A multivariate time-frequency approach for tracking QT variability changes unrelated to heart rate variability

The beat-to-beat variability of the QT interval (QTV) is a marker of ventricular repolarization (VR) dynamics and it has been suggested as an index of sympathetic ventricular outflow and cardiac instability. However, QTV is also affected by RR (or heart rate) variability (RRV), and QTV due to RRV may reduce QTV specificity as a VR marker. Therefore, it would be desirable to separate QTV due to VR dynamics from QTV due to RRV. To do that, previous work has mainly focused on heart rate corrections or time-invariant autoregressive models. This paper describes a novel framework that extends classical multiple inputs/single output theory to the time-frequency (TF) domain to quantify QTV and RRV interactions. Quadratic TF distributions and TF coherence function are utilized to separate QTV into two partial (conditioned) spectra representing QTV related and unrelated to RRV, and to provide an estimates of intrinsic VR dynamics. In a simulation study, a time-varying ARMA model was used to generate signals representing realistic RRV and VR dynamics with controlled instantaneous frequencies and powers. The results demonstrated that the proposed methodology is able to accurately track changes in VR dynamics, with a correlation between theoretical and estimated patterns higher than 0.88. Data from healthy volunteers undergoing a tilt table test were analyzed and representative examples are discussed. Results show that the QTV unrelated to RRV dynamics quickly increased during orthostatic challenge.