Cardiac therapy systems include multiple electrodes respectively positionable at multiple left ventricular electrode sites. A pulse generator is coupled to the electrodes and configured to deliver a cardiac resynchronization therapy (CRT). A processor is configured to measure, for each left ventricular electrode site, a timing interval between first and second cardiac signal features associated with left ventricular depolarization. The timing interval is associated with a degree of responsiveness of each left ventricular electrode site to CRT. The processor is configured to determine a pacing output configuration that provides improved patient responsiveness to CRT based on the timing interval measurements and to select at least one left ventricular electrode site from the plurality of left ventricular electrode sites based on the timing interval measurements. The processor may be configured to monitor for a change in hemodynamic status of the patient based on a change in the timing interval.