ANCILLARY STUDY OF SUBSTRATE AND INTERVENTION MECHANISMS FOR MALIGNANT ARRHYTHMIA

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DESCRIPTION (provided by applicant): Life-threatening ventricular tachycardia (VT) remains a major complication of myocardial infarction. The VT substrate is diseased myocardium that slows local conduction sufficiently to perpetuate circuit reentry. This proposal aims to enhance our understanding of the anatomic details of the VT substrate and its effects upon patient response to antiarrhythmic drug therapy and catheter ablation, an alternative mode of therapy that aims to destroy the VT substrate. Currently, ablation is performed by use of local, point-by-point acquired, intra- cardiac electrograms, which serve as surrogates for each patient's unique VT substrate. This strategy is limited by low sampling density and lack of specificity. Direct evaluation of the anatomic VT substrate has recently become feasible with imaging techniques such as computed tomography (CT). We propose a time-sensitive ancillary study to the "Ventricular Tachycardia Ablation vs. Enhanced Drug Therapy In Structural Heart Disease" (VANISH) and the "Early Ablation Therapy for the Treatment of Ischemic Ventricular Tachycardia in Patients with Implantable Cardioverter Defibrillators" (ASPIRE) multicenter randomized clinical trials. We will acquire resting myocardial CT perfusion and delayed contrast-enhanced CT infarct imaging in 200 VANISH and ASPIRE participants prior to randomization, and at 1-year follow-up. The data will be used to a) define anatomic features that predict the optimal mode of VT therapy thereby allowing proper selection of ablation versus antiarrhythmic drugs, b) define the anatomic details of slow conduction VT substrates, c) determine the substrate changes necessary for VT suppression, and d) characterize the resultant cardiac remodeling from ablation versus drug therapy. We have assembled a team of experts in CT image acquisition and analysis, epidemiology, biostatistics, and VT management. The findings of this study will have wide applicability to optimization of management strategies for patients with post-infarct VT.