Signs and Symptoms of Transthyretin Amyloidosis (ATTR)

Recognising the signs and symptoms of ATTR amyloidosis could help accelerate earlier identification of the disease¹

Click or tap categories to view additional red flags.

Tap categories to view additional red flags.

SENSORIMOTOR NEUROPATHY CARDIAC MUSCULOSKELETAL AUTONOMIC DYSFUNCTION NEPHROPATHY

SENSORIMOTOR NEUROPATHY¹

Painful neuropathy
in hands and feet

Falls

Difficulty walking

Muscle weakness

CARDIAC¹

HF (right-sided), HFpEF, or intolerance to ACEi, ARBs, ARNi, or beta blockers

Atrial fibrillation

Bradyarrhythmias/conduction abnormalities/need for pacemaker

MUSCULOSKELETAL^{1, 4–6}

Back pain/lumbar spinal stenosis

Ruptured distal biceps tendon/Popeye sign

Shoulder, knee and hip pain or surgery

Trigger finger

Bilateral carpal tunnel syndrome

AUTONOMIC DYSFUNCTION¹

Orthostatic hypotension

Unexplained weight loss

Cycles of diarrhoea  and constipation

Erectile dysfunction

NEPHROPATHY⁷

Proteinuria

Renal failure

This list of signs and symptoms of ATTR amyloidosis is not intended to be exhaustive.

Watch this video to understand the disease course and signs/symptoms of ATTR amyloidosis

When progressive neuropathy is accompanied by autonomic  and/or cardiac red flags, think ATTR amyloidosis

The “HIDDEN” mnemonic is a useful tool to help remember some of the commonly encountered “red flags” associated with ATTR-CM¹⁰

HFpEF and other cardiac conditions, including atrial fibrillation, arrhythmia and atrioventricular block¹¹

Intolerance to standard heart failure therapies (e.g. ACEi/ARBs and beta blockers)¹²

Discordance of QRS voltage and left ventricular wall thickness seen on echocardiography^13,14

Diagnosis of carpal tunnel syndrome, distal biceps tendon rupture or lumbar spinal stenosis^15,16

Echocardiography showing increased left ventricular wall thickness and/or low-flow gradient aortic stenosis and additional echocardiography parameters*¹³

Nervous system—autonomic nervous system dysfunction, including gastrointestinal complaints or unexplained weight loss¹⁷

Figure adapted from Sabbour H, et al. Front Cardiovasc Med. 2021.¹⁰
*Echocardiographic, speckle-strain and tissue doppler “red flags”: Heart failure normal or mid-range ejection fraction; increased wall thickness; left atrial enlargement; low stroke volume index; low-flow, low-gradient aortic stenosis (per ESC/EACTS Guidelines);¹⁸ low myocardial contraction fraction; advanced diastolic dysfunction; impaired global longitudinal strain with apical sparing; low mitral annular tissue Doppler S' (average septal and lateral annulus).⁸

Misdiagnosis or delayed diagnosis of ATTR amyloidosis may contribute to continued disease progression and reduced quality of life^1,19

ATTR amyloidosis is a progressive and potentially fatal disease caused by the buildup of amyloid fibrils in different tissues and organs¹

Late-stage disease impacts responsiveness to certain treatments²⁰

Increased burden of symptoms and disease^20-22

Decreased life expectancy^1,20–22

ATTR amyloidosis is associated with reduced survival, although prognosis varies by subtype^1,20,21

Symptom deterioration may indicate disease progression

Worsening of symptoms can be a serious and potentially life-altering sign of disease progression^1,21

Timely diagnosis and treatment of ATTR amyloidosis may help to improve patient outcomes³

UNDERSTAND DIAGNOSIS

Early intervention for ATTR amyloidosis may improve quality of life^{1–3,7,24–26}

DISCOVER TREATMENT OPTIONS

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin receptor blocker; ARNi=angiotensin receptor/neprilysin inhibitor; ATTR=transthyretin amyloidosis; ATTR(v)-CM=(hereditary) transthyretin amyloidosis with cardiomyopathy; ATTR(v)-PN=(hereditary) transthyretin amyloidosis with polyneuropathy; EACTS=European Association for Cardio-Thoracic Surgery; ESC=European Society of Cardiology; GI=gastrointestinal; HF=heart failure; HFpEF=heart failure with preserved ejection fraction.

References: 1. Nativi-Nicolau JN, et al. Heart Fail Rev. 2022;27(3):785–793; 2. Keohane D, et al. Amyloid. 2017;24(1):30–36; 3. Rozenbaum MH, et al. J Comp Eff Res. 2021;10(11):927–938; 4. Gertz MA. Am J Manag Care. 2017;23(7 Suppl):S107–S112; 5. Adams D, et al. Orphanet J Rare Dis. 2021;16(1):411; 6. Tojo, K, et al. Amyloid. 2010;17(1):, 32–35; 7. Conceição I, et al. J Peripher Nerv Syst. 2016;21:5–9; 8. Gertz M, et al. BMC Fam Pract. 2020;21(1):198; 9. Adams D, et al. J Neurol. 2021;268:2109–2122; 10. Sabbour H, et al. Front Cardiovasc Med. 2021;8:644508; 11. González-López E, et al. Eur Heart J. 2015;36(38):2585–2594; 12. Castaño A, et al. Eur Heart J. 2017;38(38):2879–2887; 13. Quarta CC, et al. Circulation. 2014;129:1840–1849; 14. Carroll JD, et al. Am J Cardiol. 1982;49:9–13; 15. Nakagawa M, et al. Amyloid. 2016;23:58–63; 16. Westermark P, et al. Ups J Med Sci. 2014;119:223–228; 17. Coelho T, et al. Curr Med Res Opin. 2013;29:63–76; 18. Vahanian A, et al. Eur Heart J. 2022;43(7):561–632; 19. Lovely A, et al. J Patient Rep Outcomes. 2021;5:3; 20. Griffin JM, et al. JACC CardioOncol. 2021;3(4):488–505; 21. Kittleson MM, et al. J Am Coll Cardiol. 2023;81(11):1076–1126; 22. Hawkins PN, et al. Ann Med. 2015;47(8):625–638; 23. Witteles RM, et al. JACC Heart Fail. 2019;7(8):709–716; 24. Coelho T, et al. J Neurol. 2019;267:1070–1079; 25. Adams D, et al. N Engl J Med. 2018;379:11–21; 26. Obici L, et al. Amyloid. 2020;27(3):1–10.

GB-77260 | August 2026

RECOGNISING THE CONSTELLATION OF ATTR AMYLOIDOSIS SIGNS AND SYMPTOMS IS IMPORTANT

Recognising the signs and symptoms of ATTR amyloidosis could help accelerate earlier identification of the disease1

Watch this video to understand the disease course and signs/symptoms of ATTR amyloidosis

When progressive neuropathy is accompanied by autonomic and/or cardiac red flags, think ATTR amyloidosis

The “HIDDEN” mnemonic is a useful tool to help remember some of the commonly encountered “red flags” associated with ATTR-CM10

Misdiagnosis or delayed diagnosis of ATTR amyloidosis may contribute to continued disease progression and reduced quality of life1,19