Disease ImpactIf you have patients with HFpEF in your practice, they may have transthyretin cardiac amyloidosis1-3*Also known as transthyretin amyloid cardiomyopathy (ATTR-CM).ATTR cardiac amyloidosis may be underdiagnosed in patients with HFpEF due to the 2 conditions’ similar clinical characteristics.4~1 in 10 patients over the age of 60 with HFpEF were found to have ATTR cardiac amyloidosis2,3†
Without treatment, patients with ATTR cardiac amyloidosis have a median survival of ~2 to 3.5 years.5-7 Proactive identification and early intervention are critical to slow disease progression.8,9
Patients with ATTR cardiac amyloidosis may go over 3 years from experiencing their first symptoms to receiving the appropriate diagnosis10Patients with ATTR cardiac amyloidosis may go over 3 years from experiencing their first symptoms to receiving the appropriate diagnosis10According to the 2023 ACC Expert Consensus Decision Pathway, ATTR cardiac amyloidosis may be mistaken for3:
- Hypertensive heart disease
- Hypertrophic cardiomyopathy
- Concentric hypertrophy from aortic stenosis
- HFpEF
Misdiagnosis occurs in greater than 1/3 of ATTR cardiac amyloidosis patients11
You can help extend patient survival with timely diagnosis and treatment of ATTR cardiac amyloidosis.12
Delayed diagnosis and treatment of ATTR cardiac amyloidosis can have a significant impact on patients9,12,13
Mechanism of DiseaseATTR cardiac amyloidosis is characterized by the accumulation of amyloid fibrils of misfolded transthyretin protein in the myocardium, leading to heart failure5,14TTR plays a vital role in everyday biologic functions15,16 TTR transports:
-
Thyroxine (metabolism-regulating hormone)15,17
- 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)15
- Vitamin A is important for vision, reproduction, growth, and development
Destabilization of TTR causes ATTR cardiac amyloidosis18-21
- Unstable tetramers break apart into monomers5,14
- Monomers misfold and form amyloid fibrils5,14
- Fibrils accumulate in heart tissue5
There are 2 subtypes of ATTR cardiac amyloidosis9
-
Wild-type ATTR cardiac amyloidosis (wtATTR cardiac amyloidosis)
- Presents most commonly in older white men, >60 years of age1,7,22,23
- Prevalence increases with age24
-
Hereditary ATTR cardiac amyloidosis (hATTR cardiac amyloidosis)‡
- Affects both men and women22
- May occur as early as 50 to 60 years of age22,25
- Onset varies according to mutation22
- The most common variant in the United States, Val122lle, is carried by ~3%-4% of African Americans5,22§
BadgeNext: Learn when to rule out ATTR cardiac amyloidosis ContinueLoadingStudy designs: 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.1,2In the United States, Val122lle and Thr60AIa are the most common mutations that typically manifest as cardiomyopathy symptoms.5Although not all individuals with the V122I mutation develop symptoms.ACC=American College of Cardiology; ATTR=transthyretin amyloidosis; CV=cardiovascular; HFpEF=heart failure with preserved ejection fraction; TTR=transthyretin.
References: 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. Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC expert consensus decision pathway on comprehensive multidisciplinary care for the patient with cardiac amyloidosis. J Am Coll Cardiol. 2023;81(11):1076-1126.Oghina S, Bougouin W, Bézard M, et al. The impact of patients with cardiac amyloidosis in HFpEF trials. JACC Heart Fail. 2021;9(3):169-178. 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. Grogan M, Scott CG, Kyle RA, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68:1014-1020. 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. 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. Witteles RM, Bokhari S, Damy T, et al. Screening for transthyretin amyloid cardiomyopathy in everyday practice. JACC Heart Fail. 2019;7(8):709-716.Papoutsidakis N, Miller EJ, Rodonski A, Jacoby D. Time course of common clinical manifestations in patients with transthyretin cardiac amyloidosis: Delay from symptom onset to diagnosis. J Card Fail. 2018;24(2):131-133.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.Ioannou A, Patel RK, Razvi Y, et al. Impact of earlier diagnosis in cardiac ATTR amyloidosis over the course of 20 years. Circulation. 2022;146:1657-1670. Lane T, Fontana M, Martinez-Naharro A, et al. Natural history, quality of life, and outcome in cardiac transthyretin amyloidosis. Circulation. 2019;140(1):16-26.Bulawa CE, Connelly S, DeVit M, et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade. Proc Natl Acad Sci USA. 2012;109(24):9629-9634. Vieira M, Saraiva MJ. Transthyretin: a multifaceted protein. Biomol Concepts. 2014;(1):45-54.Adams D, et al. TTR kinetic stabilizers and TTR gene silencing: a new era in therapy for familial amyloidotic polyneuropathies. Expert Opin Pharmacother. 2016;17(6):791-802.Shahid MA, Ashraf MA, Sharma S. Physiology, Thyroid Hormone. [Updated May 12, 2021] In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. Coelho T, Merlini G, Bulawa CE, et al. Mechanism of action and clinical application of tafamidis in hereditary transthyretin amyloidosis. Neurol Ther. 2016;5(1):1-25. Donnelly JP, Hanna M. Cardiac amyloidosis: an update on diagnosis and treatment. Cleve Clin J Med. 2017;84(12 suppl 3):12-26. Sekijima Y. Transthyretin (ATTR) amyloidosis: clinical spectrum, molecular pathogenesis and disease-modifying treatments. J Neurol Neurosurg Psychiatry. 2015;86(9):1036-1043. Judge DP, Heitner SB, Falk RH, et al. Transthyretin stabilization by AG10 in symptomatic transthyretin amyloid cardiomyopathy. J Am Coll Cardiol. 2019;74(3):285-295.Maurer MS, Hanna M, Grogan M, et al; on behalf of THAOS Investigators. Genotype and phenotype of transthyretin cardiac amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016;68(2):161-172.Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213.Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28(1):10-21.Adams D, Algalarrondo V, Polydefkis M, et al. Expert opinion on monitoring symptomatic hereditary transthyretin-mediated amyloidosis and assessment of disease progression. Orphanet J Rare Dis. 2021;16(1):411.