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This study was done to evaluate the accuracy of radionuclide dipyridamole stress imaging to detect multivessel disease and ischemia in segments of myocardium supplied by the most stenotic vessel.A retrospective analysis of consecutive patients with known triple-vessel disease of at least 50% stenosis in each of the three major epicardial coronary arteries who had exercise (n = 44) or dipyridamole (n = 86) stress testing, or both, within 6 months of coronary angiography.The accuracy of dipyridamole stress testing to detect three-vessel disease was 52% and ischemia was detected in the region supplied by the most stenotic vessel in 67% of patients. The sensitivity and specificity rates of radionuclide imaging to detect ischemia in the region supplied by the vessel of tightest stenosis were 69% and 74% for the left anterior descending coronary artery (LAD), 61% and 78% for the right coronary artery (RCA), and 61% and 57% for the left circumflex coronary artery (LCX). Based on these values, in 39% of patients in whom the RCA or LCX was the most stenotic vessel and in 31% of patients in whom the LAD was the most stenotic vessel, perfusion defects were not present on their nuclear scans.These results have important implications for interventional cardiologists who perform angioplasty on the most stenotic vessel, because the regions supplied by these vessels may not be the most ischemic. Furthermore, dipyridamole stress imaging may significantly underestimate the number of patients with substantial three-vessel coronary artery disease when qualitative imaging is done.