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Project Director: Gordon F. Tomaselli, M.D.
Co-Investigators: Raimond L. Winslow, Ph.D., Jennifer E. Van Eyk, Ph.D., Ronald D. Berger, M.D., Hugh G. Calkins, M.D., Sumeet Chugh, M.D., Douglas P. Zipes, M.D.
Associates: David R. Thiemann, M.D., Roselle Abraham, M.D., Lili A. Barouch, Ph.D., Daniel P. Judge, M.D. Project 3 investigators seek to answer the basic question – Who is susceptible to developing a lethal arrhythmia that can lead to SCD and why? This project addresses the central theme of improved prevention and treatment to reduce the prevalence of SCD in several significant ways. Project 3 aims to define the genetic and proteomic characteristics of substrates and triggers that predispose to sudden death in patients with coronary artery disease (CAD). The objectives are two-fold: to gain a better understanding of the biological mechanisms that predispose to SCD, and to develop biomarkers to identify patients at risk. RNA expression profiles are performed on heart tissue and the peripheral blood of patients with CAD who are at high risk for SCD and those that have experienced malignant ventricular arrhythmias. To enhance the specificity of gene expression profiling, we are examining changes in protein expression by characterizing subproteomes of the serum to correlate with changes in gene expression and to seek biomarkers of SCD risk. In pursuit of these goals, we have established a multicenter registry of high-risk patients undergoing ICD implantation for primary prevention of SCD, which includes recipients with CAD and reduced left ventricular ejection fraction that have not experienced malignant ventricular arrhythmias, cardiac arrest or syncope. This registry includes the patients studied in Project 2 as well as others who have not necessarily undergone intensive structural phenotyping. | |
