The Effect of Feedback on Alternans Formation in the Heart

A beat-to-beat alternation in the duration of the action potential (APD) of myocytes, i.e. alternans, is believed to be a direct precursor of ventricular fibrillation (VF) in the whole heart. A common technique for the prediction of alternans uses the restitution curve, the nonlinear functional relationship between the APD and the preceding diastolic interval (DI). It was proposed that alternans appears when the magnitude of the slope of the restitution curve exceeds one, known as the restitution hypothesis. However, this restitution hypothesis was derived in the presence of feedback, i.e. the partial dependence of the DI on the immediate preceding APD. Physiologically, the heart rate exhibits substantial variations, known as heart rate variability (HRV), which might affect the feedback relationship. In this manuscript, we aim to investigate the effect of feedback on alternans formation in the heart.