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 #
2R01HL033343-28
Application #
8352873
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
2012-08-01
Budget End
2013-05-31
Support Year
28
Fiscal Year
2012
Total Cost
$380,000
Indirect Cost
$130,000
Name
Washington University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Vijayakumar, Ramya; Silva, Jennifer N A; Desouza, Kavit A et al. (2014) Electrophysiologic substrate in congenital Long QT syndrome: noninvasive mapping with electrocardiographic imaging (ECGI). Circulation 130:1936-43
Rudy, Yoram (2013) Noninvasive electrocardiographic imaging of arrhythmogenic substrates in humans. Circ Res 112:863-74
Zhang, Junjie; Cooper, Daniel H; Rudy, Yoram (2013) Electrophysiologic mechanism of deteriorating cardiac function in a patient with inappropriate CRT indication and frequent ventricular ectopy. Pacing Clin Electrophysiol 36:1024-6
O'Hara, Thomas; Rudy, Yoram (2012) Quantitative comparison of cardiac ventricular myocyte electrophysiology and response to drugs in human and nonhuman species. Am J Physiol Heart Circ Physiol 302:H1023-30
O'Hara, Thomas; Rudy, Yoram (2012) Arrhythmia formation in subclinical ("silent") long QT syndrome requires multiple insults: quantitative mechanistic study using the KCNQ1 mutation Q357R as example. Heart Rhythm 9:275-82
Cuculich, Phillip S; Zhang, Junjie; Wang, Yong et al. (2011) The electrophysiological cardiac ventricular substrate in patients after myocardial infarction: noninvasive characterization with electrocardiographic imaging. J Am Coll Cardiol 58:1893-902
Wang, Yong; Cuculich, Phillip S; Zhang, Junjie et al. (2011) Noninvasive electroanatomic mapping of human ventricular arrhythmias with electrocardiographic imaging. Sci Transl Med 3:98ra84
Gaur, Namit; Rudy, Yoram (2011) Multiscale modeling of calcium cycling in cardiac ventricular myocyte: macroscopic consequences of microscopic dyadic function. Biophys J 100:2904-12
Heijman, Jordi; Volders, Paul G A; Westra, Ronald L et al. (2011) Local control of *-adrenergic stimulation: Effects on ventricular myocyte electrophysiology and Ca(2+)-transient. J Mol Cell Cardiol 50:863-71
Nekouzadeh, Ali; Rudy, Yoram (2011) Three-residue loop closure in proteins: a new kinematic method reveals a locus of connected loop conformations. J Comput Chem 32:2515-25

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