Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis

Abstract

Aims To perform evaluation of widely embraced bone scintigraphy-based non-biopsy diagnostic criteria (NBDC) for ATTR amyloid cardiomyopathy (ATTR-CM) in clinical practice, and to refine serum free light chain (sFLC) ratio cut-offs that reliably exclude monoclonal gammopathy (MG) in chronic kidney disease. Methods and results A multi-national retrospective study of 3354 patients with suspected or histologically proven cardiac amyloidosis (CA) referred to specialist centres from 2015 to 2021; evaluations included radionuclide bone scintigraphy, serum and urine immunofixation, sFLC assay, eGFR measurement and echocardiography. Seventy-nine percent (1636/2080) of patients with Perugini grade 2 or 3 radionuclide scans fulfilled NBDC for ATTR-CM through absence of a serum or urine monoclonal protein on immunofixation together with a sFLC ratio falling within revised cut-offs incorporating eGFR; 403 of these patients had amyloid on biopsy, all of which were ATTR type, and their survival was comparable to non-biopsied ATTR-CM patients (p = 0.10). Grade 0 radionuclide scans were present in 1091 patients, of whom 284 (26%) had CA, confirmed as AL type (AL-CA) in 276 (97%) and as ATTR-CM in only one case with an extremely rare TTR variant. Among 183 patients with grade 1 radionuclide scans, 122 had MG of whom 106 (87%) had AL-CA; 60/61 (98%) without MG had ATTR-CM. Conclusion The NBDC for ATTR-CM are highly specific [97% (95% CI 0.91-0.99)] in clinical setting, and diagnostic performance was further refined here using new cut-offs for sFLC ratio in patients with CKD. A grade 0 radionuclide scan all but excludes ATTR-CM but occurs in most patients with AL-CA. Grade 1 scans in patients with CA and no MG are strongly suggestive of early ATTR-type, but require urgent histologic corroboration.

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy

“…The key finding of this study is that diffuse RV uptake of bone tracer at SPECT imaging is associated with worse outcomes in ATTR-CM. Although myocardial uptake at planar imaging (measured as Perugini visual score, ratio of heart to contralateral, or ratio of heart to whole body) has established and unequivocal diagnostic value, 27 its prognostic role remains controversial. [13][14][15][16][17][18] Different protocols for image acquisition and characteristics of specific bone tracers 28 may have influenced results from previous studies.…”

Light-chain cardiac amyloidosis for the non-expert: pearls and pitfalls

“…As underlined in the first tragic clinical case report, patients with AL-CA most frequently show no or mild (grade 1) uptake at bone scintigraphy [ 21 ] (Fig. 1 ).…”

Renal AL Amyloidosis: Updates on Diagnosis, Staging, and Management

“…A grade 0 radionuclide scan almost excludes ATTR amyloidosis, and most cases are due to AL cardiac amyloidosis. CKD can affect serum FLC levels, and refining FLC cut-offs in these patients further improves the diagnostic performance of the NBDC algorithm [ 30 ].…”