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ATTR-CMATTR-CMATTR-CM HomeAbout ATTR-CMMechanism of DiseaseWild-Type ATTR-CMHereditary ATTR-CMSuspect ATTR-CMDetect ATTR-CMResourcesEventsMaterialsVideos
Suspect ATTR-CM with cardiac and non-cardiac clues1 Multidisciplinary team collaboration can help ensure an early and accurate diagnosis.2

ATTR-CM is characterised by multiorgan involvement, and it can manifest in many ways1,3. It is important to include a multidisciplinary healthcare team in the diagnostic process. Coordinated care and effective communication among the team can help ensure that the patient receives the right diagnosis.2

Routine heart failure assessments such as echo and CMR can help identify clues on the diagnostic pathway.4

Consider these clinical clues, especially in combination, to raise suspicion and the need for further testing:

HFpEF or other cardiac conditions (e.g. severe AS* and arrhythmias) in patients typically >60 years of age5-7

Intolerance to standard heart failure therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and beta-blockers8

Discordance between QRS voltage on ECG and LV wall thickness9,10

Diagnosis of orthopaedic conditions such as carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon ruptures and/or hip/knee arthroplasty11-14

Echo showing increased LV wall thickness9

Nervous system dysfunction1 (e.g. polyneuropathy) and autonomic dysfunction (e.g. gastrointestinal symptoms and/or unexplained weight loss)15

ESC recommendations2

The ESC working group recommends screening for ATTR-CM if the LV wall thickness is ≥12 mm along with the presence of ≥1 red flag or clinical scenario.

Meet ABE, the Amyloid Body of Evidence

ABE is an interactive experience designed to help locate various TTR amyloid deposition sites and to identify cardiac and noncardiac clues throughout the body.

Using echo to suspect ATTR-CM​​​​​​​

Echo, including TDI and strain analysis, can play a role in the non-invasive diagnosis of ATTR-CM due to4:

  • Widespread availability and portability
  • Capacity to assess cardiac structure and diastolic function
Echo can help identify the characteristics related to amyloid infiltration but cannot distinguish between ATTR-CM and other types of cardiac amyloidosis.4
Characteristic appearance of cardiac amyloidosis on echo4

Transthoracic echo of the parasternal long axis view showing LV hypertrophy with preserved ejection fraction.
Adapted from Filiale d'Imagerie Cardiovasculaire​.

Echo findings that are strongly suggestive of cardiac amyloidosis and should be reported include4:

  • Increased LV wall thickness
  • Increased LV mass
  • Typical LV longitudinal strain pattern
  • Mitral annular TDI <5 cm/s
  • Biatrial enlargement
  • Small A-wave in sinus rhythm
  • Small pericardial and/or pleural effusions
Get more information about echo imaging. Download now Loading Using CMR: Clues to suspect ATTR-CMCMR may raise suspicion of disease in 2 scenarios4:
  • Differentiation between cardiac amyloidosis and other cardiomyopathic conditions with increased wall thickening
  • Detection of early cardiac involvement in patients presenting with symptoms of systemic amyloidosis
CMR may be advantageous in the following scenarios (if echocardiographic acoustic windows are poor4):
  • To characterise the right ventricle
  • To characterise the tissue based on the contrast-enhanced patterns of myocardial infiltration
  • To precisely quantify cardiac chamber volumes and ventricular mass
Characteristic imaging of cardiac amyloidosis with CMR4

Patient A: Normal heart. 
Patient B: Heart shows a significantly high amyloid burden (elevated native T1, transmural late gadolinium enhancement and increased extracellular volume).

Adapted from Dorbala et al. J Nucl Cardiol. 2019. Review additional information about CMR imaging Download now Loading ​​​​​​​Dr. Detective Series: Raising Suspicion of ATTR-CM

Meet Dr. Detective, a cardiologist who is specialised in diagnosing tough cases. Watch as he suspects that his patient has ATTR-CM.

Encountering ATTR-CM

Raising suspicion of ATTR-CM 

Detecting ATTR-CM

Detect ATTR-CM > Loading*Notably in those patients with a low-flow, low-gradient AS pattern.6

ABE, Amyloid Body of Evidence; AS, aortic stenosis; ATTR-CM, transthyretin amyloid cardiomyopathy; CMR, cardiac magnetic resonance; ECG, electrocardiography; echo, echocardiography; ECV, external electrical cardioversion; ESC, European Society of Cardiology; HFpEF, heart failure with preserved ejection fraction; LGE; Late gadolinium enhancement, LV, left ventricular; 
T1, longitudinal relaxation time constant; TDI, tissue Doppler imaging; TTR, Transthyretin.
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.2019.04.010Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J. 2021;42(16):1554-1568. doi:10.1093/eurheartj/ehab072Maurer 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. doi:10.1161/CIRHEARTFAILURE.119.006075Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2 – evidence base and standardized methods of imaging. J Nucl Cardiol. 2019;26(6):2065-2123. doi:10.1007/s12350-019-01760-6. Addendum: J Nucl Cardiol. Published online July 1, 2021. doi:10.1007/s12350-020-02455-zGonzález-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/ehv338 Castaño A, Narotsky DL, Hamid N, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017;38(38):2879-2887. doi:10.1093/eurheartj/ehx350Ruberg 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.2019.04.003Castaño A, Drachman BM, Judge D, Maurer MS. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015;20(2):163-178. doi:10.1007/s10741-014-9462-7Quarta CC, Solomon SD, Uraizee I, et al. Left ventricular structure and function in transthyretin-related versus light-chain cardiac amyloidosis. Circulation. 2014;129(18):1840-1849. doi:10.1161/CIRCULATIONAHA.113.006242 Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982;49(1):9-13. doi:10.1016/0002-9149(82)90270-3Nakagawa 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, Mirto TM, Falk RH. Association between ruptured distal biceps tendon and wild-type transthyretin cardiac amyloidosis. JAMA. 2017;318(10):962-963. doi:10.1001/jama.2017.9236Rubin J, Alvarez J, Teruya S, et al. Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloid diagnosis: can we identify affected patients earlier? Amyloid. 2017;24(4):226-230. doi:10.1080/13506129.2017.1375908Coelho 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:10.1185/03007995.2012.754348
ATTR-CM Detect ATTR-CM noninvasively with nuclear scintigraphy4

Review the evidence and consensus recommendations for diagnosis.

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