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Extracardiac soft tissue uptake, evidenced on early 99mTc-HMDP SPECT/CT, helps typing cardiac amyloidosis and demonstrates high prognostic value

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Abstract

Purpose

Increased cardiac uptake (CU) on early-phase 99mTc-HMDP scintigraphy has demonstrated diagnostic and prognostic values in amyloid transthyretin (ATTR) cardiac amyloidosis (CA). Extracardiac uptake (ECU) has been poorly studied. We assessed the clinical value of ECU, in combination with CU, on 99mTc-HMDP scintigraphy using a novel Methodological Amyloidosis Diagnostic Index (MADI).

Methods

We reviewed all patients referred for suspicion of CA, who underwent 99mTc-HMDP scintigraphy over an 8-year period. ECU, CU, and MADI were determined: MADI0 = neither ECU or CU, MADI1 = ECU alone, MADI2 = CU alone, and MADI3 = ECU + CU.

Results

Of 308 eligible patients, 247 had CA, including 75 ATTRv, 107 ATTRwt, and 65 light-chain (AL), while 61 had another cardiopathy (controls). ECU was observed in 29% of CA and 3% of controls. Most frequent sites of ECU were pleuropulmonary (16% of CA, 3% of controls) followed by the digestive tract and subcutaneous tissues. The liver and spleen ECU was only observed in AL-CA (n = 8). CU was only observed in CA patients (n = 187), of whom 182 had ATTR-CA vs. 5 AL-CA, P < 0.001. MADI0 was only observed in controls (97%) and in AL-CA (60%). MADI1 was mainly observed in AL-CA (positive predictive value, PPV = 91%) while MADI2/3 were more frequent in ATTR-CA (PPV = 97%), P < 0.0001. MADI > 0 vs. MADI0 in AL and MADI3 vs. MADI2 in ATTR were associated with a worse prognosis (P = 0.03 and P = 0.002, respectively).

Conclusions

ECU combined with CU demonstrates high diagnostic and prognostic values in CA patients. MADI seems an easy and reliable score in clinical practice.

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Abbreviations

AP-HP:

Assistance Publique – Hôpitaux de Paris

DHU A-TVB:

Département Hospitalo-Universitaire Ageing-Thorax Vessels Blood

ATTRv:

Amyloid transthyretin, variants

IMRB:

Institut Mondor de Recherche Biomédicale

INSERM:

Institut National de la Santé et de la Recherche Médicale

ATTRwt:

Amyloid transthyretin, wild-type

U-PEC:

Université-Paris Est Créteil

References

  1. Damy T, Kristen AV, Suhr OB, Maurer MS, Plante-Bordeneuve V, Yu CR, et al. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS). Eur Heart J. 2019;5425268. https://doi.org/10.1093/eurheartj/ehz173.

  2. Gertz MA, Benson MD, Dyck PJ, Grogan M, Coelho T, Cruz M, et al. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol. 2015;66:2451–66. https://doi.org/10.1016/j.jacc.2015.09.075.

    Article  CAS  PubMed  Google Scholar 

  3. Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, et al. AL amyloidosis. Orphanet J Rare Dis. 2012;7:54. https://doi.org/10.1186/1750-1172-7-54.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Khoor A, Colby TV. Amyloidosis of the lung. Arch Pathol Lab Med. 2017;141:247–54. https://doi.org/10.5858/arpa.2016-0102-RA.

    Article  PubMed  Google Scholar 

  5. Simpson GT 2nd, Strong MS, Skinner M, Cohen AS. Localized amyloidosis of the head and neck and upper aerodigestive and lower respiratory tracts. Ann Otol Rhinol Laryngol. 1984;93:374–9. https://doi.org/10.1177/000348948409300418.

    Article  PubMed  Google Scholar 

  6. Rowe K, Pankow J, Nehme F, Salyers W. Gastrointestinal amyloidosis: review of the literature. Cureus. 2017;9:e1228. https://doi.org/10.7759/cureus.1228.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Skok P, Knehtl M, Ceranic D, Glumbic I. Splenic rupture in systemic amyloidosis - case presentation and review of the literature. Z Gastroenterol. 2009;47:292–5. https://doi.org/10.1055/s-2008-1027628.

    Article  CAS  PubMed  Google Scholar 

  8. Buck FS, Koss MN. Hepatic amyloidosis: morphologic differences between systemic AL and AA types. Hum Pathol. 1991;22:904–7. https://doi.org/10.1016/0046-8177(91)90180-w.

    Article  CAS  PubMed  Google Scholar 

  9. Perugini E, Guidalotti PL, Salvi F, Cooke RM, Pettinato C, Riva L, et al. Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy. J Am Coll Cardiol. 2005;46:1076–84. https://doi.org/10.1016/j.jacc.2005.05.073.

    Article  PubMed  Google Scholar 

  10. Galat A, Van Der Gucht A, Guellich A, Bodez D, Cottereau AS, Guendouz S, et al. Early phase 99Tc-HMDP scintigraphy for the diagnosis and typing of cardiac amyloidosis. JACC Cardiovasc Imaging. 2017;10:601–3. https://doi.org/10.1016/j.jcmg.2016.05.007.

    Article  PubMed  Google Scholar 

  11. Cappelli F, Gallini C, Costanzo EN, Tutino F, Ciaccio A, Vaggelli L, et al. Lung uptake during 99mTc-hydroxymethylene diphosphonate scintigraphy in patient with TTR cardiac amyloidosis: an underestimated phenomenon. Int J Cardiol. 2018;254:346–50. https://doi.org/10.1016/j.ijcard.2017.10.027.

    Article  PubMed  Google Scholar 

  12. Damy T, Jaccard A, Guellich A, Lavergne D, Galat A, Deux JF, et al. Identification of prognostic markers in transthyretin and AL cardiac amyloidosis. Amyloid. 2016;23:194–202. https://doi.org/10.1080/13506129.2016.1221815.

    Article  CAS  PubMed  Google Scholar 

  13. Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation. 2016;133:2404–12. https://doi.org/10.1161/CIRCULATIONAHA.116.021612.

    Article  CAS  PubMed  Google Scholar 

  14. Kula RW, Engel WK, Line BR. Scanning for soft-tissue amyloid. Lancet. 1977;1:92–3. https://doi.org/10.1016/s0140-6736(77)91102-3.

  15. Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with 123I-labeled serum amyloid P component. N Engl J Med. 1990;323:508–13. https://doi.org/10.1056/NEJM199008233230803.

    Article  CAS  PubMed  Google Scholar 

  16. Abulizi M, Sifaoui I, Wuliya-Gariepy M, Kharoubi M, Israel JM, Emsen B, et al. (18)F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis. J Nucl Cardiol. 2019. https://doi.org/10.1007/s12350-019-01885-8.

  17. Wagner T, Page J, Burniston M, Skillen A, Ross JC, Manwani R, et al. Extracardiac (18)F-florbetapir imaging in patients with systemic amyloidosis: more than hearts and minds. Eur J Nucl Med Mol Imaging. 2018;45:1129–38. https://doi.org/10.1007/s00259-018-3995-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Baratto L, Park SY, Hatami N, Gulaka P, Vasanawala S, Yohannan TK, et al. (18)F-florbetaben whole-body PET/MRI for evaluation of systemic amyloid deposition. EJNMMI Res. 2018;8:66. https://doi.org/10.1186/s13550-018-0425-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kristen AV, Maurer MS, Rapezzi C, Mundayat R, Suhr OB, Damy T. Impact of genotype and phenotype on cardiac biomarkers in patients with transthyretin amyloidosis - report from the Transthyretin Amyloidosis Outcome Survey (THAOS). PLoS One. 2017;12:e0173086.

    Article  Google Scholar 

  20. Dorbala S, Ando Y, Bokhari S, Dispenzieri A, Falk RH, Ferrari VA, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 1 of 2-evidence base and standardized methods of imaging. J Nucl Cardiol. 2019;26:2065–123. https://doi.org/10.1007/s12350-019-01760-6.

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Professor Emmanuel Itti and Thibaud Damy are joint senior authors.

Authors and Affiliations

  1. French Referral Center for Cardiac Amyloidosis, Mondor Network, F-94010, Créteil, France

    Nathan Malka, Mukedaisi Abulizi, Mounira Kharoubi, Silvia Oghina, Arnault Galat, Fabien Le Bras, Anissa Moktefi, Soulef Guendouz, Valérie Molinier-Frenkel, Pascale Fanen, Benoît Funalot, Jean-Pascal Lefaucheur, Paul Blanc-Durand, Jean-François Deux, Vincent Audard, Diane Bodez, Emmanuel Itti & Thibaud Damy

  2. Department of Nuclear Medicine, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Nathan Malka, Mukedaisi Abulizi, Paul Blanc-Durand & Emmanuel Itti

  3. Department of Cardiology, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Mounira Kharoubi, Silvia Oghina, Arnault Galat, Soulef Guendouz, Diane Bodez & Thibaud Damy

  4. INSERM U955 IMRB, Teams 5, 8, 9 and 21, U-PEC, F-94000, Créteil, France

    Mounira Kharoubi, Valérie Molinier-Frenkel, Pascale Fanen, Paul Blanc-Durand, Jean-François Deux, Vincent Audard, Emmanuel Itti & Thibaud Damy

  5. Lymphoid Malignancies Unit, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Fabien Le Bras

  6. Department of Pathology, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Anissa Moktefi

  7. Department of Immunology, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Valérie Molinier-Frenkel

  8. Department of Genetics, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Pascale Fanen & Benoît Funalot

  9. Neurophysiology Unit, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Jean-Pascal Lefaucheur

  10. Department of Radiology, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Jean-François Deux

  11. DHU A-TVB, Henri Mondor Hospital/AP-HP/U-PEC, F-94010, Créteil, France

    Jean-François Deux, Emmanuel Itti & Thibaud Damy

  12. Nephrology and Renal Transplantation, Henri Mondor Hospital/AP-HP, F-94010, Créteil, France

    Vincent Audard

  13. Service de Médecine Nucléaire, Hôpital Henri Mondor, 51 av. du Maréchal de Lattre de Tassigny, 94010, Créteil, FR, France

    Emmanuel Itti

Authors
  1. Nathan Malka
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  2. Mukedaisi Abulizi
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  15. Vincent Audard
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  16. Diane Bodez
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  17. Emmanuel Itti
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  18. Thibaud Damy
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Corresponding author

Correspondence to Emmanuel Itti.

Ethics declarations

Conflict of interest

Dr. Abulizi received a travel grant from GE Healthcare. Dr. Oghina received research grants from Pfizer. Dr. Funalot received honoraria and travel grants from Alnylam, Sanofi-Genzyme, and Pfizer. Dr. Bodez received honoraria from Alnylam and travel grants from Pfizer, Servier, and Novartis. Dr. Damy received research grants, financial grants (honoraria and speaking), and travel grants from Alnylam, GSK, AKCEA-Ionis, Pfizer, and Prothena. All other authors declare that they have no conflicts of interest.

Ethical approval

The study was conducted in accordance with the Helsinki declarations. All patients signed an informed written consent form. The study protocol was approved by our local ethics committee (CPP Ile-de-France IX, Créteil) and by the National Computer and Freedom Committee (CNIL - number 1431858). The data collection was approved by the Direction Régionale de la Recherche Clinique Ile-de-France (DC 2009-930).

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Malka, N., Abulizi, M., Kharoubi, M. et al. Extracardiac soft tissue uptake, evidenced on early 99mTc-HMDP SPECT/CT, helps typing cardiac amyloidosis and demonstrates high prognostic value. Eur J Nucl Med Mol Imaging 47, 2396–2406 (2020). https://doi.org/10.1007/s00259-020-04753-7

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