TY - JOUR
T1 - Phenotypic and genotypic heterogeneity in transthyretin-related cardiac amyloidosis
T2 - Towards tailoring of therapeutic strategies?
AU - Rapezzi, Claudio
AU - Perugini, Enrica
AU - Salvi, Fabrizio
AU - Grigioni, Francesco
AU - Riva, Letizia
AU - Cooke, Robin M T
AU - Ferlini, Alessandra
AU - Rimessi, Paola
AU - Bacchi-Reggiani, Letizia
AU - Ciliberti, Paolo
AU - Pastorelli, Francesca
AU - Leone, Ornella
AU - Bartolomei, Ilaria
AU - Pinna, Antonio D.
AU - Arpesella, Giorgio
AU - Branzi, Angelo
PY - 2006/9/1
Y1 - 2006/9/1
N2 - 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.
AB - 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.
KW - Amyloidosis
KW - Cardiomyopathy
KW - Gene mutations
KW - Prognosis
KW - Transthyretin
UR - http://www.scopus.com/inward/record.url?scp=33750308148&partnerID=8YFLogxK
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U2 - 10.1080/13506120600877136
DO - 10.1080/13506120600877136
M3 - Article
C2 - 17062380
AN - SCOPUS:33750308148
VL - 13
SP - 143
EP - 153
JO - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
JF - Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
SN - 1350-6129
IS - 3
ER -