A single strain-based growth law predicts concentric and eccentric cardiac growth during pressure and volume overload.

Abstract Adult cardiac muscle adapts to mechanical changes in the environment by growth and remodeling (G&R) via a variety of mechanisms. Hypertrophy develops when the heart is subjected to chronic mechanical overload. In ventricular pressure overload (e.g. due to aortic stenosis) the heart typically reacts by concentric hypertrophic growth, characterized by wall thickening due to myocyte radial growth when sarcomeres are added in parallel. In ventricular volume overload, an increase in filling pressure (e.g. due to mitral regurgitation) leads to eccentric hypertrophy as myocytes grow axially by adding sarcomeres in series leading to ventricular cavity enlargement that is typically accompanied by some wall thickening. The specific biomechanical stimuli that stimulate different modes of ventricular hypertrophy are still poorly understood. In a recent study, based on in vitro studies in micropatterned myocyte cell cultures subjected to stretch, we proposed that cardiac myocytes grow longer to maintain a preferred sarcomere length in response to increased fiber strain and grow thicker to maintain interfilament lattice spacing in response to increased cross-fiber strain. Here, we test whether this growth law is able to predict concentric and eccentric hypertrophy in response to aortic stenosis and mitral valve regurgitation, respectively, in a computational model of the adult canine heart coupled to a closed loop model of circulatory hemodynamics. A non-linear finite element model of the beating canine ventricles coupled to the circulation was used. After inducing valve alterations, the ventricles were allowed to adapt in shape in response to mechanical stimuli over time. The proposed growth law was able to reproduce major acute and chronic physiological responses (structural and functional) when integrated with comprehensive models of the pressure-overloaded and volume-overloaded canine heart, coupled to a closed-loop circulation. We conclude that strain-based biomechanical stimuli can drive cardiac growth, including wall thickening during pressure overload.