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-CM^1,3
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 AL^1†‡
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 birefringence^1,6

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 delay^1,6

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 emission 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

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

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 approaches^4,5
- 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 hATTR^1‡

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

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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