A system and method for monitoring left ventricular cardiac contractility and for optimizing a cardiac therapy based on left ventricular lateral wall acceleration (LVA) are provided. The system includes an implantable or external cardiac stimulation device in association with a set of leads including a left ventricular epicardial or coronary sinus lead equipped with an acceleration sensor. The device receives and processes acceleration sensor signals to determine a signal characteristic indicative of LVA during isovolumic contraction. A therapy optimization method evaluates the LVA during varying therapy settings and selects the setting(s) that correspond to a maximum LVA during isovolumic contraction. In one embodiment, the optimal inter-ventricular pacing interval for use in cardiac resynchronization therapy is determined as the interval corresponding to the highest amplitude of the first LVA peak during isovolumic contraction.