A Role of Preload Variability in Quantifying Cardiac Repolarization Reserve in Baseline

Ventricular arrhythmias compose a heterogeneous group of cardiac complications that can lead to sudden cardiac death. An increased susceptibility to (prolonged) repolarization associated arrhythmias is suggested to be the result of a reduced ‘repolarization reserve’, associated with an increase in the beat-to-beat variability in repolarization (BVR). Multiple parameters, related to ventricular remodelling as occurs in the chronic atrioventricular block (CAVB) dog model or in patients in heart failure have already been demonstrated to increase BVR in baseline, which further increases upon infusion with APD prolonging drugs. We demonstrate that the beat-to-beat variability in preload, as a result of atrioventricular dyssynchrony, can assist to determine the status of repolarization reserve. The increase in BVR, induced by varying the preload, could be diminished by infusion with streptomycin, an inhibitor of the stretchactivated channels (SACs). We therefore identified the SACs as important components of the process that contributes to the beat-to-beat variability in preload to increase the BVR. The preload-variability induced increase in BVR was
however not associated with an increase in the incidence of ventricular arrhythmias. Therefore, the effect of variability in preload is able to unmask a latent decrease of repolarization reserve. The identification of a new method
to determine repolarization reserve status opens numerous doors for future research in the field of arrhythmias. For instance, preload variability could be used in the optimization of the BVR as a predictor of arrhythmias. Furthermore,
clinical applicability and anti-arrhythmic efficacy of diminishing effects of variable preload on SACs in cardiac patients as (part of) an anti-arrhythmic therapy could also be further explored.