The implantable cardioverter defibrillator (ICD) is the most effective means of detecting and treating arrhythmias, such as ventricular tachycardia (VT) or ventricular fibrillation (VF). However, despite its rapid acceptance, the main limitation of the current ICD technology is that it aims to terminate an arrhythmia only after the arrhythmia has started. Given that failure, delay or false detection in detecting VT/VF is a life- threatening concern, it is imperative that the next generation of ICD technology is able to prevent arrhythmias from starting rather than terminating them after their initiation. Electrical alternans is a pattern of variation in the shape of electrocardiographic waveform that appears on an every other beat basis. Alternation in ventricular repolarization, namely repolarization alternans (RA), has been associated with increased vulnerability to VT/VF and sudden cardiac death (SCD) in patients with heart failure. Thus, in this R21 grant application, we propose to investigate the hypothesis that therapy application by an ICD before the abnormal heart rhythm develops will provide a significant improvement not only in preventing SCD but also in patient acceptance of ICD therapy and quality of life. We have developed a system that can both estimate RA in real- time from intracardiac electrograms and deliver electrical pulses that are timely coupled to the cardiac electrical activity. In this proposal we will investigate the applicability of RA-triggered delivery of clinically appropriate electrical therapy to suppress/terminate RA and prevent the development of VT/VF in an animal model of chronic myocardial infarction. To achieve the aims of this proposal we will (i) establish criteria for the detection of statistically significant RA preceding the onset of a tachyarrhythmic event in a swine animal model, (ii) develop effective algorithms to trigger electrical therapy and investigate the efficacy of electrical therapy in reducing/suppressing the level of RA preceding the onset of a tachyarrhythmic event.

Public Health Relevance

The implantable cardioverter defibrillator (ICD) is a device that detects arrhythmias, such as VT or VF, and terminates them by delivery of one or more electrical impulses to the heart. However, failure, delay or false detection in detecting VT or VF are of great concern. This research proposal investigates the application of therapy by an ICD before the abnormal heart rhythm develops, thus providing a significant improvement not only in preventing sudden cardiac death but also in patient acceptance of ICD therapy and quality of life.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG035128-02
Application #
8118799
Study Section
Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
Program Officer
Zieman, Susan
Project Start
2010-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
2
Fiscal Year
2011
Total Cost
$164,587
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Merchant, Faisal M; Sayadi, Omid; Puppala, Dheeraj et al. (2014) A translational approach to probe the proarrhythmic potential of cardiac alternans: a reversible overture to arrhythmogenesis? Am J Physiol Heart Circ Physiol 306:H465-74
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Merchant, Faisal M; Sayadi, Omid; Moazzami, Kasra et al. (2013) T-wave alternans as an arrhythmic risk stratifier: state of the art. Curr Cardiol Rep 15:398
Sayadi, Omid; Merchant, Faisal M; Puppala, Dheeraj et al. (2013) A novel method for determining the phase of T-wave alternans: diagnostic and therapeutic implications. Circ Arrhythm Electrophysiol 6:818-26
Merchant, Faisal M; Zheng, Hui; Bigger, Thomas et al. (2013) A combined anatomic and electrophysiologic substrate based approach for sudden cardiac death risk stratification. Am Heart J 166:744-52
Lee, Kichang; Lv, Wener; Ter-Ovanesyan, Evgeny et al. (2013) Cardiac ablation catheter guidance by means of a single equivalent moving dipole inverse algorithm. Pacing Clin Electrophysiol 36:811-22
Armoundas, Antonis A; Mela, Theofanie; Merchant, Faisal M (2012) On the estimation of T-wave alternans using the spectral fast fourier transform method. Heart Rhythm 9:449-56
Merchant, Faisal M; Ikeda, Takanori; Pedretti, Roberto F E et al. (2012) Clinical utility of microvolt T-wave alternans testing in identifying patients at high or low risk of sudden cardiac death. Heart Rhythm 9:1256-64.e2
Merchant, Faisal M; Armoundas, Antonis A (2012) Role of substrate and triggers in the genesis of cardiac alternans, from the myocyte to the whole heart: implications for therapy. Circulation 125:539-49

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