{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T20:54:40Z","timestamp":1783198480271,"version":"3.54.6"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"13","license":[{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T00:00:00Z","timestamp":1747958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      To determine whether\n                      <jats:italic>TTRv<\/jats:italic>\n                      carriers with Perugini grade 1 cardiac radiotracer uptake on [\n                      <jats:sup>99m<\/jats:sup>\n                      Tc]Tc- hydroxydiphosphonate bone scintigraphy have or develop ATTR-CM.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective observational study was conducted at the Groningen Amyloidosis Centre of Expertise between April 2012 and June 2023.\n                      <jats:italic>TTRv<\/jats:italic>\n                      carriers with Perugini grade 1 uptake on bone scintigraphy were followed until to June 2024. Data on symptoms, biomarkers, imaging, and biopsies were collected. A descriptive analysis was performed to evaluate whether carriers met the diagnostic criteria for ATTR-CM or \u2018probable ATTR-CM\u2019 at baseline and follow-up.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Out of 178\n                      <jats:italic>TTRv<\/jats:italic>\n                      carriers in screening, 12 carriers had Perugini grade 1 cardiac radiotracer uptake on bone scintigraphy. At baseline, 2 carriers met the diagnostic criteria for ATTR-CM and 3 carriers met the criteria for probable ATTR-CM. Of the 7 carriers without (probable) ATTR-CM at baseline, 3 carriers were diagnosed with ATTR-CM during follow-up and 1 carrier developed probable ATTR-CM during follow-up. Three carriers showed signs of cardiomyopathy during follow-up, but did not meet the criteria for (probable) ATTR-CM. One of these cases may have been false-positive due to hydroxychloroquine use.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggest that Perugini grade 1 cardiac radiotracer uptake is an early marker of ATTR-CM in\n                      <jats:italic>TTRv<\/jats:italic>\n                      carriers, potentially enabling earlier diagnosis and intervention.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07328-6","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T19:55:34Z","timestamp":1747943734000},"page":"5000-5005","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Detecting early cardiomyopathy in transthyretin variant carriers: reappraising the diagnostic value of Perugini grade 1 radiotracer uptake on bone scintigraphy"],"prefix":"10.1007","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8572-9428","authenticated-orcid":false,"given":"H. S. A.","family":"Tingen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Berends","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Tubben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"van der Meer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. H. J. A.","family":"Slart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bijzet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. A.","family":"van der Zwaag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Kimmich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Knackstedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. L. H.","family":"Muntinghe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. J.","family":"Houwerzijl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. P. C.","family":"Hazenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. L. A.","family":"Nienhuis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,23]]},"reference":[{"issue":"7","key":"7328_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41582-019-0210-4","volume":"15","author":"D Adams","year":"2019","unstructured":"Adams D, Koike H, Slama M, et al. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol. 2019;15(7):387\u2013404.","journal-title":"Nat Rev Neurol"},{"key":"7328_CR2","doi-asserted-by":"crossref","unstructured":"Elliott P, Drachman BM, Gottlieb SS et al. Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Failure. 2022;15(1):e008193.","DOI":"10.1161\/CIRCHEARTFAILURE.120.008193"},{"issue":"1","key":"7328_CR3","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3109\/13506129.2013.871250","volume":"21","author":"AWJM Glaudemans","year":"2014","unstructured":"Glaudemans AWJM, van Rheenen RWJ, van den Berg MP, et al. Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis. Amyloid. 2014;21(1):35\u201344.","journal-title":"Amyloid"},{"issue":"24","key":"7328_CR4","doi-asserted-by":"publisher","first-page":"2404","DOI":"10.1161\/CIRCULATIONAHA.116.021612","volume":"133","author":"JD Gillmore","year":"2016","unstructured":"Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133(24):2404\u201312.","journal-title":"Circulation"},{"issue":"5","key":"7328_CR5","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1007\/s12350-019-01950-2","volume":"28","author":"F Minutoli","year":"2021","unstructured":"Minutoli F, Di Bella G, Mazzeo A, et al. Serial scanning with 99mTc-3, 3-diphosphono-1, 2-propanodicarboxylic acid (99mTc-DPD) for early detection of cardiac amyloid deposition and prediction of clinical worsening in subjects carrying a transthyretin gene mutation. J Nucl Cardiol. 2021;28(5):1949\u201357.","journal-title":"J Nucl Cardiol"},{"issue":"16","key":"7328_CR6","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1093\/eurheartj\/ehab072","volume":"42","author":"P Garcia-Pavia","year":"2021","unstructured":"Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2021;42(16):1554\u201368.","journal-title":"Eur Heart J"},{"issue":"6","key":"7328_CR7","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.jacc.2005.05.073","volume":"46","author":"E Perugini","year":"2005","unstructured":"Perugini E, Guidalotti PL, Salvi F, et al. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99m Tc-3,3-Diphosphono-1,2-Propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005;46(6):1076\u201384.","journal-title":"J Am Coll Cardiol"},{"issue":"7","key":"7328_CR8","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1093\/eurheartj\/ehs123","volume":"34","author":"C Rapezzi","year":"2013","unstructured":"Rapezzi C, Quarta CC, Obici L, et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J. 2013;34(7):520\u20138.","journal-title":"Eur Heart J"},{"issue":"1","key":"7328_CR9","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.amjcard.2017.09.029","volume":"121","author":"SHC Klaassen","year":"2018","unstructured":"Klaassen SHC, Tromp J, Nienhuis HLA, et al. Frequency of and prognostic significance of cardiac involvement at presentation in hereditary Transthyretin-Derived amyloidosis and the value of N-Terminal Pro-B-Type natriuretic peptide. Am J Cardiol. 2018;121(1):107\u201312.","journal-title":"Am J Cardiol"},{"issue":"24","key":"7328_CR10","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1093\/eurheartj\/ehad139","volume":"44","author":"MU Rauf","year":"2023","unstructured":"Rauf MU, Hawkins PN, Cappelli F, et al. Tc-99m labelled bone scintigraphy in suspected cardiac amyloidosis. Eur Heart J. 2023;44(24):2187\u201398.","journal-title":"Eur Heart J"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-025-07328-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-025-07328-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-025-07328-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T07:31:49Z","timestamp":1762327909000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-025-07328-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,23]]},"references-count":10,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["7328"],"URL":"https:\/\/doi.org\/10.1007\/s00259-025-07328-6","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-6275795\/v1","asserted-by":"object"}]},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,23]]},"assertion":[{"value":"24 March 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the institutional review board of the University Medical Centre Groningen (registration number: 17471).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}},{"value":"HSA Tingen was reimbursed for traveling costs by Pfizer and Alnylam. M Berends was reimbursed for traveling costs by Pfizer and Alnylam. A Tubben has nothing to declare. P van der Meer is supported by grant from the European Research Council (ERC CoG 101045236, DISSECT-HF) and received consultancy fees and\/or grants from Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis, all paid to the institute. RHJA Slart is supported by unrestricted research grants of Siemens Healthineers and Pfizer, all paid to the institute. J Bijzet has nothing to declare C Kimmich was reimbursed for traveling costs by Gilead and Janssen and received consultancy fees from Amgen, AstraZeneca, EUSA Pharma, Gilead, GSK, Incyte, Janssen, Pfizer and Sanofi-Aventis. C Knackstedt has received speaker honoraria from Pfizer and consulting fees from Bayer, Pfizer, Novartis, BMS, and Alnylam, all paid to the institute. PA van der Zwaag received consultancy fees from Pfizer, Alnylam and Novartis, all paid to the institute. FLH Muntinghe has nothing to declare EJ Houwerzijl has nothing to declare. BPC Hazenberg was reimbursed for traveling costs by Pfizer. HLA Nienhuis received consultancy fees from Pfizer, Alnylam and Novartis, all paid to the institute.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}