Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonate scintigraphy in TTR mutation carriers

  • Eve Piekarski
  • Renata Chequer
  • Vincent Algalarrondo
  • Ludivine Eliahou
  • Besma Mahida
  • Jonathan Vigne
  • David Adams
  • Michel S. Slama
  • Dominique Le Guludec
  • Francois Rouzet
Original Article



Cardiac involvement in familial transthyretin (TTR) amyloidosis is of major prognostic value, and the development of early-diagnostic tools that could trigger the use of new disease-modifying treatments is crucial. The aim of our study was to compare the respective contributions of 99mTc-diphosphonate scintigraphy (DPD, detecting amyloid deposits) and 123I-MIBG (MIBG, assessing cardiac sympathetic denervation) in patients with genetically proven TTR mutation referred for the assessment of cardiac involvement.


We prospectively studied 75 consecutive patients (classified as symptomatic or asymptomatic carriers), using clinical evaluation, biomarkers (troponin and BNP), echocardiography, and nuclear imaging. Patients were classified as having normal heart-to-mediastinum (HMR) MIBG uptake ratio 4 h after injection (defined by HM4 ≥ 1.85) or abnormal HM4 < 1.85, and positive DPD uptake (grade ≥ 1 of Perugini classification) or negative DPD uptake.


Among 75 patients, 49 (65%) presented with scintigraphic sympathetic cardiac denervation and 29 (39%) with myocardial diphosphonate uptake. When MIBG was normal, DPD was negative except for two patients. Age was an independent predictor of abnormal scintigraphic result of both MIBG and DPD (HR 1.08 and 1.15 respectively), whereas echocardiographic-derived indicators of increased left ventricular filling pressure (E/e’ ratio) was an independent predictor of abnormal MIBG (HR 1.33) and global longitudinal strain of positive DPD (HR 1.45). In asymptomatic patients (n = 31), MIBG was abnormal in 48% (n = 15) among whom 50% had a normal DPD; all those with a normal MIBG (n = 16) had a normal DPD.


In TTR mutation carriers, cardiac sympathetic denervation evidenced by decreased MIBG uptake is detected earlier than amyloid burden evidenced by DPD. These results raise the possibility of a diagnostic role for MIBG scintigraphy at an early stage of cardiac involvement in TTR-mutated carriers, in addition to its well-established prognostic value.


Amyloidosis Transthyretin Cardiac amyloidosis MIBG scintigraphy Diphosphonate scintigraphy 



This study has been supported by the Association Française Contre l’Amylose.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

259_2018_3963_MOESM1_ESM.doc (114 kb)
ESM 1 (DOC 114 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Eve Piekarski
    • 1
  • Renata Chequer
    • 1
  • Vincent Algalarrondo
    • 2
    • 3
  • Ludivine Eliahou
    • 2
    • 3
  • Besma Mahida
    • 1
  • Jonathan Vigne
    • 1
  • David Adams
    • 3
    • 4
  • Michel S. Slama
    • 2
    • 3
  • Dominique Le Guludec
    • 1
  • Francois Rouzet
    • 1
  1. 1.Nuclear Medicine Department, Bichat Claude Bernard Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), DHU FIRE, Inserm UMR-S 1148Paris Diderot UniversityParisFrance
  2. 2.Cardiology Department, Antoine Béclère Hospital, AP-HPParis-Sud UniversityClamartFrance
  3. 3.French Referent Center for Rare Diseases for FAP (Familial Amyloid Polyneuropathy) (CRMR-NNERF)Bicêtre HospitalLe Kremlin-BicêtreFrance
  4. 4.Neurology Department, AP-HPParis-Sud UniversityLe Kremlin-BicêtreFrance

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