Cardiac arrhythmias continue to be a leading cause of death and disability. Despite this alarming fact, a noninvasive imaging modality (analogous to CT or MRI) for cardiac electrophysiology and arrhythmia has not been available for clinical diagnosis and guidance of therapy. Importantly, such imaging modality is also greatly needed for the study of arrhythmia mechanisms in humans, where the arrhythmic substrate and disease processes differ considerably from that in experimental animal models. During the current grant period, we have developed, implemented and validated a novel noninvasive imaging modality (Electrocardiographic Imaging, ECGI) and demonstrated its successful application in humans. In the next period of support, we will apply ECGI to study arrhythmic substrates and arrhythmia mechanisms in humans. Goals for the next period are: (1) To characterize the electrophysiological substrate associated with anatomical scars in post myocardial infarction (post-MI) patients. (2) To image scar-related ventricular tachyarrhythmias (VT) in these patients. (3) To image activation and repolarization in patients with the Wolff-Parkinson-White (WPW) syndrome before and after accessory pathway ablation, and to study cardiac memory in these patients. (4) To image the electrophysiological substrate in non-ischemic dilated cardiomyopathy patients and to study pacing-induced changes during cardiac resynchronization therapy (CRT). (5) To extend the ECGI method (presently formulated for epicardial reconstructions) to include the endocardial surface of the heart. Public Health Relevance: An estimated 400,000 Americans die each year from erratic heart rhythms, and many more are disabled (estimated annual fatalities worldwide is seven million). The proposed research is aimed at the continued development of a noninvasive imaging modality for cardiac arrhythmias (Electrocardiographic Imaging, ECGI) and its application in the study of arrhythmia properties and mechanisms in humans.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033343-27
Application #
8085840
Study Section
Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Lathrop, David A
Project Start
1985-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
27
Fiscal Year
2011
Total Cost
$340,465
Indirect Cost
Name
Washington University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Andrews, Christopher M; Srinivasan, Neil T; Rosmini, Stefania et al. (2017) Response by Andrews et al to Letter Regarding Article, ""Electrical and Structural Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging"". Circ Arrhythm Electrophysiol 10:
Rudy, Yoram (2017) Noninvasive ECG imaging (ECGI): Mapping the arrhythmic substrate of the human heart. Int J Cardiol 237:13-14
Zhang, Junjie; Hocini, Mélèze; Strom, Maria et al. (2017) The Electrophysiological Substrate of Early Repolarization Syndrome: Noninvasive Mapping in Patients. JACC Clin Electrophysiol 3:894-904
Andrews, Christopher M; Srinivasan, Neil T; Rosmini, Stefania et al. (2017) Electrical and Structural Substrate of Arrhythmogenic Right Ventricular Cardiomyopathy Determined Using Noninvasive Electrocardiographic Imaging and Late Gadolinium Magnetic Resonance Imaging. Circ Arrhythm Electrophysiol 10:
Cuculich, Phillip S; Schill, Matthew R; Kashani, Rojano et al. (2017) Noninvasive Cardiac Radiation for Ablation of Ventricular Tachycardia. N Engl J Med 377:2325-2336
Lee, Hsiang-Chun; Rudy, Yoram; Liang, Hongwu et al. (2017) Pro-arrhythmogenic Effects of the V141M KCNQ1 Mutation in Short QT Syndrome and Its Potential Therapeutic Targets: Insights from Modeling. J Med Biol Eng 37:780-789
Nekouzadeh, Ali; Rudy, Yoram (2016) Conformational changes of an ion-channel during gating and emerging electrophysiologic properties: Application of a computational approach to cardiac Kv7.1. Prog Biophys Mol Biol 120:18-27
Zhang, Junjie; Cooper, Daniel H; Desouza, Kavit A et al. (2016) Electrophysiologic Scar Substrate in Relation to VT: Noninvasive High-Resolution Mapping and Risk Assessment with ECGI. Pacing Clin Electrophysiol 39:781-91
Vijayakumar, Ramya; Vasireddi, Sunil K; Cuculich, Phillip S et al. (2016) Methodology Considerations in Phase Mapping of Human Cardiac Arrhythmias. Circ Arrhythm Electrophysiol 9:
Rudy, Yoram; Lindsay, Bruce D (2015) Electrocardiographic imaging of heart rhythm disorders: from bench to bedside. Card Electrophysiol Clin 7:17-35

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