Early diagnosis and treatment of ATTR-CM are critical to extend life1ATTR-CM is an underdiagnosed cause of heart failure2,3Prognosis worsens rapidly with continued amyloid deposition, resulting in advancing organ dysfunction, significant reduction in quality of life, and, ultimately, death2,4
| Timely diagnosis and treatment matter |
Normal, healthy heart vs thickened walls of an ATTR amyloidosis heart
Normal healthy heart Illustrative representation. ATTR amyloidosis heart Illustrative representation.Once diagnosed, untreated patients with ATTR-CM have a median survival of ~2 to 3.5 years4 | It has been shown that the mean time to diagnosis of ATTR-CM was: |
6.1 years for wild-type5 5.7 years for hereditary5
6.1 years for wild-type5
5.7 years for hereditary5
| Timely diagnosis and treatment of ATTR-CM were predicted to extend mean life expectancy by 5.46 years (wild-type) and 7.76 years (hereditary) compared with delayed diagnosis6 |
Suspicion and Detection It is important to clinically differentiate between ATTR and AL5,7Although there are multiple proteins that can cause amyloidosis, 98% of currently diagnosed cardiac amyloidosis cases result from fibrils composed of AL or ATTR8
wtATTR-CM
wtATTR-CM is a type of amyloidosis caused by age-related changes in the stability of TTR proteins.2,3,9,11,12
- Idiopathic and not considered to be a hereditary disease
- Most common in older adults, and the average age at diagnosis is >60 years
- Accounts for the majority of ATTR-CM cases
Common characteristics that may present in patients with wtATTR-CM
- Heart failure3,12,13
- Cardiac arrhythmias, particularly atrial fibrillation3,4,12,13
-
History of orthopedic manifestations, such as bilateral carpal tunnel syndrome, lumbar spinal stenosis, and/or biceps tendon rupture14-16
~3.5 years
Median Survival
Once diagnosed, untreated patients have a median survival of approximately 3.5 years4 |
~60% of patients
Exhibited Carpal Tunnel Syndrome as an Early
Manifestation
~60% of patients with wtATTR-CM experience carpal tunnel syndrome as many as 5 to 7 years prior to the start of cardiac manifestations/heart failure17,18 |
hATTR-CMhATTR-CM is a type of amyloidosis caused by a mutation in the TTR gene9
hATTR-CM is inherited in an autosomal dominant pattern, meaning only 1 affected relative is required to pass on the mutation19
About 75% of patients with hATTR-CM exhibited cardiomyopathic features of the disease.20
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.21
There is great heterogeneity in penetrance data depending on the phenotype, genotype, and environmental factors.22
Overview of hATTR-CM
Patient considerations
- Men and women3
- Symptom onset may occur as early as 50-60 years of age23*
Prognosis
- Once diagnosed, untreated patients have a median survival of ~2 to 3 years4
Common characteristics that may present in patients with hATTR-CM:
- Heart failure3
- Autonomic dysfunction3,23
- History of bilateral carpal tunnel syndrome3
- Peripheral dysfunction3
Recognition of cardiac involvement (via NT-proBNP measurements)
- Increased serum levels of NT-proBNP can reveal cardiac involvement24
Early recognition of cardiac involvement in hATTR-CM is critical.
If left untreated, it can result in adverse outcomes, including increased mortality.24 |
Diagnosis of hATTR-CM in an index patient should prompt
genetic counseling and testing of relatives25
A targeted approach may enable diagnosis of disease upon the first detectable sign or symptom25 |
Age of onset varies depending on the causative mutation and geographic area.AL=immunoglobulin light chain amyloidosis; ATTR=transthyretin amyloidosis; ATTR-CM=transthyretin amyloid cardiomyopathy; hATTR-CM=hereditary transthyretin amyloid cardiomyopathy; NT-proBNP=N-terminal pro-B-type natriuretic peptide; TTR=transthyretin; wtATTR-CM=wild-type transthyretin amyloid cardiomyopathy.
Explore More Pivotal and 5-year data for ATTR-CM View the Body of Evidence
References:Elliott P, Drachman BM, Gottlieb SS, et al. Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Fail. 2022;153e008193:1-8.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.2019.04.010Maurer 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.2016.03.596Maurer 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.116.024438Rozenbaum 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. doi:10.1007/s40119-021-00219-56Rozenbaum MH, Large S, Bhambri R, et al. Estimating the health benefits of timely diagnosis and treatment of transthyretin amyloid cardiomyopathy. J Comp Eff Res. 2021;10(11):927-938. doi:10.2217/cer-2021-00711Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203-1212. doi 10.1161/CIRCULATIONAHA.108.843334Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis. A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur J Heart Fail. 2021;23(4):512-526. doi:10.1002/ejhf.2140 Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018: recommendations by the lnternabonal Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215-219. doi:10.1080/13506129.2018.1549825Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med. 2017;84(12)(suppl 3):12-26. doi:10.3949/ccjm.84.s3.02Ruberg 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. doi:10.1016/j.jacc.2019.04.003Connors 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.115.018852Pinney 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.113.000098Nakagawa 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:10.3109/13506129.2015.1135792Westermark P, Westermark GT, Suhr OB, Berg S. Transthyretin-derived amyloidosis: probably a common cause of lumbar spinal stenosis. Ups J Med Sci. 2014;119(3):223-228. doi:10.3109/03009734.2014.895786Geller HI, Singh A, Alexander KM, et al. Association between ruptured distal biceps tendon and wild-type transthyretin cardiac amyloidosis. JAMA. 2017;318(10):962-963. doi:10.1001/jama.2017.9236Stern LK, Kittleson MM. Updates in cardiac amyloidosis diagnosis and treatment. Curr Oncol Rep. 2021;23(4):47. doi:10.1007/s11912-021-01028-8aus dem Siepen F, Hein S, Prestel S, et al. Carpal tunnel syndrome and spinal canal stenosis: harbingers of transthyretin amyloid cardiomyopathy? Clin Res Cardiol. 2019;108(12):1324-1330. doi:10.1007/s00392-019-01467-1Sekijima Y. Hereditary transthyretin amyloidosis. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, eds. GeneReviews [Internet]. Seattle, WA: University of Washington; 1993-2019.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/ehs123Kapoor 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 MA, Gracia Gutierrez A, Bueno Juana E, Menao Guillen 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/s41431-019-0337-1Rapezzi 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.2010.67Klaassen SHC, Tromp J, Nienhuis HLA, et al. 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