title: Sudden cardiac death, genes, and arrhythmogenesis : consideration of new population and mechanistic approaches from a national heart, lung, and blood institute workshop, part I.
abstract: Malignant ventricular arrhythmias are the leading mechanism of death in patients with acute and chronic cardiac pathologies. The extent to which inherited mutations and polymorphic variation in genes determining arrhythmogenic mechanisms affect these patients remains unknown, but based on recent population studies, this risk appears significant, deserving much greater investigation. This report summarizes a National Heart, Lung, and Blood Institute workshop that considered sources of genetic variation that may contribute to sudden cardiac death in common cardiac diseases. Evidence on arrhythmogenic mechanisms in recent population studies suggests a significant portion of the risk of sudden cardiac death in such broad populations may be unrelated to traditional risk factors for predisposing conditions such as atherosclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptibility more directly. Additional population and genetic studies directed at discovering the sources of inherited molecular risk that are most directly linked to arrhythmia initiation and propagation, in addition to studies on previously well-described risk factors, would appear to have considerable potential for reducing premature cardiovascular mortality.
authors.affiliation: National Heart, Lung, and Blood Institute, Bethesda, Md, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Spooner
authors.forename: C
authors.initials: C
authors.lastname: Albert
authors.forename: E J
authors.initials: EJ
authors.lastname: Benjamin
authors.forename: R
authors.initials: R
authors.lastname: Boineau
authors.forename: R C
authors.initials: RC
authors.lastname: Elston
authors.forename: A L
authors.initials: AL
authors.lastname: George
authors.forename: X
authors.initials: X
authors.lastname: Jouven
authors.forename: L H
authors.initials: LH
authors.lastname: Kuller
authors.forename: J W
authors.initials: JW
authors.lastname: MacCluer
authors.forename: E
authors.initials: E
authors.lastname: Marbán
authors.forename: J E
authors.initials: JE
authors.lastname: Muller
authors.forename: P J
authors.initials: PJ
authors.lastname: Schwartz
authors.forename: D S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: R P
authors.initials: RP
authors.lastname: Tracy
authors.forename: W
authors.initials: W
authors.lastname: Zareba
authors.forename: D P
authors.initials: DP
authors.lastname: Zipes
mesh_terms: D001145:Arrhythmias, Cardiac / Q000150:complications / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D006801:Humans; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics; D009154:Mutation; D009316:National Institutes of Health (U.S.); D010641:Phenotype; D014481:United States