Sudden cardiac death, genes, and arrhythmogenesis - Consideration of new population and mechanistic approaches from a national heart, lung, and bloodinstitute workshop, part I

Malignant ventricular arrhythmias are the leading mechanism of death in pat ients with acute and chronic cardiac pathologies. The extent to which inher ited mutations and polymorphic variation in genes determining arrhythmogeni c mechanisms affect these patients remains unknown, but based on recent pop ulation studies, this risk appears significant, deserving much greater inve stigation. This report summarizes a National Heart, Lung, and Blood Institu te workshop that considered sources of genetic variation that may contribut e to sudden cardiac death in common cardiac diseases. Evidence on arrhythmo genic mechanisms in recent population studies suggests a significant portio n of the risk of sudden cardiac death in such broad populations may be unre lated to traditional risk factors for predisposing conditions such as ather osclerosis, hypertension, and diabetes and instead may involve unrecognized genetic and environmental interactions that influence arrhythmic susceptib ility 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 p otential for reducing premature cardiovascular mortality.