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. Evaluation over synthetic and experimental data is presented.
Results: Results on synthetically generated data show the ability of the methodology to: first, filter out measurement noise from action potential (AP) traces; second, identify model parameters and state variables from each of those individual AP traces, thus allowing robust characterization of cell-to-cell variability; and, third, replicate statistical population's distributions of input AP-based markers, including dynamic markers quantifying beat-to-beat variability. Application onto experimental data demonstrates the ability of the methodology to match input AP traces while concomitantly inferring the characteristics of underlying stochastic cell models.
Conclusion: A novel methodology is presented for estimation of parameters and hidden variables of stochastic cardiac computational models, with the advantage of providing a one-to-one match between each individual AP trace and a corresponding set of model characteristics.
Significance: The proposed methodology can greatly help in the characterization of temporal (beat-to-beat) and spatial (cell-to-cell) variability in human ventricular repolarization and in ascertaining the corresponding underlying mechanisms, particularly in scenarios with limited available experimental data.