There is described a system for assessing the severity of a stenosis in a vessel without administration of a hyperemic agent. The system comprises a first instrument and a processing unit. The first instrument is sized and shaped for introduction into the vessel of the patient. The processing unit is in communication with the first instrument. The processing unit is configured to: obtain distal pressure measurements for a cardiac cycle of the patient from the first instrument while the first instrument is positioned within the vessel at a position distal of the stenosis； obtain proximal pressure measurements for the cardiac cycle of the patient from a second instrument while the second instrument is positioned within the vessel at a position proximal of the stenosis； select a diagnostic window within the cardiac cycle of the patient, wherein the diagnostic window encompasses only a portion of the cardiac cycle of the patient； and calculate a pressure ratio between the distal pressure measurements obtained during the diagnostic window and the proximal pressure measurements obtained during the diagnostic window to thereby assess the severity of the stenosis. Ways in which starting and ending points of the diagnostic window are selected are also described.
