Systems and methods for detecting circulatory anomalies such as, for example, right-to-left cardiac and pulmonary shunts. A fluorescing indicator is injected into the bloodstream of a subject. An optical sensor is used to transcutaneously excite the indicator into fluorescence and to transcutaneously detect the fluorescence, and a relative concentration of the indicator is determined as a function of time. An indicator dilution curve is generated from the relative concentration readings, the curve shape is analyzed for the indication of a shunt and, if a shunt is detected, a ratiometric area under the curve analysis is performed and combined with a calculated cardiac output value to provide a shunt conductance value. A Valsalva maneuver may be performed as a part of the method. System embodiments may include a controller/monitor that monitors, times, cues and/or analyzes various steps of a shunt detection test.