ABS0538 DETECTING EARLY CARDIOMYOPATHY IN TRANSTHYRETIN VARIANT CARRIERS: REAPPRAISING THE DIAGNOSTIC VALUE OF PERUGINI GRADE 1 RADIOTRACER UPTAKE ON BONE SCINTIGRAPHY

Background: Individuals carrying a pathogenic transthyretin gene variant ( TTRv ) are at high risk for developing hereditary ATTR (ATTRv) amyloidosis, a progressive protein misfolding disease. Screening for cardiomyopathy (ATTRv-CM) is crucial for early detection of subclinical cardiac amyloidosis and prompt treatment initiation. Perugini grade 2 or 3 cardiac radiotracer uptake on bone scintigraphy is considered diagnostic for ATTR-CM, provided cardiac light chain amyloidosis is ruled out. In the case of Perugini grade 1 cardiac radiotracer uptake, additional criteria must be met. However, in a population with a high a priori risk of developing ATTRv amyloidosis, namely TTRv carriers, Perugini grade 1 cardiac radiotracer uptake alone might be diagnostic for ATTRv-CM. Objectives: To evaluate whether TTRv carriers with Perugini grade 1 cardiac radiotracer uptake on bone scintigraphy exhibit or develop additional signs of ATTR-CM and to determine if Perugini grade 1 could be considered diagnostic of early-stage ATTR-CM in TTRv carriers. Methods: A retrospective observational study was conducted among TTRv carriers screened at the Groningen Amyloidosis Centre of Expertise between 2012 and 2023. For carriers with Perugini grade 1 cardiac radiotracer uptake, single-photon emission computed tomography (SPECT/CT) scans were reviewed to confirm myocardial involvement. Clinical data, including biomarkers, imaging, and biopsy results, were collected from the time of the bone scintigraphy until most recent screening assessments. These data were used to determine whether individuals fulfilled the European Society of Cardiology (ESC) diagnostic criteria for ATTR-CM at baseline and during follow-up. Additionally, carriers who did not meet the ESC diagnostic criteria were evaluated for signs indicative of ATTR-CM. Results: Of 178 TTRv carriers, 12 (7%) exhibited Perugini grade 1 cardiac radiotracer uptake (Figure 1). At baseline, 2 out of 12 individuals met the ESC diagnostic criteria for ATTR-CM based on extracardiac biopsy and echocardiography criteria. Three others were classified as having probable ATTR-CM of which 1 carrier met the ESC diagnostic criteria after a follow-up of 3.5 years. The other 2 carriers showed worsening of cardiac parameters over follow-up periods of 4 and 12 years. Of the remaining 7 individuals, 3 carriers progressed to Perugini grade 2 over follow-up periods of 2, 2 and 4 years, confirming ATTR-CM. Of the last 4 individuals, 1 TTRv carrier developed increased wall thickness on echocardiography and a positive fat tissue aspirate 11 years after the baseline scan and was classified as having probable ATTR-CM. The other 3 TTRv carriers showed signs of cardiomyopathy, including abnormal gadolinium kinetics on cardiac magnetic resonance imaging, reduced global longitudinal strain and increased interventricular septal thickness on echocardiography during follow-up periods of 4, 11 and 14 years. However, they did not meet the criteria for ATTR-CM or probable ATTR-CM. In 1 of these TTRv carriers, bone scintigraphy results might have been false-positive due concomitant use of hydroxychloroquine. Conclusion: Our findings suggest that Perugini grade 1 tracer uptake is an early marker of ATTRv-CM in TTRv carriers and support its potential as a diagnostic criterion for early-stage ATTR-CM in these high-risk population, enabling timely diagnosis and treatment that may improve patient outcomes. Further investigation, including prospective studies and validation against endomyocardial biopsy, is warranted to refine its role in early detection of ATTRv-CM. REFERENCES: NIL . Figure 1 Flow chart of inclusion . TTRv = transthyretin gene variant; GrACE=Groningen Amyloidosis Centre of Expertise . Acknowledgements: NIL . Disclosure of Interests: Hendrea S.A. Tingen: None declared, Milou Berends: None declared, Alwin Tubben: None declared, Peter van der Meer Novartis, Pharmacosmos, Vifor Pharma, Astra Zeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis, all paid to the institute, European Research Council (ERC CoG 101045236, DISSECT-HF), Riemer H.J.A. Slart Siemens Healthineers and Pfizer, all paid to the institute, Johan Bijzet: None declared, Paul van der Zwaag Pfizer, Alnylam and Novartis, all paid to the institute, Friso Muntinghe: None declared, Ewout Houwerzijl: None declared, Bouke Hazenberg: None declared, Hans L.A. Nienhuis Pfizer, Alnylam and Novartis, all paid to the institute. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.