A system and method provide detecting and monitoring cardiac electrophysiological changes by determining differences between a reference signal representing a heartbeat signal and an analysis signal representing another heartbeat signal. A set of signal data consisting of a number of heartbeat signals is acquired as a function of time. Individual heartbeat signals within the set of acquired signals are identified, an individual signal comprising data values representing a plurality of sample points during a single heartbeat. One of the identified individual signals or a derived signal representing an average of a subset of the identified individual signals is selected as an analysis signal. A reference signal is identified. The sample points of the reference signal are aligned with the sample points of the analysis signal. A single value representative of mutual correspondence between the sample points of the reference signal and the corresponding sample points of the analysis signal is calculated. Data indicating a calculated value is communicated to a destination for viewing by a user.