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Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy

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Abstract

Purpose

Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged.

The aim of this study was to examine the performance of 18F-florbetaben-PET/CT in detection of CA, and compare it to echocardiography (echo), cardiac MRI (CMR) and scintigraphy. Additionally, the use of 18F-florbetaben-PET/CT for quantification of amyloid burden and monitoring of treatment response was assessed.

Methods

Twenty-two patients with proven (n = 5) or clinical suspicion (n = 17) of CA underwent 18F-florbetaben-PET/CT for diagnostic work-up. Qualitative and quantitative assessment including calculation of myocardial tracer retention (MTR) was performed, and compared to echo (n = 20), CMR (n = 16), scintigraphy (n = 16) and serologic biomarkers (NT-proBNP, cTnT, free light chains). In four patients, follow-up PET/CT was available (after treatment initiation, n = 3; surveillance, n = 1).

Results

PET demonstrated myocardial 18F-florbetaben retention consistent with CA in 14/22 patients. Suspicion of CA was subsequently dropped in all eight PET-negative patients. Amyloid subtypes showed characteristic retention patterns (AL > AA > ATTR; all p < 0.005). MTR correlated with morphologic and functional parameters, as measured by CMR and echo (all r| > 0.47|, all p < 0.05), but not with cardiac biomarkers. Changes in MTR from baseline to follow-up corresponded well to treatment response, as assessed by cardiac biomarkers and performance status.

Conclusions

Imaging of cardiac amyloidosis (CA) with 18F-florbetaben-PET/CT is feasible and might be useful in differentiating CA subtypes.

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References

  1. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337:898–909. https://doi.org/10.1056/NEJM199709253371306.

    Article  CAS  PubMed  Google Scholar 

  2. Merlini G, Bellotti V. Molecular mechanisms of amyloidosis. N Engl J Med. 2003;349:583–96. https://doi.org/10.1056/NEJMra023144.

    Article  CAS  PubMed  Google Scholar 

  3. Alexander KM, Singh A, Falk RH. Novel pharmacotherapies for cardiac amyloidosis. Pharmacol Ther. 2017;180:129-138. https://doi.org/10.1016/j.pharmthera.2017.06.011.

  4. Falk RH. Cardiac amyloidosis: a treatable disease, often overlooked. Circulation. 2011;124:1079–85. https://doi.org/10.1161/CIRCULATIONAHA.110.010447.

    Article  PubMed  Google Scholar 

  5. Lousada I, Comenzo RL, Landau H, Guthrie S, Merlini G. Light chain amyloidosis: patient experience survey from the amyloidosis research consortium. Adv Ther. 2015;32:920–8. https://doi.org/10.1007/s12325-015-0250-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR. Amyloidosis: diagnosis and management. Clin Lymphoma Myeloma. 2005;6:208–19. https://doi.org/10.3816/CLM.2005.n.048.

    Article  CAS  PubMed  Google Scholar 

  7. Fernandez de Larrea C, Verga L, Morbini P, Klersy C, Lavatelli F, Foli A, et al. A practical approach to the diagnosis of systemic amyloidoses. Blood. 2015;125:2239–44. https://doi.org/10.1182/blood-2014-11-609883.

    Article  CAS  PubMed  Google Scholar 

  8. Foli A, Palladini G, Caporali R, Verga L, Morbini P, Obici L, et al. The role of minor salivary gland biopsy in the diagnosis of systemic amyloidosis: results of a prospective study in 62 patients. Amyloid. 2011;18(Suppl 1):80–2. https://doi.org/10.3109/13506129.2011.574354029.

    Article  PubMed  Google Scholar 

  9. Kristen AV, Dengler TJ, Katus HA. Suspected cardiac amyloidosis: endomyocardial biopsy remains the diagnostic gold-standard. Am J Hematol. 2007;82:328. https://doi.org/10.1002/ajh.20745.

    Article  PubMed  Google Scholar 

  10. Phelan D, Collier P, Thavendiranathan P, Popovic 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. https://doi.org/10.1136/heartjnl-2012-302353.

    Article  PubMed  Google Scholar 

  11. Liu D, Hu K, Niemann M, Herrmann S, Cikes M, Stork S, et al. Effect of combined systolic and diastolic functional parameter assessment for differentiation of cardiac amyloidosis from other causes of concentric left ventricular hypertrophy. Circ Cardiovasc Imaging. 2013;6:1066–72. https://doi.org/10.1161/CIRCIMAGING.113.000683.

    Article  PubMed  Google Scholar 

  12. 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. https://doi.org/10.1016/j.jcmg.2009.09.023.

    Article  PubMed  Google Scholar 

  13. Ruberg FL, Appelbaum E, Davidoff R, Ozonoff A, Kissinger KV, Harrigan C, et al. Diagnostic and prognostic utility of cardiovascular magnetic resonance imaging in light-chain cardiac amyloidosis. Am J Cardiol. 2009;103:544–9. https://doi.org/10.1016/j.amjcard.2008.09.105.

    Article  PubMed  Google Scholar 

  14. Austin BA, Tang WH, 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. https://doi.org/10.1016/j.jcmg.2009.08.008.

    Article  PubMed  Google Scholar 

  15. Reiter T, Ritter O, Prince MR, Nordbeck P, Wanner C, Nagel E, et al. Minimizing risk of nephrogenic systemic fibrosis in cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2012;14:31. https://doi.org/10.1186/1532-429X-14-31.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sommer T, Bauer W, Fischbach K, Kolb C, Luechinger R, Wiegand U, et al. MR imaging in patients with cardiac pacemakers and implantable cardioverter defibrillators. Rofo. 2017;189:204–17. https://doi.org/10.1055/s-0043-102029.

    Article  PubMed  Google Scholar 

  17. Falk RH, Quarta CC, Dorbala S. How to image cardiac amyloidosis. Circ Cardiovasc Imaging. 2014;7:552–62. https://doi.org/10.1161/CIRCIMAGING.113.001396.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S. Cardiac T1 mapping and extracellular volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson. 2016;18:89. https://doi.org/10.1186/s12968-016-0308-4.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Martinez-Naharro A, Kotecha T, Norrington K, Boldrini M, Rezk T, Quarta C, et al. Native T1 and extracellular volume in transthyretin amyloidosis. JACC Cardiovasc Imaging. 2018. https://doi.org/10.1016/j.jcmg.2018.02.006.

  20. 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 

  21. Dorbala S, Bokhari S, Miller EJ, Bullock-Palmer R, Soman P, Thompson RE, et al. 99mTechnetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. ASNC Pract Points, 2016.

  22. 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. https://doi.org/10.3109/13506129.2012.682833.

    Article  CAS  PubMed  Google Scholar 

  23. Dorbala S, Vangala D, Semer J, Strader C, Bruyere JR Jr, Di Carli MF, et al. Imaging cardiac amyloidosis: a pilot study using (1)(8)F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging. 2014;41:1652–62. https://doi.org/10.1007/s00259-014-2787-6.

    Article  CAS  PubMed  Google Scholar 

  24. Antoni G, Lubberink M, Estrada S, Axelsson J, Carlson K, Lindsjo L, et al. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J Nucl Med. 2013;54:213–20. https://doi.org/10.2967/jnumed.111.102053.

    Article  CAS  PubMed  Google Scholar 

  25. Law WP, Wang WY, Moore PT, Mollee PN, Ng AC. Cardiac amyloid imaging with 18F-Florbetaben PET: a pilot study. J Nucl Med. 2016;57:1733–9. https://doi.org/10.2967/jnumed.115.169870.

    Article  CAS  PubMed  Google Scholar 

  26. Palladini G, Merlini G. What is new in diagnosis and management of light chain amyloidosis? Blood. 2016;128:159–68. https://doi.org/10.1182/blood-2016-01-629790.

    Article  CAS  PubMed  Google Scholar 

  27. Gertz MA, Comenzo R, Falk RH, Fermand JP, Hazenberg BP, Hawkins PN, et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th international symposium on amyloid and amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005;79:319–28. https://doi.org/10.1002/ajh.20381.

    Article  PubMed  Google Scholar 

  28. Boellaard R. Need for standardization of 18F-FDG PET/CT for treatment response assessments. J Nucl Med. 2011;52(Suppl 2):93S–100S. https://doi.org/10.2967/jnumed.110.085662.

    Article  PubMed  Google Scholar 

  29. Schulz-Menger J, Bluemke DA, Bremerich J, Flamm SD, Fogel MA, Friedrich MG, et al. Standardized image interpretation and post processing in cardiovascular magnetic resonance: Society for Cardiovascular Magnetic Resonance (SCMR) board of trustees task force on standardized post processing. J Cardiovasc Magn Reson. 2013;15:35. https://doi.org/10.1186/1532-429X-15-35.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 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 

  31. Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30:989–95. https://doi.org/10.1200/JCO.2011.38.5724.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Grogan M, Scott CG, Kyle RA, Zeldenrust SR, Gertz MA, Lin G, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68:1014–20. https://doi.org/10.1016/j.jacc.2016.06.033.

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank all people involved in this project, particularly our colleagues from the departments of cardiology and haematology, who left no stone unturned when caring for and treating our common patients.

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Author notes

  1. Wolfgang R. Bauer and Constantin Lapa contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97078, Würzburg, Germany

    Malte Kircher, Joachim Brumberg, Andreas K. Buck & Constantin Lapa

  2. Comprehensive Heart Failure Center, University Hospital Würzburg, Würzburg, Germany

    Malte Kircher, Sandra Ihne, Caroline Morbach & Stefan Störk

  3. Department of Internal Medicine II, Hemato-Oncology, University Hospital Würzburg, Würzburg, Germany

    Sandra Ihne, Stefan Knop & K. Martin Kortüm

  4. Department of Internal Medicine I, Cardiology, University Hospital Würzburg, Oberdürrbacher Str. 6, 97078, Würzburg, Germany

    Caroline Morbach, Stefan Störk, Theresa Reiter & Wolfgang R. Bauer

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  1. Malte Kircher
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Correspondence to Theresa Reiter.

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Kircher, M., Ihne, S., Brumberg, J. et al. Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy. Eur J Nucl Med Mol Imaging 46, 1407–1416 (2019). https://doi.org/10.1007/s00259-019-04290-y

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