Global Sensitivity Analysis and Uncertainty Quantification for Simulated Atrial Electrocardiograms

The numerical modeling of cardiac electrophysiology has reached a mature and advanced state that allows for quantitative modeling of many clinically relevant processes. As a result, complex computational tasks such as the creation of a variety of electrocardiograms (ECGs) from virtual cohorts of models representing biological variation are within reach. This requires a correct representation of the variability of a population by suitable distributions of a number of input parameters. Hence, the assessment of the dependence and variation of model outputs by sensitivity analysis and uncertainty quantification become crucial. Since the standard metrological approach of using Monte–Carlo simulations is computationally prohibitive, we use a nonintrusive polynomial chaos-based approximation of the forward model used for obtaining the atrial contribution to a realistic electrocardiogram. The surrogate increases the speed of computations for varying parameters by orders of magnitude and thereby greatly enhances the versatility of uncertainty quantification. It further allows for the quantification of parameter influences via Sobol indices for the time series of 12 lead ECGs and provides bounds for the accuracy of the obtained sensitivities derived from an estimation of the surrogate approximation error. Thus, it is capable of supporting and improving the creation of synthetic databases of ECGs from a virtual cohort mapping a representative sample of the human population based on physiologically and anatomically realistic three-dimensional models.