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

Looking for information about hereditary ATTR-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
  • 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 wtATTRCM
  • Heart failure1,5,8: In 2 studies, ~7% to 13% of older patients with heart failure with preserved ejection fraction (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
A prospective analysis in 108 patients (61% women, age range: 57-74 years) seen at the Johns Hopkins University HFpEF Clinic who underwent endomyocardial biopsy (EMB) to evaluate myocardial tissue histopathology. Approximately 10% had ATTR-CM confirmed.9A prospective, cross-sectional, single-centre study at a tertiary university hospital in Madrid, Spain. Included 120 patients ≥60 years of age (59% women, mean age: 82 ± 8 years) admitted for HFpEF, with left ventricular (LV) ejection fraction ≥50% and LV hypertrophy ≥12 mm. 99mtechnetium-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy used to confirm ATTR-CM. wtATTR was confirmed in 13% (13.3%; 95% CI: 7.2-19.5) of the patients.10​​​​​​​Carpal tunnel syndrome: an early manifestation

60% of patients with wtATTR-CM experienced carpal tunnel syndrome as many as 5 to 9 years prior to 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 the 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 artificial intelligence/machine learning (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, the 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 healthcare professionals resident in the Republic of Ireland. 
The wtATTR-CM estimATTR is only to be used as an educational tool to learn how different 
combinations of clinical conditions for hypothetical patients can yield different probability 
scores. It is not to be used in a clinical setting for the suspicion or diagnosis of wtATTR-CM in 
individual patients.
Hereditary ATTR-CM > LoadingReferences: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. 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.111.078915 Maurer 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-2021-0071 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. 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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