Heart rhythm disorders are the leading cause of morbidity and mortality in the developed world. Despite a profound difference in physiological mechanisms, anatomic and genetic determinants, and etiology of various arrhythmias, there are only two predominant treatments: electric and ablative therapies. Pharmacological therapy has been mostly ineffective or hampered by side effects. Ablative therapy for atrial tachyarrhythmias is growing in acceptance. However, the ablation procedure is complex, time-consuming, and has a number of side effects. Several modalities of electrotherapy have been effective in preventing sudden cardiac death due to ventricular tachycardia and fibrillation (VT/VF), and in arresting atrial tachycardia and fibrillation (AT/AF). However, the current bioelectric therapy paradigm has a number of limitations. Antitachycardia pacing (ATP) is the most desirable approach due to its low energy requirement, but the efficacy of ATP is limited. High- voltage biphasic shock defibrillation has evolved over the last 70 years as the dominant and highly effective electrotherapy against both AF and VF. However, the energy requirements for AF are suboptimal: high-energy shocks are painful and could cause myocardial damage. In our project we aim to address the limitations of current electrotherapy and present a novel hypothesis: multi-stage phased bioelectric therapy will allow significant reduction in DFT for atrial fibrillaton. Based on previous NIH-funded research from our laboratory we have developed an approach that terminates atrial tachyarrhythmia based on several types of multiple pulse electrotherapies with low, phased (i.e. progressively reducing) energy levels and frequencies: (1) far-field low energy multiple shocks, (2) far-field ultra-low energy entrainment stimulation, and (3) near-field entrainment pacing. We will explore two technological platforms to implement and further investigate our novel method: (1) state-of-the-art lead-based implantable device and (2) flexible electronics developed by the Rogers laboratory at the University of Illinois, Urbana-Champagne. Successful completion of this project will advance implantable bioelectric therapy of cardiac arrhythmias by (1) reducing high-voltage shock induced myocardial damage and post-shock conduction abnormalities secondary to this damage, (2) reducing pain associated with termination of tachyarrhythmias, and (3) reducing energy consumption in the implantable devices. Reduction of the DFT below 0.2J is likely to make implantable atrial defibrillation possible for millions of AF patients. Novel stretchable electronic technology developed by John A. Rogers is likely to transform electrotherapy of cardiac arrhythmias based on high anatomic resolution local sensing and multi-stage therapy of aberrant rhythms.

Public Health Relevance

Atrial fibrillation (AF) is a heart rhythm disorder that affects 3-5 million Americans. There are only two predominant treatments of AF: electric and ablative therapies. High-voltage electric shock defibrillation is the dominant and highly effective electrotherapy against ventricular arrhythmias, but it is not as widely applied against AF, because the high energy shocks are painful and cannot be tolerated by patients. In our project we aim to address the limitations of current electrotherapy and present a novel hypothesis: multi-stage phased bioelectric therapy will allow significant reduction in energy required for AF defibrillation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL115415-02
Application #
8665479
Study Section
Special Emphasis Panel (ZRG1-CVRS-E (02))
Program Officer
Lathrop, David A
Project Start
2013-06-01
Project End
2017-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
2
Fiscal Year
2014
Total Cost
$1,026,006
Indirect Cost
$226,962
Name
Washington University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Koh, Ahyeon; Gutbrod, Sarah R; Meyers, Jason D et al. (2016) Ultrathin Injectable Sensors of Temperature, Thermal Conductivity, and Heat Capacity for Cardiac Ablation Monitoring. Adv Healthc Mater 5:373-81
Xu, Lizhi; Gutbrod, Sarah R; Ma, Yinji et al. (2015) Materials and fractal designs for 3D multifunctional integumentary membranes with capabilities in cardiac electrotherapy. Adv Mater 27:1731-7
Gutbrod, Sarah R; Walton, Richard; Gilbert, Stephen et al. (2015) Quantification of the transmural dynamics of atrial fibrillation by simultaneous endocardial and epicardial optical mapping in an acute sheep model. Circ Arrhythm Electrophysiol 8:456-65
Boukens, Bastiaan J; Gutbrod, Sarah R; Efimov, Igor R (2015) Imaging of Ventricular Fibrillation and Defibrillation: The Virtual Electrode Hypothesis. Adv Exp Med Biol 859:343-65
Ripplinger, Crystal M; Efimov, Igor R (2015) Dual Vm/Ca imaging of premature ventricular contractions: bridging the gap of anatomical scales. Circ Arrhythm Electrophysiol 8:529-30
Gutbrod, Sarah R; Sulkin, Matthew S; Rogers, John A et al. (2014) Patient-specific flexible and stretchable devices for cardiac diagnostics and therapy. Prog Biophys Mol Biol 115:244-51
Janardhan, Ajit H; Gutbrod, Sarah R; Li, Wenwen et al. (2014) Multistage electrotherapy delivered through chronically-implanted leads terminates atrial fibrillation with lower energy than a single biphasic shock. J Am Coll Cardiol 63:40-8
Villongco, Christopher T; Krummen, David E; Stark, Paul et al. (2014) Patient-specific modeling of ventricular activation pattern using surface ECG-derived vectorcardiogram in bundle branch block. Prog Biophys Mol Biol 115:305-13
Sulkin, Matthew S; Boukens, Bas J; Tetlow, Megan et al. (2014) Mitochondrial depolarization and electrophysiological changes during ischemia in the rabbit and human heart. Am J Physiol Heart Circ Physiol 307:H1178-86
Xu, Lizhi; Gutbrod, Sarah R; Bonifas, Andrew P et al. (2014) 3D multifunctional integumentary membranes for spatiotemporal cardiac measurements and stimulation across the entire epicardium. Nat Commun 5:3329

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