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Molecular Imaging of Cardiac Amyloidosis

  • Matthieu Pelletier-GalarneauEmail author
  • Gad Abikhzer
  • Genevieve Giraldeau
  • Francois Harel
Nuclear Cardiology (V Dilsizian, Section Editor)
  • 74 Downloads
Part of the following topical collections:
  1. Topical Collection on Nuclear Cardiology

Abstract

Purpose of Review

The aim of this review is to give an update on the molecular imaging tools currently available as well as to discuss the potential roles and limitations of molecular imaging in cardiac amyloidosis.

Recent Findings

Molecular imaging plays a central role in the evaluation of patients with suspected cardiac amyloidosis. It can be used to diagnose and distinguish between the different types of cardiac amyloidosis. The diagnostic properties of bone scintigraphy are such that it allows reliable diagnosis of transthyretin cardiac amyloidosis without the need of endomyocardial biopsy in a significant proportion of patients. Furthermore, molecular tracers assessing amyloid plaque burden and sympathetic innervation may be useful for the non-invasive evaluation diagnosis and risk stratification of patients with suspected cardiac amyloidosis.

Summary

Cardiac amyloidosis is an under-recognized cause of left ventricular hypertrophy and heart failure in the elderly. The role of molecular imaging in cardiac amyloidosis is expected to grow considering the arrival of new therapies and molecular imaging probes.

Keywords

Positron emission tomography SPECT Cardiac amyloidosis Transthyretin Bone scintigraphy 

Notes

Compliance with Ethical Standards

Conflict of Interest

Matthieu Pelletier-Galarneau, Gad Abikhzer, Genevieve Giraldeau, and Francois Harel declare that they have no conflict of interest.

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 importance •• Of major importance

  1. 1.
    Maleszewski JJ. Cardiac amyloidosis: pathology, nomenclature, and typing. Cardiovasc Pathol. 2015;24:343–50.CrossRefGoogle Scholar
  2. 2.
    Fikrle M, Paleček T, Kuchynka P, Němeček E, Bauerová L, Straub J, et al. Cardiac amyloidosis: a comprehensive review. Cor Vasa. 2013;55:e60–75.CrossRefGoogle Scholar
  3. 3.
    Merlini G, Seldin DC, Gertz MA. Amyloidosis: pathogenesis and new therapeutic options. J Clin Oncol. 2011;29:1924–33.CrossRefGoogle Scholar
  4. 4.
    Pereira NL, Grogan M, Dec GW. Spectrum of restrictive and infiltrative cardiomyopathies: part 1 of a 2-part series. J Am Coll Cardiol. 2018;71:1130–48.CrossRefGoogle Scholar
  5. 5.
    Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing common questions encountered in the diagnosis and management of cardiac amyloidosis. Circulation. 2017;135:1357–77.CrossRefGoogle Scholar
  6. 6.
    Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med. 2018;28:10–21.CrossRefGoogle Scholar
  7. 7.
    Lobato L. Portuguese-type amyloidosis (transthyretin amyloidosis, ATTR V30M). J Nephrol. 2003;16:438–42.PubMedGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583–96.CrossRefGoogle Scholar
  10. 10.
    Dharmarajan K, Maurer MS. Transthyretin cardiac amyloidoses in older North Americans. J Am Geriatr Soc. 2012;60:765–74.CrossRefGoogle Scholar
  11. 11.
    Mohammed SF, Mirzoyev SA, Edwards WD, Dogan A, Grogan DR, Dunlay SM, et al. Left ventricular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2:113–22.CrossRefGoogle Scholar
  12. 12.
    Tanskanen M, Peuralinna T, Polvikoski T, Notkola I-L, Sulkava R, Hardy J, et al. Senile systemic amyloidosis affects 25% of the very aged and associates with genetic variation in alpha2-macroglobulin and tau: a population-based autopsy study. Ann Med. 2008;40:232–9.CrossRefGoogle Scholar
  13. 13.
    Falk RH, Quarta CC, Dorbala S. How to image cardiac amyloidosis. Circ Cardiovasc Imaging. 2014;7:552–62.CrossRefGoogle Scholar
  14. 14.
    Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112:2047–60.CrossRefGoogle Scholar
  15. 15.
    Falk RH, Quarta CC. Echocardiography in cardiac amyloidosis. Heart Fail Rev. 2015;20:125–31.CrossRefGoogle Scholar
  16. 16.
    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. 2012;98:1442–8.CrossRefGoogle Scholar
  17. 17.
    Syed IS, Glockner JF, Feng D, Araoz PA, Martinez MW, Edwards WD, et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging. 2010;3:155–64.CrossRefGoogle Scholar
  18. 18.
    Mongeon F-P, Jerosch-Herold M, Coelho-Filho OR, Blankstein R, Falk RH, Kwong RY. Quantification of extracellular matrix expansion by CMR in infiltrative heart disease. JACC Cardiovasc Imaging. 2012;5:897–907.CrossRefGoogle Scholar
  19. 19.
    Fontana M, Pica S, Reant P, Abdel-Gadir A, Treibel TA, Banypersad SM, et al. Prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2015;132:1570–9.CrossRefGoogle Scholar
  20. 20.
    Boynton SJ, Geske JB, Dispenzieri A, Syed IS, Hanson TJ, Grogan M, et al. LGE provides incremental prognostic information over serum biomarkers in AL cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9:680–6.CrossRefGoogle Scholar
  21. 21.
    Austin BA, Tang WHW, Rodriguez ER, Tan C, Flamm SD, Taylor DO, et al. Delayed hyper-enhancement magnetic resonance imaging provides incremental diagnostic and prognostic utility in suspected cardiac amyloidosis. JACC Cardiovasc Imaging. 2009;2:1369–77.CrossRefGoogle Scholar
  22. 22.
    Pawar S, Haq M, Ruberg FL, Miller EJ. Imaging options in cardiac amyloidosis: differentiating AL from ATTR. Curr Cardiovasc Imaging Rep. 2017;10:1.CrossRefGoogle Scholar
  23. 23.
    Wizenberg TA, Muz J, Sohn YH, Samlowski W, Weissler AM. Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis. Am Heart J. 1982;103:468–73.CrossRefGoogle Scholar
  24. 24.
    Vallabhajosula S, Owunwanne A. Basis of radiopharmaceutical localization. Pathophysiol Basis Nucl Med [Internet]. Springer, Cham; 2015 [cited 2018 Jun 8]. p. 45–68. Available from: https://link.springer.com/chapter/10.1007/978-3-319-06112-2_3.
  25. 25.
    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.CrossRefGoogle Scholar
  26. 26.
    Rapezzi C, Gagliardi C, Milandri A. Analogies and disparities among scintigraphic bone tracers in the diagnosis of cardiac and non-cardiac ATTR amyloidosis. J Nucl Cardiol. 2018.Google Scholar
  27. 27.
    Puille M, Altland K, Linke RP, Steen-Müller MK, Kiett R, Steiner D, et al. 99mTc-DPD scintigraphy in transthyretin-related familial amyloidotic polyneuropathy. Eur J Nucl Med Mol Imaging. 2002;29:376–9.CrossRefGoogle Scholar
  28. 28.
    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.CrossRefGoogle Scholar
  29. 29.
    Quarta CC, Guidalotti PL, Longhi S, Pettinato C, Leone O, Ferlini A, et al. Defining the diagnosis in echocardiographically suspected senile systemic amyloidosis. JACC Cardiovasc Imaging. 2012;5:755–8.CrossRefGoogle Scholar
  30. 30.
    •• 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 This large multicentric study of 1217 patients proposes and validates a non-invasive algorithm for the investigation of patients with suspected cardiac amyloidosis. CrossRefGoogle Scholar
  31. 31.
    •• Treglia G, Glaudemans AWJM, Bertagna F, Hazenberg BPC, Erba PA, Giubbini R, et al. Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis. Eur J Nucl Med Mol Imaging. 2018;45(11):1945–55 This meta-analysis reviews the diagnosis accuracy of bone scintigraphy in patient with suspected ATTR cardiac amyloidosis and confirms the high sensitivity and specificity of the modality. CrossRefGoogle Scholar
  32. 32.
    Bokhari S, Castaño A, Pozniakoff T, Deslisle S, Latif F, Maurer MS. 99mTc-Pyrophosphate scintigraphy for differentiating light-chain cardiac amyloidosis from the transthyretin-related familial and senile cardiac amyloidoses. Clinical perspective. Circ Cardiovasc Imaging. 2013;6:195–201.CrossRefGoogle Scholar
  33. 33.
    Galat A, Rosso J, Guellich A, Van Der Gucht A, Rappeneau S, Bodez D, et al. Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis. Amyloid. 2015;22:210–20.CrossRefGoogle Scholar
  34. 34.
    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.CrossRefGoogle Scholar
  35. 35.
    Gagliardi C, Tabacchi E, Bonfiglioli R, Diodato S, Nanni C, Guidalotti P, et al. Does the etiology of cardiac amyloidosis determine the myocardial uptake of [18F]-NaF PET/CT? J Nucl Cardiol. 2017;24:746–9.CrossRefGoogle Scholar
  36. 36.
    Morgenstern R, Yeh R, Castano A, Maurer MS, Bokhari S. 18 Fluorine sodium fluoride positron emission tomography, a potential biomarker of transthyretin cardiac amyloidosis. J Nucl Cardiol. 2017:1–9.Google Scholar
  37. 37.
    • Trivieri MG, Dweck MR, Abgral R, Robson PM, Karakatsanis NA, Lala A, et al. 18F-sodium fluoride PET/MR for the assessment of cardiac amyloidosis. J Am Coll Cardiol. 2016;68:2712–4 A first prospective study demonstrating the feasibility of NaF imaging to detect cardiac amyloidosis and differentiate between ATTR and AL cardiac amyloidoses. CrossRefGoogle Scholar
  38. 38.
    Glaudemans AWJM, Slart RHJA, Zeebregts CJ, Veltman NC, Tio RA, Hazenberg BPC, et al. Nuclear imaging in cardiac amyloidosis. Eur J Nucl Med Mol Imaging. 2009;36:702–14.CrossRefGoogle Scholar
  39. 39.
    •• Bateman RJ, Xiong C, Benzinger TLS, Fagan AM, Goate A, Fox NC, et al. Clinical and biomarker changes in dominantly inherited Alzheimer’s disease. N Engl J Med. 2012;367:795–804.CrossRefGoogle Scholar
  40. 40.
    • Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR, Carli MFD, et al. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;41:1652–62 First trial demonstrating increased uptake of amyloid tracer in the heart of patients with cardiac amyloidosis. CrossRefGoogle Scholar
  41. 41.
    • 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 A small study showing that 11C-PiB can differentiate between patients with cardiac amyloidosis and controls. CrossRefGoogle Scholar
  42. 42.
    Law WP, Wang WYS, Moore PT, Mollee PN, Ng ACT. Cardiac amyloid imaging with 18F-florbetaben PET: a pilot study. J Nucl Med. 2016;57:1733–9.CrossRefGoogle Scholar
  43. 43.
    Park M-A, Padera RF, Belanger A, Dubey S, Hwang DH, Veeranna V, Falk RH, di Carli MF, Dorbala S 18F-Florbetapir binds specifically to myocardial light chain and transthyretin amyloid deposits: autoradiography study. Circ Cardiovasc Imaging. 2015;8:e002954Google Scholar
  44. 44.
    Carrió I, Cowie MR, Yamazaki J, Udelson J, Camici PG. Cardiac sympathetic imaging with mIBG in heart failure. JACC Cardiovasc Imaging. 2010;3:92–100.CrossRefGoogle Scholar
  45. 45.
    Nakata T, Shimamoto K, Yonekura S, Kobayashi N, Sugiyama T, Imai K, et al. Cardiac sympathetic denervation in transthyretin-related familial amyloidotic polyneuropathy: detection with iodine-123-MIBG. J Nucl Med. 1995;36:1040–2.PubMedGoogle Scholar
  46. 46.
    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.CrossRefGoogle Scholar
  47. 47.
    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.CrossRefGoogle Scholar
  48. 48.
    •• 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 diphosphonate scintigraphy in TTR mutation carriers. Eur J Nucl Med Mol Imaging. 2018;45:1108–18 This study demonstrates that in carriers of TTR mutation, sympathetic denervation as demonstrated by decreased MIBG uptake occurs before amyloid accumulation can be detected by increased uptake on bone scan. They concluded that MIBG could allow early detection of cardiac involvement in TTR mutation carriers. CrossRefGoogle Scholar
  49. 49.
    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.CrossRefGoogle Scholar
  50. 50.
    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.CrossRefGoogle Scholar
  51. 51.
    Algalarrondo V, Piekarski E, Eliahou L, Le Guludec D, Slama MS, Rouzet F. Can nuclear imaging techniques predict patient outcome and guide medical management in hereditary transthyretin cardiac amyloidosis? Curr Cardiol Rep. 2018;20:33.CrossRefGoogle Scholar
  52. 52.
    Slart RHJA, Glaudemans AWJM, Hazenberg BPC, Noordzij W. Imaging cardiac innervation in amyloidosis. J Nucl Cardiol. 2017:1–14.Google Scholar
  53. 53.
    Lee JH, Lee GY, Kim SJ, Kim KH, Jeon E-S, Lee K-H, et al. Imaging findings and literature review of 18F-FDG PET/CT in primary systemic AL amyloidosis. Nucl Med Mol Imaging. 2015;49:182–90.CrossRefGoogle Scholar
  54. 54.
    Mekinian A, Jaccard A, Soussan M, Launay D, Berthier S, Federici L, et al. 18F-FDG PET/CT in patients with amyloid light-chain amyloidosis: case-series and literature review. Amyloid. 2012;19:94–8.CrossRefGoogle Scholar
  55. 55.
    Ng B, Connors LH, Davidoff R, Skinner M, Falk RH. Senile systemic amyloidosis presenting with heart failure: a comparison with light chain-associated amyloidosis. Arch Intern Med. 2005;165:1425–9.CrossRefGoogle Scholar
  56. 56.
    Dungu JN, Valencia O, Pinney JH, Gibbs SDJ, Rowczenio D, Gilbertson JA, et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC Cardiovasc Imaging. 2014;7:133–42.CrossRefGoogle Scholar
  57. 57.
    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.CrossRefGoogle Scholar
  58. 58.
    Stats MA, Stone JR. Varying levels of small microcalcifications and macrophages in ATTR and AL cardiac amyloidosis: implications for utilizing nuclear medicine studies to subtype amyloidosis. Cardiovasc Pathol. 2016;25:413–7.CrossRefGoogle Scholar
  59. 59.
    Ansari-Lari MA, Ali SZ. Fine-needle aspiration of abdominal fat pad for amyloid detection: a clinically useful test? Diagn Cytopathol. 2004;30:178–81.CrossRefGoogle Scholar
  60. 60.
    Fine NM, Arruda-Olson AM, Dispenzieri A, Zeldenrust SR, Gertz MA, Kyle RA, et al. Yield of noncardiac biopsy for the diagnosis of transthyretin cardiac amyloidosis. Am J Cardiol. 2014;113:1723–7.CrossRefGoogle Scholar
  61. 61.
    Holzmann M, Nicko A, Kühl U, Noutsias M, Poller W, Hoffmann W, et al. Complication rate of right ventricular endomyocardial biopsy via the femoral approach: a retrospective and prospective study analyzing 3048 diagnostic procedures over an 11-year period. Circulation. 2008;118:1722–8.CrossRefGoogle Scholar
  62. 62.
    Promislow SJ, Ruddy TD. The evolving landscape of nuclear imaging in cardiac amyloidosis. J Nucl Cardiol 2018;Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Matthieu Pelletier-Galarneau
    • 1
    • 2
    Email author
  • Gad Abikhzer
    • 3
  • Genevieve Giraldeau
    • 4
  • Francois Harel
    • 1
  1. 1.Department of Medical ImagingMontreal Heart InstituteMontrealCanada
  2. 2.Gordon Center for Medical ImagingMassachusetts General HospitalBostonUSA
  3. 3.Department of Radiology and Nuclear MedicineJewish General HospitalMontrealCanada
  4. 4.Department of MedicineMontreal Heart InstituteMontrealCanada

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