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ATTR-CMATTR-CMATTR-CM HomeAbout ATTR-CMMechanism of DiseaseWild-Type ATTR-CMHereditary ATTR-CMSuspect ATTR-CMDetect ATTR-CMResourcesEventsMaterialsVideos
Wild-Type ATTR-CM wtATTR-CM is idiopathic and not considered to be a hereditary disease1

Looking for information about hATTR-CM? Read more

wtATTR-CM is a type of amyloidosis caused by age-related changes in the stability of TTR proteins2-7:
  • Most common in older adults, and the average age at diagnosis is >60 years
  • The wild type accounts for most ATTR-CM cases
  • The mean time to diagnosis of wtATTR-CM has been shown to be 6.1 years
  • Timely diagnosis and treatment of wtATTR-CM have been predicted to extend mean life expectancy by 5.46 years compared with delayed diagnosis
Common characteristics of wtATTR-CM
  • Heart failure1,5,8: In 2 studies, ~7% to 13% of older patients with HFpEF had wtATTR9,10,*,†
  • Cardiac arrhythmias, particularly atrial fibrillation1,5,8,11
  • History of orthopaedic manifestations, such as bilateral carpal tunnel syndrome, lumbar spinal stenosis and/or biceps tendon rupture3,12-14

[Note: claim below for European markets]

Carpal tunnel syndrome: an early manifestation

About 60% of patients with wtATTR-CM experienced carpal tunnel syndrome for as many as 5 to 9 years prior to their wtATTR-CM diagnosis.15,16

Suspect the signs  Loading

Urgent need for diagnosis

Once diagnosed, untreated patients have a median survival of ~2 to 3.5 years.11

Use estimATTR to learn about clinical conditions associated with wtATTR-CM A probability estimator for wtATTR-CM Start estimating  LoadingAbout the estimATTR

The wtATTR-CM estimATTR was developed based on an AI/ML algorithm using diagnosis codes from a large, real-world claims dataset comprising more than 1500 patients with wtATTR-CM. 

Using hypothetical patient cases presenting with heart failure, estimATTR can highlight the types of combinations of cardiac and noncardiac conditions that should raise suspicion for wtATTR-CM by: 

  • Estimating the probability of wtATTR-CM based on combinations of clinical features known to be associated with the disease
  • Illustrating important features that may help distinguish between wtATTR-CM and heart failure from other causes​​​​​​​
This tool is only to be used by US healthcare professionals. It is for educational purposes only, and it is not to be used for the suspicion of a diagnosis of wtATTR-CM in individual patients in a clinical setting. Hereditary ATTR-CM > Loading*A prospective analysis in 108 patients (61% women, age range: 57-74 years) seen at the Johns Hopkins University HFpEF Clinic who underwent EMB to evaluate myocardial tissue histopathology. ATTR-CM was confirmed in approximately 10% of the patients.9

A prospective, cross-sectional, single-centre study at a tertiary university hospital in Madrid, Spain. There were 120 patients admitted for HFpEF with ≥50% LV ejection fraction and ≥12 mm LV hypertrophy who were ≥60 years of age (59% women, mean age: 82 ± 8 years). 99mTc-DPD scintigraphy was used to confirm ATTR-CM. wtATTR was confirmed in 13% (13.3%; 95% CI: 7.2-19.5) of the patients.10

99mTc-DPD, 99mtechnetium-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid; AL, immunoglobulin light chain amyloidosis; ATTR-CM, transthyretin amyloid cardiomyopathy; CI, confidence interval;
EMB, endomyocardial biopsy; hATTR-CM, Hereditary ATTR-CM; HFpEF, heart failure with preserved ejection fraction; LV, left ventricular; ML, machine learning; TTR, transthyretin; wtATTR-CM, Wild-type ATTR-CM.
ReferencesConnors 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.115.018852Ruberg 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.2019.04.003Witteles 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.2019.04.010Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012;126(10):1286-1300. doi:10.1161/CIRCULATIONAHA.111.078915Maurer 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.2016.03.596Rozenbaum 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/s40119-021-00219-5 Rozenbaum 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-2021-0071Pinney 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 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. doi:10.1016/j.jchf.2020.04.007González-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. doi:10.1093/eurheartj/ehv338Maurer 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 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:10.3109/13506129.2015.1135792Westermark 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:10.3109/03009734.2014.895786 Geller 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.2017.9236 Stern LK, Kittleson MM. Updates in cardiac amyloidosis diagnosis and treatment. Curr Oncol Rep. 2021;23(4):47. doi:10.1007/s11912-021-01028-8 aus 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/s00392-019-01467-1
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