SUSPECTING ATTR

ATTR-CM is often overlooked as a cause of heart failure1-4

Time to diagnosis is typically delayed by an average of ~6 years,* in part because symptoms of ATTR-CM overlap with other common conditions.1-5

Prevalence of ATTR-CM in screening studies:

  • In approximately 13-19% of people aged 60 or older with HFpEF, the underlying cause was ATTR-CM6-8
  • Approximately 6 in 10 patients with ATTR-CM had bilateral carpal tunnel syndrome 5 to 10 years before cardiac manifestations9-12
  • Approximately 1 in 6 patients with degenerative aortic stenosis was found to have ATTR deposition13,14
  • Approximately 5-7% of patients with hypertrophic cardiomyopathy had ATTR‑CM15,16

*In a targeted literature review, mean time to diagnosis ranged from 1.3 to 7.2 years.

Men aged 60 years or older are particularly at risk of having ATTR-CM.13,17

Use echocardiography, electrocardiography, and cardiac MRIs to help raise clinical suspicion for patients with red-flag symptoms

Echocardiography7,18-24
2D echocardiogram
Look for:
  • Left ventricular (LV) wall thickness ≥12 mm
  • Thickening of valves/septum
  • Refractile myocardium (granular sparkling)
Longitudinal strain bull's-eye map
Look for:
Reduction in longitudinal strain with relative apical sparing
  • Presents in a "cherry-on-top" pattern
  • Red indicates normal longitudinal strain at apex
  • Pink and blue indicate abnormal longitudinal strain at mid/basal LV
Tissue Doppler Imaging (TDI)
Look for:
Diastolic dysfunction
  • Abnormal E/A ratio, E/e' ratio, and TDI lateral e'
  • 5-5-5 pattern in TDI tracings is seen in more advanced cardiac amyloidosis
Look for:
Reduction in longitudinal strain with relative apical sparing
  • Presents in a "cherry-on-top" pattern
  • Red indicates normal longitudinal strain at apex
  • Pink and blue indicate abnormal longitudinal strain at mid/basal LV
Look for:
Diastolic dysfunction
  • Abnormal E/A ratio, E/e' ratio, and TDI lateral e'
  • 5-5-5 pattern in TDI tracings is seen in more advanced cardiac amyloidosis
While echocardiographs may help raise clinical suspicion of ATTR, they lack specificity to diagnose ATTR-CM alone.
Sinus rhythm with marked 1st degree AV block, low limb lead QRS voltage, left bundle branch block
Atrial fibrillation, anterolateral and inferior infarcts (pseudo‑infarcts)
Look for:
  • Low QRS voltage
  • AV conduction block
  • Pseudo-infarction
  • Atrial arrhythmia
    (eg, atrial fibrillation)
While electrocardiographs may help raise clinical suspicion of ATTR, they lack specificity to diagnose ATTR-CM alone.
AV=atrioventricular; QRS=Q wave, R wave, S wave.
Look for:
  • Diffuse, subendocardial or transmural late gadolinium enhancement
  • Left ventricular hypertrophy
  • Increased extracellular volume fraction
Left ventricular hypertrophy
Late gadolinium enhancement 
While cardiac MRIs may help raise clinical suspicion of ATTR, they lack specificity to diagnose ATTR-CM alone.
NEXT Diagnosing ATTR

A=late (atrial) mitral inflow velocity; ATTR=transthyretin-mediated amyloidosis; ATTR‑CM=cardiomyopathy of transthyretin-mediated amyloidosis; E=early mitral inflow velocities; e'=early diastolic mitral annulus velocity; HFpEF=heart failure with preserved ejection fraction; MRI=magnetic resonance imaging.

References:

  1. Hanna M. Curr Heart Fail Rep. 2014;11(1):50-57.
  2. Mohty D, et al. Arch Cardiovasc Dis. 2013;106(10):528-540.
  3. Maurer MS, et al. Circ Heart Fail. 2019;12(9):e006075.
  4. Maurer MS, et al. J Am Coll Cardiol. 2016;68(2):161-172.
  5. Rozenbaum MH, et al. Cardiol Ther. 2021;10(1):141-159.
  6. Lo Presti S, et al. Crit Pathw Cardiol. 2019;18(4):195-199.
  7. González-López E, et al. Eur Heart J. 2015;36(38):2585-2594.
  8. Garcia-Pavia P, et al. Rev Esp Cardiol. 2025;78(4):301-310.
  9. Grogan M, et al. J Am Coll Cardiol. 2022;80(10):978-981.
  10. Milandri A, et al. Eur J Heart Fail. 2020;22(3):507-515.
  11. Ruberg FL, et al. J Am Coll Cardiol. 2019;73(22):2872-2891.
  12. Witteles RM, et al. JACC Heart Fail. 2019 Aug;7(8):709-716.
  13. Kittleson MM, et al. Circulation. 2020;142(1):e7-e22.
  14. Antonopoulos AS, et al. Euro J Heart Fail. 2022;24(9):1677-1696.
  15. Tomasoni D, et al. Front Cardiovasc Med. 2023;10.
  16. Aimo A, et al. Eur J Heart Fail. 2022;24(12):2342-2351.
  17. Nativi-Nicolau JN, et al. Heart Fail Rev. 2022;27(3):785-793.
  18. Dharmarajan K, et al. J Am Geriatr Soc. 2012;60(4):765-774.
  19. Dorbala S, et al. Circ Cardiovasc Imaging. 2021;14(7):e000029.
  20. Kittleson MM, et al. J Am Coll Cardiol. 2023;81(11):1076-1126.
  21. Maurer MS, et al. Circulation. 2017;135(14):1357-1377.
  22. Falk RH, et al. Heart Fail Rev. 2015;20(2):125-131.
  23. Baptista P, et al. Cureus. 2023;doi:10.7759/cureus.33364
  24. Cuddy S, et al. J Am Soc Echocardiogr. 2022;35(9):A31-A40.
  25. Maloberti A, et al. Int J Cardio Cardiovasc Risk Prev. 2024;21:200271.
  26. Quarta G, et al. Br J Radiol. 2011;84 Spec No 3(Spec Iss 3):S296-S305.