This proposal describes a five-year training program to develop an academic career in cardiac electrophysiology. The principal investigator has a long-standing interest in cardiac electrophysiology research. Over the course of this grant, the applicant will obtain the training and funding to become an independent investigator with the long-term goal of understanding arrhythmia mechanisms and developing new technologies, leading to more efficacious treatment regimens. Over the next five years the applicant will undergo formal didactic training in Magnetic Resonance Imaging (MRI) techniques and clinical investigation. The investigator will be mentored by Dr. Dennis Parker, along with a committee comprised of experts in the field of MRI research, clinical electrophysiology, image processing and biostatistics. Dr. Parker is a leader in the field of MRI research with independent NIH funding and many years of mentoring experience. At the onset of this training program, the research program will be focused on developing MRI visualization techniques to visualize gaps in ablation lesion sets with the goal to test the hypothesis that targeting these gaps acutely will lead to improved outcomes. The success rate for ablation in atrial fibrillation remains persistently low and can require multiple procedures, leaving room for significant improvement. The goal in most of these ablation procedures is to isolate a region with sources of electrical triggers from tissue susceptible to such triggers by creating a line of tissue burns or ablation lesions. For such ablation lines to be effective, the lines should have no gaps. Currently, there i no effective means to provide direct proof of successful lines of lesion or ablation and the evaluation of success depends on indirect markers that are often poor predictors. MRI has exceptional capabilities for visualizing soft tissue. These proposed studies aim to develop MRI-based techniques to visualize and evaluate radiofrequency ablation lesions and target gaps in lesion sets.
The specific aims for this project are: 1) to determine the smallest gap in ablation lesion sets that can be detected by MRI and then targeted acutely, 2) to test the hypothesis that identifying and targeting gaps acutely will lead to significant improvement in maintaining electrical isolation over time, and 3) to test the hypothesis that gaps detected by MRI in ablation lines will predict electrical reconnection and arrhythmia recurrence in humans. Success in these studies will greatly expand our ability to target gaps in ablation lesion sets acutely leading to improved outcomes from ablation procedures. Moreover, these studies, didactic training in MRI, and clinical investigation and mentoring during this period, will prepare the applicant to pursue rigorous hypothesis testing research. These studies will also form the basis of the next set of studies in animal models of atrial fibrillation, and finally, in humans. We already have a number of species of large animal models of atrial fibrillation as part of another funded project, which makes this research all the more attractive.

Public Health Relevance

The recurrence rate of arrhythmias after catheter ablation procedures remains high. This proposal investigates the role of gaps in ablation lesions in the poor outcome and examines if acutely targeting them will lead to significant improvement in outcomes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
4K23HL115084-05
Application #
9069091
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Scott, Jane
Project Start
2012-08-23
Project End
2017-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Utah
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Yamashita, Kennosuke; Kholmovski, Eugene; Ghafoori, Elyar et al. (2018) Characterization of edema after cryo and radiofrequency ablations based on serial magnetic resonance imaging. J Cardiovasc Electrophysiol :
Yamashita, Kennosuke; Quang, Claire; Schroeder, Joyce D et al. (2018) Distance between the left atrium and the vertebral body is predictive of esophageal movement in serial MR imaging. J Interv Card Electrophysiol 52:149-156
Kholmovski, Eugene G; Silvernagel, Josh; Angel, Nathan et al. (2018) Acute noncontrast T1-weighted magnetic resonance imaging predicts chronic radiofrequency ablation lesions. J Cardiovasc Electrophysiol 29:1556-1562
Thomas, Samuel; Silvernagel, Josh; Angel, Nathan et al. (2018) Higher contact force during radiofrequency ablation leads to a much larger increase in edema as compared to chronic lesion size. J Cardiovasc Electrophysiol 29:1143-1149
Ghafoori, Elyar; Kholmovski, Eugene G; Thomas, Sam et al. (2017) Characterization of Gadolinium Contrast Enhancement of Radiofrequency Ablation Lesions in Predicting Edema and Chronic Lesion Size. Circ Arrhythm Electrophysiol 10:
Panitchob, Nuttanont; Li, Li; Huang, Jian et al. (2017) Endocardial Activation Drives Activation Patterns During Long-Duration Ventricular Fibrillation and Defibrillation. Circ Arrhythm Electrophysiol 10:
Huang, Shangwei; Wu, Liqun; Huang, Jian et al. (2017) Restitution characteristics of His bundle and working myocardium in isolated rabbit hearts. PLoS One 12:e0186880
Kholmovski, Eugene G; Coulombe, Nicolas; Silvernagel, Joshua et al. (2016) Real-Time MRI-Guided Cardiac Cryo-Ablation: A Feasibility Study. J Cardiovasc Electrophysiol 27:602-8
Polejaeva, Irina A; Ranjan, Ravi; Davies, Christopher J et al. (2016) Increased Susceptibility to Atrial Fibrillation Secondary to Atrial Fibrosis in Transgenic Goats Expressing Transforming Growth Factor-?1. J Cardiovasc Electrophysiol 27:1220-1229
Ranjan, Ravi; McGann, Christopher J; Jeong, Eun-Kee et al. (2015) Wideband late gadolinium enhanced magnetic resonance imaging for imaging myocardial scar without image artefacts induced by implantable cardioverter-defibrillator: a feasibility study at 3 T. Europace 17:483-8

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