Value of Electrophysiologic Testing in Post MI Patients with Low EF

Abstract & Commentary

By John P. DiMarco, MD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.

Synopsis: In the MADIT II study patients, inducibility was associated with an increased likelihood of VT.

Source: Daubert JP, et al. Predictive Value of Ventricular Arrhythmia Inducibility for Subsequent Ventricular Tachycardia or Ventricular Fibrillation in Multicenter Automatic Defibrillation Implantation Trial (MADIT) II Patients. J Am Coll Cardiol. 2006;47:98-107.

The multicenter automatic defibrillation Implantation Trial (MADIT) II enrolled patients with coronary artery disease, prior myocardial infarction, and an ejection fraction of less than 0.30. MADIT II included an evaluation of the prognostic value of inducibility of ventricular arrhythmias by programmed electrical stimulation as a pre-specified secondary objective. The MADIT II protocol strongly encouraged, but did not require, patients randomized to the ICD arm to undergo electrophysiologic (EP) testing. This report describes the predictive value of the results of the EP study results.

MADIT II randomized 742 patients to the ICD arm of the trial, and 720 received an ICD. Of these, 593 underwent electrophysiologic testing, and the results from this cohort are the subject of this report. The study used a standard EP testing protocol. One to 3 extrastimuli were delivered at 2 basic cycle lengths. The protocol specified that stimulation be preformed via an electrode catheter at 2 right ventricular sites but, in 13% of the patients, inducibility was determined only through the ICD lead at the apex. The EP study end points included the induction of a sustained episode of monomorphic ventricular tachycardia (VT), polymorphic VT, ventricular fibrillation (VF) episode, or completion of the protocol. Daubert and colleagues examined 3 different criteria for inducibility. The standard inducibility definition included sustained monomorphic VT or polymorphic VT initiated by 3 or fewer extrastimuli and ventricular fibrillation with 2 or fewer extrastimuli. The narrow inducibility criterion included only sustained monomorphic VT as a significant response. The broad definition of inducibility included any sustained arrhythmia with any portion of the protocol.

Patients in the MADIT II study underwent quarterly ICD interrogation, as well as interim visits after ICD shocks. ICD interrogation data were reviewed by an ICD end point committee. The committee was blinded to the results of the initial EP study. Only appropriate ICD therapy was included in the data analyzed in this report.

At baseline electrophysiologic study, sustained monomorphic VT was induced in 169 of 593 patients (29%), sustained polymorphic VT in 26 (4%) patients, VF with one or 2 extrastimuli in 16 (3%) patients, and VF with triple extrastimuli in 32 (5%) patients. Only minor differences in clinical characteristics were seen in patients with inducible arrhythmias and those who did not have inducible arrhythmias. At least one appropriate ICD therapy was delivered in 141 (24%) of the 593 patients who underwent EP testing. By log rank analysis, patients with inducible arrhythmias were not more likely to receive appropriate ICD therapy, either shock or antitachycardia pacing (ATP), than patients without inducible arrhythmias using the standard definition. The 2-year point estimates for appropriate ICD therapy were 29.4% and 25.5%, respectively in the 2 groups. Inducibility at electrophysiologic study did predict ICD treatment for VT only but noninducibility predicted ICD treatment for a VF episode. The alternate inducibility definitions were also examined. The narrow definition of inducibility was a better predictor of ICD therapy for VT, and there was still a trend for less VF among patients with induced monomorphic VT. The broad definition, which included induction of VF with triple extrastimuli, performed less well as a predictor for any combination of events than either the narrow definition or the standard inducibility definition.

Daubert et al also examined whether the cycle length of the induced VT was a valuable predictor. Induction of VT with a cycle length of less than 240 m/sec (> 250 bpm) did not predict subsequent occurrence of VT better than noninducibility. Additional analyses which concluded ICD therapy for VT, ICD therapy for VF, or sudden death without ICD interrogation showed similar results to those described above. Overall, patients with inducible arrhythmias had a lower mortality than patients without inducible arrhythmias. Even after multivariate analysis, inducibility was independently, although weakly, associated with improved survival.

Daubert et al conclude that for postinfarction patients with an ejection fraction of less than or equal to 0.30, inducibility of ventricular arrhythmias at electrophysiologic testing is not a useful predictor of future ICD therapy.

Commentary

Electrophysiologic testing to induce ventricular arrhythmias with programmed ventricular stimulation was first introduced over 30 years ago. Stimulation protocols, then developed, had a high sensitivity for inducing sustained monomorphic VT in patients with a history of recurrent episodes of VT. Studies in cardiac arrest survivors showed a lower rate of inducibility, but EP testing was still considered to be useful for many years. Although earlier trials that studied the use of ICD therapy for primary prevention used VT induction as an entry criterion (MADIT I and MUSTT), the value of VT induction has been recently questioned. These data from the MADIT II study confirmed that VT induction is of only limited, if any, value. Similar observations have been reported by follow-up analyses from other trials such as the AVID study. Even the observation that monomorphic VT was more common in patients in whom arrhythmia could be induced is of questionable value given the possibility that changes in programming and the delivery of ATP early in an episode that may have terminated on its own, may be responsible for this finding.

VT induction is a valuable technique when used for diagnosis of tachycardias of unknown mechanism and if the goal is catheter ablation of the ventricular tachycardia. However, data from several studies now indicate that its value for either serial drug testing or for risk prediction is quite limited.