Progression of myocardial sympathetic denervation assessed by 123I-MIBG imaging in familial amyloid polyneuropathy and the effect of liver transplantation

INTRODUCTIONFamilial amyloid polyneuropathy (FAP) is a rare disease caused by systemic deposition of amyloidogenic variants of the transthyretin (TTR) protein. The TTR-V30M mutation is caused by the substitution of valine by methionine at position 30 and mainly affects the peripheral and autonomic nervous systems. Cardiovascular manifestations are common and are due to autonomic denervation and to amyloid deposition in the heart. Cardiac sympathetic denervation detected by iodine-123 labeled metaiodobenzylguanidine (MIBG) is an important prognostic marker in TTR-V30M FAP. Liver transplantation, widely used to halt neurological involvement, appears to have a varying effect on the progression of amyloid cardiomyopathy. Its effect on the progression of cardiac denervation remains unknown.METHODSIn this observational study, patients with the TTR-V30M mutation underwent annual cardiac assessment and serial MIBG imaging with quantification of the late heart-to-mediastinum (H/M) ratio.RESULTSWe studied 232 patients (median age 40 years, 54.7% female, 37.9% asymptomatic at the time of inclusion) who were followed for a median of 4.5 years and underwent a total of 558 MIBG scans. During follow-up, 47 patients (20.3%) died. MIBG scintigraphy at inclusion was a strong predictor of prognosis, with the risk of death increasing by 27.8% for each one-tenth reduction in the late H/M ratio. The late H/M ratio decreased with age (0.082/year, p