Response to Letter Regarding Article, “Implantable Cardioverter-Defibrillators in Tetralogy of Fallot”
We thank Witte et al for their interest in our article and encourage the critical appraisal of implantable cardioverter-defibrillator (ICD) therapy at large and in tetralogy of Fallot (TOF) in particular. We concur that decisions regarding ICD implantation should be thoughtfully considered in light of anticipated risks, known complications, and potential benefits. Indeed, one of our stated objectives was to provide caregivers with evidence-based data regarding ICD-related complications, as derived from a multicenter experience. These complications were undeniably substantial. Inappropriate shocks were observed in 5.8% of patients per year, and 80% of those shocks were triggered by sinus or supraventricular tachycardia.1 Complications other than inappropriate shocks occurred in 30% and were predominantly late lead–related. From a psychosocial perspective, feelings of anxiety and depression have been previously characterized in youths with ICDs, although most remain rather resilient.2
Witte et al submit that the rate of sudden cardiac death in patients with TOF is far inferior to that in patients with ischemic or dilated cardiomyopathy, such that a marginal reduction in the rate of death is expected from ICDs. We appreciate the opportunity to further clarify our perspective so as to avoid misguided generalizations. Importantly, it was never argued (and would be ill-advised to suggest) that all patients with TOF should receive an ICD or, alternatively, that TOF is itself a sufficient sole indication for ICD therapy. The incidence of sudden cardiac death in patients with TOF at large, including children, is likely 10-fold less than the 1.2% to 1.8% annualized rate proposed by Witte et al.3 The challenge lies in reliably identifying a sufficiently at-risk subgroup who may benefit from ICD therapy. Risk stratification remains imperfect and worthy of refinement. Nevertheless, significant strides have been achieved over the past decade in identifying noninvasive4 and invasive predictors of clinical ventricular tachycardia and sudden death. A combination of static and dynamic factors is likely to provide the most accurate risk estimates.5 Denying a high-risk subgroup of patients with TOF ICD therapy because of an overall low population risk is analogous to claiming that patients with ischemic left ventricular dysfunction are not appropriate ICD candidates given the low incidence of sudden death in coronary artery disease at large.
Issues surrounding appropriate ICD shocks as an endpoint were previously extensively discussed.1 We share the regrettable but realistic opinion of Witte et al that an adequately powered randomized ICD trial in TOF with total mortality as an outcome would be helpful but may not be feasible, especially if secondary prevention patients are aptly excluded. Although we fully recognize the limitations of our study design, we believe that it has added considerably to our knowledge base. It enabled the study of a rare exposure, that is, ICDs in TOF; permitted calculations of incidence-density rates including mortality and ICD shocks (appropriate and inappropriate); allowed comparisons between ICD recipients with primary and secondary prevention indications; provided a temporal sequence between ICD implantation and outcomes; and enabled identification of risk factors, their relative risks,and elaboration of a risk score. To date, it is the largest ICD study in congenital heart disease and the only one specific to TOF.
Finally, Witte et al appeared unconvinced of the appropriateness of ICD guidelines for repaired congenital heart disease given the absence of randomized studies. We, however, applaud the initiative by Zipes et al6 and advocate the inclusion of patients with congenital heart disease. The population of patients with congenital heart disease is growing and aging. It is becoming increasingly important to ensure that their particular needs and specific issues are attentively addressed and incorporated into proposed standards of care that respect the current state of knowledge. Overlooking a patient population with a high risk of sudden death because of lack of randomized data is clearly not desirable. As we continue to aspire to higher levels of evidence, the patients of today cannot be ignored. Hopefully, our multicenter study provides caregivers with useful data to assist in selecting individual patients with repaired TOF who may potentially benefit from ICD therapy.
Khairy P, Harris L, Landzberg MJ, Viswanathan S, Barlow A, Gatzoulis MA, Fernandes SM, Beauchesne L, Therrien J, Chetaille P, Gordon E, Vonder Muhll I, Cecchin F. Implantable cardioverter-defibrillators in tetralogy of Fallot. Circulation. 2008; 117: 363–370.
Gatzoulis MA, Balaji S, Webber SA, Siu SC, Hokanson JS, Poile C, Rosenthal M, Nakazawa M, Moller JH, Gillette PC, Webb GD, Redington AN. Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study. Lancet. 2000; 356: 975–981.
Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Smith SC Jr, Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Blanc JJ, Budaj A, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL. ACC/AHA/ESC 2006 Guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association task force and the European Society of Cardiology committee for practice guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation. 2006; 114: e385–e484.