Reduced Myocardial 123-Iodine Meta-iodobenzylguanidine Uptake: A Prognostic Marker in Familial Amyloid Polyneuropathy

Background —Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a hereditary form of amyloidosis characterized by sensorimotor and autonomic neuropathy, cardiac conduction defects and infiltrative cardiomyopathy. Previous studies have suggested that myocardial sympathetic denervation assessed by 123-iodine metaiodobenzylguanidine (MIBG) imaging occurs early in disease progression. However, its prognostic significance was never evaluated. We aimed to study the long-term prognostic value of myocardial sympathetic denervation detected by MIBG imaging in TTR-FAP. Methods and Results —A total of 143 individuals with V30M TTR mutation underwent Holter, ambulatory blood pressure monitoring, echocardiography and MIBG imaging. Time to all-cause death was compared with late heart-to-mediastinum MIBG uptake ratio (H/M) [either in relation to the estimated lower limit of normal (1.60) or as a continuous variable] using Cox proportional hazards regression. Multivariable analyses were performed to test the prognostic accuracy of clinical, neurological and cardiovascular parameters. During a median follow-up of 5.5 years, 32 (22%) patients died. Five-year mortality rate was 42% for late H/M <1.60 and 7% for late H/M ≥1.60 (hazard ratio 7.19, p < 0.001). Late H/M was identified as an independent prognostic predictor. Fifty-three patients were submitted to liver transplantation. In comparison to neurophysiological score-matched controls, transplanted patients had lower long-term mortality (hazard ratio 0.32, p = 0.012). Patients with late H/M <1.60 were at higher risk of unfavourable outcome but seemed to benefit from liver transplantation. Conclusions —Cardiac sympathetic denervation as assessed by MIBG imaging is a useful prognostic marker in TTR-FAP.