A system comprising: an implantable device configured to sense or receive cardiac signals and deliver cardiac stimulation; and a lead longitudinally extending from a single lead proximal end portion to a single lead distal end portion, the lead including a lead body, and four or more tissue electrodes disposed along the lead body and configured for both sensing and stimulating and wherein all of the four or more electrodes are implantable within, on, or about a heart of a subject; the single lead proximal end portion of the lead is sized and shaped to couple to the implantable device, the coupling electrically connecting each of the four or more tissue electrodes to a signal processing circuit of the implantable device; and the signal processing circuit is adapted to sense in a first instance and stimulate in a second instance, the sensing and stimulation occurring by way of one or more selected tissue electrode configurations, wherein the basis of choosing a selected tissue electrode sensing configuration is an analysis of a plurality of different sensing configurations of the four or more tissue electrodes using one or more sense parameters, and wherein the signal processing circuit automatically selects one of the plurality of different sensing configurations of the four or more tissue electrodes for sensing after implantation in view of the analysis of the plurality of different sensing configurations of the four or more tissue electrodes, wherein the signal processing circuit is further adapted to select one of the plurality of different sensing configurations using, at least in part, one or a combination of a blood volume parameter, a spatial distance parameter, or a blood oxygen parameter, each parameter evaluated by way of a logic module of the signal processing circuit. an implantable device configured to sense or receive cardiac signals and deliver cardiac stimulation; and a lead longitudinally extending from a single lead proximal end portion to a single lead distal end portion, the lead including a lead body, and four or more tissue electrodes disposed along the lead body and configured for both sensing and stimulating and wherein all of the four or more electrodes are implantable within, on, or about a heart of a subject; a lead body, and four or more tissue electrodes disposed along the lead body and configured for both sensing and stimulating and wherein all of the four or more electrodes are implantable within, on, or about a heart of a subject; the single lead proximal end portion of the lead is sized and shaped to couple to the implantable device, the coupling electrically connecting each of the four or more tissue electrodes to a signal processing circuit of the implantable device; and the signal processing circuit is adapted to sense in a first instance and stimulate in a second instance, the sensing and stimulation occurring by way of one or more selected tissue electrode configurations, wherein the basis of choosing a selected tissue electrode sensing configuration is an analysis of a plurality of different sensing configurations of the four or more tissue electrodes using one or more sense parameters, and wherein the signal processing circuit automatically selects one of the plurality of different sensing configurations of the four or more tissue electrodes for sensing after implantation in view of the analysis of the plurality of different sensing configurations of the four or more tissue electrodes, wherein the signal processing circuit is further adapted to select one of the plurality of different sensing configurations using, at least in part, one or a combination of a blood volume parameter, a spatial distance parameter, or a blood oxygen parameter, each parameter evaluated by way of a logic module of the signal processing circuit.