Remodeling-Mediated Changes in Left Ventricular Mechanics Under Settings of Chronic Pressure Overload and Exercise

Abstract

Abstract. Left ventricular (LV) remodeling, whether occurring with somatic growth or as a chronic response to a sustained stimulus, is a primary factor underlying cardiac mechanical function. Although LV remodeling is a complex process that can be described at several levels, response variables that govern cardiac mechanics include changes in LV wall and chamber geometry, the mechanical properties of the LV myocardium, and LV structural mechanical properties such as LV chamber stiffness. We leverage two-dimensional speckle-tracking echocardiography (STE) to serially monitor key LV remodeling response variables in porcine models of LV pressure overload (LVPO), chronic exercise (CE), and the superposition of both settings (CE+LVPO), and compare changes to those occurring in age-matched referent control (RC) animals. Our findings show that over 28-days, LVPO and CE both induce hypertrophy, but passive LV myocardial stiffness increases with the former and decreases with the latter. As a net effect of geometrical and mechanical property changes, these settings induce divergent changes in LV chamber stiffness, namely, an elevation with LVPO and reduction with CE. In the CE+LVPO cohort, exercise was found to attenuate the LVPO-induced increase in LV myocardial and LV chamber stiffnesses. Data obtained were used to identify a phenomenological model of LV chamber stiffness and develop a predictive mathematical model of late changes in LV chamber stiffness based on early remodeling response variables irrespective of stimulus. Our findings support exercise in cardiac therapy and the use of STE to predict cardiac disease risk/progression.