A novel approach to identifying antiarrhythmic drug targets.

Sudden cardiac death, secondary to ventricular fibrillation (VF), remains the leading cause of death in the USA. Recent experimental and theoretical studies suggest that VF could be caused by spiral wave re-entry. The initiation and subsequent break-up of spiral waves has been linked to electrical alternans, a phenomenon produced in cardiac tissue that has a steeply sloped restitution relation. Agents that reduce the slope of the restitution relation have been shown to suppress alternans and, presumably by that mechanism, terminate VF. These results suggest that electrical restitution could be a promising new target for antiarrhythmic therapies.