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About ATTR-CMAbout

Learn about ATTR-CM and uncover the differences between hereditary and wild-type ATTR-CM

Types of ATTR-CM

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Suspect ATTR-CMDetect ATTR-CMSupporting ResourcesTreatment Option

Click here for Vyndaqel®▼ (tafamidis) Prescribing Information.

Detect ATTR-CM

What is nuclear scintigraphy?
​​​​​​​

Nuclear scintigraphy using both planar and single-photon emission computed tomography (SPECT) imaging is a noninvasive, commonly available diagnostic tool with high sensitivity and specificity for ATTR-CM when combined with testing to rule out immunoglobulin light chain (AL) amyloidosis.1-3

Nuclear scintigraphy with 99mTc-PYP/99mTc-DPD/99mTc-HMDP* provides a unique myocardial uptake pattern in amyloid3
  • Studies comparing 99mTc-PYP/99mTc-DPD/99mTc-HMDP* scintigraphy with endomyocardial biopsy (EMB) found that bone radiotracers have avidity for ATTR deposits, whereas avidity for AL cardiac amyloid deposits is minimal or absent3
  • According to the expert recommendations, SPECT imaging is required in all studies (irrespective of time between injection and scan) to ensure direct visualisation of tracer uptake in the myocardium.3
  • A multicentre international study of scintigraphy at amyloid centres of excellence demonstrated 100% specificity for ATTR-CM using visual grade 2 or 3 with concurrent testing to rule out AL amyloidosis.1
​​​​​​
Important considerations for the acquisition of 99mTc-PYP/99mTc-DPD/99mTc-HMDP* imagingMultisocietal expert consensus recommendations for diagnosing ATTR-CM with nuclear scintigraphy3†
  • The recommended time between injection of 99mTc-PYP/99mTc-DPD/99mTc-HMDP* and scan is 2 or 3 hours3; 1-hour planar-only imaging is not recommended3
  • Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches irrespective of the timing of acquisition3
Interpret scans in 3 stepsStep 1: Visual interpretation3,4
  • Evaluate planar and SPECT images to confirm diffuse radiotracer uptake in the myocardium
  • Differentiate myocardial radiotracer uptake from residual blood pool activity, focal myocardial infarct, and overlapping bone (eg, from rib hot spots from fractures) on SPECT images
  • If excess blood pool activity is noted, recommend repeating SPECT imaging at 3 hours

If myocardial tracer uptake is visually present on SPECT, proceed to step 2, semiquantitative visual grading.

If no myocardial tracer uptake is present on SPECT, the visual grade is 0.

Positive SPECT with no blood pool

Adapted from Sennott J, Ananthasubramanaim K. Heart Fail Rev. 2022;27(5):1515-30. doi:10.1007/s10741-021-10179-6

Step 2: Semiquantitative  
  • Semiquantitative visual grading comparison to bone (rib) uptake at 3 hours3
  • Examine planar and SPECT images for tracer uptake in the myocardium relative to ribs and grade using the following scale:

Illustrative representation of 99mTc-PYP/99mTc-DPD/99mTc-HMDP* uptake.
Adapted from Dorbala et al. Expert consensus recommendations for multimodality imaging in cardiac amyloidosis. J Nucl Cardiol. 2019.

Visual scoring method in relation to bone (rib) uptake at 3 hours3

  • Strongly suggestive of ATTR-CM: Visual grade of ≥2 on planar and SPECT images with concurrent testing to rule out AL3
  • Not suggestive or equivocal of ATTR-CM: Visual grade of <23

When cardiac amyloidosis is suspected, Grade 2 or 3 myocardial uptake with concurrent testing to rule out AL is diagnostic of ATTR-CM.3*

Step 3: H/CL uptake ratio assessment (when applicable)3  Diagnosis of ATTR-CM cannot be made solely based on heart-to-contralateral lung (H/CL) ratio alone. H/CL ratio is not recommended if there is absence of myocardial uptake on SPECT imaging.

H/CL ratio is typically concordant with visual grade3
  • If the visual grade is 2 or 3, diagnosis is confirmed, and H/CL ratio assessment is not necessary
  • If discordant, or the visual grade is equivocal, H/CL ratio may be helpful to classify equivocal visual grade 1 vs 2 as positive or negative
An H/CL ratio is calculated as the fraction of heart region of interest (ROI) mean counts to contralateral lung ROI mean counts3
  • H/CL ratios of ≥1.5 at 1 hour can accurately identify ATTR-CM if myocardial 99mTc-PYP* uptake is visually confirmed on SPECT imaging and systemic AL amyloidosis is excluded
  • An H/CL ratio of ≥1.3 at 3 hours can identify ATTR cardiac amyloidosis

 Quantification of cardiac 99mTc-PYP* uptake using H/CL ratio5 

Illustrative representation. Adapted from American Society of Nuclear Cardiology (ASNC). ASNC practice points: 99mTechnetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. https://www.asnc.org/Files/Amyloid/ASNC Practice Point-99mTechnetium-Pyrophosphate.2019.pdf. © 2019 American Society of Nuclear Cardiology [Last accessed: January 2024]

Genetic testing—used in the ATTR-CM diagnostic process

  • Used to determine if the disease is hereditary due to a mutation in the TTR gene or if it is wild-type6
  • Genetic counselling and gene sequencing are recommended following confirmation of ATTR-CM6


99mTc-PYP/99mTc-DPD/99mTc-HMDP is not currently licensed for cardiac nuclear scintigraphy in the UK. Please consult individual Summaries of Product Characteristics for further details. 99mTc-PYP/99mTc-DPD/99mTc-HMDP uptake could be seen in other causes of myocardial injury, including pericarditis, myocardial infarction (regional uptake), and chemotherapy- or drug-associated myocardial toxicity.3 
† Written by a writing group of experts in cardiovascular imaging and amyloidosis assembled by the American Society of Nuclear Cardiology and endorsed by 9 societies including the American College of Cardiology, American Heart Association, American Society for Echocardiography, European Association of Nuclear Medicine, Heart Failure Society of America, International Society of Amyloidosis, Society for Cardiovascular Magnetic Resonance, and Society of Nuclear Medicine and Molecular Imaging.‡ Rule out AL: testing for presence of monoclonal protein via serum and urine immunofixation (IFE) and serum free light chain (SFLC) assay.1

ATTR=transthyretin amyloidosis; AL=lightchain amyloidosis; AS=aortic stenosis; CMR=cardiac magnetic resonance; CTS=carpal tunnel syndrome; DPD=99mtechnetium-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid; Echo=echocardiography; ECG= electrocardiography; HFpEF= Heart failure with preserved ejection fraction; HMDP=99mtechnetium-labelled hydroxymethylene diphosphonate; LV=left ventricle; PYP=99mtechnetium-labelled pyrophosphate; SFLC=serum-free light chain assay; SPECT= single photon emission computed tomography; TDI=tissue Doppler imaging; TTR= transthyretin.

References:Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24): doi:10.1161/CIRCULATIONAHA.116.021612;Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. 99mTc-Pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amylodoses. Circ Cardiovasc Imaging. 2013;6(2):195-201. doi:10.1161/CIRCIMAGING.112.000132;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): doi:10.1007/s12350-019-01760-6. Addendum: J Nucl Cardiol. Published online July 1, 2021. doi:10.1007/s12350-020-02455-z;Sennott J, Ananthasubramaniam K. Multimodality imaging approach to cardiac amyloidosis: part 2. Heart Fail Rev. 2022;27:1515-1530;American Society of Nuclear Cardiology (ASNC). ASNC practice points: 99mTechnetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. Available at: https://www.asnc.org/Files/Amyloid/ASNC Practice Point-99mTechnetium-Pyrophosphate.2019.pdf. © 2019 American Society of Nuclear Cardiology [Last accessed: January 2024]; Maurer 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.Explore more Explore available supporting resources Supporting Resources Loading
Early diagnosis of ATTR-CM is critical  About ATTR-CM Loading What imaging modalities help raise suspicion of ATTR-CM? Suspect ATTR-CM Loading
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