Modeling of cardiac growth and remodeling of myofiber orientation

The heart has the ability to respond to long-term changes in its environment through changes in mass (growth), shape (morphogenesis) and tissue properties (remodeling). For improved quantitative understanding of cardiac growth and remodeling (G&R) experimental studies need to be complemented by mathematical models. This paper reviews models for cardiac growth and remodeling of myofiber orientation, as induced by mechanical stimuli. A distinction is made between optimization models, that focus on the end stage of G&R, and adaptation models, that aim to more closely describe the mechanistic relation between stimulus and effect. While many models demonstrate qualitatively promising results, a lot of questions remain, e.g. with respect to the choice of the stimulus for G&R or the long-term stability of the outcome of the model. A continued effort combining information on mechanotransduction at the cellular level, experimental observations on G&R at organ level, and testing of hypotheses on stimulus-effect relations in mathematical models is needed to answer these questions on cardiac G&R. Ultimately, models of cardiac G&R seem indispensable for patient-specific modeling, both to reconstruct the actual state of the heart and to assess the long-term effect of potential interventions.