title: Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy.
abstract: BACKGROUND
  Transthyretin familial amyloid polyneuropathy 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 transthyretin familial amyloid polyneuropathy.
  
  
  RESULTS
  A total of 143 individuals with V30M transthyretin 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 with 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 unfavorable outcome but seemed to have benefited from liver transplantation.
  
  
  CONCLUSIONS
  Cardiac sympathetic denervation as assessed by MIBG imaging is a useful prognostic marker in transthyretin familial amyloid polyneuropathy.
authors.affiliation: Departments of Cardiology and Neurosciences, Santa Maria University Hospital, Lisbon, Portugal; University Clinic of Cardiology, Translational Clinical Physiology Unit, Instituto de Medicina Molecular, and Institute of Nuclear Medicine, Lisbon Medical School, University of Lisbon, Portugal; and Programme for Advanced Medical Education, Lisbon, Portugal.
authors.forename: Maria C Azevedo
authors.initials: MC
authors.lastname: Coutinho
authors.forename: Nuno
authors.initials: N
authors.lastname: Cortez-Dias
authors.forename: Guilhermina
authors.initials: G
authors.lastname: Cantinho
authors.forename: Isabel
authors.initials: I
authors.lastname: Conceição
authors.forename: António
authors.initials: A
authors.lastname: Oliveira
authors.forename: Armando
authors.initials: A
authors.lastname: Bordalo e Sá
authors.forename: Susana
authors.initials: S
authors.lastname: Gonçalves
authors.forename: Ana G
authors.initials: AG
authors.lastname: Almeida
authors.forename: Mamede
authors.initials: M
authors.lastname: de Carvalho
authors.forename: António Nunes
authors.initials: AN
authors.lastname: Diogo
mesh_terms: D019797:3-Iodobenzylguanidine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D028227:Amyloid Neuropathies, Familial / Q000000981:diagnostic imaging* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D004452:Echocardiography; D015716:Electrocardiography, Ambulatory; D005260:Female; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000294:innervation*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016031:Liver Transplantation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D012307:Risk Factors; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging*; D013997:Time Factors; D055815:Young Adult
chemical_list: D011228:Prealbumin; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine
keywords: amyloid; prognosis; radionuclide imaging