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

JACC Cardiovasc Imaging. 2020 Jun;13(6):1314-1321. doi: 10.1016/j.jcmg.2019.10.015. Epub 2019 Dec 18.

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.

Keywords: Phe64Leu mutation; bone scintigraphy; cardiac amyloidosis.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Amyloid Neuropathies, Familial / diagnostic imaging*
  • Amyloid Neuropathies, Familial / genetics
  • Bone and Bones / diagnostic imaging*
  • Cardiomyopathies / diagnostic imaging*
  • Cardiomyopathies / genetics
  • Diphosphonates / administration & dosage*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Italy
  • Male
  • Middle Aged
  • Mutation*
  • Prealbumin / genetics*
  • Predictive Value of Tests
  • Radionuclide Imaging*
  • Radiopharmaceuticals / administration & dosage*
  • Reproducibility of Results
  • Retrospective Studies
  • Technetium Compounds / administration & dosage*
  • Technetium Tc 99m Medronate / administration & dosage
  • Technetium Tc 99m Medronate / analogs & derivatives*
  • Whole Body Imaging*

Substances

  • Diphosphonates
  • Prealbumin
  • Radiopharmaceuticals
  • TTR protein, human
  • Technetium Compounds
  • technetium Tc 99m hydroxymethylene diphosphonate
  • technetium Tc 99m diphosphonate
  • Technetium Tc 99m Medronate

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related