title: Transthyretin-related amyloidoses and the heart: a clinical overview.
abstract: A nonhereditary form of systemic amyloidosis associated with wild-type transthyretin causes heart involvement predominantly in elderly men (systemic senile amyloidosis, or SSA). However, hereditary transthyretin-related amyloidosis (ATTR) is the most frequent form of familial systemic amyloidosis, a group of severe diseases with variable neurological and organ involvement. ATTR remains a challenging and widely underdiagnosed condition, owing to its extreme phenotypic variability: the clinical spectrum of the disease ranges from an almost exclusive neurologic involvement to a strictly cardiac presentation. Such heterogeneity principally results from differential effects of the various reported transthyretin mutations, the geographic region the patient is from and, in the case of the most common mutation, Val30Met, whether or not large foci of cases occur (endemic versus nonendemic aggregation). Genetic or environmental factors (such as age, sex, and amyloid fibril composition) also contribute to the heterogeneity of ATTR, albeit to a lesser extent. The existence of exclusively or predominantly cardiac phenotypes should lead clinicians to consider the possibility of ATTR in all patients who present with an unexplained increase in left ventricular wall thickness at echocardiography. Assessment of such patients should include an active search for possible red flags that can point to the correct final diagnosis.
authors.affiliation: Institute of Cardiology, University of Bologna and S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. claudio.rapezzi@unibo.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.forename: Candida Cristina
authors.initials: CC
authors.lastname: Quarta
authors.forename: Letizia
authors.initials: L
authors.lastname: Riva
authors.forename: Simone
authors.initials: S
authors.lastname: Longhi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Gallelli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Lorenzini
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciliberti
authors.forename: Elena
authors.initials: E
authors.lastname: Biagini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.forename: Angelo
authors.initials: A
authors.lastname: Branzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000686:Amyloidosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D028226:Amyloidosis, Familial / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D009202:Cardiomyopathies / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D011228:Prealbumin