This Mentored Patient-Oriented Research Career Development Award application focuses on a program of research designed to study the intracardiac mechanisms underlying T-wave alternans (TWA) of the electrocardiogram in individuals with prior myocardial infarcts and depressed cardiac systolic function in order to improve its computation and therefore its ability to predict those who are at risk for ventricular tachycardia (VT) or fibrillation (VF). This work will build on the applicant?s prior research and training in clinical cardiology and invasive electro-physiology, as well as in basic science, computer science and numerical methods. The proposed research will test the hypothesis that programmed ventricular stimulation in patients with ischemic heart disease and left ventricular dysfunction induces proarrhythmic nonuniformities in ventricular repolarization, and results in redistribution of TWA late in the T-wave, and TWA phase reversal, that are detectable by novel analyses of the ECG. There are two specific aims: 1) To establish that an increased magnitude of TWA late in the T-wave and TWA phase reversal parallel changes in the endocardial dispersion of ventricular repolarization measured, using monophasic action potentials, during progressive programmed ventricular stimulation leading to the induction of VT/VF. 2) To prospectively test, in patients with ischemic heart disease and left ventricular dysfunction, the performance of a new index of myocardial electrical instability, derived from the data calibrating TWA late magnitude and phase to the dispersion of monophasic action potential duration obtained in the research performed to fulfill Specific Aim 1, in predicting the incidence of spontaneous VT/VF. The applicant will perform this work under the supervision and guidance of his Mentor, and with guidance from a Scientific Advisory Committee comprising experts in basic and clinical electrophysiology, in the interpretation of monophasic action potentials, in numeric modeling and signal processing, in statistics and in clinical research. This structured approach will ensure the successful completion of this project and, in this way, the development of the applicant into an independent clinician-investigator.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
1K23HL070529-01
Application #
6494956
Study Section
Special Emphasis Panel (ZHL1-CSR-F (F1))
Program Officer
Commarato, Michael
Project Start
2001-09-17
Project End
2006-08-31
Budget Start
2001-09-17
Budget End
2002-08-31
Support Year
1
Fiscal Year
2001
Total Cost
$148,531
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Baykaner, Tina; Rogers, Albert J; Zaman, Junaid A B et al. (2018) Editorial commentary: What can lung transplantation teach us about the mechanisms of atrial arrhythmias? Trends Cardiovasc Med 28:62-63
Zaman, Junaid A B; Baykaner, Tina; Narayan, Sanjiv M (2016) New Mechanism-based Approaches to Ablating Persistent AF: Will Drug Therapy Soon Be Obsolete? J Cardiovasc Pharmacol 67:1-8
Lalani, Gautam G; Coysh, Thomas; Baykaner, Tina et al. (2016) Organized Sources Are Spatially Conserved in Recurrent Compared to Pre-Ablation Atrial Fibrillation: Further Evidence for Non-Random Electrical Substrates. J Cardiovasc Electrophysiol 27:661-9
Rappel, Wouter-Jan; Zaman, Junaid A B; Narayan, Sanjiv M (2015) Mechanisms for the Termination of Atrial Fibrillation by Localized Ablation: Computational and Clinical Studies. Circ Arrhythm Electrophysiol 8:1325-33
Schricker, Amir A; Lalani, Gautam G; Krummen, David E et al. (2014) Rotors as drivers of atrial fibrillation and targets for ablation. Curr Cardiol Rep 16:509
Narayan, Sanjiv M; Baykaner, Tina; Clopton, Paul et al. (2014) Ablation of rotor and focal sources reduces late recurrence of atrial fibrillation compared with trigger ablation alone: extended follow-up of the CONFIRM trial (Conventional Ablation for Atrial Fibrillation With or Without Focal Impulse and Rotor Modulat J Am Coll Cardiol 63:1761-8
Schricker, Amir A; Lalani, Gautam G; Krummen, David E et al. (2014) Human atrial fibrillation initiates via organized rather than disorganized mechanisms. Circ Arrhythm Electrophysiol 7:816-24
Rappel, Wouter-Jan; Narayan, Sanjiv M (2013) Theoretical considerations for mapping activation in human cardiac fibrillation. Chaos 23:023113
Jones, Aled R; Krummen, David E; Narayan, Sanjiv M (2013) Non-invasive identification of stable rotors and focal sources for human atrial fibrillation: mechanistic classification of atrial fibrillation from the electrocardiogram. Europace 15:1249-58
Lalani, Gautam G; Kahn, Andrew M; Narayan, Sanjiv M (2013) Can we still rely on the ECG for detecting past myocardial injury? JACC Cardiovasc Imaging 6:332-4

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