title: Phenotypic and genotypic heterogeneity in transthyretin-related cardiac amyloidosis: towards tailoring of therapeutic strategies?
abstract: Transthyretin-related hereditary amyloidosis (ATTR) is genotypically/phenotypically heterogeneous. We investigated myocardial involvement in ATTR in a cohort of patients with a wide range of mutations. Clinical/echocardiographic follow-up of 41 consecutive symptomatic ATTR patients from a single referral center was analyzed according to TTR mutation. Diagnosis was based on histology, immunohistochemistry and genotyping. Median follow up was 40 months (range 8-120). Among the 12 different mutations identified, Val30Met was found in 10 patients and Glu89Gln in seven. Compared with Val30Met, Glu89Gln was associated with higher LV mass index, lower left ventricular ejection fraction and shorter E-wave deceleration time. All Glu89Gln carriers had cardiomyopathy, which was more severe (for left ventricular thickness, left ventricular mass and restrictive pathophysiology) than in the six affected Val30Met patients. Glu89Gln was independently associated with higher risk of major cardiovascular events among cardiomyopathy patients. This follow-up study of ATTR patients carrying a wide range of mutations indicates that (1) cardiac involvement is a very important component of phenotypic expression; and (2) genotype is an important source of heterogeneity in myocardial involvement, with Glu89Gln being associated with a severe, heart-driven prognosis. We think that combined heart-liver transplantation could be considered for Glu89Gln carriers with established, morphologically severe cardiomyopathy.
authors.affiliation: Institute of Cardiology, University of Bologna and S. Orsola-Malpighi Hospital, Bologna, Italy. crapezzi@aosp.bo.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Rapezzi
authors.forename: Enrica
authors.initials: E
authors.lastname: Perugini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Salvi
authors.forename: Francesco
authors.initials: F
authors.lastname: Grigioni
authors.forename: Letizia
authors.initials: L
authors.lastname: Riva
authors.forename: Robin M T
authors.initials: RM
authors.lastname: Cooke
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
authors.forename: Paola
authors.initials: P
authors.lastname: Rimessi
authors.forename: Letizia
authors.initials: L
authors.lastname: Bacchi-Reggiani
authors.forename: Paolo
authors.initials: P
authors.lastname: Ciliberti
authors.forename: Francesca
authors.initials: F
authors.lastname: Pastorelli
authors.forename: Ornella
authors.initials: O
authors.lastname: Leone
authors.forename: Ilaria
authors.initials: I
authors.lastname: Bartolomei
authors.forename: Antonio D
authors.initials: AD
authors.lastname: Pinna
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arpesella
authors.forename: Angelo
authors.initials: A
authors.lastname: Branzi
mesh_terms: D000328:Adult; D000686:Amyloidosis / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006321:Heart / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011228:Prealbumin / Q000502:physiology*
chemical_list: D011228:Prealbumin