Background Increased activity of the sympathetic nervous system contributes significantly to the pathophysiology of heart failure. However, cardiac efferent sympathetic function has not been well characterized in this disorder. In this study, we evaluated cardiac sympathetic innervation using (Iodine-123)metaiodobenzylguanidine (MIBG) and compared this with left ventricular (LV) tissue norepinephrine concentration and myocardial perfusion, assessed by Thallium-201, in a canine model of heart failure.Methods and Results Planar and tomographic cardiac imaging was performed for MIBG and Thallium-201 in 23 dogs: 8 normal dogs (group 1) and 15 dogs with heart failure induced by right ventricular pacing at 250 beats per minute either continuously for 3 weeks (group 2) or intermittently for 7 weeks (group 3). Plasma and LV tissue norepinephrine concentrations were also measured. Scintigraphic studies in group 2 demonstrated reduced cardiac MIBG activity at heart failure (0.17+-0.04 versus 0.29+-0.05 counts per megabecquerel per pixel at baseline, mean+-SD; P=.0001), whereas thallium activity was unchanged from baseline. This reduction in cardiac MIBG activity with heart failure was associated with increased intraimage variability in the distribution of MIBG activity (21+-8% versus 13+-7% at baseline, mean+-SD; P=.0001). The MIBG heart-to-lung ratio was calculated for all groups to control for the inhibitory effect that plasma norepinephrine has on the neuronal uptake of MIBG. There was a positive correlation between LV tissue norepinephrine and the MIBG heart-to-lung ratio (r=.67; P<.001; n=22), for which the group 2 heart failure animals had the lowest values. No relation existed between plasma norepinephrine concentration and the MIBG heart-to-lung ratio. In addition, regional LV tissue norepinephrine concentration and MIBG activity were both lowest at the apex in normal (group 1) and heart failure (group 2) dogs. The MIBG heart-to-lung ratio also correlated inversely with cardiac filling pressure (r=-.59; P<.05) and heart rate (r=-.65; P<.01) and positively with cardiac output (r=.53; P<.05).Conclusions Heart failure is associated with severe cardiac adrenergic dysfunction manifested by reduced MIBG activity and increased heterogeneity in the LV distribution of MIBG. Furthermore, MIBG scintigraphy is a simple noninvasive method for assessing global and regional LV tissue norepinephrine levels. (Circulation. 1994;89:2843-2851.)