Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review

J Am Coll Cardiol. 2019 Jun 11;73(22):2872-2891. doi: 10.1016/j.jacc.2019.04.003.


Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of heart failure (HF) in older adults, resulting from myocardial deposition of misfolded transthyretin (TTR) or pre-albumin. Characteristic patterns of echocardiography and cardiac magnetic resonance can strongly suggest the disease but are not diagnostic. The diagnosis can be made with noninvasive nuclear imaging when there is no evidence of a monoclonal protein. Amyloid fibril formation results from a destabilizing mutation in hereditary ATTR amyloidosis (hATTR) or from an aging-linked process in wild-type ATTR amyloidosis (wtATTR). Recent studies have suggested that up to 10% to 15% of older adults with HF may have unrecognized wtATTR. Associated features, including carpal tunnel syndrome and lumbar spinal stenosis, raise suspicion and may afford a means for early diagnosis. Previously treatable only by organ transplantation, pharmaceutical therapy that slows or halts ATTR-CM progression and favorably affects clinical outcomes is now available. Early recognition remains essential to afford the best treatment efficacy.

Keywords: amyloidosis; cardiomyopathy; transthyretin.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid Neuropathies, Familial / diagnosis*
  • Amyloid Neuropathies, Familial / genetics
  • Cardiomyopathies / diagnosis*
  • Cardiomyopathies / genetics
  • DNA Mutational Analysis
  • Echocardiography
  • Female
  • Genotype
  • Heart Failure / diagnosis*
  • Heart Failure / genetics
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prealbumin / genetics
  • Prognosis
  • Radionuclide Imaging


  • Prealbumin
  • TTR protein, human

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related