This site is intended only for healthcare professionals resident in India




Sign InLog Out
Our medicinesTherapy areasExplore ContentExplore content


Let's connectLet's ConnectPfizer medical information



ATTR-CMATTR-CMATTR-CM HomeAbout ATTR-CMMechanism of DiseaseWild-Type ATTR-CMHereditary ATTR-CMSuspect ATTR-CMDetect ATTR-CMResourcesEventsMaterialsVideos
Detect ATTR-CM

What is nuclear scintigraphy?

Nuclear scintigraphy, using both planar and SPECT imaging, is a non-invasive, commonly available diagnostic tool with high sensitivity and specificity for ATTR-CM when combined with testing to rule out AL amyloidosis.1-3

To facilitate early diagnosis of ATTR-CM, nuclear scintigraphy should be more broadly considered in patients with the following characteristics3:

  • Unexplained increased left ventricular (LV) wall thickness
  • Heart failure with preserved ejection fraction (HFpEF)
  • Familial amyloid polyneuropathy
  • Family history of amyloidosis
  • Low-flow, low-gradient degenerative aortic stenosis in the elderly
  • History of bilateral carpal tunnel syndrome
Evidence for nuclear scintigraphy 
  • Nuclear scintigraphy with 99mTc-PYP/99mTc-DPD/99mTc-HMDP* reveals a unique myocardial uptake pattern of amyloid3
  • Nuclear scintigraphy may detect ATTR deposits early in the course of disease3
  • Studies comparing 99mTc-PYP/99mTc-DPD/99mTc-HMDP* scintigraphy with EMB found that the bone radiotracers have strong avidity for ATTR deposits but little or no avidity for AL cardiac amyloid deposits
  • Experts recommend that SPECT imaging be used in all studies (irrespective of time between injection and scan) to ensure direct visualisation of tracer uptake in the myocardium3​​​​​​
Specificity of nuclear scintigraphy for ATTR-CMA multicentre international study of scintigraphy at amyloidosis centres of excellence demonstrated 100% specificity for ATTR-CM using visual grade 2 or 3, with concurrent testing to rule out AL amyloidosis.1​​​​Important considerations for the acquisition of 99mTc-PYP/99mTc-DPD/99mTc-HMDP* imaging dataFollowing are the multi-societal expert consensus recommendations for diagnosing ATTR-CM with nuclear scintigraphy3,†
  • 99mTc-PYP/99mTc-DPD/99mTc-HMDP* is to be considered for their avidity for cardiac amyloid deposits3
  • The recommended time between injection of 99mTc-PYP/99mTc-DPD/99mTc-HMDP* and scan is 2 to 3 hours3; 1-hour planar-only imaging is not recommended3
  • Both planar and SPECT imaging should be reviewed and interpreted using visual and quantitative approaches, irrespective of the timing of acquisition3
Step 1: Visual interpretation3
  • Evaluate planar and SPECT images to confirm any diffuse radiotracer uptake in the myocardium
  • Differentiate myocardial radiotracer uptake from residual blood pool activity, focal myocardial infarct, and overlapping bone (e.g. from rib hotspots due to fractures) on SPECT images
  • If excess blood pool activity is noted, recommend repeating SPECT imaging at 3 hours

If myocardial tracer uptake is visually present on the SPECT image, then proceed to step 2; Semiquantitative visual grading.

Radiograph showing 99mTc-PYP/99mTc-DPD/99mTc-HMDP* uptake. ​​​​​

Adapted from Dorbala et al. J Nucl Cardiol. 2019.

If no myocardial tracer uptake is present on SPECT, then visual grade is 0

Radiograph showing 99mTc-PYP/99mTc-DPD/99mTc-HMDP* uptake.

Adapted from Dorbala et al. J Nucl Cardiol. 2019.

Step 2: Semiquantitative visual grading
  • Semiquantitative visual grade comparison of myocardial and bone (rib) uptakes at 3 hours3
  • Examination of planar and SPECT images for tracer uptake in the myocardium relative to the ribs and grading using the following scale

Radiograph showing 99mTc-PYP/99mTc-DPD/99mTc-HMDP* uptake.
Adapted from Dorbala et al. J Nucl Cardiol. 2019.

Interpretation of the visual scoring method in relation to the bone (rib) uptake at 3 hours3 is as follows:

  • Strongly suggestive of ATTR-CM: Visual grade of ≥2 on planar and SPECT images with concurrent testing3 to rule out AL
  • Not suggestive or equivocal of ATTR-CM: Visual grade3 <2

When cardiac amyloidosis is suspected, Grade 2 or 3 myocardial uptake with concurrent testing to rule out AL is diagnostic of ATTR-CM.3,‡,§

Step 3: H/CL uptake ratio assessment (when applicable)3  The diagnosis of ATTR-CM cannot be made solely based on the H/CL ratio alone.  The H/CL ratio is not recommended if there is an absence of myocardial uptake on SPECT imaging.

The H/CL ratio is typically concordant with visual grade3:
  • If the visual grade is 2 or 3, then the diagnosis is confirmed, and the H/CL ratio assessment is not necessary
  • If discordant or the visual grade is equivocal, then the H/CL ratio may be helpful to classify equivocal visual grade 1 versus 2 as positive or negative
The H/CL ratio is calculated as the fraction of heart ROI mean counts to contralateral lung ROI mean counts3:
  • An H/CL ratio of ≥1.5 at 1 hour can accurately identify ATTR-CM if myocardial 99mTc-PYP* uptake is visually confirmed on SPECT imaging and systemic AL amyloidosis is excluded
  • An H/CL ratio of ≥1.3 at 3 hours can identify ATTR cardiac amyloidosis

      Quantification of cardiac 99mTc-PYP* uptake using the H/CL ratio4 

Radiograph showing quantification of cardiac 99mTc-PYP* uptake using H/CL ratio.

Review more information about nuclear scintigraphy here.
Download Loading

EMB — an invasive approach to diagnose ATTR-CM 

If the clinical suspicion for cardiac amyloidosis remains high despite a negative or inconclusive scintigraphy scan, then consider EMB.1 

EMB requires histology for diagnosis; positive Congo red staining with apple-green birefringence under polarised light is indicative of ATTR-CM.1,5

Congo red staining of myocardial tissue in light microscopy and apple-green birefringence in polarised light microscopy1

Congo red positive staining for myocardial biopsy tissue
Apple-green birefringence for myocardial biopsy tissue
  • To determine the amyloid type, IHC tests and/or mass spectrometry should be performed1
  • The risk of complications and the need for specialised centres and expertise may contribute to a diagnostic delay1,5

Genetic testing — in the ATTR-CM diagnostic process

  • To determine if the disease is hereditary due to a mutation in the TTR gene or if it is wild type6
  • Genetic counselling and gene sequencing are recommended following the confirmation of ATTR-CM6
The diagnostic flow chart shown below takes you through the first signs of ATTR-CM to diagnosis.7

An approach for patients with suspected cardiac amyloidosis; this approach includes testing for monoclonal protein followed by scintigraphy and/or biopsy.7

Download flow chart Loading
Dr. Detective Series: Detecting ATTR-CM

Meet Dr. Detective, a cardiologist who is specialised in diagnosing tough cases. Watch as he detects ATTR-CM in his patients.

Encountering ATTR-CM

Raising suspicion of ATTR-CM

Detecting ATTR-CM

ATTR-CM Resources > Loading*99mTc-PYP/99mTc-DPD/99mTc-HMDP is not approved for the diagnosis of ATTR-CM [local regulatory agency]. Please consult individual labelling for risks.
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 American College of Cardiology, American Heart Association, American Society for Echocardiography, European Association of Nuclear Medicine, Heart Failure Society of America, International Society of Amyloidosis, Society for Cardiovascular Magnetic Resonance and Society of Nuclear Medicine and Molecular Imaging.
99mTc-PYP/99mTc-DPD/99mTc-HMDP uptake could be seen in other causes of myocardial injury including pericarditis, myocardial infarction (regional uptake) and chemotherapy- or drug-associated myocardial toxicity.3
§Rule out AL: Tests to detect the presence of monoclonal protein using serum and urine IFE and SFLC assay.1

99mTc-DPD, 99mtechnetium-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid; 99mTc-HMDP, 99mtechnetium-labelled hydroxymethylene diphosphonate; 99mTc-PYP, 99mtechnetium-labelled pyrophosphate; AL, amyloid immunoglobulin light chain amyloidosis; AS, aortic stenosis; ATTR, transthyretin amyloidosis; ATTR-CM, transthyretin amyloid cardiomyopathy; CT, computed tomography; EMB, endomyocardial biopsy;  H/CL, heart-to-contralateral lung; HFpEF, heart failure with preserved ejection fraction; hATTR-CM, hereditary ATTR-CM; IFE, immunofixation electrophoresis; IHC, immunohistochemistry; LV, left ventricular; ROI, region of interest; SFLC, serum-free light chain; SPECT, single-photon emission computed tomography; TTR, Transthyretin; wtATTR-CM, wild-type ATTR-CM.
Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404-2412. doi:10.1161/CIRCULATIONAHA.116.021612 Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. 99mTc-Pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidosis. Circ Cardiovasc Imaging. 2013;6(2):195-201. doi:10.1161/CIRCIMAGING.112.000132Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2 – evidence base and standardized methods of imaging [published correction appears in J Nucl Cardiol. 2021 Aug;28(4):1761-1762]. J Nucl Cardiol. 2019;26(6):2065-2123.American Society of Nuclear Cardiology (ASNC). ASNC practice points: 99mTechnetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. ASNC. 2019. Accessed January 31, 2023. DL, Castaño A, Weinsaft JW, Bokhari S, Maurer MS. Wild-type transthyretin cardiac amyloidosis: novel insights from advanced imaging. Can J Cardiol. 2016;32(9):1166.e1-1166.e10. doi:10.1016/j.cjca.2016.05.008Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135(14):1357-1377. doi:10.1161/CIRCULATIONAHA.116.024438 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(9):1-11. doi:10.1161/CIRCHEARTFAILURE.119.006075
ATTR-CM Which imaging modalities help raise the suspicion of ATTR-CM?

Gain a deeper understanding of echo and CMR.

See the tools  Loading
PP-UNP-IND-0084 13 March 2023
PfizerPro AccountPfizerPro Account

To access further materials, resources and receive communication about medicines and vaccines promoted by Pfizer.

Sign in or RegisterSign inRegisterAccountSign Out
These pages are not intended for patients or for members of the general public. The web pages contain promotional content. For the use only of Registered Medical Practitioners or a Hospital or a Laboratory. Full prescribing information available on request. For more details on, Who is a Registered Medical Practitioner, please visit "", Page No. 39, Rule 2 part (ee), last accessed on 26th April2021.
Address: The Capital,  A Wing, 1802, 18th Floor, Plot No. C-70, ‘G’ Block, Bandra Kurla Complex, Bandra East, Mumbai – 400051, India.

Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.


Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.


Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua. Hac habitasse platea dictumst quisque sagittis purus sit amet volutpat. Lectus magna fringilla urna porttitor rhoncus. Venenatis urna cursus eget nunc scelerisque viverra. Id donec ultrices tincidunt arcu non sodales.

Sagittis aliquam malesuada bibendum arcu vitae elementum curabitur. Pellentesque elit ullamcorper dignissim cras tincidunt. Orci ac auctor augue mauris augue neque. Dui vivamus arcu felis bibendum ut tristique et egestas quis. Sed vulputate mi sit amet mauris commodo.

Nunc eget lorem dolor sed viverra ipsum. Sed ullamcorper morbi tincidunt ornare.

Copyright © 2023 Pfizer Limited, India. All rights reserved. Applicable for Pfizer Products, Product Microsites and Therapy Areas section of the website:
  • All content published herein is intended and strictly only for informational, educational, academic and/or research purposes and shall not be utilized to diagnose or treat a health problem or disease without referring to the full prescribing information for list of approved indications as contained in the product package insert
  • While due care and caution has been taken to ensure that the content herein is free from mistakes or omissions, Pfizer makes no claims, promises or guarantees about the accuracy, completeness or adequacy of the information herein
For the use only of Registered medical practitioners* or a Hospital or a Laboratory

These pages are not intended for patients or for members of the general public. The web pages contain promotional content.


If you select 'No', you will be redirected to

For more details on, Who is a Registered medical practitioner*, please visit "", Page No. 39, Rule 2 part (ee), last accessed on 26th April 2021.
Address: The Capital, A Wing, 1802, 18th Floor, Plot No. C-70, 'G' Block, Bandra Kurla Complex, Bandra East, Mumbai - 400051.

PP-DOL-IND-0251 18 JAN 2023
Yes No
You are now leaving PfizerPro website

​​​​​You are now leaving Pfizer Pro website and will be redirected to another website. Note that you will be governed by the Terms & Conditions and Privacy Policy of the external website. Would you like to continue?
PP-DOL-IND-0251 18 JAN 2023