EVIDENCE FOR NUCLEAR SCINTIGRAPHY

When ATTR-CM is suspected, diagnosis can be made noninvasively with nuclear scintigraphy and testing to rule out AL amyloidosis^1,2

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 2: Semiquantitative Grading

Visual comparison to bone (rib) uptake at 1 or 3 hours

Grade 0

Grade 1

Grade 2

Grade 3

No myocardial uptake and normal rib uptake

Myocardial uptake less than rib uptake

Myocardial uptake equal to rib uptake

Myocardial 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

Positive uptake

H/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

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

Apple-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 delay^1,4

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

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.