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Noradrenergic uptake in the liver on BACKGROUND AND AIM: Imaging noradrenergic uptake in the liver with norepinephrine analog 123 I-meta-iodobenzylguanidine (mIBG) was explored in normal controls and patients with heart failure (HF). METHODS: A total of 961 HF (343 with diabetes mellitus [DM]) and 94 control subjects underwent anterior planar mIBG images including upper abdomen at 15 min (early) and 3 h 50 min (late) post-injection. Decay-corrected liver activity normalized to injected activity and body surface area (counts/pixel [cpp]/MBq/m2 ) was compared in three groups: HF with DM; HF without DM; and controls. Associations with plasma norepinephrine, liver function tests, and level of cardiac innervation were explored. RESULTS: In controls, liver mIBG activity decreased over time (early: 2.78 vs late: 2.43 cpp/MBq/m2 , P < 0.0001); in HF subjects, activity increased during this interval (HF without DM: 2.85 vs 2.93 [P = 0.005]; HF with DM: 2.37 vs 2.43 [P = 0.054]). Early liver activity was lower in HF with DM subjects than in the other groups (P < 0.001); late liver activity was higher in HF without DM than in the other two groups (P < 0.01). Subjects with elevated plasma norepinephrine (> 520 pg/mL) or ≥ 1 abnormal liver function test had lower early and late liver activity. In subjects with preserved cardiac mIBG uptake, HF subjects had higher and control subjects lower liver activity than comparable subjects with decreased cardiac innervation. CONCLUSIONS: In HF subjects, liver mIBG activity increased over time, reversing the normal washout pattern, suggesting a compensatory change in sympathetic nerve function. DM, abnormal liver function tests, and decreased cardiac innervation were associated with decreased liver mIBG uptake in HF.