Test–retest reproducibility of myocardial 99mTc-HMDP uptake quantification by SPECT-CT in suspected transthyretin cardiac amyloidosis

BACKGROUND: Diagnosing transthyretin-related cardiac amyloidosis (ATTR-CA) relies on excluding plasma cell dyscrasia and performing bone-avid tracer cardiac scintigraphy. However, visual assessment of cardiac uptake has limitations in evaluating amyloid burden. Whole-body single-photon emission computed tomography-computed tomography (SPECT-CT) may overcome these limitations by enabling quantitative assessment, but data on test-retest reproducibility are lacking. OBJECTIVES: This study aimed to evaluate the test-retest, intraobserver and interobserver reproducibility of cardiac amyloid quantification in suspected ATTR-CA using whole-body cadmium zinc telluride SPECT-CT. METHODS: Twenty patients with suspected ATTR-CA underwent repeated planar bone-avid tracer cardiac scintigraphy and thoracic SPECT-CT one week apart (October 2020-December 2022; Clinical Trial: NCT04535349). The Perugini score was assessed using planar acquisition. Cardiac 99mTc-HMDP uptake was quantified on SPECT images with CT-based cardiac contouring and attenuation correction. The evaluated metrics included maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), percentage of injected dose (%ID), and cardiac amyloid activity (CAA). Concordance was evaluated by Lin's concordance correlation coefficient (CCC). Test-retest reproducibility was assessed using the mean absolute difference, coefficient of variation, and intraclass correlation coefficient (ICC). RESULTS: Intraobserver and interobserver reproducibility was excellent for all metrics (CCC ≥.99). Test-retest reproducibility demonstrated substantial agreement for SUVmean (CCC: .79) and almost perfect agreement for SUVmax (CCC: .81), %ID (CCC: .88), and CAA (CCC: .93). All parameters correlated with the Perugini score. Test-retest reliability was high across metrics, with ICC values of .80-.97. CONCLUSIONS: Bone-avid tracer cardiac SPECT-CT shows excellent reproducibility for quantifying cardiac amyloid burden in suspected ATTR-CA, with %ID and CAA being especially reliable for future longitudinal studies. CLINICAL TRIAL REGISTRATION: NCT04535349.