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 journalArticle

Abstract

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
Volume34
Issue number7
DOIs
Publication statusPublished - Feb 14 2013

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Differential Diagnosis
Hypertrophic Cardiomyopathy
Amyloidosis
Phenotype
Nervous System
Electrocardiography
Inborn Genetic Diseases
Amyloidosis, Hereditary, Transthyretin-Related
Neurologic Examination
Left Ventricular Hypertrophy
Nervous System Diseases
Liver Transplantation
Stroke Volume
Multicenter Studies
Heart Failure
Mutation

Keywords

  • 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

Cite this

Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype : An Italian perspective. / Rapezzi, Claudio; Quarta, Candida Cristina; Obici, Laura; Perfetto, Federico; Longhi, Simone; Salvi, Fabrizio; Biagini, Elena; Lorenzini, Massimiliano; Grigioni, Francesco; Leone, Ornella; Cappelli, Francesco; Palladini, Giovanni; Rimessi, Paola; Ferlini, Alessandra; Arpesella, Giorgio; Pinna, Antonio Daniele; Merlini, Giampaolo; Perlini, Stefano.

In: European Heart Journal, Vol. 34, No. 7, 14.02.2013, p. 520-528.

Research output: Contribution to journalArticle

Rapezzi, C, Quarta, CC, Obici, L, Perfetto, F, Longhi, S, Salvi, F, Biagini, E, Lorenzini, M, Grigioni, F, Leone, O, Cappelli, F, Palladini, G, Rimessi, P, Ferlini, A, Arpesella, G, Pinna, AD, Merlini, G & Perlini, S 2013, 'Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: An Italian perspective', European Heart Journal, vol. 34, no. 7, pp. 520-528. https://doi.org/10.1093/eurheartj/ehs123
Rapezzi, Claudio ; Quarta, Candida Cristina ; Obici, Laura ; Perfetto, Federico ; Longhi, Simone ; Salvi, Fabrizio ; Biagini, Elena ; Lorenzini, Massimiliano ; Grigioni, Francesco ; Leone, Ornella ; Cappelli, Francesco ; Palladini, Giovanni ; Rimessi, Paola ; Ferlini, Alessandra ; Arpesella, Giorgio ; Pinna, Antonio Daniele ; Merlini, Giampaolo ; Perlini, Stefano. / Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype : An Italian perspective. In: European Heart Journal. 2013 ; Vol. 34, No. 7. pp. 520-528.
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T1 - Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype

T2 - An Italian perspective

AU - Rapezzi, Claudio

AU - Quarta, Candida Cristina

AU - Obici, Laura

AU - Perfetto, Federico

AU - Longhi, Simone

AU - Salvi, Fabrizio

AU - Biagini, Elena

AU - Lorenzini, Massimiliano

AU - Grigioni, Francesco

AU - Leone, Ornella

AU - Cappelli, Francesco

AU - Palladini, Giovanni

AU - Rimessi, Paola

AU - Ferlini, Alessandra

AU - Arpesella, Giorgio

AU - Pinna, Antonio Daniele

AU - Merlini, Giampaolo

AU - Perlini, Stefano

PY - 2013/2/14

Y1 - 2013/2/14

N2 - 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.

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KW - Genotypic-phenotypic correlations

KW - Hereditary transthyretin-related amyloidosis

KW - Hypertrophic cardiomyopathy

KW - Senile systemic amyloidosis

KW - Symmetric left ventricular hypertrophy

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