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ATTR Amyloidosis: A Life-Threatening Disease That Can Go Undiagnosed

  • Amyloidosis is a group of diseases in which amyloid fibrils deposit into the extracellular spaces of different organs, ultimately leading to progressive organ dysfunction. The amyloid fibrils are formed by an aggregation of misfolded proteins1,2 
     
  • ATTR stands for amyloid transthyretin, an amyloid protein that forms from the protein transthyretin1 
     
  • Transthyretin is a tetrameric transporter of thyroxine and retinol-binding protein and is secreted predominantly by the liver3
     
  • There are 2 major phenotypes of ATTR amyloidosis: transthyretin amyloid cardiomyopathy (ATTR-CM) and transthyretin amyloid polyneuropathy (ATTR-PN)3 
    • Some patients may present with a mixed phenotype with both cardiomyopathy and polyneuropathy symptoms
       
  • ATTR amyloidosis can be caused by a mutation in the TTR gene, known as hereditary ATTR (hATTR)* amyloidosis, or by idiopathic changes in the amyloid fibrils leading to wild-type ATTR (wtATTR) amyloidosis1,4
    *Also known as variant ATTR.1

How to Suspect ATTR-CM

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How to Detect ATTR-CM

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Video Resources ATTR-CM

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References:
1. Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215-219.
2. Narotsky DL, Castaño A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10.
3. Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31.
4. Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290.

PP-RDP-IRL-0111 Date of Preparation February 2021