Closed-loop effects in coupling cardiac physiological models to clinical interventions

There have been impressive methodological advancements in the mathematical modelling of cardio-physiological processes. The majority of recent articles have focused on the forward problem: developing flexible mathematical models and robust numerical simulation procedures to match characteristics of physiological target data, and the inverse problem: inferring model parameters from cardiac physiological data with reliable uncertainty quantification. However, when connecting mathematical model predictions to the clinical decision process, new challenges arise. This paper briefly discusses the complications that poten- tially result from closed-loop effects, and the model extensions that are required to reduce the ensuing bias.