Model of Anisotropic Reverse Cardiac Growth in Mechanical Dyssynchrony.

Based on recent single-cell experiments showing that longitudinal myocyte stretch produces both parallel and serial addition of sarcomeres, we developed an anisotropic growth constitutive model with elastic myofiber stretch as the growth stimuli to simulate long-term changes in biventricular geometry associated with alterations in cardiac electromechanics. The constitutive model is developed based on the volumetric growth framework. In the model, local growth evolutions of the myocyte's longitudinal and transverse directions are driven by the deviations of maximum elastic myofiber stretch over a cardiac cycle from its corresponding local homeostatic set point, but with different sensitivities. Local homeostatic set point is determined from a simulation with normal activation pattern. The growth constitutive model is coupled to an electromechanics model and calibrated based on both global and local ventricular geometrical changes associated with chronic left ventricular free wall pacing found in previous animal experiments. We show that the coupled electromechanics-growth model can quantitatively reproduce the following: (1) Thinning and thickening of the ventricular wall respectively at early and late activated regions and (2) Global left ventricular dilation as measured in experiments. These findings reinforce the role of elastic myofiber stretch as a growth stimulant at both cellular level and tissue-level.