1188 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 52, NO. 7, JULY 2005 Detection of Repolarization Alternans With an Implantable Cardioverter Defibrillator Lead in a Porcine Model Anil Maybhate*, Steven C. Hao, Sei Iwai, Jae Ung Lee, Amit B. Guttigoli, Kenneth M. Stein, Bruce B. Lerman, and David J. Christini, Member, IEEE Abstract—Mechanistic links have been suggested between repolarization alternans (RPA) and the onset of ventricular tachy- cardia (VT) and/or fibrillation. Endocardial detection of RPA may, therefore, be an important step in future device-based treatments of arrhythmias. Here, we investigate if RPA could be detected during acute ischemia using an implantable cardioverter defibril- lator (ICD) lead (tip to distal coil) located in the right ventricular apex. In 18 pigs, the right coronary or left anterior descending coronary artery was occluded for 10 min using a balloon catheter, followed by reperfusion for 30 min, and re-occlusion for 30 min. RPA magnitude, computed using the modified moving average (MMA) method, showed a sharp increase in all 18 animals, from a mean baseline level of mV to mV during first occlusion . RPA magnitude showed a prominent increase in 10 animals during re-occlusion, from a mean baseline level of mV to mV . The protocol was terminated during the first two stages of occlusion and reperfusion for the remaining 8 animals due to the occurrence of ventricular fibrillation (VF). These results confirm that RPA increases under ischemic condi- tions and that it is possible to detect and track RPA dynamics with an ICD lead that is positioned in a clinically realistic location. Such an approach may be useful in formulating improved arrhythmia detection and control algorithms. Index Terms—Alternans, repolarization, T-wave, ventricular tachycardia. I. INTRODUCTION T HE implantable cardioverter defibrillator (ICD) is the most effective therapy for patients at high risk of sudden car- diac death due to ventricular tachyarrhythmias [1]–[5]. This de- vice continuously monitors the electrical activity of the heart and aims to detect and terminate arrhythmias. In response to a lethal arrhythmia, the device restores normal rhythm with a DC shock. Thus, by design the device acts only after the onset of ar- rhythmias. Although this approach is usually successful, the DC Manuscript received May 10, 2004; revised November 14, 2004. This work was supported by the Whitaker Foundation under Biomedical Engineering Research Grant RG-02-0369, in part by a Kenny Gordon Foundation Ar- rhythmia Research Grant, and inpart by the Medtronic CRM External Research Program.Asterisk indicates corresponding author. *A. Maybhate was with the Weill Medical College of Cornell University, 520 East 70th Street, Starr-463, New York, NY 10021 USA. He is now with Depart- ment of Kinesiology, Pennsylvania State University, University Park, PA 16802 USA (e-mail: axm55@psu.edu). S. C. Hao, S. Iwai, J. U. Lee, A. B. Guttigoli, K. M. Stein, B. B. Lerman, and D. J. Christini are with the Weill Medical College of Cornell University, New York, NY 10021 USA (e-mail: dchristi@med.cornell.edu). Digital Object Identifier 10.1109/TBME.2005.847537 shock can be painful, or it may occasionally fail to terminate the arrhythmia. A better approach might be to prevent ventricular tachyarrhythmias by recognizing and controlling the precursor events. One such precursor event may be repolarization alternans (RPA), which is a beat-to-beat alternation in magnitude of the transmembrane voltage of ventricular cells during repolari- zation. RPA manifests as T-wave alternans in the surface electrocardiogram (ECG). A close relationship has been established between T-wave alternans and vulnerability to ven- tricular fibrillation (VF) in animals [6]–[8]. Clinically, T-wave alternans has been correlated with risk for recurrent ventricular arrhythmias and sudden cardiac death [9]–[17]. Furthermore, recent experimental evidence supports the hypothesis that RPA may be a mechanistic precursor to ventricular tachyarrhythmias [18]–[22]. These studies have suggested that increased heart rate can induce concordant alternans (i.e., all spatial regions of the ventricles alternate in phase), which can progress to discordant alternans (i.e., neighboring regions of the ventricles alternate out of phase). Discordant alternans causes steep gradients of repolarization that can provide the substrate for unidirectional functional block and the initiation of reentrant propagation—the mechanism by which alternans may initiate arrhythmias and cause fibrillation. Given that alternans may trigger arrhythmias, its control may be of therapeutic value. Earlier works have shown that closed- loop control methods can, in principle, be used to suppress some types of alternans [23]–[27]. Indeed, it was shown that dynam- ical control methods could be employed toterminate action po- tential duration alternans in small in vitro frog ventricle sections [28]. More recently, a theoretical study suggested that the ability to control alternans in large cardiac tissues may have significant rate and distance limitations [29]. However, because that study modeled a Purkinje fiber, which has a conduction velocity (CV) approximately four times that of ventricular tissue and because the proposed theory suggests that control efficacy increases as CV decreases [29], there is reason to believe that alternans con- trol in the ventricles will be more feasible than predicted in [29]. To achieve such control clinically, it will be necessary to use an implantable device such as an ICD. As a first step toward evaluating the feasibility of such an implementation, we sought to determine whether an ICD lead could be used to detect RPA and track its variation during ischemia. The ICD lead that we tested is used clinically and the placement of the lead in our experiments is similar to that used in clinical implantation pro- 0018-9294/$20.00 © 2005 IEEE