doi: 10.1161/01.RES.0000123861.16082.95
© 2004 American Heart Association, Inc.
Reviews |
Genomics in Sudden Cardiac Death
From the McKusick-Nathans Institute of Genetic Medicine (D.E.A., A.C.), Johns Hopkins University School of Medicine, Baltimore, Md; Division of Cardiology (S.S.C.), Oregon Health and Science University, Portland, Ore; and D.W. Reynolds Clinical Cardiovascular Center (P.M.S.), Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Dan E. Arking, Johns Hopkins University School of Medicine, 733 N Broadway, Room 580, Baltimore, MD 21205. E-mail arking{at}jhmi.edu
This Review is part of a thematic series on the Biology of Cardiac Arrhythmias, which includes the following articles:
Antiarrhythmic Drug Target Choices and Screening
Inherited Arrhythmogenic Diseases: The Complexity Beyond Monogenic Disorders
Genomics in Sudden Cardiac Death
Ion Channel Protein Processing
Regulation of Expression and Distribution of Ion Channels
Computational Insights: Chaos and Wave Theory
Gene Therapy and Cell Therapy of Cardiac Arrhythmias
Gordon Tomaselli Editors
This series is in honor of Harry A. Fozzard, 8th Editor of Circulation Research.
Sudden cardiac death (SCD) remains a public health problem of major magnitude. Contrary to earlier expectations, and despite decreased overall cardiac mortality, SCD rates appear to be rising in concert with escalating global prevalence of coronary disease and heart failure, the two major conditions predisposing to SCD. With the exception of the implantable defibrillator, there are few effective approaches to SCD prevention and even fewer clues concerning patient phenotypes predisposed to life-threatening arrhythmias. Clinical variables such as ejection fraction predict mortality but are not sensitive enough to identify many high SCD risk patients. The predictive power of autonomic dysregulation and markers such as lipid levels, hypertension, diabetes, and smoking is quite low in subclinical heart disease, the population in which the majority of SCDs occur. This review addresses advances in genomic science applicable to the SCD public health problem in both rare and common forms of heart disease. These include novel bioinformatic approaches to both identify candidate genes/pathways and identify previously unknown functional genetic elements, as well as methods to comprehensively screen these elements. We also discuss the possibility of applying high-density genome-wide SNP analyses to examine genetic contributions to arrhythmia susceptibility in community-based, case-control studies of common forms of SCD. The development of novel strategies to identify contributors to susceptibility in common cardiac phenotypes is most likely to lead to new and relevant therapeutic targets for SCD.
Key Words: genomics • sudden cardiac death • arrhythmias • risk stratification
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