A novel model for the coupling between ventricular repolarisation and heart rate (QT/RR) is presented. It is based upon a transfer function (TRF) formalism that describes the static and dynamic properties of this coupling, i.e., the behaviour after a sudden change in heart rate. Different TRF models were analysed by comparing their capability to describe experimental data collected from 19 healthy volunteers using several RR stimulation protocols: (i) rest with deep breathing at 0.1 Hz; (ii) tilt with controlled breathing at 0.1 and 0.33 Hz; and (iii) cycling. A search for the best TRF led to unambiguous identification of a three-parameter model as the most suitable descriptor of QT/RR coupling. Compared with established static models (linear or power-law), our model predictions are substantially closer to the experimental results, with errors approximately 50% smaller. The shape of the frequency and step responses of the TRF presented is essentially the same for all subjects and protocols. Moreover, each TRF may be uniquely identified by three parameters obtained from the step response, which are believed to be of physiological relevance: (i) gain for slow RR variability; (ii) gain for fast RR variability; and (iii) time during which QT attains 90% of its steady-state value. The TRF successfully describes the behaviour of the RR control following an abrupt change in RR interval, and its parameters may offer a tool for detecting pharmacologically induced changes, particularly those leading to increased arrhythmogenic risk.

Institute of Scientific Instruments Academy of Sciences of the Czech Republic Brno 612 64 Czech Republic