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ATTR-CMATTR-CMATTR-CM HomeAbout ATTR-CMMechanism of DiseaseWild-Type ATTR-CMHereditary ATTR-CMSuspect ATTR-CMDetect ATTR-CMResourcesMaterialsVideosTreatment Option
Hereditary ATTR-CM (hATTR-CM)​​​​​​​ hATTR-CM is a type of amyloidosis caused by a mutation in the TTR gene1 

Looking for infomation about wild-type ATTR-CM? Read more

hATTR-CM is inherited in an autosomal dominant pattern, meaning only 1 affected relative is required to pass on the mutation.2 The most common mutations responsible for a cardiac phenotype are in patients of African American (V122I), Irish (T60A), Italian (I68L), and Danish (L111M) descent.3

  • Not all patients who carry a TTR mutation will go on to have clinical signs and symptoms of this disease4

About 75% of patients with hATTR-CM exhibited cardiomyopathic features of the disease.3

Carpal tunnel syndrome is also common and can often be the initial symptom in more than 30% of hATTR-CM patients, with cardiomyopathy symptoms following as the disease progresses.5

Penetrance data has shown great heterogeneity of the disease, depending on the phenotype, genotype, and environmental factors.6

An overview of hATTR-CM patient populationWho is at risk?
  • Men and women7
  • Age at symptom onset depends on the mutation, but may occur as early as 30 to 40 years (V30M, L111M), or 50 to 60 years (V122I, V30M, T60A), and 55 years (I68L)8-10
Common characteristics of hATTR-CM
  • Heart failure11
  • Peripheral dysfunction (eg, peripheral sensorimotor dysfunction, peripheral neuropathy)11
  • History of bilateral carpal tunnel syndrome11,12
  • Autonomic dysfunction (eg, autonomic neuropathy, gastrointestinal symptoms, unexplained weight loss, orthostatic hypotension, erectile dysfunction)11,13
Early detection is critical​​​​​​​

Advanced hATTR-CM in untreated patients is associated with rapid progression, serious cardiac complications, and increased mortality, regardless of phenotype.7,11,14


  • Once diagnosed, untreated patients have a median survival of ~2 to 3 years11

Early recognition of cardiac involvement in hereditary amyloidosis is critical15

  • Increased serum levels of NT-proBNP can reveal cardiac involvement
NT-proBNP, N-terminal pro-B-type natriuretic peptide. Understanding genetic risk for hATTR-CM​​​​​​​

Diagnosis of hATTR-CM in an index patient should prompt genetic counselling and testing of relatives.10

A targeted approach may enable diagnosis of disease at the first detectable sign or symptom10:

  • Early identification of ATTR-CM is important to enable timely treatment
  • Genetic testing is used to detect the presence of a mutation in the TTR gene and therefore confirm a diagnosis of hATTR-CM
  • Genetic counselling and testing can be especially beneficial in at-risk relatives of an index patient

Timing of genetic testing in at-risk relatives should take into account10:

  • The particular mutation
  • The penetrance of the mutation
  • The age of onset and severity of disease in the index patient
Suspect ATTR-CM > LoadingReferences:Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215-219. doi:10.1080/13506129.2018.1549825 Sekijima Y. Hereditary Transthyretin Amyloidosis. In: Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet]. Seattle, WA: University of Washington; 1993-2022. Rapezzi C, Quarta CC, Obici L, et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J. 2013;34(7):520-528. doi:10.1093/eurheartj/ehs123 Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31. doi:10.1186/1750-1172-8-31Kapoor M, Rossor AM, Laura M, Reilly MM. Clinical presentation, diagnosis, and treatment of TTR amyloidosis. J Neuromuscul Dis. 2019;6(2):189-199. doi:10.3233/JND-180371Lahuerta Pueyo C, Aibar Arregui MÁ, Gracia Gutierrez A, Bueno Juana E, Menao Guillén S. Estimating the prevalence of allelic variants in the transthyretin gene by analysing large-scale sequencing data. Eur J Hum Genet. 2019;27(5):783-791. doi:10.1038/s41431-019-0337-1Maurer 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.2016.03.596Rapezzi 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 Adams D, Koike H, Slama M, Coelho T. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol. 2019;15(7):387-404. doi:10.1038/s41582-019-0210-4 Conceição I, Damy T, Romero M, et al. Early diagnosis of ATTR amyloidosis through targeted follow-up of identified carriers of TTR gene mutations. Amyloid. 2019;26(1):3-9. doi:10.1080/13506129.2018.1556156 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 Coelho T, Maurer MS, Suhr OB. THAOS-The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63-76. doi:10.1185/03007995.2012.754348Conceição I, Coelho T, Rapezzi C, et al. Assessment of patients with hereditary transthyretin amyloidosis–understanding the impact of management and disease progression. Amyloid. 2019;26(3):103-111. doi:10.1080/13506129.2019.1627312 Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799-2806. doi:10.1093/eurheartj/ehx589 
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