Detecting early cardiomyopathy in transthyretin variant carriers: reappraising the diagnostic value of Perugini grade 1 radiotracer uptake on bone scintigraphy

Purpose: To determine whether TTRv carriers with Perugini grade 1 cardiac radiotracer uptake on [^99mTc]Tc- hydroxydiphosphonate bone scintigraphy have or develop ATTR-CM. Methods: This retrospective observational study was conducted at the Groningen Amyloidosis Centre of Expertise between April 2012 and June 2023. TTRv 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 ‘probable ATTR-CM’ at baseline and follow-up. Results: Out of 178 TTRv 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. Conclusion: Our findings suggest that Perugini grade 1 cardiac radiotracer uptake is an early marker of ATTR-CM in TTRv carriers, potentially enabling earlier diagnosis and intervention.