A Comparison of Phenomenologic Growth Laws for Myocardial Hypertrophy

The heart grows in response to changes in hemodynamic loading during normal development and in response to valve disease, hypertension, and other pathologies. In general, a left ventricle subjected to increased afterload (pressure overloading) exhibits concentric growth characterized by thickening of individual myocytes and the heart wall, while one experiencing increased preload (volume overloading) exhibits eccentric growth characterized by lengthening of myocytes and dilation of the cavity. Predictive models of cardiac growth could be important tools in evaluating treatments, guiding clinical decision making, and designing novel therapies for a range of diseases. Thus, in the past 20 years there has been considerable effort to simulate growth within the left ventricle. While a number of published equations or systems of equations (often termed "growth laws") can capture some aspects of experimentally observed growth patterns, no direct comparisons of the various published models have been performed. Here we examine eight of these laws and compare them in a simple test-bed in which we imposed stretches measured during in vivo pressure and volume overload. Laws were compared based on their ability to predict experimentally measured patterns of growth in the myocardial fiber and radial directions as well as the ratio of fiber-to-radial growth. Three of the eight laws were able to reproduce most key aspects of growth following both pressure and volume overload. Although these three growth laws utilized different approaches to predict hypertrophy, they all employed multiple inputs that were weakly correlated during in vivo overload and therefore provided independent information about mechanics.