Therapy optimization includes tracking electrode motion using an electroanatomic mapping system and generating, based on tracked electrode motion, one or more mechanical dyssynchrony metrics to thereby guide a clinician in therapy optimization (e.g., via optimal electrode sites, optimal therapy parameters, etc.). Such a method may include a vector analysis of electrode motion with respect to factors such as times in cardiac cycle, phases of a cardiac cycle, and therapy conditions, e.g., pacing sites, pacing parameters and pacing or no pacing. Differences in position-with-respect-to-time data for electrodes may also be used to provide measurements of mechanical dyssynchrony.