Advertisement

Can Nuclear Imaging Techniques Predict Patient Outcome and Guide Medical Management in Hereditary Transthyretin Cardiac Amyloidosis?

  • Vincent Algalarrondo
  • Eve Piekarski
  • Ludivine Eliahou
  • Dominique Le Guludec
  • Michel S. Slama
  • François Rouzet
Nuclear Cardiology (V Dilsizian, Section Editor)
  • 154 Downloads
Part of the following topical collections:
  1. Topical Collection on Nuclear Cardiology

Abstract

Purpose of Review

Nuclear imaging recently gained a key role in the diagnosis and prognostic assessment of transthyretin (TTR)-related cardiac amyloidosis. This review aims at summarizing the state-of-the art regarding the implementation of nuclear imaging in the management of hereditary mutated TTR-cardiac amyloidosis (mTTR-CA).

Recent Findings

Although cardiac uptake of bone tracers is acknowledged as a specific marker of TTR amyloid cardiac burden, recent studies validated the implementation of bone scan in the flow chart for non-invasive diagnosis and follow-up of CA in multicenter trials. Simultaneously, cardiac denervation evidenced by MIBG scintigraphy proved to be a strong and independent prognostic marker of poor outcome in mTTR-CA.

Summary

By its unique ability to assess both amyloid burden and cardiac denervation, nuclear imaging may prove useful as part of multimodality imaging tools to trigger treatment initiation and monitoring in patients with mTTR-CA.

Keywords

Cardiac amyloidosis Nuclear imaging Diagnosis Prognosis 

Notes

Acknowledgements

The study has been supported by the Association Française Contre l'Amylose.

Compliance with Ethical Standards

Conflict of Interest

Eve Piekarski and Ludivine Eliahou declare that they have no conflict of interest.

Vincent Algalarrondo reports grants from Medtronic, St. Jude Medical, Sorin, and Boston Scientific.

François Rouzet reports grants from Alnylam and General Electrics.

Dominique Le Guludec reports grants from GE Healthcare, Alnylam, and Advanced Accelerator Application.

Michel S. Slama has received consulting fees from Pfizer, Alnylam, and Eidos, and his department has received a grant from Ionis-GSK.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Rapezzi C, Quarta CC, Obici L, Perfetto F, Longhi S, Salvi F, et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusively cardiac phenotype: an Italian perspective. Eur Heart J. 2013;34:520–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112:2047–60.CrossRefPubMedGoogle Scholar
  3. 3.
    Martinez-Naharro A, Treibel TA, Abdel-Gadir A, Bulluck H, Zumbo G, Knight DS, et al. Magnetic resonance in transthyretin cardiac amyloidosis. J Am Coll Cardiol. 2017;70:466–77.CrossRefPubMedGoogle Scholar
  4. 4.
    González-López E, Gagliardi C, Dominguez F, Quarta CC, de Haro-Del Moral FJ, Milandri A, et al. Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths. Eur Heart J. 2017;38:1895–904.CrossRefPubMedGoogle Scholar
  5. 5.
    Phelan D, Collier P, Thavendiranathan P, Popović ZB, Hanna M, Plana JC, et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart Br Card Soc. 2012;98:1442–8.Google Scholar
  6. 6.
    Perugini E, Guidalotti PL, Salvi F, Cooke RMT, 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.CrossRefPubMedGoogle Scholar
  7. 7.
    Rapezzi C, Quarta CC, Guidalotti PL, Longhi S, Pettinato C, Leone O, et al. Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2011;38:470–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. (99m)Tc-pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6:195–201.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Hutt DF, Quigley A-M, Page J, Hall ML, Burniston M, Gopaul D, et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging. 2014;15:1289–98.CrossRefPubMedGoogle Scholar
  10. 10.
    Castano A, Haq M, Narotsky DL, Goldsmith J, Weinberg RL, Morgenstern R, et al. Multicenter study of planar technetium 99m pyrophosphate cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol. 2016;1:880–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Rapezzi C, Quarta CC, Guidalotti PL, Pettinato C, Fanti S, Leone O, et al. Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. JACC Cardiovasc. Imaging. 2011;4:659–70.CrossRefPubMedGoogle Scholar
  12. 12.
    •• 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. Validation of the diagnostic value of bone scintigraphy in TTR-CA in a multicenter study. CrossRefPubMedGoogle Scholar
  13. 13.
    Longhi S, Guidalotti PL, Quarta CC, Gagliardi C, Milandri A, Lorenzini M, et al. Identification of TTR-related subclinical amyloidosis with 99mTc-DPD scintigraphy. JACC Cardiovasc. Imaging. 2014;7:531–2.CrossRefPubMedGoogle Scholar
  14. 14.
    Kristen AV, Scherer K, Buss S, Aus dem Siepen F, Haufe S, Bauer R, et al. Noninvasive risk stratification of patients with transthyretin amyloidosis. JACC Cardiovasc. Imaging. 2014;7:502–10.CrossRefPubMedGoogle Scholar
  15. 15.
    •• Sperry BW, Vranian MN, Tower-Rader A, Hachamovitch R, Hanna M, Brunken R, et al. Regional variation in technetium pyrophosphate uptake in transthyretin cardiac amyloidosis and impact on mortality. JACC Cardiovasc Imaging. 2018;11(2 Pt 1):234–42.  https://doi.org/10.1016/j.jcmg.2017.06.020. First description of the apical sparring pattern with bone scintigraphy in TTR-CA.
  16. 16.
    Van Der Gucht A, Galat A, Rosso J, Guellich A, Garot J, Bodez D, et al. [18F]-NaF PET/CT imaging in cardiac amyloidosis. J Nucl Cardiol Off Publ Am Soc Nucl Cardiol. 2016;23:846–9.CrossRefGoogle Scholar
  17. 17.
    Trivieri MG, Dweck MR, Abgral R, Robson PM, Karakatsanis NA, Lala A, et al. (18)F-sodium fluoride PET/MR for the assessment of cardiac amyloidosis. J Am Coll Cardiol. 2016;68:2712–4.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Antoni G, Lubberink M, Estrada S, Axelsson J, Carlson K, Lindsjö L, et al. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J. Nucl. Med. Off. Publ. Soc. Nucl. Med. 2013;54:213–20.Google Scholar
  19. 19.
    Lee S-P, Lee ES, Choi H, Im H-J, Koh Y, Lee M-H, et al. 11C-Pittsburgh B PET imaging in cardiac amyloidosis. JACC Cardiovasc. Imaging. 2015;8:50–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR, Di Carli MF, et al. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;41:1652–62.CrossRefPubMedGoogle Scholar
  21. 21.
    Park MA, Padera RF, Belanger A, Dubey S, Hwang DH, Veeranna V, et al. 18F-florbetapir binds specifically to myocardial light chain and transthyretin amyloid deposits: autoradiography study. Circ Cardiovasc Imaging. 2015;8(8):e002954.  https://doi.org/10.1161/CIRCIMAGING.114.002954.
  22. 22.
    Law WP, Wang WYS, Moore PT, Mollee PN, Ng ACT. Cardiac amyloid imaging with 18F-florbetaben PET: a pilot study. J Nucl Med Off Publ Soc Nucl Med. 2016;57:1733–9.Google Scholar
  23. 23.
    Delahaye N, Le Guludec D, Dinanian S, Delforge J, Slama MS, Sarda L, et al. Myocardial muscarinic receptor upregulation and normal response to isoproterenol in denervated hearts by familial amyloid polyneuropathy. Circulation. 2001;104:2911–6.CrossRefPubMedGoogle Scholar
  24. 24.
    •• Algalarrondo V, Antonini T, Théaudin M, Chemla D, Benmalek A, Lacroix C, et al. Cardiac dysautonomia predicts long-term survival in hereditary transthyretin amyloidosis after liver transplantation. JACC Cardiovasc. Imaging. 2016;9:1432–41. Prognostic value of cardiac MIBG scintigraphy after liver transplantation. CrossRefPubMedGoogle Scholar
  25. 25.
    Tanaka M, Hongo M, Kinoshita O, Takabayashi Y, Fujii T, Yazaki Y, et al. Iodine-123 metaiodobenzylguanidine scintigraphic assessment of myocardial sympathetic innervation in patients with familial amyloid polyneuropathy. J Am Coll Cardiol. 1997;29:168–74.CrossRefPubMedGoogle Scholar
  26. 26.
    Delahaye N, Dinanian S, Slama MS, Mzabi H, Samuel D, Adams D, et al. Cardiac sympathetic denervation in familial amyloid polyneuropathy assessed by iodine-123 metaiodobenzylguanidine scintigraphy and heart rate variability. Eur J Nucl Med. 1999;26:416–24.CrossRefPubMedGoogle Scholar
  27. 27.
    Delahaye N, Rouzet F, Sarda L, Tamas C, Dinanian S, Plante-Bordeneuve V, et al. Impact of liver transplantation on cardiac autonomic denervation in familial amyloid polyneuropathy. Medicine (Baltimore). 2006;85:229–38.CrossRefGoogle Scholar
  28. 28.
    Coutinho MCA, Cortez-Dias N, Cantinho G, Conceição I, Oliveira A, Bordalo e Sá A, et al. Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy. Circ Cardiovasc Imaging. 2013;6:627–36.CrossRefPubMedGoogle Scholar
  29. 29.
    Denier C, Ducot B, Husson H, Lozeron P, Adams D, Meyer L, et al. A brief compound test for assessment of autonomic and sensory-motor dysfunction in familial amyloid polyneuropathy. J Neurol. 2007;254:1684–8.CrossRefPubMedGoogle Scholar
  30. 30.
    Feng D, Edwards WD, Oh JK, Chandrasekaran K, Grogan M, Martinez MW, et al. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation. 2007;116:2420–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefPubMedGoogle Scholar
  32. 32.
    Algalarrondo V, Dinanian S, Juin C, Chemla D, Bennani SL, Sebag C, et al. Prophylactic pacemaker implantation in familial amyloid polyneuropathy. Heart Rhythm. 2012;9:1069–75.CrossRefPubMedGoogle Scholar
  33. 33.
    Hamon D, Algalarrondo V, Gandjbakhch E, Extramiana F, Marijon E, Elbaz N, et al. Outcome and incidence of appropriate implantable cardioverter-defibrillator therapy in patients with cardiac amyloidosis. Int J Cardiol. 2016;222:562–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, Camm J, et al. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J. 2015;36:2793–867.CrossRefPubMedGoogle Scholar
  35. 35.
    Olofsson B-O, Backman C, Karp K, Suhr OB. Progression of cardiomyopathy after liver transplantation in patients with familial amyloidotic polyneuropathy, Portuguese type. Transplantation. 2002;73:745–51.CrossRefPubMedGoogle Scholar
  36. 36.
    Ericzon B-G, Wilczek HE, Larsson M, Wijayatunga P, Stangou A, Pena JR, et al. Liver transplantation for hereditary transthyretin amyloidosis: after 20 years still the best therapeutic alternative? Transplantation. 2015;99:1847–54.CrossRefPubMedGoogle Scholar
  37. 37.
    Algalarrondo V, Antonini T, Théaudin M, Ducot B, Lozeron P, Chemla D, et al. Prediction of long-term survival after liver transplantation for familial transthyretin amyloidosis. J Am Coll Cardiol. 2015;66:2154–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Gillmore JD, Damy T, Fontana M, Hutchinson M, Lachmann HJ, Martinez-Naharro A, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2017.  https://doi.org/10.1093/eurheartj/ehx589.
  39. 39.
    Arbustini E, Merlini G. Early identification of transthyretin-related hereditary cardiac amyloidosis. JACC Cardiovasc Imaging. 2014;7:511–4.CrossRefPubMedGoogle Scholar
  40. 40.
    Noordzij W, Glaudemans AWJM, van Rheenen RWJ, Hazenberg BPC, Tio RA, Dierckx RAJO, et al. (123)I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis. Eur J Nucl Med Mol Imaging. 2012;39:1609–17.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Piekarski E, Chequer R, Algalarrondo V, Eliahou L, Mahida B, Vigne J, et al. Cardiac denervation evidenced by MIBG occurs earlier than amyloid deposits detection by diphosphonates scintigraphy in TTR mutation carriers. Eur J Nucl Med Mol Imaging. 2018.  https://doi.org/10.1007/s00259-018-3963-x.

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Vincent Algalarrondo
    • 1
    • 2
  • Eve Piekarski
    • 3
    • 4
  • Ludivine Eliahou
    • 1
    • 2
  • Dominique Le Guludec
    • 3
    • 4
  • Michel S. Slama
    • 1
    • 2
  • François Rouzet
    • 3
    • 4
  1. 1.Cardiology Department, Antoine Béclère Hospital, Assistance Publique Hôpitaux de Paris (AP-HP), UMR-S 1180University of Paris-SudClamartFrance
  2. 2.French Referral Center for Familial Amyloidotic Polyneuropathy and Other Rare Peripheral Neuropathies (CRMR-NNERF)BicêtreFrance
  3. 3.Nuclear Medicine Department and DHU FIRE, Bichat Claude Bernard Hospital, AP-HPUniversity Paris VIIParisFrance
  4. 4.Inserm UMR-S 1148ParisFrance

Personalised recommendations