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Mechanism of Disease

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Is ATTR hiding in plain sight?

Transthyretin amyloidosis (ATTR) is an underdiagnosed disease. Learn to suspect and detect the clinical clues.¹

Find out more

What is ATTR amyloidosis?

Amyloidosis refers to a group of diseases in which amyloid fibrils deposit into the extracellular spaces of multiple organs and nerves, ultimately leading to progressive organ dysfunction and nerve damage.^1,2

ATTR amyloidosis is caused by the destabilisation and misfolding of transthyretin (TTR) protein—a tetrameric transporter of thyroxine and retinol-binding protein.^1,3

Because the symptoms are similar to other conditions, and it impacts multiple systems in the body, ATTR is often underdiagnosed.¹

A multidisciplinary approach can help recognise the red flags of ATTR that present throughout the body.⁴

ATTR amyloidosis can manifest as cardiomyopathy and/or polyneuropathy⁵

There are 2 primary manifestations of ATTR amyloidosis: transthyretin amyloid cardiomyopathy (ATTR-CM) and transthyretin amyloid polyneuropathy (ATTR-PN).^5,6

Some patients may present with a mixed phenotype, namely, symptoms of both cardiomyopathy and polyneuropathy⁷

ATTR-CM is an underdiagnosed cause of heart failure^2,8

Patients with ATTR-CM present with symptoms of heart failure and may also present with other symptoms, such as atrial fibrillation, carpal tunnel syndrome, or peripheral neuropathy.^1,8-11

Suspicion of cardiac involvement should prompt immediate cardiac evaluation to assess for ATTR-CM.⁴

Multidisciplinary care that involves partnership with cardiologists can uncover appropriate treatments that may lead to improved outcomes.⁴

Learn about ATTR-CM

ATTR-PN causes irreversible deterioration in neurologic function¹²

Patients with ATTR-PN often present with symptoms of progressive sensorimotor neuropathy and autonomic dysfunction and can present with concomitant cardiomyopathy.¹²

ATTR-PN is progressive and irreversible, and early diagnosis is critical to improve outcomes.¹²

Learn about ATTR-PN

References:

Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. doi:10.1161/CIRCULATIONAHA.116.024438

Witteles RM, Bokhari S, Damy T, et al. Screening for transthyretin amyloid cardiomyopathy in everyday practice. JACC Heart Fail. 2019;7(8):709-716. doi:10.1016/j.jchf.2019.04.010

Liz MA, Coelho T, Bellotti V, Fernandez-Arias MI, Mallaina P, Obici L. A narrative review of the role of transthyretin in health and disease. Neurol Ther. 2020;9(2):395-402. doi:10.1007/s40120-020-00217-0

Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. doi:10.1093/eurheartj/ehab072

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. doi:10.1016/j.cjca.2016.05.008

Rapezzi C, Quarta CC, Riva L, et al. Transthyretin-related amyloidoses and the heart: a clinical overview. Nat Rev Cardiol. 2010;7(7):398-408. doi:10.1038/nrcardio.2010.67

Maurer MS, Bokhari S, Damy T, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12:e006075. doi:10.1161/CIRCHEARTFAILURE.119.e006075

Maurer MS, Hanna M, Grogan M, et al. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172. doi:10.1016/j.jacc.2016.03.596

Connors LH, Sam F, Skinner M, et al. Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290. doi:10.1161/CIRCULATIONAHA.115.018852

Pinney JH, Whelan CJ, Petrie A, et al. Senile systemic amyloidosis: clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098. doi:10.1161/JAHA.113.000098

Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58-63. doi:10.3109/13506129.2015.1135792

PP-UNP-IRL-0334. December 2022

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