How To Detect

Detect Transthyretin Amyloid Cardiomyopathy (ATTR-CM)


Discover the tools to diagnose ATTR-CM

See how nuclear scintigraphy, EMB, and genetic testing can support an early ATTR-CM diagnosis

Evidence

Diagnosing

Histology

Testing

DISCOVER A PATH TO DIAGNOSIS

EVIDENCE FOR NUCLEAR SCINTIGRAPHY

When ATTR-CM is suspected, diagnosis can be made noninvasively with nuclear scintigraphy and testing to rule out AL amyloidosis1,2

Nuclear scintigraphy with 99mTc-PYP* provides a unique myocardial uptake pattern in amyloid3

  • Studies comparing 99mTc-PYP scintigraphy with EMB found that bone radiotracers have avidity for ATTR deposits, whereas avidity for AL cardiac amyloid deposits is minimal or absent3
  • Nuclear scintigraphy may identify ATTR deposits early in the course of disease3
  • The mechanism for the differential uptake in ATTR vs AL cardiac amyloidosis is unknown, but it has been suggested that the preferential uptake by ATTR may be the result of higher calcium content3

Sensitivity and specificity of nuclear scintigraphy for ATTR-CM

  • 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

NUCLEAR SCINTIGRAPHY USING BOTH PLANAR AND SPECT IS A NONINVASIVE, READILY AVAILABLE DIAGNOSTIC TOOL WITH HIGH SENSITIVITY AND SPECIFICITY FOR ATTR-CM WHEN COMBINED WITH TESTING TO RULE OUT AL AMYLOIDOSIS.1,2

*99mTc-PYP is not FDA approved for the diagnosis of ATTR-CM. Please consult individual labeling for risks.

MULTISOCIETAL EXPERT CONSENSUS RECOMMENDATIONS FOR DIAGNOSING ATTR-CM WITH NUCLEAR SCINTIGRAPHY3*

DIAGNOSING ATTR-CM WITH 99mTc-PYP IMAGING

IMAGING

The role of 99mTc-PYP imaging in the diagnosis of ATTR-CM3

  • 99mTc-PYP has avidity for cardiac amyloid deposits3
  • The recommended time between injection of 99mTc-PYP and scan is 2 or 3 hours3
  • Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches irrespective of the timing of acquisition3

INTERPRETATION

3-step interpretation of 99mTc-PYP images to diagnose ATTR-CM3

Step 1: Visual Interpretation

  • Visual interpretation should include an evaluation of planar and SPECT images to confirm diffuse radiotracer uptake in the myocardium3
  • SPECT imaging can be used to differentiate myocardial radiotracer uptake from residual blood pool activity, focal myocardial infarct, and overlapping bone (eg, from rib hot spots from fractures). Recommend repeating SPECT at 3 hours if excess blood pooling is noted at 1 hour3
  • If myocardial tracer uptake is visually present on SPECT, proceed to step 2, semiquantitative grading3

Step 2: Semiquantitative Grading

Visual comparison to bone (rib) uptake at 1 or 3 hours
planer grade 0Grade 0
Planer grade 1Grade 1
Planer grade 2Grade 2
Planer grade 3Grade 3
Spect garde 0No myocardial uptake and normal rib uptake
Spect grade 1Myocardial uptake less than rib uptake
Spect grade 2Myocardial uptake equal to rib uptake
Spect grade 3Myocardial uptake greater than rib uptake with mild/absent rib uptake
Illustrative representation.
WHEN CARDIAC AMYLOIDOSIS IS SUSPECTED, GRADE 2 OR 3 MYOCARDIAL UPTAKE (PLANAR AND SPECT), WITH CONCURRENT TESTING TO RULE OUT AL, IS DIAGNOSTIC OF ATTR-CM.5,†

Step 3: Quantitative Grading (when applicable)

Heart-to-contralateral lung (H/CL) ratio (validated for 99mTc-PYP)3,6
planer grade 3Positive uptake
cts per pixelH/CL = 1.86
Illustrative representation.
  • Diagnosis of ATTR-CM cannot be made solely based on H/CL ratio alone with 99mTc-PYP
  • If visual grade is 2 or 3, diagnosis is confirmed and H/CL ratio assessment is not necessary
  • H/CL ratio is not recommended if there is absence of myocardial uptake on SPECT
  • H/CL ratio is typically concordant with visual grade
H/CL ratios of ≥1.5 at 1 hour can accurately identify ATTR-CM if myocardial 99mTc-PYP uptake is visually confirmed on SPECT and systemic AL amyloidosis is excluded. An H/CL ratio of >1.3 at 3 hours can identify ATTR-CM.

 

*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 of Echocardiography, European Association of Nuclear Medicine, Heart Failure Society of America, International Society of Amyloidosis, Society of 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 assay.1

EMB—AN INVASIVE APPROACH TO DIAGNOSE ATTR-CM

Congo red staining of myocardial tissue on light microscopy and apple-green birefringence on polarized light microscopy images

transthyretin biopsyCongo red positive for amyloid myocardial biopsy imageImage courtesy of Filiale d’Imagerie Cardiovasculaire.

Transthyretin biopsy polarizedApple-green birefringence myocardial biopsy imageIllustrative representation rendered from image courtesy of Filiale d’Imagerie Cardiovasculaire.

  • To determine amyloid type, immunohistochemistry (IHC) tests and/or mass spectrometry should be performed1
  • Risk of complications and the need for specialized centers and expertise may contribute to a diagnostic delay1,4

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 type5
  • Genetic counseling and gene sequencing are recommended following confirmation of ATTR-CM5

A DIAGNOSTIC APPROACH

FOR PATIENTS WITH SUSPECTED CARDIAC AMYLOIDOSIS THAT INCLUDES TESTING FOR MONOCLONAL PROTEIN FOLLOWED BY SCINTIGRAPHY AND/OR BIOPSY7

 

Dignostic Algorithm

Dignostic Algorithm

Reprinted with permission from Maurer MS, Bokhari S, Damy T, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12:e006075. doi:10.1161/ CIRCHEARTFAILURE.119.006075 © 2019 American Heart Association, Inc. All rights reserved.

  • 99mTc-PYP is a noninvasive radioactive tracer utilized as an adjunct in the diagnosis of ATTR-CM, though not FDA approved for that use
  • Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches3

DOWNLOAD DIAGNOSTIC ALGORITHM

*If fat pad is negative, biopsy of involved organ is required.

Please consult individual labeling for risks.

 

ATTRm, mutant transthyretin amyloidosis; MGUS, monoclonal gammopathy of undetermined significance; MRI, magnetic resonance imaging.

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.

 

 

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