Session S73.5

Development of a Model of the Infarcted Canine Heart that Predicts Arrhythmia Generation from Specific Cardiac Geometry and Scar Distribution

HJ Arevalo*, PA Helm, NA Trayanova

Johns Hopkins University
Baltimore, MD, USA

Ventricular tachyarrhythmias (VT) in structurally abnormal hearts remain therapeutic challenges since they can be difficult to ablate. Major limitations in studying and ablating VT include the difficulty in finding the location(s) of reentrant pathways arising from the infarct zone. The goals of this study are to 1) develop a high resolution infarcted canine heart model and 2) use the resulting model to explore the role of infarct in VT formation and maintenance.
The model was developed from standard magnetic resonance (MR) and diffusion tensor (DT) images obtained from a canine heart ~4 weeks post-infarction at a resolution of 400x400x400um. Fractional anisotropy and gray level thresholding were used to segment the tissue into three zones: normal myocardium, an inexcitable scar, and a partially viable border zone. Fiber orientations were assigned based on primary eigenvectors calculated from the DT data. The resulting model consisted of 29 million elements. Membrane kinetics in excitable tissue were represented by the Luo-Rudy II model. Electrophysiology in the BZ was modified based on data in the literature which reports reduction in peak sodium current to 38% of the normal value; in peak L-type calcium current to 31% of normal; and in peak potassium currents IKr and IKs to 30 and 20% of the maximum, respectively. VT was induced in the model by delivering an aggressive pacing protocol at 6 sites on the heart.
Our simulations show that the decreased excitability, longer APD, and reduced conduction velocity in the BZ promote conduction block and reentry formation. The VT morphology induced differed depending on the pacing site. While most VT were maintained by reentrant circuits visible on the epicardium, the simulations showed that reentrant sources originating from within the BZ contributes to the heart's arrhythmogenecity.
In conclusion, this study shows that the combination of high resolution imaging and computer modeling provides a unique opportunity to predict generation of VT from specific cardiac geometry and scar distribution.

(Abstract Control Number: 125)