CLINICAL PERSPECTIVE

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(Circulation. 2008;117:363-370.)
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Congenital Heart Disease

Implantable Cardioverter-Defibrillators in Tetralogy of Fallot

Paul Khairy, MD, PhD; Louise Harris, MD; Michael J. Landzberg, MD; Sangeetha Viswanathan, MRCPCH; Amanda Barlow, MD; Michael A. Gatzoulis, MD; Susan M. Fernandes, MHP, PA-C; Luc Beauchesne, MD; Judith Therrien, MD; Philippe Chetaille, MD; Elaine Gordon, MD; Isabelle Vonder Muhll, MD; Frank Cecchin, MD

From the Canadian Adult Congenital Heart (CACH) Network (P.K., L.H., A.B., L.B., J.T., E.G., I.V.M.), Canada; Alliance for Congenital heart Quebec Interinstitutional REsearch (ACQUIRE) (P.K., J.T., P.C.), Canada; Leeds General Infirmary (S.V.), Leeds, United Kingdom; Royal Brompton Hospital (M.A.G.), London, United Kingdom; and Children’s Hospital, (P.K., M.J.L., S.M.F., F.C.), Boston, Mass.

Reprint requests to Dr Paul Khairy, Adult Congenital Heart Center, Montreal Heart Institute, 5000 Bélanger St, Montreal, Quebec, Canada H1T 1C8. E-mail paul.khairy{at}umontreal.ca

Received July 6, 2007; accepted October 18, 2007.

	Abstract

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Background— Tetralogy of Fallot is the most common form of congenital heart disease in implantable cardioverter-defibrillator (ICD) recipients, yet little is known about the value of ICDs in this patient population.

Methods and Results— We conducted a multicenter cohort study in high-risk patients with Tetralogy of Fallot to determine actuarial rates of ICD discharges, identify risk factors, and characterize ICD-related complications. A total of 121 patients (median age 33.3 years; 59.5% male) were enrolled from 11 sites and followed up for a median of 3.7 years. ICDs were implanted for primary prevention in 68 patients (56.2%) and for secondary prevention in 53 (43.8%), defined by clinical sustained ventricular tachyarrhythmia or resuscitated sudden death. Overall, 37 patients (30.6%) received at least 1 appropriate and effective ICD discharge, with a median ventricular tachyarrhythmia rate of 213 bpm. Annual actuarial rates of appropriate ICD shocks were 7.7% and 9.8% in primary and secondary prevention, respectively (P=0.11). A higher left ventricular end-diastolic pressure (hazard ratio 1.3 per mm Hg, P=0.004) and nonsustained ventricular tachycardia (hazard ratio 3.7, P=0.023) independently predicted appropriate ICD shocks in primary prevention. Inappropriate shocks occurred in 5.8% of patients yearly. Additionally, 36 patients (29.8%) experienced complications, of which 6 (5.0%) were acute, 25 (20.7%) were late lead-related, and 7 (5.8%) were late generator-related complications. Nine patients died during follow-up, which corresponds to an actuarial annual mortality rate of 2.2%, which did not differ between the primary and secondary prevention groups.

Conclusions— Patients with tetralogy of Fallot and ICDs for primary and secondary prevention experience high rates of appropriate and effective shocks; however, inappropriate shocks and late lead-related complications are common.

Key Words: tetralogy of Fallot • defibrillation • tachyarrhythmias • death, sudden • heart defects, congenital

	Introduction

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Implantable cardioverter-defibrillators (ICDs) are increasingly utilized in the growing and aging population with congenital heart disease. Patients with tetralogy of Fallot (TOF), the most common form of cyanotic heart disease, constitute the largest subgroup of ICD recipients with congenital heart disease.^1,2 Indeed, the propensity for late-onset ventricular tachyarrhythmias is well recognized in TOF, and sudden cardiac death constitutes the most frequent mode of demise in infant survivors.^3–5 The actuarial incidence of clinical sustained ventricular tachycardia and sudden death is estimated to be 11.9% and 8.3%, respectively, 35 years after corrective surgery.³

Clinical Perspective p 370

Little is known about ICD therapy in patients with TOF, whether device implantation was prompted by a sustained ventricular tachyarrhythmia and/or resuscitated cardiac arrest (secondary prevention indication) or by a clinical profile deemed high-risk in the absence of a near-fatal event (primary prevention indication). We therefore conducted an international retrospective cohort study in patients with TOF, with the objectives of determining actuarial rates of appropriate and inappropriate ICD shocks in primary and secondary prevention, identifying associated risk factors, and characterizing ICD-related complications.

	Methods

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Study Population
The study cohort consisted of patients with surgically repaired TOF and an ICD implanted before January 2006 from 11 participating sites: 8 centers within the Canadian Adult Congenital Heart (CACH) Network (Montreal Heart Institute, Quebec; Toronto General Hospital, Ontario; Walter Mackenzie Health Sciences Center, Alberta; Ottawa Heart Institute, Ontario; McGill University Health Center, Quebec; McMaster University Medical Center, Ontario; St. Paul Hospital, British Columbia; and Hôpital Laval de Québec, Quebec); and 3 additional centers (Leeds General Infirmary, Leeds, United Kingdom; Royal Brompton Hospital, London, United Kingdom; and Children’s Hospital, Boston, Mass). Patients with unrepaired TOF, atrioventricular canal, and double-outlet right ventricle were excluded.

Baseline Characteristics
Data collection was conducted in accordance with individual hospital institutional review board policies. Details on demographic variables, surgical history, associated anomalies, interventions before or concomitant with surgical repair, ECG, chest radiography, 24-hour Holter monitoring, 2-dimensional 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.

Surgical characteristics included the presence of a ventriculotomy incision and type of repair (ie, pulmonary valvotomy and/or infundibular muscle resection; nontransannular right ventricular outflow tract patch; transannular right ventricular outflow tract patch; pulmonary valve implantation; and extracardiac right ventricle–to–pulmonary artery conduit). ECG data included heart rate, presence of an underlying ventricular-paced rhythm, longest dominant QRS duration, and QT intervals. Cardiothoracic ratios were derived from posteroanterior chest radiographs. The number of premature ventricular complexes in 24 hours and the presence of nonsustained ventricular tachycardia (3 beats or more, <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 that prompted ICD implantation were recorded and included presyncope/dizziness, syncope, palpitations, clinical nonsustained ventricular tachycardia, QRS duration 180 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 to be indicated for primary prevention. Procedural characteristics were logged, and medical therapy at the time of discharge was noted, with particular attention given to the use of β-blockers, amiodarone, sotalol, and class IA or IC antiarrhythmic agents.

ICD Shocks
The main outcome consisted of appropriate ICD shocks. A secondary composite outcome consisted of appropriate ICD discharges, including antitachycardia pacing and/or shocks. The ventricular tachycardia cycle length, programmed defibrillator zone (eg, slow ventricular tachycardia, fast ventricular tachycardia, or ventricular fibrillation), and success or failure of therapy were noted. Data on 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 at least 2 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 probable 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 due to 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 were plotted with 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 proportional-hazards assumptions were verified. Variables with probability values <0.25 in univariate analyses were considered in multivariate models, with final model selection based on most favorable goodness-of-fit measures (ie, Akaike information criterion and Schwartz bayesian criterion). Relative values of β-coefficients were used to devise a risk score for appropriate ICD shocks. Two-tailed probability values <0.05 were considered statistically significant. Analyses were performed with SAS software 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 agree to the manuscript as written.

	Results

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Baseline Characteristics
A total of 121 patients (median age 33.3 years [21.3, 40.9 years]; 59.5% male), were enrolled from 11 sites. ICDs were implanted for primary prevention in 68 patients (56.2%) and for secondary prevention in 53 (43.8%). 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. ECGs were available in all patients, echocardiograms in 118 (97.5%), Holter recordings in 94 (77.8%), electrophysiological studies in 86 (71.1%), cardiac catheterization in 72 (59.5%), chest radiographs in 67 (55.4%), and CMR in 36 (29.8%).

View larger version (35K): [in this window] [in a new window]   Figure 1. Age at ICD implantation in patients with TOF according to primary or secondary prevention indications.

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics

In patients with primary prevention indications, defibrillator implantation was prompted by the following nonexclusive reasons: presyncope in 13 (19.1%), syncope in 30 (44.1%), palpitations in 33 (48.5%), QRS duration 180 ms in 19 (27.9%), nonsustained ventricular tachycardia in 25 (36.8%), left ventricular ejection fraction 35% in 2 (2.9%), and inducible sustained ventricular tachycardia in 28 (41.2%). Indications for secondary prevention were ventricular fibrillation and/or resuscitated cardiac arrest in 16 patients (30.2%) and clinical sustained ventricular tachycardia without cardiac arrest in 37 (69.8%).

Appropriate Antitachycardia Pacing or Shocks
Overall, 508 ICD discharges occurred over a median follow-up of 3.7 years (1.5, 5.6 years). Of all first ICD discharges, 63.5% were appropriate. A total of 37 patients (30.6%) received at least 1 appropriate discharge. The median detected ventricular tachyarrhythmia rate was 213 bpm (182, 264 bpm), with a trend toward faster rates in secondary versus primary prevention groups (P=0.068). Monomorphic ventricular tachycardia constituted 81.5% of appropriately treated arrhythmias, with the remainder classified as polymorphic ventricular tachycardia or ventricular fibrillation. First ICD discharges consisted of antitachycardia pacing alone in 11 patients, antitachycardia pacing followed by shocks in 3, and shocks alone in 23. Six of the 11 patients with initial antitachycardia pacing alone later received appropriate ICD shocks.

Appropriate ICD Shocks in Primary and Secondary Prevention
High rates of appropriate ICD shocks were noted for both primary prevention (23.5%) and secondary prevention (30.2%) indications, with annualized actuarial event rates of 7.7% and 9.8% per year, respectively (P=0.11). Freedom from appropriate ICD shocks in primary and secondary prevention is plotted in Figure 2A. Importantly, all first appropriate ICD shocks were successful. The actuarial rate of appropriate shocks for polymorphic ventricular tachycardia or ventricular fibrillation was 3.6% per year, with rates of 3.3% and 4.2% in primary and secondary prevention, respectively (P=0.66).

View larger version (19K): [in this window] [in a new window]   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 TOF having primary vs secondary prevention indications.

When all patients were considered, the only independent predictor of appropriate ICD shocks was a prior ventriculotomy incision (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.1 to 5.4, P=0.025). The use of β-blockers (HR 0.7, 95% CI 0.3 to 1.5, P=0.37), amiodarone (HR 0.8, 95% CI 0.3 to 2.3, P=0.69), and sotalol (HR 1.3, 95% CI 0.4 to 3.6, P=0.67) did not significantly modulate the risk of appropriate shocks. A tendency toward more appropriate shocks was noted with class IA or IC agents (HR 2.0, 95% CI 0.7 to 5.8, P=0.19).

Univariate and multivariate predictors of appropriate ICD shocks in patients with primary prevention indications are listed in Table 2. Multivariate predictors of appropriate shocks in primary prevention were higher left ventricular end-diastolic pressure (LVEDP; HR 1.3 per mm Hg, 95% CI 1.1 to 1.6, P=0.004) and nonsustained ventricular tachycardia (HR 3.7, 95% CI 1.2 to 11.3, P=0.023). In patients with and without appropriate ICD shocks, the mean LVEDP was 16 mm Hg (95% CI 12 to 20 mm Hg) versus 10 mm Hg (95% CI 8 to 11 mm Hg), respectively (P=0.001). LVEDP was significantly inversely correlated with left ventricular ejection fraction (P=0.0496) and was positively correlated with age (P=0.035), cardiothoracic ratio (P=0.007), right ventricular systolic pressure (P=0.042), left ventricular end-diastolic size (P=0.007), mean pulmonary artery pressure (P<0.0001), and inducible sustained monomorphic ventricular tachycardia (P=0.031).

View this table: [in this window] [in a new window]   Table 2. Predictors of Appropriate ICD Shock in Primary Prevention

Risk Score for Appropriate ICD Shocks in Primary Prevention
For patients with primary prevention indications, actuarial annualized rates of appropriate ICD shocks according to various clinical characteristics are displayed in Figure 3. A risk score to predict appropriate ICD shocks in primary prevention was derived from 6 clinical variables identified by multivariate analyses. Exponential values of β-coefficients and points attributed to each characteristic are summarized in Table 3. A 1-point increase in risk score was associated with an HR of 1.5 (95% CI 1.2 to 1.8, P=0.0003). From a possible maximum of 12 points, 3 risk categories were identified: low (0 to 2 points), intermediate (3 to 5 points), and high (6 points). Freedom from appropriate ICD shocks according to risk score strata and actuarial annualized rates are depicted in Figure 4. Although no appropriate shock occurred in the low-risk subgroup, 2 of 18 patients experienced appropriate antitachycardia pacing, which corresponds to a 2.4% yearly rate of appropriate ICD discharges.

View larger version (21K): [in this window] [in a new window]   Figure 3. Mean actuarial annualized rates of appropriate ICD shocks in primary prevention according to clinical characteristics. For each clinical characteristic, the mean annual rate of appropriate ICD shocks is represented by a black diamond, bounded by lower and upper 95% confidence limits. The vertical dotted line represents the actuarial annualized rate of appropriate ICD shocks (ie, 7.7%) in all primary prevention patients. RV indicates right ventricular.

View this table: [in this window] [in a new window]   Table 3. Risk Score for Appropriate ICD Shocks in Primary Prevention

View larger version (23K): [in this window] [in a new window]   Figure 4. Freedom from appropriate ICD shocks in primary prevention according to risk category. In patients with primary prevention indications, Kaplan-Meier survival curves for freedom from first appropriate ICD shock are plotted and compared according to risk score classification. Risk score, corresponding risk category, number of patients, and annualized rate of appropriate shocks are summarized below the graph.

Inducible Ventricular Tachycardia and Appropriate ICD Shocks
Of the 86 patients with electrophysiological studies, 55 (64.0%) had primary and 31 (36.0%) had secondary prevention indications. Overall, 62 patients (72.1%) had inducible sustained ventricular tachycardia, subclassified as monomorphic in 54 and polymorphic in 8. Appropriate ICD shocks were received by 3 noninducible patients (12.5%) and 23 patients with inducible sustained ventricular tachycardia (37.1%; P=0.063). Of these 23 patients, 10 received appropriate shocks for ventricular fibrillation, all of whom had monomorphic ventricular tachycardia induced by programmed ventricular stimulation. One of 8 patients with inducible sustained polymorphic ventricular tachycardia received an appropriate shock for monomorphic ventricular tachycardia.

Inappropriate ICD Shocks
Overall, 30 patients (24.8%) received at least 1 inappropriate ICD shock, due to lead fracture, failure, or oversensing in 20.0%; sinus tachycardia in 30.0%; and supraventricular tachyarrhythmia in 50.0%. Freedom from inappropriate ICD shocks at 1, 2, and 5 years was 87.3%, 86.4%, and 74.3%, respectively, which corresponds to an average actuarial rate of 5.8% per year. No difference was observed between primary and secondary prevention groups. Independent predictors of inappropriate ICD shocks were higher right ventricular systolic pressure (HR 1.03 per mm Hg, 95% CI 1.00 to 1.05, P=0.026) and QRS duration 180 ms (HR 3.6, 95% CI 1.2 to 10.9, P=0.020).

Complications
Complications other than inappropriate shocks occurred in 36 patients (29.8%). Six (5.0%) experienced periprocedural complications, which consisted of pneumothorax in 1 patient (0.8%), hemothorax in 1 patient (0.8%), and need for lead reintervention within the first 30 days in 4 patients (3.3%) due to lead dislodgement (n=3) or high defibrillation threshold (n=1). Seven patients (5.8%) had late generator-related complications, which consisted of chronic pain that required reintervention in 2 patients (1.7%), erosion or pocket infection in 2 (1.7%), and malfunction or recall in 4 (3.3%). Late lead-related complications occurred in 25 patients (20.7%); these resulted from dislodgement in 3 patients (2.5%), failure and/or fracture in 11 (9.1%), endocarditis in 1 (0.8%), undersensing and/or oversensing in 10 (8.3%), and thrombosis that prompted anticoagulation in 1 (0.8%).

Overall Survival
Nine patients (7.4%) died during the course of follow-up, 4 of heart failure (3.3%) and 5 suddenly (4.1%). Three of the 5 sudden cardiac deaths were attributed to presumed electromechanical dissociation, because no tachyarrhythmia was detected on ICD interrogation. One patient experienced a ventricular tachyarrhythmia storm and died after exhaustion of ICD therapy. The final patient had received >50 predominantly appropriate ICD shocks in the past, pleaded for the ICD to be inactivated (fully understanding the implications), and died suddenly 6 months later.

The overall actuarial survival rate was 98.1%, 96.9%, and 89.6% at 1, 2, and 5 years, respectively, which corresponds to an averaged actuarial mortality rate of 2.2% per year. As depicted in Figure 2B, no difference in survival was noted among ICD recipients with primary versus secondary prevention indications.

	Discussion

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As early as 1975, sudden death due to presumed ventricular tachyarrhythmia was recognized as a devastating consequence of surgically repaired TOF.⁶ Studies have since consistently reported sudden cardiac death to be the most common cause of late mortality.^3,4,7 Nevertheless, prevention of sudden death in TOF continues to be a major challenge. One complexity lies in reliably identifying high-risk patients within a population that experiences an overall low incidence of sudden cardiac death, estimated to be 0.15% per year.^4,8 In this regard, major advances have been achieved over the past decade. Large multicenter studies reported both noninvasive³ and invasive⁵ risk factors for ventricular tachycardia and sudden death. As risk stratification algorithms improve and the population with TOF ages, an increasing number of patients deemed at high risk for sudden death are receiving ICDs; however, ICD studies specific to this population of patients have not been conducted previously. Prior case series explored ICD utilization patterns in congenital heart disease at large.^1,2,9 The largest series included 64 patients, 40 with TOF, and reported appropriate ICD discharges in 23% at a median of 3.7 years.¹

The results of the present multicenter study suggest an important role for ICD therapy in preventing sudden death in high-risk patients with TOF. The defibrillator proved reliable in sensing and terminating ventricular tachyarrhythmias. Appropriate ICD discharges occurred in 31% and appropriate shocks in 26% of 121 patients during a median follow-up of 3.7 years. Rates of appropriate ICD shocks were high in patients with both primary and secondary prevention indications, at 7.7% and 9.8% per year, respectively.

However, the present study was conducted in carefully selected patients deemed to be at high risk for sudden death. Moreover, it remains unknown what proportion of ventricular tachyarrhythmias would have truly been fatal without appropriate ICD shocks. As an end point, appropriate ICD shocks is an imperfect surrogate marker for sudden cardiac death that likely overestimates risk.¹⁰ In patients with TOF in particular, monomorphic ventricular tachycardia may occur without hemodynamic compromise despite rapid rates. Nevertheless, the ventricular arrhythmias noted in the present study were similar in distribution to those in other primary prevention patient populations with demonstrated survival benefits from ICDs.¹¹ In post–myocardial infarction patients with a left ventricular ejection fraction 30% (MADIT-II [Multicenter Automatic Defibrillator Implantation Trial II]) and the present study population with TOF, 82% of detected ventricular arrhythmias were monomorphic ventricular tachycardia, and 18% were polymorphic ventricular tachycardia or ventricular fibrillation.¹² Furthermore, the 7.7% annual rate of appropriate ICD shocks noted in the present study exceeds reported rates in primary prevention studies of hypertrophic cardiomyopathy (5%)¹³ and ischemic or nonischemic cardiomyopathy with a left ventricular ejection fraction 35% (5.1%).¹⁴ It approaches that of MADIT-II subgroups (eg, 9.0% in New York Heart Association class I or II patients).^11,12

Although the present study was not designed to prospectively assess a particular risk-stratification scheme for prophylactic implantation of defibrillators in TOF, the high rates of appropriate ICD shocks suggest that caregivers are successfully identifying a sufficiently at-risk subgroup. Among ICD recipients with primary prevention indications, elevated LVEDP and nonsustained ventricular tachycardia independently predicted appropriate shocks. Increased right ventricular afterload may contribute to the complex pathophysiology of right ventricular failure, particularly in the setting of pulmonary regurgitation with chronic volume overload.¹⁵ Indeed, electrical instability of the right ventricle appears to closely parallel mechanical properties.¹⁶ Not surprisingly, LVEDP also correlated with left ventricular size and systolic function. Left ventricular systolic dysfunction has been linked to sudden death in TOF.¹⁷ An increased LVEDP independently predicted mortality in 3024 consecutive patients undergoing cardiac surgery.¹⁸

Although a risk score was presented to enhance the clinical applicability of the present findings, it must be placed in context. First, it was derived in a selected population of patients with ICDs for primary prevention and should not, therefore, be generalized to patients with TOF at large. Second, the precision of the risk estimates was limited by the sample size of the primary prevention subgroup. The study population was insufficient for intrastudy crossover validation, and only 2 of 6 clinical variables included independently predicted appropriate shocks. Validation in an independent data set is therefore recommended. Notwithstanding these limitations, the risk score sheds some light on gradients of hazard in TOF patients without prior sustained ventricular arrhythmias or sudden death deemed at sufficiently high risk to receive an ICD. Identification of a low-risk stratum (2 points), which constituted 26.5% of the study population, seems noteworthy. Despite drawbacks inherent to the use of appropriate shocks as an end point, it may be reasonably inferred that long-term survival without an appropriate discharge indicates lack of benefit from ICDs.

Complications associated with ICD therapy in TOF remain substantial. In particular, a high rate of inappropriate ICD shocks was noted, which averaged 5.8% per year. Predictors of inappropriate shocks consisted of QRS duration 180 ms and higher right ventricular systolic pressure. These indices may reflect chronic right ventricular volume overload, which has been associated with an increased incidence of right-sided atrial arrhythmias.¹⁹ The high rate of inappropriate ICD shocks consistently reported in patients with congenital heart disease likely reflects the relatively young age of the study population, the propensity for coexisting supraventricular tachyarrhythmias, and the higher susceptibility for lead failure.²⁰ Indeed, 21% of patients experienced late lead-related complications. High rates of lead-related complications have been reported previously in patients with congenital heart disease with pacemakers and ICDs.^{1,2,9,20–22}

Study Limitations
The present study was retrospective in nature. As such, medical decisions were not allocated randomly. Patients deemed at highest risk for ventricular arrhythmias may have been more likely to receive additional pharmacological therapy to prevent appropriate ICD discharges. Although no significant associations were noted, we controlled for medical therapy in multivariate analyses to minimize this potential bias. Likewise, antitachycardia pacing protocols and detection rates for ICD shocks were not uniformly programmed, which introduces the potential for detection bias (ie, patients with lower programmed thresholds have more "sensitive" settings for the detection and treatment of ventricular arrhythmias). This may potentially overestimate differences between primary and secondary prevention indications. Nevertheless, most detected ventricular arrhythmias were >200 bpm, which lessens the potential impact of this bias. Although efforts were made to minimize misclassification of appropriate versus inappropriate ICD therapy through systematic appraisal by a blinded expert adjudicating committee, potential for human error remains. Importantly, ICD recipients were not compared with patients with similarly high-risk features but without defibrillators, which precludes the quantification of survival benefits.

Conclusions
High rates of appropriate and effective shocks are noted in high-risk candidates with TOF, which suggests that ICDs may play an important role in the primary and secondary prevention of sudden death in this patient population. In ICD recipients with primary prevention indications, the risk of appropriate shocks is modulated by a combination of surgical, hemodynamic, ECG, and electrophysiological factors. However, the drawbacks are considerable and include a high incidence of inappropriate shocks and late lead-related complications.

	Acknowledgments

 
We are indebted to Maude Bergeron, RN (Montreal Heart Institute), for her expert assistance. We also wish to thank the following investigators for their participation: Drs Lise-Andrée Mercier, Annie Dore, Mario Talajic, Marc Dubuc, Peter G. Guerra, Laurent Macle, Bernard Thibault, and Denis Roy, Montreal Heart Institute; Dr Janice Till, Royal Brompton Hospital; Dr Anthony Tang, Ottawa Heart Institute; Dr Ariane Marelli, McGill University Health Center; 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.

Sources of Funding

This study was funded in part by the Alliance for Congenital heart QUebec Interinstitutional REsearch (ACQUIRE) and Fonds de Recherche en Santé du Québec (FRSQ). Dr Khairy is supported by a Canada Research Chair in Electrophysiology and Adult Congenital Heart Disease.

Disclosures

None.

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CLINICAL PERSPECTIVE

Tetralogy of Fallot represents the most common form of congenital heart disease in implantable cardioverter-defibrillator (ICD) recipients; however, little is known about the utility of ICDs in this patient population. We conducted a multicenter cohort study in high-risk patients with tetralogy of Fallot to assess this therapy. In particular, we sought to quantify rates of appropriate and inappropriate ICD shocks, identify risk factors, and characterize ICD-related complications. Overall, 121 patients from 11 sites were included and followed up for a median of 3.7 years. ICD placement was indicated for primary (56%) or secondary (44%) prevention; major indications for primary prevention included syncope, prolonged QRS duration, nonsustained ventricular tachycardia, and inducible sustained ventricular tachycardia. A high rate of appropriate shocks was present in both primary (7.7%/year) and secondary (9.8%/year) prevention groups, and ICDs were highly effective in interrupting ventricular tachyarrhythmias. In patients with primary prevention indications, the risk of appropriate shocks was modulated by a combination of surgical, hemodynamic, ECG, and electrophysiological factors. Overall, these results suggest that ICDs are effective in primary and secondary prevention against sudden death in this patient population; however, major drawbacks include a high rate of inappropriate shocks (5.8% per year) and late lead-related complications (21%).

	Footnotes

 
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