title: Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective.
abstract: OBJECTIVE
  Hereditary transthyretin (TTR)-related amyloidosis (ATTR) is mainly considered a neurologic disease. We assessed the phenotypic and genotypic spectra of ATTR in a Caucasian area and evaluated the prevalence, genetic background, and disease profile of cases with an exclusively cardiac phenotype, highlighting possible hints for the differential diagnosis with hypertrophic cardiomyopathy (HCM) and senile systemic amyloidosis (SSA).
  
  
  RESULTS
  In this Italian multicentre study, 186 patients with ATTR were characterized at presentation. Thirty patients with SSA and 30 age-gender-matched HCM patients were used for comparison. Phenotype was classified as exclusively cardiac (n = 31, 17%), exclusively neurologic (n = 46, 25%), and mixed cardiac/neurologic (n = 109, 58%). Among the eight different mutations responsible for an exclusively cardiac phenotype, Ile68Leu was the most frequent. Five patients with an exclusively cardiac phenotype developed mild abnormalities at neurological examination, but no symptoms during a 36-month follow-up (range: 14-50). Exclusively cardiac phenotype was characterized by male gender, age >65 years, heart failure symptoms, symmetric left ventricular (LV) 'hypertrophy', and moderately depressed LV ejection fraction. This profile was similar to SSA, but relatively distinct from HCM. Compared with patients with a mixed phenotype, patients with an exclusively cardiac phenotype showed a more pronounced cardiac involvement on both echocardiogram and electrocardiogram (ECG).
  
  
  CONCLUSIONS
  A clinically relevant subset of Caucasian ATTR patients present with an exclusively cardiac phenotype, mimicking HCM or SSA. Echocardiographic and ECG findings are useful to differentiate ATTR from HCM but not from SSA. The role of liver transplantation in these patients should be reconsidered.
authors: Cardiovascular Department, University of Bologna and S. Orsola-Malpighi Hospital, via Massarenti 9, 40138 Bologna, Italy. claudio.rapezzi@unibo.it
authors: Claudio
authors: C
authors: Rapezzi
authors: Candida Cristina
authors: CC
authors: Quarta
authors: Laura
authors: L
authors: Obici
authors: Federico
authors: F
authors: Perfetto
authors: Simone
authors: S
authors: Longhi
authors: Fabrizio
authors: F
authors: Salvi
authors: Elena
authors: E
authors: Biagini
authors: Massimiliano
authors: M
authors: Lorenzini
authors: Francesco
authors: F
authors: Grigioni
authors: Ornella
authors: O
authors: Leone
authors: Francesco
authors: F
authors: Cappelli
authors: Giovanni
authors: G
authors: Palladini
authors: Paola
authors: P
authors: Rimessi
authors: Alessandra
authors: A
authors: Ferlini
authors: Giorgio
authors: G
authors: Arpesella
authors: Antonio Daniele
authors: AD
authors: Pinna
authors: Giampaolo
authors: G
authors: Merlini
authors: Stefano
authors: S
authors: Perlini
mesh_terms: D000328:Adult; D000368:Aged; D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000235:genetics*; D002312:Cardiomyopathy, Hypertrophic / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D004452:Echocardiography; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype