Engineers and cardiologists have taken divergent approaches to analysis of regional heart function. Our group is interested in developing clinically useful quantitative measures of endocardial wall motion, which is routinely assessed qualitatively by cardiologists using ultrasound images of the heart. We begin by parameterizing the motion of the endocardial surface in space and time, and then seek to derive quantitative measures for specific clinical applications. We illustrate here a model-based approach to designing wall motion measures using published finite element models of altered cardiac activation to screen wall-motion-based measures of synchrony of contraction. We illustrate the utility of the model in screening out measures that were initially expected to be useful, developing new measures that were not previously considered, and identifying potential limitations of these new measures to be verified experimentally in the next step of this process. Our results indicate that early systolic events and specifically early systolic rates of endocardial motion are likely the best wall-motion-based indicators of synchrony of contraction, confirming that fully four-dimensional wall motion analysis will be essential for this clinical application.