Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: An Italian perspective

Claudio Rapezzi, Candida Cristina Quarta, Laura Obici, Federico Perfetto, Simone Longhi, Fabrizio Salvi, Elena Biagini, Massimiliano Lorenzini, Francesco Grigioni, Ornella Leone, Francesco Cappelli, Giovanni Palladini, Paola Rimessi, Alessandra Ferlini, Giorgio Arpesella, Antonio Daniele Pinna, Giampaolo Merlini, Stefano Perlini

Research output: Contribution to journalArticlepeer-review


Aims 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).Methods and resultsIn 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).ConclusionA 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.

Original languageEnglish
Pages (from-to)520-528
Number of pages9
JournalEuropean Heart Journal
Issue number7
Publication statusPublished - Feb 14 2013


  • Cardiac phenotype
  • Genotypic-phenotypic correlations
  • Hereditary transthyretin-related amyloidosis
  • Hypertrophic cardiomyopathy
  • Senile systemic amyloidosis
  • Symmetric left ventricular hypertrophy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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