A pacemaker provides multi-chamber pacing with a pacing interval that can be programmed and adapted in response to cardiac output measurements for a given patient. In a typical embodiment, the pacemaker may provide pacing stimuli to both ventricles of a heart. In addition, the invention may include a measurement device that incorporates first and second blood oxygen saturation sensors for deployment in the left and right ventricle. The oxygen saturation sensors provide a differential measurement that can be used to calculate cardiac output in accordance with the Fick method. The oxygen saturation sensors may be carried by a common trans-septal lead that positions one of the sensors proximate the right ventricle and the other sensor proximate the left ventricle. Alternatively, the oxygen saturation sensors may be deployed via separate leads. Whether single or dual leads are used to carry the oxygen saturation sensors, a respective lead may optionally carry electrodes for sensing, pacing, or both.