Clinical potential of beat-to-beat diastolic interval control in preventing cardiac arrhythmias

Life-threatening ventricular arrhythmias and sudden cardiac death are often preceded by cardiac alternans, a beat-to-beat oscillation in the T-wave morphology or duration. However, given the spatiotemporal and structural complexity of the human heart, designing algorithms to effectively suppress alternans and prevent fatal rhythms is challenging. Recently, an antiarrhythmic constant diastolic interval pacing protocol was proposed and shown to be effective in suppressing alternans in 0-, 1-, and 2-dimensional in silico studies as well as in ex vivo whole heart experiments. Herein, we provide a systematic review of the electrophysiological conditions and mechanisms that enable constant diastolic interval pacing to be an effective antiar-rhythmic pacing strategy. We also demonstrate a successful translation of the constant diastolic interval pacing protocol into an ECG-based real-time control system capable of modulating beat-to-beat cardiac electrical activity and preventing alter-nans. Furthermore, we present evidence of the clinical utility of real-time alternans suppression in reducing arrhythmia suscep-tibility in vivo. We provide a comprehensive overview of this promising pacing technique, which can potentially be translated into a clinically viable device that could radically improve the quality of life of patients experiencing abnormal cardiac rhythms.