Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC156
Clinical evidence of spatial heterogeneity in heart rate adaptation and associated arrhythmic risk in the human ventricles
A. Bueno-Orovio1, B. Hanson2, J. S. Gill3, P. Taggart2, B. Rodriguez1
1. Oxford University Computing Laboratory, Oxford University, Oxford, United Kingdom. 2. University College of London, London, United Kingdom. 3. Guy's and St. Thomas' Hospital, London, United Kingdom.
Motivation: Adaptation of action potential duration (APD) refers to the slow change in APD following a sustained change in heart rate. The main function of this slow APD adaptation is to optimize the ratio of diastolic filling time to systolic ejection time (1). However, slow dynamics of adaptation of repolarization to changes in heart rate have been proposed as an arrhythmic risk biomarker (2). Heterogeneity in APD adaptation has been reported in animals (3,4), but has not been characterised in humans. In this study, we provide evidence of spatial differences in APD adaptation in the in-vivo left and right ventricles (LV/RV) in humans. Methods: Unipolar electrograms were simultaneously recorded at 20 endocardial sites covering apex to base on the RV septum and LV free wall of 7 patients with normal ventricles. Local time constants (τ) for activation-recovery interval (ARI, as a surrogate of APD) adaptation were calculated following a heart rate change from sinus rhythm (846.6 ± 133.9 ms) to 500 ms cycle length, paced at RV apex. Computer simulations of the observed scenarios were carried out to investigate the effect of heterogeneity in APD adaptation in modulating dispersion of repolarization. Results: Adaptation dynamics in RV were spatially homogeneous in most patients (Fig A), but high inter-patient variability in time constants exists (mean τ range: 21.2 to 46.8 s). In LV, 3 patients showed longer time constants (slower adaptation) at base than apex (Fig B). These trends were also observed in the mean values of time constants (Fig C), with time constants between the base of LV and RV being significantly different (Fig D, Student's T-test, p<0.05). Computer simulations show that marked gradients in adaptation dynamics enhance transient dispersion of repolarization in the human ventricles, providing a pro-arrhythmic substrate following changes in heart rate. Conclusions: We show in humans that: 1. Regional heterogeneity of repolarization occurs dynamically in the ventricles during adaptation to a change in heart rate; 2. Marked inter-patient variability is present in the maximum local repolarization gradients; 3. Computer simulations indicate that these spatial differences may be able to detect tissue's propensity to develop transient conduction block after changes in heart rate, and that suitable substrates for reentry which may not be present at baseline may form dynamically due to this regional heterogeneity in APD adaptation.
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