Cardiac monitoring and/or stimulation methods and systems that provide one or more of monitoring, diagnosing, defibrillation, and pacing. Cardiac signal separation is employed to detect, monitor, track and/or trend ischemia using cardiac activation sequence information. Ischemia detection may involve sensing composite cardiac signals using implantable electrodes, and performing a signal separation that produces one or more cardiac activation signal vectors associated with one or more cardiac activation sequences. A change in the signal vector may be detected using subsequent separations. The change may be an elevation or depression of the ST segment of a cardiac cycle or other change indicative of myocardial ischemia, myocardial infarction, or other pathological change. The change may be used to predict, quantify, and/or qualify an event such as an arrhythmia, a myocardial infarction, or other pathologic change. Information associated with the vectors may be stored and used to track the vectors.