Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis

Maria Beatrice Musumeci, Francesco Cappelli, Domitilla Russo, Giacomo Tini, Marco Canepa, Agnese Milandri, Rachele Bonfiglioli, Gianluca Di Bella, Filomena My, Marco Luigetti, Marina Grandis, Camillo Autore, Stefano Perlini, Federico Perfetto, Claudio Rapezzi

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Objectives: The aim of this study was to assess the diagnostic accuracy of bone scintigraphy in a large multicenter cohort of patients with cardiac amyloidotic involvement and Phe64Leu transthyretin (TTR) mutation. Background: Diagnostic accuracy of bone scintigraphy for transthyretin-related cardiac amyloidosis (TTR-CA) is considered extremely high, enabling this technique to be the noninvasive diagnostic standard for TTR-CA. Nevertheless, this approach has not been systematically validated across the entire spectrum of TTR mutations. Methods: A total of 55 patients with Phe64Leu TTR mutation were retrospectively analyzed and evaluated between 1993 and 2018 at 7 specialized Italian tertiary centers. Cardiac involvement was defined as presence of an end-diastolic interventricular septum thickness ≥12 mm, without other possible causes of left ventricular hypertrophy (i.e., arterial hypertension or valvulopathies). A technetium-99m (99mTc)–diphosphonate (DPD) or 99mTc–hydroxyl-methylene-diphosphonate (HMDP) bone scintigraphy was reviewed, and visual scoring was evaluated according to Perugini's method. Results: Among 26 patients with definite cardiac involvement, 19 underwent 99mTc-DPD or 99mTc-HMDP bone scintigraphy. Of them, 17 (89.5%) patients had low or absent myocardial bone tracer uptake, whereas only 2 (10.5%) showed high-grade myocardial uptake. The sensitivity and the accuracy of bone scintigraphy in detecting TTR-CA were 10.5% and 37%, respectively. Patients with cardiac involvement and low or absent bone tracer uptake were similar to those with high-grade myocardial uptake in terms of age, sex, and electrocardiographic and echocardiographic findings. Conclusions: The sensitivity of bone scintigraphy (DPD and HMDP) in detecting TTR-CA is extremely low in patients with Phe64Leu TTR mutation, suggesting the need to assess diagnostic accuracy of bone scintigraphy to identify cardiac involvement across a wider spectrum of TTR mutations.
Original languageEnglish
Pages (from-to)1314-1321
Number of pages8
Publication statusPublished - 2020


  • Phe64Leu mutation
  • bone scintigraphy
  • cardiac amyloidosis


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