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 those in experimental animal models. During the current grant period, we have made the transition from the development, implementation and validation of a novel noninvasive imaging modality (Electrocardiographic Imaging, ECGI) to its first successful applications in the study of human cardiac electrophysiology and arrhythmia. In the next period of support, we will apply ECGI to study arrhythmic substrates, mechanisms and outcomes of therapy in selected disorders of clinical importance and scientific interest. Goals for the next period are: (1) to study the mechanisms of persistent atrial fibrillation and to follow pot-ablation changes over time in the atrial electrophysiologic substrate and activation patterns, including recurrences of atrial arrhythmias. (2) To investigate the mechanisms of cardiac repolarization abnormalities associated with arrhythmias and sudden death. Two arrhythmogenic syndromes will be investigated: Long QT and Early Repolarization. (3) To investigate the coupling between electrical excitation and mechanical contraction in the normal human heart, its alteration in heart failure and modification by cardiac resynchronization therapy (CRT) in the failing 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 studying arrhythmia properties and mechanisms in humans, using a novel noninvasive imaging modality for cardiac arrhythmias (Electrocardiographic Imaging, ECGI) developed in our laboratory.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033343-30
Application #
8680298
Study Section
Electrical Signaling, Ion Transport, and Arrhythmias Study Section (ESTA)
Program Officer
Lathrop, David A
Project Start
1985-07-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
30
Fiscal Year
2014
Total Cost
$372,400
Indirect Cost
$127,400
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:
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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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