How To Detect

Detect Transthyretin Amyloid Cardiomyopathy (ATTR-CM)


Discover the tools to diagnose ATTR-CM

See how nuclear scintigraphy, endomyocardial biopsy (EMB), and genetic testing can support or inform an ATTR-CM diagnosis

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

NonInvasive Nuclear Scintigraphy

  • A noninvasive, widely available diagnostic tool with high sensitivity and specificity for ATTR-CM1,3
  • Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches4
  • SPECT imaging is necessary for studies that show planar myocardial uptake because it can help differentiate myocardial uptake from blood pool or overlying bone uptake4

Learn about visual grades in nuclear scintigraphy

  • Uses 99mtechnetium-pyrophosphate (99mTc-PYP), a radioactive tracer utilized as an adjunct in the diagnosis of ATTR-CM, though not FDA approved for that use*
  • A multicenter international study of scintigraphy at amyloid centers of excellence demonstrated 100% specificity for ATTR-CM using visual grade 2 or 3 with concurrent testing to rule out AL1†‡
  • American Society of Nuclear Cardiology (ASNC) Practice Points§ highlight the importance of PYP cardiac imaging in diagnosing ATTR-CM noninvasively and thereby guide patient management5
  • If clinical suspicion remains high for cardiac amyloidosis in spite of a negative or inconclusive 99mTc-PYP scan, biopsy should be considered5

Invasive Endomyocardial Biopsy

  • Histology with positive Congo red staining with apple-green birefringence1,6
  • Additional tests to determine amyloid type are recommended following diagnosis of cardiac amyloidosis1
  • Risk of complications and the need for specialized centers and expertise may contribute to a diagnostic delay1,6

Genetic Testing

  • Used to determine if the disease is hereditary due to a mutation in the TTR gene7
  • Genetic counseling and gene sequencing are recommended following confirmation of ATTR-CM7
  • Learn more about hATTR-CM and genetic testing

PYP, pyrophosphate; SPECT, single-photon emmision computed tomography. *Please consult individual labeling for risks. Multicenter study conducted to determine the diagnostic value of bone scintigraphy in ATTR-CM patients. Of 1217 evaluable patients, 374 underwent EMB, and 843 were diagnosed with presence and type or absence of amyloid on basis of extracardiac histology combined with echocardiography with or without cardiac magnetic resonance imaging (CMR). Rule out AL: testing for presence of monoclonal protein via serum and urine immunofixation + serum free light chain assay. §The Practice Points have been developed by ASNC; Pfizer is not responsible for the content.

Making an ATTR-CM Diagnosis

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.

 

 

HOW NUCLEAR SCINTIGRAPHY IS USED TO DIAGNOSE ATTR-CM

Diagnosing ATTR-CM with nuclear scintigraphy requires quantifying uptake of the radioactive tracer 99mTc-PYP in the heart. Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches.4,5

  • SPECT imaging is necessary for studies that show planar myocardial uptake because it can help differentiate myocardial uptake from blood pool or overlying bone uptake
  • 99mTc-PYP is utilized as an adjunct in the diagnosis of ATTR-CM, though not FDA approved for that use*
  • More information on the use of PYP nuclear scintigraphy to diagnose ATTR-CM: ASNC has a downloadable Practice Points article that discusses critical points for using nuclear scintigraphy to diagnose ATTR-CM

Quantifying Myocardial PYP Uptake5

  • In clinical practice, both a semiquantitative visual scoring and quantitative approach are applied:
  • Semiquantitative: visual comparison to bone (rib) uptake at 3 hours
    • Cardiac uptake of 99mTc-PYP 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

PYP

PYP

Adapted with permission from Wolters Kluwer Health, Inc.: ASNC Practice Points. American Society of Nuclear Cardiology; 2019. https://www.asnc.org/files/19110%20ASNC%20Amyloid%20Practice%20Points%20WEB(2).pdf.

  • Quantitative: myocardial to contralateral lung ratio (referred to as heart-to-contralateral lung ratio [H/CL]) of uptake at 1 hour

PYP

PYP

Adapted with permission from Wolters Kluwer Health, Inc.: ASNC Practice Points. American Society of Nuclear Cardiology; 2019. https://www.asnc.org/files/19110%20ASNC%20Amyloid%20Practice%20Points%20WEB(2).pdf.

  • Interpretation is based on results from the semiquantitative or the quantitative approach. Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches4,5
    • 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 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 satisfied1
  • If a patient is positive for ATTR-CM with nuclear scintigraphy, genotyping is recommended to determine if it’s wtATTR or hATTR1‡

*Please consult individual labeling for risks.
The Practice Points have been developed by ASNC; Pfizer is not responsible for the content.
Also known as variant ATTR.8

A diagnostic algorithm

For patients with suspected Attr-cm2

Below is an algorithm that was proposed to aid in determining the appropriate diagnostic tool for detecting suspected ATTR-CM

Dignostic Algorithm

Image removed.

Reprinted from J Card Fail, 22/12, Brunjes DL, Castano A, Clemons A, Rubin J, Maurer MS, Transthyretin cardiac amyloidosis in older Americans, 996-1003, 2016, with permission from Elsevier.

IFE, immunofixation; SPEP, serum protein electrophoresis; UPEP, urine protein electrophoresis.

*If clinical suspicion remains high for cardiac amyloidosis in spite of a negative 99mTc-PYP scan, biopsy may be considered to evaluate for other types of infiltrative cardiomyopathy (eg, amyloid A).

Also known as variant ATTR.8

Download diagnostic
algorithm

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