The overall objective is to continue the development of an imaging modality (""""""""Electrocardiographic Imaging"""""""") for the reconstruction of cardiac electrical, activity from potentials measured away from the heart (i.e. on the torso surface and in the blood cavity), and to further our understanding of the relationship between cardiac excitation and the electric potentials that it generates. Standard electrocardiographic techniques (i.e. ECG and VCG) can not provide information on regional cardiac electrical activity and on the location of electrical events (e.g. an arrhythmogenic focus) in the heart. Potential distributions and isochrone maps on the epicardial and endocardial surfaces of the heart mirror regional and local electrophysiological events in the myocardium and can be computed from the potential distributions measured over the torso surface and over the surface of an intracavitary catheter - probe. Goals for the next grant period are: (l) To continue the development of mathematical methods for the reconstruction of potentials and of activation isochrones on the epicardial and endocardial surfaces of the heart from body surface potentials and intracavitary potentials, respectively; (2) To test the ability of the epicardial - and endocardial - reconstruction procedures to detect and locate single and multiple foci of arrhythmogenic activity; (3) To characterize the spatial resolution of these reconstruction procedures; (4) To test the ability of these procedures to determine the location and extent of an infarcted region; (5) To begin implementation in the clinical setting and to test the approach in selected groups of patients that provide an opportunity to validate the reconstruction procedure (WPW patients, patients with epicardial pacing wires, patients with implanted pacemakers, patients with right or left bundle branch block, and patients who undergo epicardial mapping during surgery). (2), (3) and (4) above will be conducted in an isolated canine heart and a human-shaped torso tank setup. Health relatedness: The availability of potential distributions and activation sequences over the surfaces of the heart will provide diagnostic information regarding electrical disturbances (e.g. conduction abnormalities, types of arrhythmias, location of reentry pathways and of the areas of slow conduction within these pathways). It will also help evaluate effects of interventions (e.g. antiarrhythmic drug therapy, neural changes) on cardiac activity and arrhythmogenesis. In addition, it will provide non-surgical means for locating foci of arrhythmogenic activity prior to surgical or catheter ablation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033343-10
Application #
2217238
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1985-07-01
Project End
1998-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
10
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Ramasubramanian, Smiruthi; Rudy, Yoram (2018) The Structural Basis of IKs Ion-Channel Activation: Mechanistic Insights from Molecular Simulations. Biophys J 114:2584-2594
Xu, Jiajing; Rudy, Yoram (2018) Effects of ?-subunit on gating of a potassium ion channel: Molecular simulations of cardiac IKs activation. J Mol Cell Cardiol 124:35-44
Robinson, Clifford G; Samson, Pamela P; Moore, Kaitlin M S et al. (2018) Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation :
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:
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:
Rudy, Yoram (2017) Noninvasive ECG imaging (ECGI): Mapping the arrhythmic substrate of the human heart. Int J Cardiol 237:13-14
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

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