Stimulus-effect relations for left ventricular growth obtained with a simple multi-scale model: the influence of hemodynamic feedback.

Cardiac growth is an important mechanism for the human body to respond to changes in blood flow demand. Being able to predict the development of chronic growth is clinically relevant, but so far models to predict growth have not reached consensus on the stimulus-effect relation. In a previously published study, we modeled cardiac and hemodynamic function through a lumped parameter approach. We evaluated cardiac growth in response to valve disease using various stimulus-effect relations and observed an unphysiological decline pump function. Here we extend that model with a model of hemodynamic feedback that maintains mean arterial pressure and cardiac output through adaptation of peripheral resistance and circulatory unstressed volume. With the combined model, we obtain stable growth and restoration of pump function for most growth laws. We conclude that a mixed combination of stress and strain stimuli to drive cardiac growth is most promising since it (1) reproduces clinical observations on cardiac growth well, (2) requires only a small, clinically realistic adaptation of the properties of the circulatory system and (3) is robust in the sense that results were fairly insensitive to the exact choice of the chosen mechanics loading measure. This finding may be used to guide the choice of growth laws in more complex finite element models of cardiac growth, suitable for predicting the response to spatially varying changes in tissue load. Eventually, the current model may form a basis for a tool to predict patient-specific growth in response to spatially homogeneous changes in tissue load, since it is computationally inexpensive.