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Sudden Death and Defibrillators in Transposition of the
Great Arteries With Intra-atrial Baffles
A Multicenter Study
Paul Khairy, MD, PhD; Louise Harris, MD; Michael J. Landzberg, MD;
Susan M. Fernandes, MHP, PA-C; Amanda Barlow, MD; Lise-Andrée Mercier, MD;
Sangeetha Viswanathan, MRCPCH; Philippe Chetaille, MD; Elaine Gordon, MD;
Annie Dore, MD; Frank Cecchin, MD
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Background—Transposition of the great arteries with intra-atrial baffle repair is among the congenital heart defects at
highest risk of sudden death. Little is known about mechanisms of sudden death and the role of implantable cardioverter
defibrillators.
Methods and Results—We conducted a multicenter cohort study in patients with transposition of the great arteries to
determine actuarial rates of implantable cardioverter defibrillator shocks, identify risk factors, assess underlying
arrhythmias, and characterize complications. Overall, 37 patients (age, 28.0⫾7.6 years; 89.2% male) were enrolled from
7 sites. Implantable cardioverter defibrillators were implanted for primary prevention in 23 (62.1%) patients and
secondary prevention in 14 patients (37.8%). Annual rates of appropriate shocks were 0.5% and 6.0% in primary and
secondary prevention, respectively (P⫽0.0366). Independent predictors were a secondary prevention indication (hazard
ratio, 18.0; P⫽0.0341) and lack of ␤-blockers (hazard ratio, 16.7; P⫽0.0301). In patients with appropriate shocks,
intracardiac electrograms documented supraventricular tachycardia preceding or coexisting with ventricular tachycardia
in 50%. No patient with inducible ventricular tachycardia received an appropriate shock in comparison with 37.5% of
noninducible patients (P⫽0.0429). Inappropriate shocks occurred in 6.6% per year, more so in patients of lesser weight
(hazard ratio, 0.91 per kg; P⫽0.0168). Additionally, 14 patients (37.8%) experienced complications: 5 (13.5%) acute,
1 (2.7%) late generator related, and 12 (32.4%) late lead related.
Conclusion—In patients with transposition of the great arteries, high rates of appropriate shocks are noted in secondary
but not primary prevention. Supraventricular arrhythmias may be implicated in the etiology of ventricular
tachyarrhythmias; ␤-blockers seem protective, and inducible ventricular tachycardia does not seem to predict future
events. Inappropriate shocks and late lead-related complications are common. (Circ Arrhythmia Electrophysiol. 2008;
1:250-257.)
Key Words: death, sudden 䡲 heart arrest 䡲 defibrillation 䡲 heart defects, congenital 䡲 tachyarrhythmias
䡲 transposition of great vessels
C
omplete transposition of the great arteries (D-TGA) with
intra-atrial redirection surgery (Mustard or Senning baffles) is among the congenital heart defects at highest risk for
sudden cardiac death. Indeed, sudden death is the most
common cause of late mortality in this patient population.1–7
A population-based study reported an incidence of 4.9 per
1000 patient-years, second only to aortic stenosis and more
than threefold greater than tetralogy of Fallot.1 Identification
of risk factors and pathophysiological mechanisms for sudden
death have been somewhat elusive. Although bradyarrhythmias were once thought to be primary triggers, this notion
was later refuted, as pacemakers were not found to afford
protection against sudden death. Identified risk factors are
largely confined to arrhythmia symptoms and documented
atrial tachyarrhythmias.4,8
Clinical Perspective see p 257
Experience with implantable cardioverter defibrillators
(ICDs) in patients with D-TGA is limited, whether prompted
by a sustained ventricular tachyarrhythmia or resuscitated
cardiac arrest (secondary prevention indication), or a clinical
profile deemed high risk in the absence of a near fatal event
(primary prevention indication). We conducted a multicenter
retrospective cohort study with the objectives of determining
Received February 26, 2008; accepted July 23, 2008.
From the Canadian Adult Congenital Heart Network, Montreal, Quebec, Canada (P.K., L.H., A.B., L.A.M., P.C., E.G., A.D.); Leeds General Infirmary,
Leeds, United Kingdom (S.V., P.C.); and Children’s Hospital, Boston, Mass (P.K., M.J.L., S.M.F., F.C.).
Correspondence to Dr Paul Khairy, Adult Congenital Heart Center, Montreal Heart Institute, 5000 Bélanger Street, Montreal, Quebec, Canada H1T
1C8. E-mail [email protected]
© 2008 American Heart Association, Inc.
Circ Arrhythmia Electrophysiol is available at http://circep.ahajournals.org
250
DOI: 10.1161/CIRCEP.108.776120
Khairy et al
actuarial rates of appropriate and inappropriate ICD shocks in
patients with D-TGA, identifying associated risk factors, and
characterizing complications. It was also our hope that
analysis of ICD electrogram recordings would provide mechanistic insights underlying sudden deaths.
Methods
Study Population
The study cohort consisted of patients with D-TGA, a Mustard or
Senning baffle, and an ICD implanted before January 2006 from the
following 7 participating sites: 5 centers within the Canadian Adult
Congenital Heart Network (Montreal Heart Institute, Quebec; Toronto General Hospital, Ontario; McMaster University Medical
Center, Ontario; St Paul Hospital, British Columbia; Hôpital Laval
de Québec, Quebec); Leeds General Infirmary (Leeds, United
Kingdom); and Children’s Hospital (Boston, Mass). Patients with
congenitally corrected TGA or TGA in the setting of a Rastelli repair
were excluded.
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Baseline Characteristics
A similar protocol was previously described in patients with tetralogy of Fallot.9 Data collection was conducted in accordance with
individual hospital institutional review board policies. Details regarding demographic variables, surgical history including type of
intra-atrial baffle repair (ie, Mustard or Senning), associated anomalies, interventions before or concomitant with surgical repair,
electrocardiography, chest radiography, 24-hour Holter monitoring,
2D and M-mode Doppler echocardiography, cardiac magnetic resonance (CMR) imaging, cardiac catheterization, and electrophysiology studies were collected. The most recent data preceding ICD
implantation were requested, with a maximum acceptable time
interval of 2 years.
Electrocardiographic data included heart rate, presence of an
underlying ventricular-paced rhythm, longest dominant QRS duration, and QT intervals. Cardiothoracic ratios were derived from
posterioanterior chest radiographs. The number of premature ventricular complexes in 24 hours and presence of nonsustained ventricular tachycardia (ⱖ3 beats, ⬍30 seconds) were captured from
Holter monitors. Echocardiographic and CMR data included biventricular size and function, degree of valvar regurgitation, and
estimates of systolic pulmonary arterial pressure. When both echocardiographic and CMR studies were performed, CMR data were
retained. Data extracted from programmed ventricular stimulation
studies included inducibility of sustained monomorphic or polymorphic ventricular tachycardia.
ICD Implantation
Indications prompting ICD implantation were recorded and included
presyncope/dizziness, syncope, palpitations, clinical nonsustained
ventricular tachycardia, QRS duration ⱖ180 ms, severe systemic
ventricular systolic dysfunction, inducible ventricular tachycardia,
clinical sustained ventricular tachycardia, ventricular fibrillation/
resuscitated cardiac arrest, and other. Patients were stratified according to whether the ICD was indicated for primary or secondary
prevention. “Secondary prevention” was defined by clinical sustained ventricular tachycardia, ventricular fibrillation, or resuscitated
cardiac arrest. As per convention, barring such events, the ICD was
considered indicated for “primary prevention.”
Procedural characteristics were logged and medical therapy at the
time of discharge was noted, with particular attention to ␤-blockers,
amiodarone, sotalol, dofetilide, and class IA or IC antiarrhythmic
agents.
ICD Shocks
The main outcome consisted of appropriate ICD shocks. The
ventricular tachycardia cycle length, programmed defibrillator zone
(ie, slow ventricular tachycardia, fast ventricular tachycardia, or
ventricular fibrillation), and success or failure of therapy was noted.
ICDs in D-TGA
251
Data regarding inappropriate ICD shocks were likewise collected.
All ICD events (ie, antitachycardia pacing or shock) and tracings
were requested, up to a maximum of 5 per “appropriate” and
“inappropriate” category for each patient.
A blinded adjudicating committee reviewed and classified all ICD
events, with each tracing analyzed by ⱖ2 independent electrophysiologists. Appropriate therapy was subclassified as monomorphic
ventricular tachycardia (ie, electrogram with a uniform and constant
morphology), polymorphic ventricular tachycardia (ie, electrogram
with relatively constant amplitude but displaying a shift in morphology or axis), or ventricular fibrillation (ie, constant shift in axis and
morphology of the electrogram accompanied by marked and variable
changes in amplitude). Inappropriate ICD shocks were further
categorized according to type of most likely underlying rhythm (ie,
noise interference or oversensing, sinus tachycardia, atrial flutter,
atrial fibrillation, and other form of supraventricular tachycardia).
ICD Complications
ICD complications were considered “periprocedural” if they occurred within 30 days of implantation and “late” thereafter. Late
complications were subdivided into lead and generator-related
events. Lead-related complications included lead dislodgement, lead
failure, endocarditis, and undersensing or oversensing. Pain, erosion,
pocket infection, migration, and device malfunction were considered
generator-related complications.
Statistical Analysis
Time zero was defined as time of ICD implantation. Patient-years
were accrued from time of entry until occurrence of an ICD shock or
the study termination date. Censoring occurred in the event of
cardiac transplantation, loss to follow-up, or death from other causes
not involving ICD therapy. Continuous variables are summarized by
mean⫾SD or median and interquartile range (25th, 75th percentile),
depending on normality of distribution. Categorical variables are
represented by frequencies and percentages. Baseline comparisons
between patients with ICDs for primary versus secondary prevention
were performed by Mann-Whitney rank sum, student t, or ␹2 tests
where appropriate. Freedom from appropriate and inappropriate ICD
shocks and overall survival was plotted using the Kaplan-Meier
method, with comparisons by log-rank statistics.
To assess predictors of ICD shocks, univariate and stepwise
multivariate Cox proportional hazard models were used after verifying proportional-hazards assumptions. Variables with probability
values ⬍0.1 in univariate analyses were considered in multivariate
models. Two-tailed probability values ⬍0.05 were considered statistically significant. Analyses were performed with SAS version 9.1
(SAS Institute, Cary, NC).
The authors had full access to and take full responsibility for the
integrity of the data. All authors have read and agreed to the
manuscript as written.
Results
Baseline Characteristic
A total of 37 patients (mean age, 28.0⫾7.6 years; 89.2%
male), were enrolled from 7 sites. ICDs were implanted for
primary prevention in 23 patients (62.1%) and secondary
prevention in 14 patients (37.8%). Age at time of ICD
implantation is graphically depicted in Figure 1. Baseline
characteristics in all patients and by primary versus secondary
prevention indications are summarized in Table 1. Patients
with ICDs for primary versus secondary prevention were
older at implantation, had a higher prevalence of documented
nonsustained ventricular tachycardia, and exhibited a trend
toward more moderate or severe right ventricular systolic
dysfunction. ECGs were available in all patients, echocardiograms in 36 patients (97.3%), chest x-rays in 34 patients
(91.9%), Holters in 29 patients (78.4%), cardiac catheteriza-
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October 2008
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Figure 1. Age at ICD implantation in patients with D-TGA and
Mustard or Senning baffles according to primary or secondary
prevention indications.
tion in 25 patients (67.6%), electrophysiological studies in 17
patients (45.9%), and CMR in 11 patients (29.7%).
In patients with primary prevention indications, defibrillator implantation was prompted by the following nonexclusive
reasons: presyncope in 3 patients (13.0%), syncope in 8
patients (34.8%), palpitations in 12 patients (52.2%), nonsustained ventricular tachycardia in 11 patients (47.8%), systemic right ventricular ejection fraction ⱕ35% in 8 patients
(34.8%), QRS duration ⱖ180 ms in 7 patients (30.4%), and
inducible sustained ventricular tachycardia in 7 patients
(30.4%). Indications for secondary prevention were ventricular fibrillation and/or resuscitated cardiac arrest in 10 patients (71.4%) and clinical sustained ventricular tachycardia
without cardiac arrest in 4 patients (28.6%).
Appropriate Antitachycardia Pacing or Shocks
Overall, 139 ICD discharges occurred in 12 patients over a
median follow-up of 3.6 (1.5, 5.5) years: 3.5 (1.4, 5.3) years
and 3.9 (2.3, 6.6) years in patients with primary and secondary prevention indications, respectively. Of all first ICD
discharges, 33.3% were appropriate. Five patients (13.5%)
received a total of 47 appropriate shocks (1 in primary
prevention; 46 in secondary prevention) clustered as follows:
1, 2, 4, 5, and 35 shocks. The median detected ventricular
tachyarrhythmia rate at time of first appropriate shock was
222 (165, 261) bpm. Monomorphic ventricular tachycardia
constituted 48.9% of appropriately treated arrhythmias, polymorphic ventricular tachycardia constituted 34.0%, and ventricular fibrillation constituted 17.0%. First ICD discharges
consisted of antitachycardia pacing alone in 1,
antitachycardia pacing followed by a shock in 1, and shocks
alone in 3 patients. The patient with initial antitachycardia
pacing alone later received an appropriate ICD shock.
Appropriate ICD Shocks
High rates of appropriate ICD shocks were noted for secondary (28.6%) but not primary (4.3%) prevention indications,
with annualized actuarial event rates of 6.0% and 0.5%,
respectively (P⫽0.0366). The only primary prevention ICD
patient to receive an appropriate shock was a 33-year-old man
with a Mustard baffle, severe systemic right ventricular dysfunction (ejection fraction 12%), moderate tricuspid regurgitation,
and nonsustained ventricular tachycardia. Freedom from
appropriate ICD shocks in primary and secondary prevention
is plotted in Figure 2A. All first appropriate ICD shocks were
successful. Univariate and multivariate predictors of appropriate ICD shocks are listed in Table 2. Figure 3 depicts
freedom from appropriate ICD shocks according to whether
or not patients received ␤-blockers. Class III antiarrhythmic
agents did not significantly modulate risk of appropriate
shocks.
Of the 18 adjudicated appropriate shocks, supraventricular
tachyarrhythmias were recognized as preceding or coexisting
with ventricular tachyarrhythmias in 9 patients (50.0%),
ventricular tachyarrhythmias appeared primary in 4 patients (22.2%), and in the remaining 5 patients (27.8%),
data provided from single-chamber ICDs precluded inferences regarding prior or concomitant supraventricular
tachyarrhythmias.
Inducible Ventricular Tachycardia and
Appropriate ICD Shocks
Of 17 patients with electrophysiological studies, 10 (58.8%)
had primary and 7 (41.2%) had secondary prevention indications. Overall, 9 patients (52.9%; 6 primary prevention) had
inducible sustained ventricular tachycardia, subclassified as
monomorphic in 3 patients (2 primary prevention) and
polymorphic in 6 patients (4 primary prevention). Appropriate ICD shocks were received by 0 of 9 patients with
inducible sustained ventricular tachycardia and 3 of 8 (ie, 0 of
4 and 3 of 4 with primary and secondary prevention indications,
respectively) noninducible patients (37.5%; P⫽0.0429). Two of
the 3 noninducible patients with appropriate ICD shocks received them for monomorphic ventricular tachycardia, whereas
the remaining patient had recurrent polymorphic ventricular
tachycardia.
Inappropriate ICD Shocks
Overall, 9 patients (24.3%) received 92 inappropriate ICD
shocks, 67 of which were in 5 patients (21.7%) with primary
prevention and 25 of which were in 4 patients (28.6%) with
secondary prevention indications. Underlying causes were
noted for 78 inappropriate shocks: lead fracture, failure, or
oversensing in 48 patients (61.5%), supraventricular
tachycardia in 21 patients (26.9%), and sinus tachycardia in 9
patients (11.5%). The 21 inappropriate shocks for supraventricular arrhythmias occurred in 7 patients and were all
designated “atrial flutter.” The median detected ventricular
tachycardia rate was 188 (165, 200) bpm, significantly slower
than appropriately shocked arrhythmias (P⫽0.0078).
Freedom from inappropriate ICD shocks at 1, 2, and 5
years was 83.2%, 75.6%, and 71.1%, respectively, corresponding to an average actuarial rate of 6.6% per year. No
difference was observed between primary and secondary
prevention groups (P⫽0.9765). In univariate analyses, risk
factors for inappropriate shocks were female sex (hazard
ratio, 4.9; 95% CI, 1.2 to 19.6; P⫽0.0261) and lighter weight
(hazard ratio, 0.91 per kg; 95% CI, 0.85 to 0.98; P⫽0.0106).
Khairy et al
Table 1.
ICDs in D-TGA
253
Baseline Characteristics
All Patients
N⫽37*
Primary
Prevention
N⫽23*
Secondary
Prevention
N⫽14*
P Value
28.0⫾7.6
30.1⫾7.8
24.7⫾6.2
0.0327
Demographics
Age at ICD implantation, years
33 (89.2)
19 (82.6)
14 (100.0)
0.0985
Height, cm
Male sex, n (%)
174.5⫾7.8
173.2⫾7.7
176.5⫾7.7
0.2220
Weight, kg
77.9⫾16.7
76.3⫾18.5
80.4⫾13.7
0.4818
Associated anomalies
Ventricular septal defect, n (%)
10 (27.0)
6 (26.1)
4 (28.6)
0.8689
Patent ductus arteriosus, n (%)
4 (10.8)
3 (13.0)
1 (7.1)
0.5751
Anomalous coronary artery, n (%)
2 (5.4)
1 (4.3)
1 (7.1)
0.7154
Mustard baffle, n (%)
29 (78.4)
18 (78.3)
11 (78.6)
0.9822
Senning baffle, n (%)
8 (21.6)
5 (21.7)
3 (21.4)
23.6⫾7.7
24.2⫾8.6
22.7⫾6.3
0.6047
21 (56.8)
13 (56.5)
8 (57.1)
0.9704
1 (2.7)
1 (4.3)
0 (0.0)
0.4289
10 (27.0)
5 (21.7)
5 (35.7)
0.3532
Dofetilide, n (%)
2 (5.4)
1 (4.3)
1 (7.1)
0.7153
Class IA or IC anti-arrhythmic agent, n (%)
0 (0.0)
0 (0.0)
0 (0.0)
-
Ventricular-paced rhythm, n (%)
9 (24.3)
5 (21.7)
4 (28.6)
0.6385
Heart rate, bpm
73⫾18
71⫾15
77⫾23
0.3319
Surgical history
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Time from intra-atrial baffle to ICD, years
Medical therapy
␤-blockers, n (%)
Sotalol, n (%)
Amiodarone, n (%)
Electrocardiogram
QRS duration, ms
153⫾51
160⫾55
143⫾45
0.3670
QTc (lead II), ms
445⫾55
487⫾60
522⫾115
0.2546
QT dispersion, ms
39 (23, 58)
31 (22, 45)
50 (23, 63)
0.2418
Cardiothoracic ratio, %
53.2⫾7.6
52.7⫾7.6
54.0⫾5.7
0.6746
625 (22, 2078)
387 (18, 2043)
1069 (26, 2113)
0.8435
10 (27.0)
10 (43.5)
0 (0.0)
0.0039
0.4613
Holter data
No. of PVCs in 24 hours
Nonsustained ventricular tachycardia, n (%)
Hemodynamics
Systemic RV ejection fraction, %
36⫾12
35⫾13
38⫾9
At least moderate systolic dysfunction, n (%)
22 (59.5)
16 (69.6)
6 (42.9)
0.0731
At least moderate tricuspid regurgitation, n (%)
12 (32.4)
7 (30.4)
5 (35.7)
0.7394
1 (2.7)
1 (4.3)
0 (0.0)
0.4074
At least moderate aortic regurgitation, n (%)
Subpulmonary LV ejection fraction, %
56⫾11
55⫾11
58⫾10
0.4921
At least moderate systolic dysfunction, n (%)
4 (10.8)
3 (13.0)
1 (7.1)
0.5456
At least moderate mitral regurgitation, n (%)
0 (0.0)
0 (0.0)
0 (0.0)
-
At least moderate pulmonary regurgitation, n (%)
1 (2.7)
1 (4.3)
0 (0.0)
0.4290
Systemic RV systolic pressure, mm Hg
103⫾20
105⫾23
98⫾12
0.4994
Systemic RV end-diastolic pressure, mm Hg
15 (9, 22)
15 (10, 24)
13 (6, 19)
0.4510
Subpulmonary LV systolic pressure, mm Hg
37 (27, 68)
29 (28, 72)
31 (24, 41)
0.2288
Subpulmonary LV end-diastolic pressure, mm Hg
8 (4, 13)
9 (5, 16)
4 (3, 10)
0.1529
Mean pulmonary artery pressure, mm Hg
24⫾14
27⫾14
21⫾15
0.4028
*Denominators for cardiothoracic ratio, Holter data, and cardiac catheterization-derived pressures in all patients are 34, 29, and 25, respectively. PVC indicates
premature ventricular complex; RV, right ventricle; LV, left ventricle.
In multivariate analyses, the latter was the only independent
predictor of inappropriate ICD shocks (hazard ratio, 0.91 per
kg; 95% CI, 0.85 to 0.98; P⫽0.0168).
Complications
Complications other than inappropriate shocks occurred in 14
patients (37.8%) overall: acute in 5 (13.5%), late generator
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October 2008
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Figure 3. Appropriate ICD shocks in patients with and without
␤-blockers. Kaplan-Meier survival curves for freedom from first
appropriate ICD shock are plotted and compared among
patients with D-TGA and Mustard or Senning baffles according
to whether they received ␤-blocker therapy.
Figure 2. Appropriate ICD shocks (A) and survival (B) in primary
and secondary prevention. Kaplan-Meier survival curves for
freedom from first appropriate ICD shock (A) and overall survival
(B) are plotted and compared among patients with D-TGA and
Mustard or Senning baffles having primary versus secondary
prevention indications.
related in 1 (2.7%), and late lead related in 12 (32.4%). Table
3 summarizes complications according to subtype; the categories are not mutually exclusive. Three patients had both
acute and late complications.
years, respectively, corresponding to an averaged actuarial
mortality rate of 1.9% per year. As depicted in Figure 2B, the
mortality rate was higher in ICD recipients with secondary
versus primary prevention indications, with annualized rates
of 3.4% versus 0% (P⫽0.0206).
The only episode of sudden death occurred in a 22-year-old
man with a Senning baffle, an ICD for secondary prevention,
and a prior appropriate and effective shock. His fatal event
was triggered by polymorphic ventricular tachycardia that
prompted 4 appropriate ICD shocks. Although the final shock
successfully interrupted ventricular fibrillation, electromechanical dissociation ensued with an agonal escape rhythm.
Discussion
D-TGA accounts for 5% to 7% of all congenital cardiac
malformations.10 Although largely supplanted by arterial
switch surgery, intra-atrial Senning and Mustard baffles
permitted survival into adulthood, often with good quality of
Table 3.
Acute and Late Complications
Overall Survival
Three patients (8.1%) died during follow-up: 2 (5.4%) from
heart failure and 1 (2.7%) suddenly. The overall actuarial
survival rate was 100%, 96.9%, and 91.0% at 1, 2, and 5
Table 2.
Predictors of Appropriate ICD Shocks
Variable
Hazard
Ratio
95% CI
P Value
Univariate analysis
N (%)
Acute complications
Hematoma
1 (2.7)
Pneumothorax
1 (2.7)
Reintervention
4 (10.5)
Lead dislodgement
3 (8.1)
Diaphragmatic stimulation
2 (5.4)
Late complications
Secondary prevention indication
5.1
1.1,45.5
0.0375
Ventricular septal defect
4.3
0.9,20.8
0.0742
At least moderate tricuspid regurgitation
4.1
0.8,20.5
0.0912
1.02
1.00,1.05
0.0767
Dislodgement
1.3,100.1
0.0303
Failure and/or fracture
6 (16.2)
Endocarditis
1 (2.7)
QTc, ms
Lack of ␤-blockers
11.3
Multivariate analysis
Generator related
Pocket infection
Lead related
1 (2.7)
1 (2.7)
12 (32.4)
3 (8.2)
Secondary prevention indication
18.0
1.2,261.0
0.0341
Under and/or over sensing
4 (10.8)
Lack of ␤-blockers
16.7
1.3,185.2
0.0301
Superior vena cava thrombosis
1 (2.7)
Khairy et al
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life.11,12 Sudden death is the most common cause of mortality.
Indeed, D-TGA with an intra-atrial baffle ranks among the
highest risk congenital heart defects, far exceeding tetralogy
of Fallot.1,13,14 Unlike some congenital heart defects where
hazard is appreciable only years after surgery,15 propensity
for sudden cardiac death in Mustard and Senning recipients
with D-TGA appears early.1 Risk seems relatively constant
over time, with estimated sudden cardiac death-free survival
rates of 96% at 10 years and 91% at 20 years.1,4,16
Little is known about ICDs in this patient population, with
the literature largely limited to case reports17 and 2 small case
series.18,19 One series of 5 patients reported no appropriate
shocks at a median of 20 months.18 The second series
included 7 patients with D-TGA as part of a larger cohort of
adults with congenital heart disease.19 Subgroup analyses
specific to D-TGA were not reported. To our knowledge, our
multicenter study is the first to explicitly address the role of
ICDs in high-risk patients with D-TGA. Importantly, a high
rate of appropriate shocks was observed in patients with
secondary prevention indications. Ventricular tachyarrhythmias were reliably sensed and effectively interrupted. In
contrast, the rate of appropriate ICD shocks in patients with
primary prevention indications was exceedingly low, highlighting our limitations in reliably identifying appropriate
high-risk candidates. Consequently, prophylactic ICDs in
D-TGA for indications such as systemic right ventricular
dysfunction, nonsustained ventricular tachycardia, syncope,
and inducible ventricular tachycardia remain unsubstantiated.
Little is known about the pathophysiology of sudden death
in patients with D-TGA and intra-atrial baffles. To this
regard, our study design provided a unique opportunity to
clarify mechanistic triggers. Intracardiac ICD tracings were
requested on all patients with shocks and subject to systematic blinded adjudication. Interestingly, supraventricular
tachyarrhythmias were often found to precede or coexist with
ventricular tachycardia. It can be conjectured, therefore, that
supraventricular tachyarrhythmias may be an important contributor to sudden death in this patient population and that
benefit may be derived from the suppression or elimination of
these substrates. This notion is consistent with reported risk
factors for sudden death. In a case-control study, Kammeraad
et al8 found that arrhythmia symptoms and documented atrial
fibrillation or flutter were most predictive of sudden death.
Several cohort studies likewise reported an increased incidence of sudden death in patients with supraventricular
arrhythmias, although it remained unclear whether these were
causative or surrogate markers for structural or hemodynamic
impairment.2,20 –22
Factors that may enhance susceptibility to degeneration of
supraventricular arrhythmias into fatal events include impaired atrioventricular transport with failure to augment right
ventricular filling rates during tachycardia,23 atrioventricular
nodal conduction capable of rapid ventricular responses,24
systemic right ventricular dysfunction,25 and subendocarial
ischemia resulting from a right coronary circulation irrigating
a systemic ventricle.26 In addition to potentially suppressing
primary ventricular arrhythmias, ␤-blockers may have salutary effects on a combination of these factors, which may
explain, in part, our finding that ␤-blockers afford protection
ICDs in D-TGA
255
against appropriate shocks. ␤-blockers may suppress supraventricular arrhythmias, increase diastolic filling time,
slow ventricular responses by increasing the atrioventricular
nodal effective refractory period, and reduce myocardial
ischemia. Unlike the lack of benefit with angiotensin receptor
blockade,27 preliminary data suggests that carvedilol may be
associated with positive right ventricular remodeling in patients with systemic right ventricles.28
Despite a predominance of supraventricular arrhythmias,
we also observed primary ventricular tachyarrhythmias. Importantly, these occurred exclusively in patients with secondary prevention indications. In a manner similar to dilated29
and hypertrophic30 cardiomyopathy, programmed ventricular
stimulation was of limited prognostic value. Fewer appropriate shocks occurred in inducible patients. Although this likely
reflects a chance finding, it is improbable that a larger sample
size would detect a statistically significant association in the
opposite direction. This is unlike tetralogy of Fallot where
inducible sustained ventricular tachycardia is of value in
predicting clinical ventricular tachyarrhythmia, sudden death,
and appropriate shocks.9,31
As for complications, in patients with congenital heart
disease, high rates of inappropriate ICD shocks are consistently reported. This likely reflects the relatively young age of
the study population, propensity for coexisting supraventricular tachyarrhythmias, and higher susceptibility for lead
failure.32 Indeed, nearly one third of our patients experienced
late lead-related complications. Prior studies have likewise
noted such high rates of complications in patients with
congenital heart disease with pacemakers and ICDs.9,19,32–36
Although we found lighter weight to independently predict
inappropriate shocks, younger age was previously identified
as a risk factor for lead fracture.32
Although some overlap was noted, supraventricular arrhythmias that provoked inappropriate shocks were generally
slower than ventricular tachyarrhythmias. Post hoc analysis
suggests that inappropriate shocks could have largely been
prevented by programming the ventricular tachycardia detection rate ⬎200 bpm. The desirability of such an approach
remains speculative, as it cannot be conclusively determined
whether inappropriate shocks for supraventricular
tachyarrhythmias may have circumvented otherwise fatal
events (ie, appropriate “inappropriate” shocks).
Limitations
Our study was retrospective, detection rates for ICD shocks
were not uniformly programmed, and medical decisions were
not randomly allocated. Primary prevention indications were
recorded and assessed, but standardized selection criteria
were not applied. Despite being the largest study of its kind,
the ability to identify relevant predictors is limited by the
overall low event rate. As such, a conservative probability
value cutoff (⬍0.1) was selected to limit potential variables
considered in multivariate models. Potential for human error
remains despite efforts to minimize misclassification of
appropriate versus inappropriate ICD shocks through systematic appraisal by a blinded expert adjudicating committee. In
28% of cases, appropriate ICD shocks were confirmed but
provided data were insufficient to comment on preceding
256
Circ Arrhythmia Electrophysiol
October 2008
supraventricular tachyarrhythmias. Importantly, ICD recipients were not compared to patients with similarly high-risk
features but without defibrillators, precluding quantification
of survival benefits.
9.
Conclusion
10.
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High rates of appropriate and effective ICD shocks were
observed in patients with D-TGA, Mustard or Senning
baffles, and clinical sustained ventricular tachyarrhythmias or
resuscitated cardiac arrest. This suggests an important role for
ICDs in secondary prevention against sudden death. In
contrast, protective effects from primary prevention ICDs
could not be surmised from our findings. Although primary
ventricular arrhythmias are observed in this population of
patients, supraventricular tachyarrhythmias seem to be a
common trigger. ␤-blockers afford protection against appropriate shocks and programmed ventricular stimulation does
not seem to be of prognostic value. Frequent adverse events
include inappropriate shocks and lead-related complications.
Acknowledgments
We are indebted to Maude Bergeron, RN (Montreal Heart Institute),
for her expert assistance. We also thank the following investigators
for their participation: Drs Mario Talajic, Marc Dubuc, Peter G.
Guerra, Laurent Macle, Bernard Thibault, and Denis Roy (Montreal
Heart Institute); Dr Jean-Marc Côté (Hôpital Laval de Québec); Dr
Mike Blackburn (Leeds General Infirmary); and Drs Edward P.
Walsh, John K. Triedman, Mark E. Alexander, and Charles I. Berul,
(Children’s Hospital, Boston).
11.
12.
13.
14.
15.
16.
17.
18.
19.
Sources of Funding
This study was funded by the Alliance for Congenital Heart Quebec
Interinstitutional Research, Fonds de Recherce en Santé du Québec, and
the Dunlevie Foundation. Dr Khairy is supported by a Canada Research
Chair in Electrophysiology and Adult Congenital Heart Disease.
20.
21.
Disclosures
None.
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CLINICAL PERSPECTIVE
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Transposition of the great arteries with Mustard or Senning baffles is among the congenital heart defects at highest risk for
sudden cardiac death. We conducted a multicenter cohort study to determine rates of appropriate and inappropriate ICD
shocks, identify risk factors, characterize complications, and elucidate potential mechanistic triggers for sudden deaths.
Overall, 37 patients (age, 28.0⫾7.6 years) were enrolled from 7 sites with ICDs for primary prevention in 23 and secondary
prevention in 14. A high rate of appropriate shocks was noted in secondary (6.0% per year) but not primary (0.5% per year)
prevention. Independent risk factors were limited to a secondary prevention indication (hazard ratio, 18.0) and lack of
␤-blockers (hazard ratio, 16.7). Inducible ventricular tachycardia did not seem to predict appropriate shocks. In 50% of
cases, intracardiac electrogram tracings recorded supraventricular tachycardia preceding or coexisting with ventricular
tachycardia. Inappropriate shocks occurred in 6.6% per year, and 37.8% of patients experienced complications,
predominantly late lead related. Although these results generally support the use of ICDs for secondary prevention, they
likewise highlight our limitations in reliably identifying appropriate candidates for prophylactic ICDs. Indications such as
systemic right ventricular dysfunction, nonsustained ventricular tachycardia, syncope, and inducible ventricular tachycardia
remain unsubstantiated. Importantly, it is unknown whether inappropriate shocks for supraventricular tachyarrhythmias
may have prevented fatal events (ie, appropriate “inappropriate” shocks). As supraventricular tachyarrhythmias seem to be
important contributors to sudden death in this patient population, it may be hypothesized that benefit may be derived from
suppressing or eliminating these substrates.
Sudden Death and Defibrillators in Transposition of the Great Arteries With Intra-atrial
Baffles: A Multicenter Study
Paul Khairy, Louise Harris, Michael J. Landzberg, Susan M. Fernandes, Amanda Barlow,
Lise-Andrée Mercier, Sangeetha Viswanathan, Philippe Chetaille, Elaine Gordon, Annie Dore
and Frank Cecchin
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Circ Arrhythm Electrophysiol. 2008;1:250-257; originally published online September 12, 2008;
doi: 10.1161/CIRCEP.108.776120
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