Nonalternans repolarization variability and arrhythmia – the calcium connection

Abstract Repolarization alternans precedes certain types of ventricular arrhythmias and its presence may be prognostically useful, but some ventricular arrhythmias are not preceded by repolarization alternans. Nonalternans changes of ventricular repolarization occur in patients with coronary artery disease and in subjects with congenital long QT syndrome. In animal experiments, nonalternans repolarization lability occurs in a canine model of chronic AV block with propensity to polymorphic ventricular tachycardia, in the perfused rabbit heart exposed to IKr block, and in a murine model of catecholaminergic polymorphic ventricular tachycardia. Optical mapping experiments indicate that heterogeneity of intracellular calcium handling underlies nonalternans repolarization variability. Detection of nonalternans repolarization lability poses specific challenges, since signal averaging does not increase the signal to noise ratio. Nonalternans repolarization lability may be erroneously reported as repolarization alternans by non-spectral methods applied to short data segments. Additional research will be needed to determine the role of nonalternans repolarization variability in mechanism of ventricular arrhythmias.