OBJECTIVES This study sought to determine the anatomic and physiologic correlates of increased right ventricular (RV) activity on exercise single photon emission computed tomography (SPECT) perfusion imaging in patients with coronary artery disease (CAD). BACKGROUND Because SPECT perfusion imaging delineates relative myocardial blood flow, patients with global left ventricular (LV) hypoperfusion but normal RV perfusion may have increased relative RV tracer uptake as an indicator of muitivessel CAD. METHODS Rest thallium-201 and exercise Tc-99m-sestamibi or Tc-99m-tetrofosmin SPECT perfusion images were analyzed for peak RV and LV activity (RV:LV index) in 315 patients, including 240 patients with documented CAD, 39 patients with no significant CAD on arteriography, and a normalcy" group of 36 patients with a low pre- and posttest probability of CAD. RESULTS Resting RV:LV perfusion index ranged from 0.32 to 0.34 in each group, increasing to 0.36 with exercise in control and normalcy groups. CAD patients with the highest exercise RV:LV were those with severe left main CAD (or "left main equivalent"), with a lesser degree of proximal right CAD (0.51, n = 14, p < 0.001 vs. other groups). An exercise RV:LV >0.42 with a exercise:rest ratio >1.2 was present in 93% patients with this pattern of CAD, but was absent-in 97% of the normalcy group, 92% of patients without significant angiographic CAD, and 100% of patients with proximal right CAD tighter than stenoses in the left system. CONCLUSIONS Increased RV:LV activity exercise may occur in patients with acute RV strain, but is otherwise an indicator of exercise-induced RV:LV perfusion imbalance associated with severe CAD, particularly high-grade left main with less severe proximal right CAD. (C) 1999 by the American College of Cardiology.