Response to Letters Regarding Article, “Long-Term Arrhythmia-Free Survival in Patients With Severe Left Ventricular Dysfunction and No Inducible Ventricular Tachycardia After Myocardial Infarction”
Authors: Sarah Zaman, Arun Narayan, Aravinda Thiagalingam, Gopal Sivagangabalan, Stuart Thomas, David L. Ross, Pramesh Kovoor
Journal: Circulation (2014)

We thank De Ferrari et al for their insightful comments about our article. 1As has been identified in our Results and discussed in our Study Limitations, we understand that bias resulting from differences in baseline characteristics invariably occurs when an observational rather than a randomized study is performed.In addition, we appreciate that recent studies have shown that some implantable cardioverterdefibrillator (ICD)-detected ventricular tachycardias may terminate spontaneously when monitoring zones are pushed out, which may have led to an overestimation of arrhythmic events.However, the ICD detection and treatment zones programmed in the present study were consistent with published guidelines at the time.We fully agree with De Ferrari et al that studies such as the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II substudy, assessing the utility of electrophysiology study (EPS) in predicting arrhythmia, were substantially influenced by the type of programmed ventricular stimulation protocol used.The evidence supporting a strict programmed ventricular stimulation protocol containing 4 extrastimuli with up to 2 inductions, with inclusion of inducible monomorphic VT cycle length >200 milliseconds (but not ventricular fibrillation) as a positive result, has been summarized in our recent Circulation review article. 2 We are pleased to hear from De Ferrari et al that almost equivocal positive and negative predictive values for EPS were elucidated with a similarly strict programmed ventricular stimulation protocol.We thank Ehdaie and Rubin for their interesting comments.Whereas repeat left ventricular ejection fraction (LVEF) at day 40 would add insight to the present study, this was not part of the study protocol.Early LVEF will not necessarily reflect late LVEF, given the phenomenon of myocardial stunning.We can hypothesize that of our EPS-negative patients, 24% would have improved to have a LVEF >40% at 6 months. 3Similarly, the control group would also have LVEF improvement with time (although not to the same extent).However, our reasons for using an early, and therefore higher, LVEF cutoff for selection for an EPS were 2-fold.First, a low LVEF cutoff value used alone to guide ICD implantation has poor specificity and sensitivity for sudden cardiac death.Whereas half of sudden cardiac deaths occur in patients with LVEF ≤30%, the remaining 50% occur in patients with a higher ejection fraction. 4LVEF alone has low specificity in selecting patients who die of arrhythmic versus nonarrhythmic (ie, heart failure) deaths.The second reason for using an early LVEF cutoff is that the risk of sudden cardiac death is 10-fold higher in the first month after myocardial infarction (MI), and waiting to repeat the LVEF would result in loss of lives. 4Ovine studies conducted at our institution have suggested that post-MI substrate for ventricular tachycardia develops within the first week and remains stable into the chronic phase. 5Our intention in using an early LVEF cutoff, with the knowledge that it would improve, was to assess a larger population during the early high-risk period but to restrict ICD implantation through the use of EPS.In the present study, the Kaplan-Meier survival analysis was not powered to detect a difference within the early post-MI period.A randomized, controlled trial is necessary to validate the benefit of EPS-guided ICD implantation.Such a multicenter trial has already