DIAGNOSING ATTR‑CM1,2

Establish a
diagnosis in 3 steps*:

1
Rule out AL amyloidosis with simple monoclonal light-chain assays
2
Detect amyloid deposition in myocardial tissue with nuclear scintigraphy (eg, 99mTc‑PYP) or cardiac biopsy
3
Once ATTR-CM is confirmed, use genetic testing to determine if it is hereditary

Follow the diagnostic algorithm for ATTR-CM

A chart showing a diagnostic algorithm for ATTR amyloidosis A chart showing a diagnostic algorithm for ATTR amyloidosis
Diagnosis is based on the independent medical judgment of the healthcare professional.
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Imaging and other assessments can be used to confirm an ATTR-CM diagnosis

Once AL amyloidosis is ruled out with simple monoclonal light-chain assays, nuclear scintigraphy, tissue biopsy, and genetic testing can be used to confirm and identify the type of ATTR.

Nuclear scintigraphy3

Planar imaging: 99mTc-PYP planar scan in a patient with wtATTR-CM: Grade 3 cardiac uptake, H/CL ratio 1.8 at 3 hours
SPECT: SPECT confirmation of myocardial uptake in the same patient
  • Scintigraphy is a noninvasive diagnostic that identifies amyloid buildup in the heart using radioactive tracers that bind to amyloid deposits4-6
  • Radiotracers like 99mTc-PYP, 99mTc-DPD, and 99mTc-HMDP all have use within ATTR7
  • SPECT or SPECT/CT imaging, in addition to planar imaging, is recommended for confirmation that uptake is in the myocardium, and not a result of blood pool radiotracer uptake8
  • Scintigraphy with Grade 2/3 uptake confirms an ATTR-CM diagnosis. If the scintigraphy returns a score of Grade 0/1, but high suspicion of ATTR-CM remains, a tissue biopsy should be performed4

TISSUE BIOPSY2,9-11

  • Biopsy of cardiac tissue with Congo red staining can detect TTR amyloid deposition
  • Tissue biopsy is used when bone scintigraphy is negative despite a high clinical suspicion of ATTR-CM or if scintigraphy is unavailable

GENETIC TESTING1,2,12

  • Genetic testing is a noninvasive process to detect TTR variants that will distinguish hATTR from wtATTR
  • Alnylam Act®—Genetic Testing and Counseling Program
  • Alnylam Act® offers third-party genetic screening and counseling programs for patients who may have hATTR amyloidosis at no charge to patients, physicians, and payers.
  • Alnylam Act® is available for patients 18 years and older who may be at risk for carrying a genetic variant known to be associated with hATTR amyloidosis.
  • The Alnylam Act® program was created to provide access to genetic testing and counseling to patients as a way to help people make more informed decisions about their health.
  • While Alnylam provides financial support for this program, tests and services are performed by independent third parties. Healthcare professionals must confirm that patients meet certain criteria to use the program
  • Alnylam receives de-identified patient data from this program, but at no time does Alnylam receive patient-identifiable information. Alnylam uses healthcare professional contact information for research and commercial purposes
  • Genetic testing is available in the US and Canada. Genetic counseling is only available in the US
  • Healthcare professionals or patients who use this program have no obligation to recommend, purchase, order, prescribe, promote, administer, use, or support any Alnylam product
  • No patients, healthcare professionals, or payers, including government payers, are billed for this program
Order a genetic test for hATTR
NEXT Treating ATTR

Not a comprehensive list of all diagnostic tools.

*Refer to American Heart Association diagnosis guidelines on amyloidosis and heart failure for further details.

†Based on signs, symptoms, and initial findings consistent with ATTR amyloidosis.

‡The 2023 American College of Cardiology Expert Consensus recommends serum and urine immunofixation electrophoresis and serum free light chain assay to exclude AL amyloidosis in the initial diagnostic workup.2

§Consider biopsy if scan is negative/equivocal but clinical suspicion is high.

Grade 0: no cardiac and normal rib uptake; Grade 1: cardiac<rib uptake; Grade 2: cardiac=rib uptake; Grade 3: cardiac>rib uptake with mild/absent rib uptake.1

**Sensitivity of a non-endomyocardial biopsy varies by site; negative fat-pad biopsy is not sufficient to exclude ATTR amyloidosis.

99mTc-DPD=technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid; 99mTc-HMDP=technetium-99m-hydroxymethylene diphosphonate; 99mTc-PYP=technetium-99m-pyrophosphate; AL=amyloid light chain; ATTR=transthyretin-mediated amyloidosis; ATTR‑CM=cardiomyopathy of transthyretin-mediated amyloidosis; CT=computed tomography; hATTR=hereditary transthyretin-mediated amyloidosis; H/CL=heart-to-contralateral lung; SPECT=single-photon emission computed tomography; TTR=transthyretin; wtATTR=wild-type transthyretin-mediated amyloidosis.

References:

  1. Kittleson MM, et al. Circulation. 2020;142(1):e7-e22.
  2. Kittleson MM, et al. J Am Coll Cardiol. 2023;81(11):1076-1126.
  3. Hanna M, et al. J Am Coll Cardiol. 2020;75(22):2851-2862.
  4. Gillmore JD, et al. Circulation. 2016;133(24):2404-2412.
  5. Ruberg FL, et al. Circulation. 2012;126(10):1286-1300.
  6. Dharmarajan K, et al. J Am Geriatr Soc. 2012;60(4):765-774.
  7. Gertz MA, et al. J Am Coll Cardiol. 2015;66(21):2451-2466.
  8. Dorbala S, et al. Circ Cardiovasc Imaging. 2021;14(7):e000029.
  9. Maurer MS, et al. Circ Heart Fail. 2019;12(9):e006075.
  10. Witteles RM, et al. JACC Heart Fail. 2019 Aug;7(8):709-716.
  11. Gonzalez-Lopez E, et al. J Am Coll Cardiol. 2024;83(11):1085-1099.
  12. Ando Y, et al. Orphanet J Rare Dis. 2013;8:31.