Tools to Diagnose    |    Nuclear Scintigraphy    |    Diagnostic Algorithm

Detect Transthyretin Amyloid Cardiomyopathy (ATTR-CM)


See how nuclear scintigraphy, endomyocardial biopsy (EMB), and genetic testing can be used to reach an ATTR-CM diagnosis.


*Should be combined with blood and urine testing to rule out AL.1,2

Nuclear Scintigraphy

  • A noninvasive diagnostic tool with high sensitivity and specificity for ATTR-CM when combined with testing to rule out AL amyloidosis1
  • A multicentre international study demonstrated 99% sensitivity for ATTR-CM (visual grade 1-3). A separate analysis within the study demonstrated 100% specificity for visual grade 2, 3 with concurrent testing to rule out AL1*                       
  • Uses a radioactive bone tracer, [99mtechnetium-labeled pyrophosphate (99mTc-PYP), 99mtechnetium-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), for detection of ATTR1

Endomyocardial Biopsy (EMB)

  • Histology with positive Congo red staining with apple-green birefringence1,3
  • Additional tests to determine amyloid type are recommended following diagnosis of cardiac amyloidosis1
  • Risk of complications and the need for specialised centres and expertise may contribute to a diagnostic delay1,3

Genetic Testing

  • Used to determine if the disease is hereditary due to a mutation in the TTR gene4
  • Genetic counseling and gene sequencing are recommended following confirmation of ATTR-CM4


Watch a cardiologist diagnose ATTR-CM. In the previous videos, Dr. Detective had a patient referred to him. He suspected ATTR-CM based on certain signs and symptoms. See what happens next.


Diagnosing ATTR-CM with nuclear scintigraphy requires quantifying uptake of the radioactive tracer [99mTc-PYP/99mTc-DPD] in the heart.1,5

Quantifying Myocardial [99mTc-PYP/99mTc-DPD]1,5

In clinical practice, [99mTc-PYP/99mTc-DPD] uptake can be quantified by a quantitative approach and a semiquantitative approach: 

  • Semiquantitative: visual comparison to bone uptake at 3 hours
    • Cardiac uptake of [99mTc-PYP/99mTc-DPD] evaluated using a visual scoring method in relation to bone uptake
    • Images are then given a visual grading score of 0 to 3
      • Grade 0: no uptake and normal rib uptake
      • Grade 1: uptake less than rib uptake
      • Grade 2: uptake equal to rib uptake
      • Grade 3: uptake greater than rib uptake with mild/absent rib uptake


Reproduced/Adapted/or Referenced with permission from ASNC. © 2019 American Society of Nuclear Cardiology.

    • Quantitative: myocardial to contralateral lung ratio of uptake at 1 hour

    Reproduced/Adapted/or Referenced with permission from ASNC. © 2019 American Society of Nuclear Cardiology.

    • Interpretation is based on results from the semiquantitative or the quantification approach
      • A ratio >1.5 or visual score of 2 or 3 is considered strongly suggestive of ATTR
      • A ratio <1 or visual score of 0 is considered not suggestive of ATTR
      • A ratio of 1-1.5 and a visual score of 1 is considered equivocal

    Making a Reliable Diagnosis

    A recent key study suggests that a reliable diagnosis of ATTR-CM can be made with nuclear scintigraphy when the following criteria are met1:

    • The patient has heart failure with evidence of cardiac amyloidosis via echocardiography or CMR
    • AL cardiac amyloidosis has been ruled out via blood and urine tests
    • Nuclear scintigraphy results fall within the parameters of the grading system (ie, grade 2 or 3)

    Histological confirmation and typing should be pursued in cases of suspected cardiac amyloidosis when the above criteria are not satisfied.1

    If a patient is positive for ATTR-CM with nuclear scintigraphy, genotyping is recommended to determine if it’s wtATTR or hATTR.1†

    *Please consult individual labeling for risks.
    Also known as variant ATTR.6




    This proposed algorithm is based on using the visual grading system with nuclear scintigraphy1:

    Flow chart for the diagnosis of cardiac amyloidosis. aserum-free light chain assay, serum/urine immunofixation. bPerugini grade 1 or 2 with or w/o positive AL amyloidosis screening, grade 3 with positive AL amyloidosis screening. HFpEF heart failure with preserved ejection fraction, AF atrial fibrillation, SVT supraventricular tachycardia, LVH left ventricular hypertrophy, HCM hypertrophic cardiomyopathy, AS aortic stenosis, ECG electrocardiogram, CMR cardiac magnetic resonance, AL amyloid light chain, ATTR amyloid transthyretin, EMB endomyocardial biopsy, IHC immunohistochemistry, MS mass spectrometry, AA amyloid serum A protein, AApoA1 amyloid apolipoprotein A1, MGUS monoclonal gammopathy of unknown significance, TTR transthyretin

    Reproduced from Oerlemans MIFJ, Rutten KHG, Minnema MC, Raymakers RAP, Asselbergs FW, de Jonge N. Cardiac amyloidosis: the need for early diagnosis. Neth Heart J. 2019;27(11):525-536. doi: 10.1007/s12471-019-1299-1, under Creative Commons Attribution 4.0 International License (

    Back to top



    1. Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-2412.
    2. Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS. Transthyretin cardiac amyloidosis in older Americans. J Card Fail. 2016;22(12):996-1003.
    3. Narotsky DL, Castaño A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10.
    4. 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.
    5. American Society of Nuclear Cardiology (ASNC). ASNC practice points: 99mTechnetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. Available at: ASNC Amyloid Practice Points WEB(2).pdf. © 2019 American Society of Nuclear Cardiology.
    6. Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid. 2018;25(4):215-219.

    PP-RDP-IRL-0111 Date of Preparation February 2021