Diagnosing Transthyretin Cardiac Amyloidosis*Screen for ALOrder the following tests1,2†
- Serum kappa/lambda free light chains
- Serum protein electrophoresis with immunofixation
- Urine protein electrophoresis with immunofixation
Order the following tests1†
| |
Serum protein electrophoresis (SPEP) with immunofixation |
Urine protein electrophoresis (UPEP) with immunofixation |
Serum free light chain assay |
| Normal range |
No M-spike present |
No M-spike present |
Kappa:lambda ratio=0.26-1.65‡ |
| |
Normal range |
| Serum protein electrophoresis (SPEP) with immunofixation |
No M-spike present |
| Urine protein electrophoresis (UPEP) with immunofixation |
No M-spike present |
| Serum free light chain assay |
Kappa:lambda ratio=0.26-1.65‡ |
| AL test results3 |
Diagnosis3 |
| Abnormal |
AL possible—refer to a hematology specialist for evaluation |
| Normal |
AL unlikely—refer to cardiac amyloid radionuclide imaging results to determine if ATTR cardiac amyloidosis is possible |
ASNC advises utilization of 99mTc-PYP or 99mTc-HMDP tracers to diagnose ATTR cardiac amyloidosis2||
-
Noninvasive cardiac amyloid radionuclide imaging using 99mTc-PYP or 99mTc-HMDP is highly sensitive and specific for ATTR-CM diagnosis.2,4
- Used as an adjunct to diagnosis after ruling out AL, though not FDA approved for the diagnosis of ATTR cardiac amyloidosis2,4
Acquisition2- The recommended time between injection of 99mTc-PYP or 99mTc-HMDP and scan is 3 hours to maximize specificity¶
If clinical suspicion is high despite a negative or inconclusive scan, a biopsy should be considered.2InterpretationSTEP 1Visual interpretation
-
Evaluate SPECT images to confirm diffuse radiotracer uptake in the myocardium and differentiate from blood or overlying bone uptake5
- SPECT provides a more effective method of radiotracer localization compared to planar images, given the inability to distinguish myocardial uptake from blood pool uptake5
-
If myocardial tracer uptake is visually present on SPECT, proceed to Step 2, semi-quantitative visual grading. If no myocardial tracer uptake is present on SPECT, the visual grade is 02
99mTc-PYP SPECT/CT fusion showing myocardial uptake6#
Illustrative representation.STEP 2Semi-quantitative grading to distinguish AL from ATTR cardiac amyloidosis (1- or 3-hour approach)2¶
Once myocardial tracer activity is confirmed on SPECT, the degree of activity can be characterized using the following scale:
PYP imaging is used as an adjunct to diagnosis after ruling out AL. AL is ruled out by testing for presence of monoclonal protein via serum and urine protein electrophoresis with immunofixation and serum free light chain assay.
STEP 3Heart/contralateral lung (H/CL) uptake ratio assessment (when applicable)2
Circular target regions of interest (ROI) are drawn over the heart on the planar images and are mirrored over the contralateral chest to account for background and ribs.
- An H/CL ratio is calculated as the fraction of heart ROI mean counts to contralateral lung ROI mean counts. If discordant or the visual grade is equivocal, H/CL ratio may be helpful to classify equivocal visual Grade 1 vs Grade 2 as positive or negative
- H/CL ratios of ≥1.5 at 1 hour can accurately identify ATTR cardiac amyloidosis if myocardial tracer 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 cardiac amyloidosis
- NOTE: Diagnosis of ATTR cardiac amyloidosis cannot be made solely based on H/CL ratio alone. H/CL ratio is not recommended if there is absence of myocardial uptake on SPECT
Quantification of cardiac 99mTc-PYP|| uptake using H/CL ratio2**
Adapted from Dorbala 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. Circ Cardiovasc Imaging. 2021;14(7);e000029.Next: See clinical data for VYNDAMAX Continue LoadingYou are now leaving PfizerPro
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it has provided or reviewed. PP-PFE-GBR-3859. November 2021
§Not FDA approved for the diagnosis of ATTR cardiac amyloidosis. Please consult individual labeling for risks.∥99mTc-PYP and 99mTc-HMDP are not FDA approved for the diagnosis of ATTR cardiac amyloidosis. Please consult individual labeling for risks.¶The recommended time between injection of 99mTc-PYP and 99mTc-HMDP scan is 2 or 3 hours. The 1-hour approach is optional; if excess blood pool activity is noted, 3-hour imaging is recommended. 99mTc-HMDP has a shorter clearance half-life than 99mTc-PYP, and earlier imaging at 1 hour may be considered to avoid loss of sensitivity.**Illustrative representation.AL=amyloid light-chain; ASNC=American Society of Nuclear Cardiology; ATTR=transthyretin amyloidosis; CT=computed tomography; HMDP=hydroxymethylene diphosphonate; PYP=pyrophosphate; SPECT=single photon emission computed tomography.
References: Witteles RM, Bokhari S, Damy T, et al. Screening for transthyretin amyloid cardiomyopathy in everyday practice. JACC Heart Fail. 2019;7(8):709-716. Dorbala 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. Circ Cardiovasc Imaging. 2021;14(7):e000029Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145(18):e895-e1032. Miller EJ, Campisi R, Shah NR, et al. Radiopharmaceutical supply disruptions and the use of 99mTc-hydroxymethylene diphosphonate as an alternative to 99mTc-pyrophosphate for the diagnosis of transthyretin cardiac amyloidosis: an ASNC Information Statement. J Nucl Cardiol. 2022;29(5):2748-2760.Hage FG, Bourque J, Pandey S, et al. American Society of Nuclear Cardiology quality metrics for cardiac amyloid radionuclide imaging. J Nucl Cardiol. 2024;40:102041Data on file. Pfizer Inc., New York, NY.