Spectral analysis of periodic fluctuations in electrocardiographic repolarization

Repolarization alternans (RPA) indicates alternate-beat fluctuations in the temporal or spatial characteristics of the echocardiogram (ECG) STU segment which may represent dispersion in repolarization. Spectral decomposition has revealed microvolt-level RPA which has been found to correlate with ventricular tachycardia (VT) and fibrillation, and is increasingly being used for clinical risk stratification. However, while interruptions in periodicity are known to affect spectral decomposition, their quantitative impact on RPA and its clinical utility have been poorly described. We therefore studied the effect of variable alignment, extrasystoles, dissimilar beats and beat exclusion on RPA magnitude in simulations and on the sensitivity and specificity of RPA for VT in a pilot clinical study. RPA magnitude was exquisitely sensitive to QRS alignment such that +/- 1 ms random beat misalignment reduced it by 68% in simulations. Correspondingly, suboptimal QRS alignment in clinical ECG's caused the sensitivity of RPA for inducible VT to fall from 93% to as low as 63%; while JT alignment was also less effective for RPA recovery. As an experiment in minimizing morphometric irregularities in clinical ECG's, we found that RPA magnitude actually fell when replacing either measurably dissimilar or ectopic beats with more representative beats. In addition, inserting or deleting beats also reduced RPA magnitude in clinical sequences and simulations. These statistical analyses suggest that the precision of beat alignment and interruptions to ECG periodicity, which may occur physiologically, may greatly reduce the clinical utility of RPA for VT. Dynamic alterations in RPA in response to sequence irregularities require further study before RPA may be optimally applied to screen for ventricular arrhythmias.