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Tools used in the suspicion of transthyretin cardiac amyloidosis*

*Also known as transthyretin amyloid cardiomyopathy (ATTR-CM).

Echocardiogram (echo): an essential tool for suspecting ATTR cardiac amyloidosis1

Echo has the advantage of being portable and widely available, and includes tissue Doppler imaging (TDI) and strain analysis. It can play a role in the noninvasive diagnosis of ATTR cardiac amyloidosis due to its capacity to assess structure and diastolic function.1

Echo findings that are strongly suggestive of cardiac amyloidosis and should be reported include1:

  • Increased left ventricular (LV) wall thickness
  • Increased LV mass
  • Typical LV longitudinal strain pattern
  • Mitral annular TDI velocity <5 cm/s
  • Biatrial enlargement
  • Small A wave in sinus rhythm
  • Small pericardial and/or pleural effusions
Characteristic appearance of cardiac amyloidosis on 2D echo

Apical 4-chamber view2

Increased biventricular wall thickness, biatrial enlargement, and increased thickening of the interatrial septum (yellow arrow) and mitral valve leaflets (white arrow) in a patient with wild-type ATTR cardiac amyloidosis1

Tissue doppler imaging1
  • TDI tracing taken at the septal mitral annulus in a patient with ATTR cardiac amyloidosis1
  • Shows the “5-5-5” sign (s' [systolic], e' [early diastolic], and a' [late (atrial) diastolic] tissue velocities are all <5 cm/s), which is seen in patients with more advanced cardiac amyloidosis1
  • Dotted lines denote the 5 cm/s cutoff for systolic and diastolic tissue velocities. In addition to the decreased tissue velocities, isovolumic contraction and relaxation times (IVCT and IVRT, respectively) are increased and ejection time (ET) is decreased1
Illustrative representation.LV longitudinal strain abnormalities1

All show abnormal longitudinal strain in the basal and mid segments with relative preservation in the apical segments (purple and green curves, white arrows) in a patient with hereditary ATTR cardiac amyloidosis

Bull’s-eye map2
  • Shows the corresponding bull’s-eye map of the longitudinal strain pattern throughout the left ventricle with the “cherry-on-the-top’’ sign1
  • Red denotes normal longitudinal strain at the apex1
  • Pink/blue denotes abnormal longitudinal strain at the mid/basal left ventricle1

Illustrative representation.

Echo can help identify characteristics related to amyloid infiltration, but cannot distinguish between cardiac amyloidosis and other types of cardiac amyloidosis.1

Echo can help identify characteristics related to amyloid infiltration, but cannot distinguish between ATTR cardiac amyloidosis and other types of cardiac amyloidosis.1

Electrocardiogram (ECG): a discordance in results is a classic clinical sign3,4Electrocardiogram (ECG): a discordance in results is a classic clinical sign3,4

The classic ECG feature of ATTR cardiac amyloidosis is a discordance between QRS voltage and LV mass ratio.3,4

The amplitude of the QRS voltage is not reflective of the increased LV wall thickness, because the increase is due to extracellular amyloid protein deposition rather than myocyte hypertrophy.5,6

 Discordance between LV wall thickness and QRS voltage

Illustrative representation.

Absence of a low QRS voltage does not rule out amyloidosis, as low voltage can vary among cardiac amyloidosis etiologies.3,7-9

Absence of a low QRS voltage does not rule out amyloidosis, as low voltage can vary among cardiac amyloidosis etiologies.3,7-9

Cardiovascular magnetic resonance imaging (CMR): raising suspicion through tissue characterization1Cardiovascular magnetic resonance imaging (CMR): raising suspicion through tissue characterization1

CMR may raise suspicion of ATTR cardiac amyloidosis in 2 scenarios1:

  • 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 poor1:

  • To characterize the right ventricle
  • To characterize 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 CMR10

Illustrative representation.

CMR is typically unable to definitively distinguish AL amyloidosis from ATTR cardic amyloidosis.1

CMR is typically unable to definitively distinguish AL amyloidosis from ATTR cardiac amyloidosis.1

Sign up to stay connected for information about suspecting and diagnosing ATTR cardiac amyloidosis.

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ATTR=transthyretin amyloidosis.

References:Dorbala 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. Circ Cardiovasc Imaging. 2021;14(7):e000029.Porcari A, Merlo M, Rapezzi C, Sinagra G. Transthyretin amyloid cardiomyopathy: an uncharted territory awaiting discovery. Eur J Intern Med. 2020;82:7-15.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.Carroll JD, Gaasch WH, McAdam KP. Amyloid cardiomyopathy: characterization by a distinctive voltage/mass relation. Am J Cardiol. 1982;49(1):9-13.Rapezzi C, Lorenzini M, Longhi S, et al. Cardiac amyloidosis: the great pretender. Heart Fail Rev. 2015;20(2):117-124.Narotsky DL, Castaño A, Weinsaft W, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10.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.Cyrile NB, Goldsmith J, Alvarez J, Maurer MS. Prevalence and prognostic significance of low QRS voltage among the three main types of cardiac amyloidosis. Am J Cardiol. 2014;114(7):1089-1093.Ng B, Connors LH, Davidoff R, et al. Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med. 2005;165(12):1425-1429.Dorbala 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.
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