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ATTR-CMATTR-CMATTR-CM HomeAbout ATTR-CMMechanism of DiseaseWild-Type ATTR-CMHereditary ATTR-CMSuspect ATTR-CMDetect ATTR-CMResourcesMaterialsVideosTreatment Option
Suspect ATTR-CM with cardiac and noncardiac clues1 Multidisciplinary team collaboration can help ensure early and accurate diagnosis2​​​​​​​

ATTR-CM is characterised by multiorgan involvement and can manifest in many ways.1,3 It is important to include a multidisciplinary health care team in the diagnostic process. Coordinated care with strong communication among the team can help ensure that the patient receives the right diagnosis.2 

Routine heart failure assessments such as echocardiography (echo) and cardiac magnetic resonance (CMR) can help identify clues on the diagnostic pathway.4

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

Heart failure with preserved ejection fraction (HFpEF) or other cardiac conditions (eg, severe aortic stenosis [AS],* arrhythmias) in patients typically over the age of 605-7

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

Discordance between QRS voltage on electrocardiography (ECG) and left ventricular (LV) wall thickness9,10

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

Echo showing increased LV wall thickness9

Nervous system dysfunction, including polyneuropathy and autonomic dysfunction, including gastrointestinal symptoms and/or unexplained weight loss15

Notably those with a low-flow, low-gradient AS pattern.6European Society of Cardiology (ESC) recommendations2

The ESC Working Group recommends screening for ATTR-CM if LV wall thickness is ≥12 mm + the presence of ≥1 red flag or clinical scenario.

Using echo to suspect ATTR-CM​​​​​​​

Echo, including tissue Doppler imaging (TDI) and strain analysis, can play a role in the noninvasive diagnosis of ATTR-CM due to its4:

  • Widespread availability and portability 
  • Capacity to assess structure and diastolic function 
Echo can help identify 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

Illustrative representation.

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
Echo and the importance of a multidisciplinary approach for ATTR-CM

Brian L. Henry, MD, PhD, board-certified cardiologist in echocardiography and nuclear cardiology.

Get more information about echo imaging. Download now Loading Using CMR 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 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)

Illustrative representation.Cardiac magnetic resonance (CMR) overview

Brian L. Henry, MD, PhD, board-certified cardiologist in echocardiography and nuclear cardiology.

Review additional information about CMR imaging. Download now Loading Revealing ATTR-CM in Clinical Practice: Seeing the Signs

Pablo Garcia-Pavia, MD, PhD, Inherited Cardiac Diseases Unit, Hospital Universitario Puerta de Hierro, Madrid, Spain. 

​​​​​​​Dr. Detective Series: Raising Suspicion of ATTR-CM

Meet Dr. Detective, a cardiologist who specialises 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 > LoadingReferences: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/CIRCHEARTFAILURE.119.e006075Dorbala 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/ehx350 Ruberg 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.2019.04.00Castaño 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/s10741-014-9462-7 Quarta 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;49:9-13. doi:10.1016/0002-9149(82)90270-3 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.2017.923 Rubin 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:10.1080/13506129.2017.1375908 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:10.1185/03007995.2012.754348
ATTR-CM Detect ATTR-CM noninvasively with nuclear scintigraphy4

Review the evidence and consensus recommendations for diagnosis.

Learn moreLoading
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