Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis
Muhammad U. Rauf, Philip N. Hawkins, Francesco Cappelli, Federico Perfetto, Mattia Zampieri, Alessia Argirò, Aviva Petrie, Steven Law, Aldostefano Porcari, Yousuf Razvi, Joshua Bomsztyk, Sriram Ravichandran, Adam Ioannou, Rishi Patel, Neasa Starr, David F. Hutt, Shameem Mahmood, Brendan Wisniowski, Ana Martinez–Naharro, Lucia Venneri, Carol Whelan, Dorota Roczenio, Janet A. Gilbertson, Helen J. Lachmann, Ashutosh Wechalekar, Claudio Rapezzi, Matteo Serenelli, Paolo Massa, Angelo Giuseppe Caponetti, Alberto Ponziani, Antonella Accietto, Alessandro Giovannetti, Giulia Saturi, Maurizio Sguazzotti, Christian Gagliardi, Elena Biagini, Simone Longhi, Marianna Fontana, Julian D. Gillmore
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.