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Diagnosing ATTR-CM/PN

ATTR-CM is a progressive disease—recognize the tools to support early diagnosis
Nuclear scintigraphy — a noninvasive  approach3-6
  • A noninvasive, widely available diagnostic tool with high sensitivity and specificity for ATTR-CM.
  • Both planar and single-photon emission computed tomography (SPECT) imaging should be reviewed and interpreted using visual and quantitative approaches — 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.
  • Uses a radioactive bone tracer,99mtechnetium-labeled pyrophosphate (99mTc-PYP), 99mtechnetium-labeled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), 99mtechnetium-labeled hydroxymethylene diphosphonate (99mTc-HMDP), for detection of ATTR.*
  • 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.
  • American Society of Nuclear Cardiology (ASNC) Practice Points highlight the importance of PYP cardiac imaging in diagnosing ATTR-CM noninvasively and thereby guide patient management.
  • If clinical suspicion remains high for cardiac amyloidosis in spite of a negative or inconclusive 99mTc-PYP scan, biopsy should be considered.

Endomyocardial biopsy (EMB)7
  • Requires histology with Congo red staining with apple-green birefringence to diagnose cardiac amyloidosis.
  • To determine amyloid type, immunohistochemistry tests and/or mass spectrometry should be performed.
  • Patients may experience diagnostic delay for a number of reasons, including risk of complications and the need for specialized centers and expertise.

 

Diagnosing ATTR-PN
Genetic testing8
  • Genetic counseling and gene sequencing should be considered in order to identify the TTR gene mutation in patients.

Tissue biopsy9,10
  • Biopsy is required for the diagnosis of ATTR-PN, in order to identify amyloid deposits by Congo red staining that demonstrates apple-green birefringence under polarized light.
  • Suitable tissues for biopsy include subcutaneous fatty tissue of the abdominal wall, kidney mucosa, skin mucosa, gastric mucosa, rectal mucosa, rural nerve tissue, retinaculum and peritendinous fat obtained at carpal tunnel surgery, and tissue from the salivary gland.*
  • Multiple biopsies may be necessary to reach diagnosis.

 

Patients are often evaluated for years before ATTR-PN is recognized as the underlying cause of their symptoms.10
Mean time to diagnosis can be up to 4 years after onset of symptoms10,11

 

*Biopsy site sensitivities vary.
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).