Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure?

BACKGROUND: Nuclear imaging modalities using (123)Iodine-metaiodobenzylguanidine ((123)I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from (123)I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. METHODS: All TTR mutation carriers and ATTRm patients who underwent both (123)I-MIBG and (99m)Technetium-hydroxymethylene diphosphonate ((99m)Tc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late (123)I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac (99m)Tc-HDP uptake were considered as abnormal. RESULTS: 39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = − 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac (99m)Tc-HDP uptake r = − 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. CONCLUSION: In case of heart failure, (123)I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. (123)I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12350-018-01477-y) contains supplementary material, which is available to authorized users.