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.

Public Health Relevance

Up to 18% of the 120,000 US patients who undergo defibrillator implantation every year will require ventricular tachycardia suppression within a yea of implant. The proposed computed tomography ancillary study provides a unique opportunity to study the post-infarct ventricular tachycardia substrate and the implications of that substrate on therapy selection for optimal VT suppression and preservation of cardiac function.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01HL116280-02
Application #
8714041
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Boineau, Robin
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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