Implications of Intra-Myocardial Fat Deposition upon Propensity for Malignant Arrhythmia

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Life-threatening ventricular tachycardia (VT) remains a major complication of myocardial infarction. Catheter ablation aims to destroy the VT substrate, diseased myocardium that slows local conduction sufficiently to perpetuate circuit reentry. The current understanding of the VT substrate revolves around the interaction of surviving strands of viable myocardium primarily at the periphery of infarct scar. Our preliminary data, however, suggests that critical VT circuit sites are viable myocardial strands that reside in the scar core, and are often surrounded by intra-myocardial fat deposition. Intra-myocardial fat is not a simple bystander; it is metabolically active and vascular, an effective insulator of conductive fibers, and modulates local conduction properties. This proposal will investigate the mechanistic consequence of intra-myocardial fat deposition upon impulse conduction and the propensity to sustain VT in adults with prior myocardial infarction. We propose to use MRI and CT images of patients with post-infarct VT to 1) to define the prevalence and distribution of myocardial fat deposition in patients with prior infarction and VT, 2) to characterize the conduction and repolarization properties of viable channels within scar based upon proximity to myocardial fat, 3) to examine the association of VT circuit sites with proximity to myocardial fat, and 4) to dissect the contribution of myocardial fat to VT events using patient-specific models, and to evaluate the diagnostic performance of model-predicted optimal ablation sites with and without inclusion of myocardial fat. Our group has extensive experience with MRI safety and image optimization in defibrillator recipients. Additionally, we have assembled a team of experts in image acquisition and analysis, epidemiology, biostatistics, simulations, and VT management. The findings of this study will have wide applicability to our mechanistic understanding and management of post-infarct VT.