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

Background: Nuclear imaging modalities using ¹²³Iodine-metaiodobenzylguanidine (¹²³I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from ¹²³I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. Methods: All TTR mutation carriers and ATTRm patients who underwent both ¹²³I-MIBG and ^99mTechnetium-hydroxymethylene diphosphonate (^99mTc-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 ¹²³I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac ^99mTc-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 ^99mTc-HDP uptake r = − 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. Conclusion: In case of heart failure, ¹²³I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. ¹²³I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.