Diagnostic Accuracy of Bisphosphonate Scintigraphy in Glu54GlnATTR Cardiomyopathy

Background: Bisphosphonate scintigraphy (BS) is a recognized tool for diagnosing amyloid transthyretin cardiomyopathy (ATTR-CA). However, its sensitivity for rare transthyretin (TTR) variants, like Glu54Gln, remains underexplored. Methods: This was a retrospective descriptive study including all known patients with the Glu54Gln variant diagnosed between 2017 and 2023 in Romania, aiming to evaluate the diagnostic performance of BS in Glu54Gln ATTR-CA. Results: All symptomatic patients (n = 22) with histologically confirmed ATTR-CA had positive BS results (100% sensitivity). No false negatives were observed in asymptomatic carriers (n = 4). The Perugini visual score correlated with disease severity, with grade 3 scores associated with advanced cardiac involvement. We proposed a new parameter, heart-to-liver-uptake (H/L) ratio, which proved a strong positive correlation with both the heart-to-contralateral-uptake (H/CL) ratio (R² = 0.768, p < 0.001) and interventricular septum thickness (R² = 0.584, p < 0.001) and a weak correlation with the global longitudinal strain (R² = 0.212, p = 0.023). Conclusions: BS demonstrates high diagnostic accuracy for Glu54GlnATTR-CA, underscoring its utility in early diagnosis and clinical management. The H/L ratio presents a novel approach to semiquantitative analysis of bisphosphonate uptake in cardiac amyloidosis, potentially addressing key limitations of the traditional H/CL ratio.