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

Research output: Contribution to journalArticle

Abstract

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
JournalJACC. Cardiovascular imaging
DOIs
Publication statusE-pub ahead of print - Dec 18 2019

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Prealbumin
Radionuclide Imaging
Bone and Bones
Mutation
Hydroxyl Radical
Technetium Tc 99m Medronate
Amyloidosis, Hereditary, Transthyretin-Related
Technetium
Diphosphonates
Left Ventricular Hypertrophy
Hypertension

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Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis. / Musumeci, Maria Beatrice; Cappelli, Francesco; Russo, Domitilla; Tini, Giacomo; Canepa, Marco; Milandri, Agnese; Bonfiglioli, Rachele; Di Bella, Gianluca; My, Filomena; Luigetti, Marco; Grandis, Marina; Autore, Camillo; Perlini, Stefano; Perfetto, Federico; Rapezzi, Claudio.

In: JACC. Cardiovascular imaging, 18.12.2019.

Research output: Contribution to journalArticle

Musumeci, Maria Beatrice ; Cappelli, Francesco ; Russo, Domitilla ; Tini, Giacomo ; Canepa, Marco ; Milandri, Agnese ; Bonfiglioli, Rachele ; Di Bella, Gianluca ; My, Filomena ; Luigetti, Marco ; Grandis, Marina ; Autore, Camillo ; Perlini, Stefano ; Perfetto, Federico ; Rapezzi, Claudio. / Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis. In: JACC. Cardiovascular imaging. 2019.
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title = "Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis",
abstract = "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.",
author = "Musumeci, {Maria Beatrice} and Francesco Cappelli and Domitilla Russo and Giacomo Tini and Marco Canepa and Agnese Milandri and Rachele Bonfiglioli and {Di Bella}, Gianluca and Filomena My and Marco Luigetti and Marina Grandis and Camillo Autore and Stefano Perlini and Federico Perfetto and Claudio Rapezzi",
note = "Copyright {\circledC} 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "12",
day = "18",
doi = "10.1016/j.jcmg.2019.10.015",
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TY - JOUR

T1 - Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis

AU - Musumeci, Maria Beatrice

AU - Cappelli, Francesco

AU - Russo, Domitilla

AU - Tini, Giacomo

AU - Canepa, Marco

AU - Milandri, Agnese

AU - Bonfiglioli, Rachele

AU - Di Bella, Gianluca

AU - My, Filomena

AU - Luigetti, Marco

AU - Grandis, Marina

AU - Autore, Camillo

AU - Perlini, Stefano

AU - Perfetto, Federico

AU - Rapezzi, Claudio

N1 - Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PY - 2019/12/18

Y1 - 2019/12/18

N2 - 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.

AB - 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.

U2 - 10.1016/j.jcmg.2019.10.015

DO - 10.1016/j.jcmg.2019.10.015

M3 - Article

C2 - 31864976

JO - JACC: Cardiovascular Imaging

JF - JACC: Cardiovascular Imaging

SN - 1936-878X

ER -