Radionuclide Cardiac Imaging in Cardiac Amyloidosis
P: 19-27
April 2024

Radionuclide Cardiac Imaging in Cardiac Amyloidosis

Nucl Med Semin 2024;10(1):19-27
1. Ankara Yıldırım Beyazıt Üniversitesi Tıp Fakültesi, Nükleer Tıp Anabilim Dalı, Ankara, Türkiye
2. Ankara Bilkent Şehir Hastanesi, Nükleer Tıp Kliniği, Ankara, Türkiye
3. Ondokuz Mayıs Üniversitesi Tıp Fakültesi, Nükleer Tıp Anabilim Dalı, Samsun, Türkiye
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Publish Date: 05.04.2024


Cardiac amyloidosis is a restrictive cardiomyopathy caused by extracellular deposition of misfolded amyloid fibrils. Although it was considered a rare disease until recently, emerging data suggests that a significant portion of patients with heart failure with preserved ejection fraction and severe aortic stenosis have underlying cardiac amyloidosis. Radionuclide imaging with bone seeking agents is a non-invasive method that plays an important for the diagnosis of ATTR cardiac amyloidosis. Increased myocardial uptake of bone seeking agents is a highly accurate diagnostic finding for ATTR cardiac amyloidosis, provided that AL amyloidosis is excluded. This review article discusses the fundamental principles of radionuclide cardiac imaging for the diagnosis of cardiac amyloidosis, its current role in light of recent literature, and future perspectives in this regard.

Keywords: Cardiac amyloidosis, ATTR, AL, SPECT/CT, PET/CT


Gilstrap LG, Dominici F, Wang Y, et al. Epidemiology of Cardiac Amyloidosis-Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States. Circ Heart Fail 2019;12:e005407.
Porcari A, Merlo M, Rapezzi C, Sinagra G. Transthyretin amyloid cardiomyopathy: An uncharted territory awaiting discovery. Eur J Intern Med 2020;82:7-15.
Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid 2018;25:215-219.
González-López E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J 2015;36:2585-2594.
Castaño A, Narotsky DL, Hamid N, et al. Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J 2017;38:2879-2887.
Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid 2015;22:123-131.
Coelho T, Maurer MS, Suhr OB. THAOS - The Transthyretin Amyloidosis Outcomes Survey: initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin 2013;29:63-76.
Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet 2016;387:2641-2654.
Gertz MA. Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment. Am J Hematol 2022;97:818-829.
Dubrey SW, Cha K, Anderson J, et al. The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement. QJM 1998;91:141-157.
Dorbala S, Ando Y, Bokhari S, et al. ASNC/AHA/ASE/EANM/HFSA/ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 2 of 2—Diagnostic criteria and appropriate utilization. J Nucl Cardiol 2020;27:659-673.
Dorbala S, Cuddy S, Falk RH. How to Image Cardiac Amyloidosis: A Practical Approach. JACC: Cardiovasc Imaging 2020;13:1368-1383.
Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation 2012;126:1286-1300.
Dorbala S, Ando Y, Bokhari S, 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;26:2065-2123.
Kittleson MM, Maurer MS, Ambardekar AV, et al. Cardiac Amyloidosis: Evolving Diagnosis and Management: A Scientific Statement From the American Heart Association. Circulation 2020;142:e7-e22.
Lachmann HJ, Goodman HJ, Gilbertson JA, et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med 2007;356:2361-2371.
Falk RH, Alexander KM, Liao R, Dorbala S. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol 2016;68:1323-1341.
Falk RH, Quarta CC, Dorbala S. How to image cardiac amyloidosis. Circ Cardiovasc Imaging 2014;7:552-562.
Palladini G, Russo P, Bosoni T, et al. Identification of Amyloidogenic Light Chains Requires the Combination of Serum-Free Light Chain Assay with Immunofixation of Serum and Urine. Clin Chem 2009;55:499-504.
Phelan D, Collier P, Thavendiranathan P, 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;98:1442-1448.
Boldrini M, Cappelli F, Chacko L, et al. Multiparametric Echocardiography Scores for the Diagnosis of Cardiac Amyloidosis. JACC Cardiovasc Imaging 2020;13:909-920.
Wang TKM, Abou Hassan OK, Jaber W, Xu B. Multi-modality imaging of cardiac amyloidosis: Contemporary update. World J Radiol 2020;12:87-100.
Benson MD, Berk JL, Dispenzieri A, et al. Tissue biopsy for the diagnosis of amyloidosis: experience from some centres. Amyloid 2022;29:8-13.
Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation 2016;133:2404-2412.
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 2019;26:1638-1641.
Coskun N, Kartal MO, Erdogan AS, Tufekcioglu O, Ozdemir E. Tc-99m pyrophosphate scintigraphy for cardiac amyloidosis: concordance between planar and SPECT/CT imaging. Int J Cardiovasc Imaging 2022;38:2081-2088.
Perugini E, Guidalotti PL, Salvi F, et al. Noninvasive Etiologic Diagnosis of Cardiac Amyloidosis Using 99mTc-3,3-Diphosphono-1,2-Propanodicarboxylic Acid Scintigraphy. J Am Coll Cardiol 2005;46:1076-1084.
Kittleson MM, Ruberg FL, Ambardekar AV, et al. 2023 ACC Expert Consensus Decision Pathway on Comprehensive Multidisciplinary Care for the Patient With Cardiac Amyloidosis: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2023;81:1076-1126.
Thelander U, Westermark GT, Antoni G, et al. Cardiac microcalcifications in transthyretin (ATTR) amyloidosis. Int J Cardiol 2022;352:84-91.
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;25:413-417.
Pilebro B, Suhr OB, Näslund U, Westermark P, Lindqvist P, Sundström T. (99m)Tc-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis. Ups J Med Sci 2016;121:17-24.
Hutt DF, Gilbertson J, Quigley AM, Wechalekar AD. (99m)Tc-DPD scintigraphy as a novel imaging modality for identification of skeletal muscle amyloid deposition in light-chain amyloidosis. Amyloid 2016;23:134-135.
Porcari A, Hutt DF, Grigore SF, et al. Comparison of different technetium-99m-labelled bone tracers for imaging cardiac amyloidosis. Eur J Prev Cardiol 2022;30:e4-e6.
Rapezzi C, Quarta CC, Guidalotti PL, et al. Role of 99mTc-DPD Scintigraphy in Diagnosis and Prognosis of Hereditary Transthyretin-Related Cardiac Amyloidosis. JACC Cardiovasc Imaging 2011;4:659-670.
Scully PR, Morris E, Patel KP, et al. DPD Quantification in Cardiac Amyloidosis: A Novel Imaging Biomarker. JACC Cardiovasc Imaging 2020;13:1353-1363.
Porcari A, Pagura L, Canepa M, et al. 351 Prevalence and prognostic significance of RV uptake (biventricular uptake) at planar scintigraphy in patients with ATTR cardiac amyloidosis. European Heart Journal Supplements 2021;23.
Ioannou A, Patel RK, Razvi Y, et al. Multi-Imaging Characterization of Cardiac Phenotype in Different Types of Amyloidosis. JACC Cardiovasc Imaging 2023;16:464-477.
Chang ICY, Bois JP, Bois MC, Maleszewski JJ, Johnson GB, Grogan M. Hydroxychloroquine-Mediated Cardiotoxicity With a False-Positive 99mTechnetium-Labeled Pyrophosphate Scan for Transthyretin-Related Cardiac Amyloidosis. Circ Cardiovasc Imaging 2018;11:e007059.
Schafer EB, Tushak Z, Trankle CR, Rao K, Cartagena LC, Shah KB. False-Positive 99mTechnetium-Pyrophosphate Scintigraphy in Two Patients With Hypertrophic Cardiomyopathy. Circ Heart Fail 2021;14:e007558.
Musumeci MB, Cappelli F, Russo D, et al. Low Sensitivity of Bone Scintigraphy in Detecting Phe64Leu Mutation-Related Transthyretin Cardiac Amyloidosis. JACC Cardiovasc Imaging 2020;13:1314-1321.
Martinez-Naharro A, Treibel TA, Abdel-Gadir A, et al. Magnetic Resonance in Transthyretin Cardiac Amyloidosis. J Am Coll Cardiol 2017;70:466-477.
Garcia-Pavia P, Bengel F, Brito D, et al. Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy. Eur J Heart Fail 2021;23:895-905.
Fontana M, Martinez-Naharro A, Chacko L, et al. Reduction in CMR Derived Extracellular Volume With Patisiran Indicates Cardiac Amyloid Regression. JACC Cardiovasc Imaging 2021;14:189-199.
Castaño A, DeLuca A, Weinberg R, et al. Serial scanning with technetium pyrophosphate (99mTc-PYP) in advanced ATTR cardiac amyloidosis. J Nucl Cardiol 2016;23:1355-1363.
Dorbala S, Park M-A, Cuddy S, et al. Absolute Quantitation of Cardiac 99mTc-Pyrophosphate Using Cadmium-Zinc-Telluride-Based SPECT/CT. J Nucl Med 2021;62:716-722.
Gerber J, Miller EJ. Optimal interpretation of Tc99m PYP in 2020: Avoiding the million-dollar mistake. J Nucl Cardiol 2021;28:503-506.
Kim YJ, Ha S, Kim Y-i. Cardiac amyloidosis imaging with amyloid positron emission tomography: A systematic review and meta-analysis. J Nucl Cardiol 2020;27:123-132.
Genovesi D, Vergaro G, Giorgetti A, et al. [18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain, Transthyretin Amyloidosis, and Mimicking Conditions. JACC Cardiovasc Imaging 2021;14:246-255.
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