About ATTR Cardiac Amyloidosis | VYNDAMAX (tafamidis)

You can help extend patient survival with timely diagnosis and treatment of ATTR cardiac amyloidosis³

Critical facts about ATTR-CM:

Some patients may take >5 years to be diagnosed with ATTR-CM⁴
If not treated, patients with ATTR-CM have an estimated median survival of ~2-6 years after diagnosis^5,6

More than 33% of patients with ATTR-CM are misdiagnosed⁷

ATTR-CM may be mistaken for⁸:

There are 2 subtypes of ATTR cardiac amyloidosis¹

Wild-type ATTR cardiac amyloidosis (wtATTR cardiac amyloidosis)
- Presents most commonly in older white men, >60 years of age^11-13
- Prevalence increases with age¹⁴

Hereditary ATTR cardiac amyloidosis (hATTR cardiac amyloidosis)^†
- Affects both men and women^15,16
- May occur as early as 50 to 60 years of age¹⁷
- Onset varies according to mutation¹⁷
- The most common variant in the United States, Val122lle, is carried by ~3%-4% of African Americans¹⁶^‡

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Study design: The study by González-López, et al was a prospective, cross-sectional, single-center study at a tertiary university hospital in Madrid, Spain, to determine the prevalence of wtATTR-CM among elderly patients admitted to the hospital due to HFpEF. The study population included 120 HFpEF patients (59% women, mean age: 82±8 years) with LV ejection fraction ≥50% and LV hypertrophy ≥12 mm. All eligible patients were offered a DPD scintigraphy scan to confirm ATTR cardiac amyloidosis. The study by Hahn, et al was a prospective analysis in 108 patients (61% women, age range: 57-74 years) seen at the Johns Hopkins Center for HFpEF who underwent endomyocardial biopsy to evaluate myocardial tissue histopathology.^9,10

In the United States, Val122lle and Thr60AIa are the most common mutations that typically manifest as cardiomyopathy symptoms.¹⁵

Not all individuals with the V122I mutation develop symptoms.¹⁶

ATTR=transthyretin amyloidosis; ATTR-CM=transthyretin amyloid cardiomyopathy; HFpEF=heart failure with preserved ejection fraction; LV=left ventricular.

References:

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

Tess DA, Maurer TS, Li Z, Bulawa C, Fleming J, Moody AT. Relationship of binding-site occupancy, transthyretin stabilisation and disease modification in patients with tafamidis-treated transthyretin amyloid cardiomyopathy. Amyloid. 2023;30(2):208-219.

Ioannou A, Patel RK, Razvi Y, et al. Impact of earlier diagnosis in cardiac ATTR amyloidosis over the course of 20 years. Circulation. 2022;146(22):1657-1670.

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.

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(9):e006075.

Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799-2806.

Rozenbaum MH, Large S, Bhambri R, et al. Impact of delayed diagnosis and misdiagnosis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM): a targeted literature review. Cardiol Ther. 2021;10(1):141-159.

Kittleson MM, Ruberg FL, Ambardekar AV, et al; Writing Committee. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023;81(11):1076-1126.

González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585-2594.

Hahn VS, Yanek LR, Vaishnav J, et al. Endomyocardial biopsy characterization of heart failure with preserved ejection fraction and prevalence of cardiac amyloidosis. JACC Heart Fail. 2020;8(9):712-724.

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.

Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(22):2872-2891.

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.

Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126(10):1286-1300.

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.

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

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.

ATTR cardiac amyloidosis is characterized by the accumulation of amyloid fibrils of misfolded transthyretin protein in the myocardium, leading to heart failure¹

Destabilization of TTR results in ATTR cardiac amyloidosis¹

TTR plays a vital role in everyday biologic functions^3,4

TTR transports³:

Thyroxine (metabolism-regulating hormone)^3,4
- Thyroid hormones play a vital role in regulating the body’s metabolism, heart and digestive functions, muscle control, brain development, and maintenance of bones

Retinol (vitamin A)³
- Vitamin A is important for vision, reproduction, growth, and development

Next: Learn the red flags of ATTR cardiac amyloidosis

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ATTR=transthyretin amyloidosis; ATTR-CM=transthyretin amyloid cardiomyopathy; TTR=transthyretin.

References:

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

Vieira M, Saraiva MJ. Transthyretin: a multifaceted protein. Biomol Concepts. 2014;5(1):45-54.

Shahid MA, Ashraf MA, Sharma S. Physiology, thyroid hormone. StatPearls. Internet. StatPearls Publishing; 2022.

Maurer MS, Schwartz JH, Gundapaneni B, et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.