A system and method control a pacing parameter in a closed-loop manner by determining a value of an EGM-based index corresponding an optimal electrical activation condition of a patient's heart and adjusting a pacing therapy to maintain the EGM-based index value. The closed loop control method performed by the system may establish a relationship between an EGM-based index and multiple settings of a pacing control parameter. Values of the EGM-based index are stored with corresponding setting shifts relative to a previously established optimal setting. A processor of an implantable medical device monitors the EGM-based index during cardiac pacing. Responsive to detecting an EGM-based index value corresponding to a non-optimal setting of the control parameter, the processor determines an adjustment of the control parameter from the stored index values and corresponding setting shifts.