While catheter ablation to terminate ventricular tachycardia (VT) due to myocardial infarction (Ml) has been shown to be a promising therapy, the technique's 30% failure rate in treating patients has prevented the wide-spread adoption of the procedure. Recent studies have speculated that the high failure rate could be due to the difficulty in identifying all the reentrant substrates arising from the complex 3D infarct architecture. The overall objective of this research is to provide a new level of understanding of the mechanisms of arrhythmogenesis under the conditions of infarction and use these insights to predict the optimal ablation sites that will eliminate infarct-related VT. This relates to the NHLBI mission to support basic research related to the causes and treatment of heart disorders. To achieve the objective of the proposed research, the following specific aims are pursued: 1) to develop and validate, from magnetic resonance imaging (MRI), diffusion tensor (DT) MRI, and electro-physiological recordings, 3D anatomically-accurate computational models of swine hearts with healed infarct;2) use the generated models to test the hypotheses that the specific 3D infarct scar structure, the presence of partially viable PZ tissue, and the specific fibroblast deposition within the infarct region determine the morphology of the VT reentrant circuits and the location of their isthmuses;and 3) the models will then be used to identify the appropriate ablation sites that will eliminate VT. This project will contribute to the knowledge of how specific infarct structure and composition promote the development of arrhythmia in the heart. These insights will help unravel the mechanisms of post-infarction arrhythmia which would aid in the improvements of ablation therapies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31HL099275-02
Application #
8020145
Study Section
Special Emphasis Panel (ZRG1-SBIB-V (29))
Program Officer
Meadows, Tawanna
Project Start
2010-02-01
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
2
Fiscal Year
2011
Total Cost
$41,800
Indirect Cost
Name
Johns Hopkins University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Arevalo, Hermenegild; Plank, Gernot; Helm, Patrick et al. (2013) Tachycardia in post-infarction hearts: insights from 3D image-based ventricular models. PLoS One 8:e68872
Trayanova, Natalia A; O'Hara, Thomas; Bayer, Jason D et al. (2012) Computational cardiology: how computer simulations could be used to develop new therapies and advance existing ones. Europace 14 Suppl 5:v82-v89
Rantner, Lukas J; Arevalo, Hermenegild J; Constantino, Jason L et al. (2012) Three-dimensional mechanisms of increased vulnerability to electric shocks in myocardial infarction: altered virtual electrode polarizations and conduction delay in the peri-infarct zone. J Physiol 590:4537-51