New approaches for identifying antiarrhythmic drug targets.

Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in many developed countries. Substantial experimental and theoretical support exists for the idea that VF is caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves have been linked to electrical alternans, a phenomenon typically associated with a steeply sloped restitution relationship. Interventions that reduce the slope of the restitution relationship have been shown to prevent the induction of VF and to terminate existing VF in experimental models. These results suggest that electrical restitution may be a promising new target for antiarrhythmic therapies.