Repolarization reserve: a moving target.

Clinicians are well aware that responses to QT-prolonging drugs vary among individuals.1 A drug dose (and concentration) that produces minimal QT prolongation in one patient may, in an apparently indistinguishable subject, produce marked QT prolongation and torsade de pointes. This variability in response to an exogenous stressor is paralleled by variability in the extent to which a given mutation in the congenital long-QT syndrome prolongs QT interval and causes arrhythmias.2 Indeed, it is depressingly common to identify an affected family after an individual subject has died, only to find many other mutation carriers within the kindred, often with normal QT intervals.