bypass tract.
2. Eccentric retrograde atrial activation sequence during
supraventricular tachycardia.
3. Ability to pre-excite the atrium with ventricular
premature depolarizations during supraventricular
tachycardia at a time when the bundle of His is either refractory or participating in antegrade conduction.
4. Prolongation of ventriculo-atrial conduction with the
development of functional bundle branch block during
supraventricular tachycardia.
From the Department of Medicine, Cardiovascular Section, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
Presented in part at the 49th Annual Scientific Sessions of the American
Heart Association, November 1976, Miami, Florida.
Address for reprints: Mark E. Josephson, M.D., Department of Medicine,
Cardiovascular Section, Hospital of the University of Pennsylvania, 34th and
Spruce Streets, Philadelphia, Pennsylvania 19104.
Received March 21, 1977; revision accepted August 17, 1977.
Results
A-V Nodal Re-entry
Two patients demonstrated typical A-V nodal re-entry.
The spontaneous occurrence of paroxysmal supraventricular
1ll
CIRCULATION
112
VOL 57, No 1, JANUARY 1978
TABLE 1. Patient Data
Patient/Sex/Age
1/M/48
2/F /17
3/M/40
4/F /28
5/F /37
6/F /53
7/M/35
8/F /28
9/F /18
10/M/63
ll/F /63
12/M/39
ECG
NL
NL
Short PR,
NL QRS
Short PR,
NL QRS
Rate of SVT
(beats/min)
200
150
200
Echo findings
Clinical findings
PLP and ALP
MSC, LSM
Mult. MSC, LSM PLP and ALP
PLP
LSM
150
Mult. MSC, LSM PLP and ALP
Short PR,
NL QRS
WPW A
10 AVB,
IVCD, LAH
162
MSC, LSM
PLP and ALP
180
200
LSM
early nonejection
click, long
PLP
holosystolic PLP and ALP, with
diastolic fluttering
NL
NL
IMI
NL
NL
230
180
170
230
200
Mult.
MSC,
MSC,
MSC,
LSM
systolic murmur
MSC, LSM PLP
PLP and ALP
LSM
LSM
PLP
LSM
PLP
PLP and ALP
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Abbreviations: ALP = anterior leaflet prolapse; AVB = atrio-ventricular block; IMI = inferior myocardial infarction; IVCD =
intraventricular conduction defect; LSM = late systolic murmur; MSC = mid-systolic click; NL = normal; PLP = posterior leaflet
prolapse; Mult. = multiple.
tachycardia is demonstrated in figure 1. Both demonstrated
dual A-V nodal pathway response characteristic of patients
with A-V nodal re-entry as depicted in figure 2. The
tachycardia rate in these patients was 150 and 200
beats/min.
Three patients (cases 3, 4, 5) demonstrated the short PR,
normal QRS, abbreviated A-V nodal conduction time, and
blunted A-V nodal response to atrial pacing characteristic of
the Lown-Ganong-Levine syndrome. The tachycardia rates
in these patients were 150, 162 and 200 beats/min. A-H intervals in these patients were 50-55 msec and all showed less
A-H prolongation in response to rapid atrial pacing than
normal. A dual pathway response was demonstrated in each
patient with the tachycardia occurring during slow pathway
conduction through the A-V node. The atrial activation sequence during the tachycardia was identical to that seen in
typical A-V nodal re-entry and atrial activation appeared
prior to or at the onset of ventricular depolarization.
Atrio-Nodal-Ventriculo-Atrial Re-entry
Seven patients demonstrated an atrioventricular bypass
tract participating in the tachycardia. The bypass tract was
III
1-11
iiiiiiili-Tliiiiii! jitijiiii i-!.,!;m -m ium
manifest in the one patient who demonstrated a WolffParkinson-White type A pattern on the electrocardiogram.
In two patients the bypass tract was latent, with the
characteristic delta wave and bizarre QRS brought out by
coronary sinus pacing (fig. 2). The supraventricular
tachycardia in the three patients with manifest or latent preexcitation was demonstrated to incorporate the accessory
pathway in the re-entrant circuit. In four patients (cases
9-12) an atrioventricular bypass tract was concealed during
antegrade stimulation studies, but was shown to be operative
during supraventricular tachycardia by a) eccentric
retrograde atrial activation during the tachycardia (fig. 3); b)
prolongation of ventriculo-atrial conduction with the
development of left bundle branch block (fig. 4); and c) the
ability to prematurely depolarize the atria with ventricular
stimulation during the tachycardia (fig. 5). The tachycardia
rates ranged from 170-230 beats/min in this group. In the
two patients with the fastest rate of supraventricular
tachycardia (230/min) the bypass tract was not manifest on
the surface electrocardiogram (cases 8 and 11). In all cases
with a functioning atrioventricular bypass tract, the location
was demonstrated to be left-sided by a retrograde atrial activation pattern with the earliest activation in the left atrium
1-11
FIGURE 1. Spontaneous A - V nodal re-entrant supraventricular tachycardia (patient I). The panel is organized from top
to bottom: surface ECG leads I, aVF, V, a high right atrial electrocardiogram (HRA), coronary sinus electrogram (CS),
His bundle electrogram (HBE) and time lines (T). Subsequent intracardiac records are similarly organized. Thefirst two
beats are sinus with a normal A H 80 msec. The third beat is an atrial premature depolarization which results in A -H
prolongation and the development of supraventricular tachycardia. Note during supraventricular tachycardia, atrial activation is earliest in the HBE and begins prior to the inscription of the QRS, a diagnosticfeature ofA - V nodal re-entrant
supraventricular tachycardia.
SVT IN MVP/Josephson, Horowitz, Kastor
aS
NRA PCO6O
,
113
Cs sCM
AI
NBEs
'A
5|
AH V
AH V
I=^tN
T
. :-;.: :..........
..
HBE
r..
T'*
,I...
v
n-
^
v
A
AH
A* IJ\
A
V
\.
A
A V
v
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is
2vV
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Tim
......
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FIGURE 2. Latent atrioventricular bypass tract (patient 7). The three panels demonstrate the QRS morphology during
sinus rhythm (NSR), high right atrial (HRA) pacing, and coronary sinus (CS) pacing. Only during CS pacing does preexcitation become manifest. HRA pacing at the same cycle length does not change the QRS from that seen in NSR. Both
rapid atrial pacing and programmed premature stimulation from the CS (not shown) produced antegrade block in the
accessory pathway and normalization of the QRS thus ruling out simultaneous CS and L V pacing.
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recorded in the coronary sinus electrogram. Further supa left-sided bypass tract was the development of
prolongation of ventriculo-atrial conduction and cycle
length with the development of left bundle branch block in
three patients. In none of our patients with bypass tracts was
A-V nodal re-entry present.13' 17
an atrioventricular accessory pathway formed one limb of
the re-entrant circuit.
Of the seven patients with atrioventricular bypass tracts
only one had electrocardiographic evidence of the WolffParkinson-White syndrome. In two, antegrade pre-excitation was only manifest during atrial pacing and was much
more evident when the left atrium (via the coronary sinus)
was paced.'2 14, 16 Of great interest was the absence of any
evidence of antegrade pre-excitation in the remaining four
patients with atrioventricular bypass tracts. In these patients
the accessory pathway was concealed during antegrade
stimulation studies.12-'" The participation of these bypass
tracts in the supraventricular tachycardia was demonstrated
by a) eccentric retrograde atrial activation; b) the ability of a
ventricular premature depolarization to pre-excite the
atrium during the tachycardia; and c) prolongation of
ventriculo-atrial conduction time with the development of
left bundle branch block.
In all patients with atrioventricular bypass tracts, the
accessory pathway was left-sided. This is intriguing in the
light of the known abnormalities of the mitral apparatus.
as
port of
Discussion
Paroxysmal supraventricular tachycardia is probably the
most common sustained tachyarrhythmia in patients with
the mitral valve prolapse syndrome.",3
The surface electrocardiograms were misleading regarding the mechanism of supraventricular tachycardia in that
eight of our twelve patients demonstrated no abnormalities
suggestive of pre-excitation. Detailed electrophysiologic
evaluation demonstrated that only five patients had A-V
nodal re-entrant supraventricular tachycardia. In each of
these patients a bypass tract in any location, free wall or septal, was excluded by the recording of retrograde atrial activation prior to the ventricular electrogram (fig. 1). In seven
SVT
NSR
,I
_1
_
III
I
-~
VII
0-
Cs
-A--
H
A
V A
V A
V A
H
H
A
¶'V
A
V'
A
--
I
'I.,----
V A;
A
A
A
A
A
NRA
V A
I
VA
HV A
,1
FIGURE 3. Concealed atrioventricular bypass tract (patient 9). The left panel demonstrates the normal QRS and
atrioventricular conduction during sinus rhythm. During supraventricular tachycardia (SVT) on the right, atrial activation is eccentric. The earliest site of atrial activation is in the CS which is characteristic of a left-sided atrioventricular
bypass tract.
CIRCULATION
114
v
I
VOL 57, No 1, JANUARY 1978
>>
_
aVF
VI
LRA~~~~~~
0! ^A
IA
LA
HBE
m
RV
:
a
FIGURE 4. Response to functional left bundle branch block during supraventricular tachycardia in a patient with concealed bypass tract (patient 12). During supraventricular tachycardia left bundle branch block (LBBB) is present for the
first three beats. Note that the cycle length of the tachycardia slows during LBBB (295 to 345 msec) because ofprolongation of the V-A interval (90 to 150 msec). Retrograde atrial activation is also earliest in the CS. Both findings are
characteristic of a left lateral wall atrioventricular bypass tract.
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Gallagher'2 also found only left-sided bypass tracts in seven
patients with mitral prolapse and the Wolff-ParkinsonWhite syndrome. This situation is analogous to Ebstein's
anomaly of the tricuspid valve which, when associated with
an atrioventricular bypass, is always associated with a type
B Wolff-Parkinson-White pattern which is due to a rightsided atrioventricular bypass tract. In both instances the
developmental abnormality giving rise to the valvular
malformation may be related to the associated electrophysiologic findings.
Significance of Results
In 60% of our patients
some
form of pre-excitation
was
present. Since a rational approach to therapy of arrhythmias
is predicated on the understanding of their underlying
mechanisms, it is obviously important that patients with
mitral valve prolapse and supraventricular tachycardia be
-
A
Cs
v-
A
V
HRA
-t
-365 - /
A
A
-
li!
'la I-PN38
V
V
r
A
AI#
A
-la380--
A
~~~~~A
H
A
H
A
H A
HI
A
T
FIGURE 5. A trial pre-excitation by ventricular premature stimulation during supraventricular tachycardia (patient 9). Supraventricular tachycardia is present with eccentric retrograde atrial activation. After the second beat a ventricular atrial depolarization results
in premature atrial depolarization of the atrium without influencing
the His bundle, i.e., the third H occurs exactly on time. This proves
apathway other than the normal atrioventricular conduction system
is operative.
evaluated for the presence of bypass tracts before
therapeutic interventions are begun. Drugs such as digitalis
and propranolol that may be extremely useful in either A-V
nodal re-entrant tachycardia or circus-movement re-entry
using an atrioventricular bypass tract, may be dangerous in
the presence of antegrade conduction over an atrioventricular bypass tract. Should any of these patients also have
atrial fibrillation or atrial flutter with rapid antegrade conduction over the accessory pathway, digitalis may facilitate
conduction over the bypass tract and lead to ventricular
fibrillation."' The absence of electrocardiographic evidence
of the Wolff-Parkinson-White syndrome should not be
taken as evidence that such an event could not occur. Three
months prior to study, case 7, who only demonstrated
evidence of pre-excitation with coronary sinus pacing, had
an episode of ventricular flutter-fibrillation induced by a
bout of atrial flutter-fibrillation with rapid conduction down
his accessory pathway in the presence of digitalis. This
mechanism may be responsible for some episodes of sudden
death in this syndrome.
Relationship to Common Mechanisms of Supraventricular
Tachycardia in the General Population
The incidence of bypass tracts participating in supraventricular tachycardia associated with mitral valve prolapse is
inordinately high. In our experience, A-V nodal re-entry is
the mechanism in two-thirds of the episodes of paroxysmal
supraventricular tachycardia in the general population4
while bypass tracts are operative in only 20% of cases. Wul'
and Akhtar (unpublished data) have similar findings. This
increased frequency of bypass tracts should be taken into
consideration when therapy is required or has failed
previously. Electrophysiologic investigation should probably
be undertaken in such patients.
References
1. Devereux RB, Perloff JK, Reichek N, Josephson ME: Mitral valve
prolapse. Circulation 54: 3, 1976
2. Procacci PM, Savran SV, Schreiter SL, Bryson AL: Prevalence of
clinical mitral valve prolapse in 1,169 young women. N Engl J Med 294:
1086, 1976
3. Gooch AS, Vincencio F, Maranhao V, Goldberg H: Arrhythmias and left
PROPRANOLOL IN VENTRICULAR ECTOPY/Nixon et al.
4.
5.
6.
7.
8.
9.
10.
11.
12.
ventricular asynergy in the prolapsing mitral leaflet syndrome. Am J Cardiol 29: 611, 1972
Josephson ME, Kastor JA: Supraventricular tachycardia: Mechanisms
and management. Ann Intern Med 87: 346, 1977
Goldreyer BN, Damato AN: The essential role of atrio-ventricular conduction delay in the initiation of paroxysmal supraventricular tachycardia. Circulation 43: 679, 1971
Wu D, Denes P: Mechanisms of paroxysmal supraventricular tachycardia. Arch Intern Med 135: 437, 1975
Denes P, Wu D, Dhingra R, Chuquimia R, Rosen KM: Demonstration
of dual A-V nodal pathways in patients with paroxysmal supraventricular tachycardia. Circulation 48: 549, 1973
Lown B, Ganong WF, Levine SA: Syndrome of short P-R interval, normal QRS complex and paroxysmal rapid heart action. Circulation 5: 693,
1952
Caracta AR, Damato AN, Gallagher JJ, Josephson ME, Varghese PJ,
Lau SH, Westura EE: Electrophysiological studies in the syndrome of
short P-R interval, normal QRS complex. Am J Cardiol 31: 245, 1973
Denes P, Wu D, Rosen KM: Demonstration of dual A-V pathways in a
patient with Lown-Ganong-Levine syndrome. Chest 65: 343, 1974
lannone LA: Electrophysiology of atrial pacing in patients with short PR
interval, normal QRS complex. Am Heart J 89: 74, 1975
Gallagher JJ, Gilbert M, Svenson RH, Sealy WC, Kasell J, Wallace AG:
13.
14.
15.
16.
17.
18.
19.
115
Wolff-Parkinson-White syndrome. The problem, evaluation and surgical
correction. Circulation 57: 767, 1975
Wellens HJJ, Durrer D: The role of an accessory atrioventricular
pathway in reciprocal tachycardia. Circulation 52: 58, 1975
Neuss H, Schlepper M, Thormann J: Analysis of re-entry mechanisms in
three patients with concealed Wolff-Parkinson-White syndrome. Circulation 51: 75, 1975
Coumel P, Attuel P: Reciprocating tachycardia in overt and latent preexcitation. Eur J Cardiol 1: 423, 1974
Svenson RH, Miller HC, Gallagher JJ, Wallace AG: Electrophysiological evaluation of the Wolff-Parkinson-White syndrome.
Circulation 52: 552, 1975
Amat-y-Leon F, Wyndham C, Wu D, Denes P, Dhingra RC, Rosen KM:
Participation of fast and slow A-V nodal pathways in tachycardias complicating the Wolff-Parkinson-White syndrome: Report of a case. Circulation 55: 663, 1977
Wellens HJJ, Durrer D: Effect of digitalis in A-V conduction and circus
movement tachycardias in patients with the Wolff-Parkinson-White syndrome. Circulation 47: 1229, 1973
Wu D, Denes P, Amat-y-Leon F, Wyndham C, Dhingra R, Rosen K:
Clinical, electrocardiographic, and electrophysiologic observations in
patients with paroxysmal supraventricular tachycardia. (abstr) Am J
Cardiol 39: 264, 1977
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Efficacy of Propranolol in the Control of
Exercise-Induced or Augmented Ventricular Ectopic Activity
J. V. NIXON, M.D., WEEMS PENNINGTON, M.D., WILLIAM RITTER, M.D.,
AND WILLIAM SHAPIRO, M.D.
SUMMARY The effect of propranolol on exercise-induced or
augmented ventricular ectopy was studied in sixteen male patients,
six of whom had documented coronary artery disease. Fifteen
patients were exercised after two weeks of oral therapy, fourteen
after single oral therapy and eight patients after intravenous therapy.
Propranolol dosage was titrated to produce maximal beta-adrenergic
blockade.
Effective reduction of exercise-induced ventricular ectopy occurred
in ten of fifteen patients (P < 0.001), and in five of six patients with
coronary disease (P < 0.02). Propranolol therapy abolished ventricular couplets in eight of twelve patients and ventricular tachycardia in four of five patients. Single oral and intravenous therapy had
similar or greater effects. Plasma propranolol levels following
different routes of administration did not correlate with exerciseinduced maximal heart rates or percent reduction in ventricular ectopy. When compared to exercise in eleven patients, ambulatory
monitoring underestimated the severity, particularly the highest
grades, of ventricular ectopy.
IT IS GENERALLY ACCEPTED that ventricular ectopic
activity in the presence of ischemic heart disease requires
therapeutic control because of its association with a high in-
recently."-'" The suggestion that both stress testing and
cidence of sudden cardiac death.'`8 However, the selection of
a suitable antiarrhythmic agent has become a cause of much
concern for reasons of either demonstrated inefficacy or a
higher than acceptable incidence of therapeutic side
effects.9"'3 Furthermore, methods for the detection of ventricular ectopic activity have come under close scrutiny
From the Veterans Administration Hospital and the Pauline and Adolf
Weinberger Laboratory for Cardiopulmonary Research, Department of
Internal Medicine of Southwestern Medical School, University of Texas
Health Science Center, Dallas, Texas.
Presented in part at the 49th Annual Scientific Session of the American
Heart Association, Miami Beach, Florida, November 1976.
Drs. Pennington and Ritter were postdoctoral research fellows supported,
respectively, by the Veterans Administration and the Hillcrest Foundation,
Dallas, Texas.
Address for reprints: J. V. Nixon, M.D., Cardiovascular Section, VA
Hospital, 4500 South Lancaster Road, Dallas, Texas 75216.
Received April 15, 1977; revision accepted August 12, 1977.
prolonged ambulatory monitoring are necessary, not only
for the demonstration of ventricular ectopic activity but also
for the evaluation of the efficacy of antiarrhythmic therapy,
requires further confirmation.'9
Although propranolol is known to be effective in the control of ventricular ectopic activity at rest, and the plasma
levels required for the suppression of ventricular ectopic activity observed at rest have been documented, only individual cases of the utilization of propranolol in exerciseinduced ventricular ectopic activity have been reported.20 21
The purpose of this study was to determine the effect of
propranolol on exercise-induced or augmented ventricular
ectopic activity, and to compare the plasma propranolol
levels required for the suppression of ectopic activity during
exercise with those previously reported to be effective in
patients at rest. The relative value of brief periods of continuous ambulatory monitoring were compared with stress
testing as a means of evaluating ventricular ectopic activity
in patients before and after the administration of
propranolol.
Paroxysmal supraventricular tachycardia in patients with mitral valve prolapse.
M E Josephson, L N Horowitz and J A Kastor
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Circulation. 1978;57:111-115
doi: 10.1161/01.CIR.57.1.111
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1978 American Heart Association, Inc. All rights reserved.
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