Uncertainty quantification of 2 models of cardiac electromechanics

Abstract

Computational models of the heart have reached a maturity level that render them useful for in silico studies of arrhythmia and other cardiac diseases. However, the translation to the clinic of cardiac simulations critically depends on demonstrating the accuracy, robustness, and reliability of the underlying computational models under the presence of uncertainties. In this work, we study for the first time the effect of parameter uncertainty on 2 state-of-the-art coupled models of excitation-contraction of cardiac tissue. To this end, we perform forward uncertainty propagation and sensitivity analyses to understand how variability in key maximal conductances affect selected quantities of interest, such as the action potential duration (APD₉₀ ), maximum intracellular calcium concentration, cardiac stretch, and stress. Our results suggest a strong linear relationship between selected maximal conductances and quantities of interest for a variability in parameters up to 25%, which justifies the construction of linear response surfaces that are used to compute the empirical probability density functions of all the quantities of interest under study. For both electromechanical models analyzed, uncertainty in the material parameters associated to the passive mechanical response of cardiac tissue does not affect the duration of action potentials, neither the amplitude of intracellular calcium concentrations. Our results confirm the poor mechanoelectric feedback that classical models of cardiac electromechanics have, even under the presence of parameter uncertainty.

Keywords: cardiac electromechanics; parameter sensitivity analysis; uncertainty propagation; uncertainty quantification.