Phenotypic and genotypic heterogeneity in transthyretin-related cardiac amyloidosis: Towards tailoring of therapeutic strategies?

Claudio Rapezzi, Enrica Perugini, Fabrizio Salvi, Francesco Grigioni, Letizia Riva, Robin M T Cooke, Alessandra Ferlini, Paola Rimessi, Letizia Bacchi-Reggiani, Paolo Ciliberti, Francesca Pastorelli, Ornella Leone, Ilaria Bartolomei, Antonio D. Pinna, Giorgio Arpesella, Angelo Branzi

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)143-153
Number of pages11
Issue number3
Publication statusPublished - Sep 1 2006


  • Amyloidosis
  • Cardiomyopathy
  • Gene mutations
  • Prognosis
  • Transthyretin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)


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