Systems and methods provide for pacing a heart to improve pumping efficiency of the heart, such as by producing a cardiac fusion response for patients subject to cardiac resynchronization therapy. A pacing parameter, such as an A-V delay, V-V delay, lead/electrode configuration or vector, is adjusted and a cardiac signal vector representative of all or a portion of one or more cardiac activation sequences is monitored during pacing parameter adjustment. A change in a characteristic of the cardiac signal vector is detected in response to an adjusted pacing parameter, the change indicative of a cardiac fusion response. A pacing therapy may be delivered to produce the cardiac fusion response using the adjusted pacing parameter.
