Characterization of Spatio-Temporal Cardiac Action Potential Variability at Baseline and Under β-Adrenergic Stimulation by Combined Unscented Kalman Filter and Double Greedy Dimension Reduction.

Objective: Elevated spatio-temporal variability of human ventricular repolarization has been related to increased risk for ventricular arrhythmias and sudden cardiac death, particularly under β-adrenergic stimulation ( β-AS). This work presents a methodology for theoretical characterization of temporal and spatial repolarization variability at baseline conditions and in response to β-AS. For any measured voltage trace, the proposed methodology estimates the parameters and state variables of an underlying human ventricular action potential (AP) model by combining Double Greedy Dimension Reduction (DGDR) with automatic selection of biomarkers and the Unscented Kalman Filter (UKF).

Complex Interaction Between Low-Frequency APD Oscillations and Beat-to-Beat APD Variability in Humans Is Governed by the Sympathetic Nervous System.

Background: Recent clinical, experimental and modeling studies link oscillations of ventricular repolarization in the low frequency (LF) (approx. 0.1 Hz) to arrhythmogenesis.

Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular Repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis.

Recent studies in humans and dogs have shown that ventricular repolarization exhibits a low-frequency (LF) oscillatory pattern following enhanced sympathetic activity, which has been related to arrhythmic risk. The appearance of LF oscillations in ventricular repolarization is, however, not immediate, but it may take up to some minutes. This study seeks to characterize the time course of the action potential (AP) duration (APD) oscillatory behavior in response to sympathetic provocations, unveil its underlying mechanisms and establish a potential link to arrhythmogenesis under disease conditions.

Mechanisms Underlying Interactions Between Low-Frequency Oscillations and Beat-to-Beat Variability of Celullar Ventricular Repolarization in Response to Sympathetic Stimulation: Implications for Arrhythmogenesis.

Enhanced beat-to-beat variability of ventricular repolarization (BVR) has been linked to arrhythmias and sudden cardiac death. Recent experimental studies on human left ventricular epicardial electrograms have shown that BVR closely interacts with low-frequency (LF) oscillations of activation recovery interval during sympathetic provocation. In this work human ventricular computational cell models are developed to reproduce the experimentally observed interactions between BVR and its LF oscillations, to assess underlying mechanisms and to establish a relationship with arrhythmic risk.

Data-Driven Identification of Stochastic Model Parameters and State Variables: Application to the Study of Cardiac Beat-to-Beat Variability.

Objective: Enhanced spatiotemporal ventricular repolarization variability has been associated with ventricular arrhythmias and sudden cardiac death, but the involved mechanisms remain elusive. In this paper, a methodology for estimation of parameters and state variables of stochastic human ventricular cell models from input voltage data is proposed for investigation of repolarization variability.

Methods: The proposed methodology formulates state-space representations based on developed stochastic cell models and uses the unscented Kalman filter to perform joint parameter and state estimation.