Download PDF
CC BY-NC-ND 4.0 · World J Nucl Med 2022; 21(03): 173-183
DOI: 10.1055/s-0042-1751057
Review Article

Multimodality Imaging in the Diagnosis and Assessment of Cardiac Amyloidosis

Jyothirmayi Velaga
1   Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore
,
Charlene Liew
2   Department of Radiology, Changi General Hospital, Singapore, Singapore
,
Angeline Choo Choo Poh
2   Department of Radiology, Changi General Hospital, Singapore, Singapore
,
Phong Teck Lee
4   National Heart Centre, Singapore, Singapore
,
Narayan Lath
1   Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore
,
Shoen Choon Low
1   Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore
,
Pushan Bharadwaj
3   Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Abstract

Amyloidosis is a rare disorder where abnormal protein aggregates are deposited in tissues forming amyloid fibrils, leading to progressive organ failure. Although any organ can be affected, cardiac involvement is the main cause of morbidity and mortality associated with amyloidosis as diagnosis is often delayed due to the indolent nature of the disease in some forms. An early diagnosis of disease and knowledge of the type/subtype of cardiac amyloidosis (CA) are essential for appropriate management and better outcome. Echocardiography is often the first line of investigation for patients suspected of CA and offers superior hemodynamic assessment. Although cardiovascular magnetic resonance (CMR) imaging is not diagnostic of CA, it provides vital clues to diagnosis and has a role in disease quantification and prognostication. Radiolabeled bone seeking tracers are the mainstay of diagnosis of CA and when combined with screening of monoclonal light chains, bone scintigraphy offers high sensitivity in diagnosing transthyretin type of CA. This review aims to describe the noninvasive imaging assessment and approach to diagnosis of patients with suspected CA. Imaging features of echocardiography, nuclear scintigraphy, and CMR are described with a brief mention on computed tomography.

Keywords

cardiac amyloidosis - strain imaging - bone scintigraphy - 99mTc pyrophosphate (PYP) - cardiac magnetic resonance - T1 mapping - late gadolinium enhancement - extracellular volume fraction - myocardial strain - cardiac computed tomography


Publication History

Article published online:
16 August 2022

© 2022. World Association of Radiopharmaceutical and Molecular Therapy (WARMTH). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 

  • References

  • 1 Sipe JD, Benson MD, Buxbaum JN. et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid 2016; 23 (04) 209-213
    CrossrefPubMedSearch in Google Scholar
  • 2 González-López E, Gagliardi C, Dominguez F. et al. Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths. Eur Heart J 2017; 38 (24) 1895-1904
    CrossrefPubMedSearch in Google Scholar
  • 3 García-Pavía P, Tomé-Esteban MT, Rapezzi C. [Amyloidosis. Also a heart disease]. Rev Esp Cardiol 2011; 64 (09) 797-808
    PubMedSearch in Google Scholar
  • 4 Gertz MA, Benson MD, Dyck PJ. et al. Diagnosis, prognosis, and therapy of transthyretin amyloidosis. J Am Coll Cardiol 2015; 66 (21) 2451-2466
    CrossrefPubMedSearch in Google Scholar
  • 5 Yanagisawa A, Ueda M, Sueyoshi T. et al. Amyloid deposits derived from transthyretin in the ligamentum flavum as related to lumbar spinal canal stenosis. Mod Pathol 2015; 28 (02) 201-207
    CrossrefPubMedSearch in Google Scholar
  • 6 Fikrle M, Paleček T, Kuchynka P. et al. Cardiac amyloidosis: a comprehensive review. Cor Vasa 2013; 55 (01) e60-e75
    CrossrefSearch in Google Scholar
  • 7 Rapezzi C, Longhi S, Milandri A. et al. Cardiac involvement in hereditary-transthyretin related amyloidosis. Amyloid 2012; 19 (Suppl. 01) 16-21
    CrossrefPubMedSearch in Google Scholar
  • 8 Kittleson MM, Maurer MS, Ambardekar AV. et al; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology. Cardiac amyloidosis: evolving diagnosis and management: a scientific statement from the American Heart Association. Circulation 2020; 142 (01) e7-e22
    CrossrefPubMedSearch in Google Scholar
  • 9 Maurer MS, Schwartz JH, Gundapaneni B. et al; ATTR-ACT Study Investigators. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018; 379 (11) 1007-1016
    CrossrefPubMedSearch in Google Scholar
  • 10 Ruberg FL, Grogan M, Hanna M, Kelly JW, Maurer MS. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol 2019; 73 (22) 2872-2891
    CrossrefPubMedSearch in Google Scholar
  • 11 Rapezzi C, Merlini G, Quarta CC. et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 2009; 120 (13) 1203-1212
    CrossrefPubMedSearch in Google Scholar
  • 12 Siddiqi OK, Ruberg FL. Cardiac amyloidosis: an update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med 2018; 28 (01) 10-21
    CrossrefPubMedSearch in Google Scholar
  • 13 Amzulescu MS, De Craene M, Langet H. et al. Myocardial strain imaging: review of general principles, validation, and sources of discrepancies. Eur Heart J Cardiovasc Imaging 2019; 20 (06) 605-619
    CrossrefPubMedSearch in Google Scholar
  • 14 Geyer H, Caracciolo G, Abe H. et al. Assessment of myocardial mechanics using speckle tracking echocardiography: fundamentals and clinical applications. J Am Soc Echocardiogr 2010; 23 (04) 351-369 , quiz 453–455
    CrossrefPubMedSearch in Google Scholar
  • 15 Ternacle J, Bodez D, Guellich A. et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging 2016; 9 (02) 126-138
    CrossrefPubMedSearch in Google Scholar
  • 16 Pagourelias ED, Mirea O, Duchenne J. et al. Echo parameters for differential diagnosis in cardiac amyloidosis: a head-to-head comparison of deformation and nondeformation parameters. Circ Cardiovasc Imaging 2017; 10 (03) e005588
    CrossrefPubMedSearch in Google Scholar
  • 17 Top RPB-P. 10 Things To Know When Performing Cardiac Imaging to Assess Cardiac Amyloidosis 2020 [Accessed April 8, 2022 from: https://www.acc.org/latest-in-cardiology/articles/2020/02/27/14/47/top-10-things-to-know-when-performing-cardiac-imaging-to-assess-cardiac-amyloidosis
  • 18 Kula RW, Engel WK, Line BR. Scanning for soft-tissue amyloid. Lancet 1977; 1 (8002): 92-93
    CrossrefPubMedSearch in Google Scholar
  • 19 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 (06) 2065-2123
    CrossrefPubMedSearch in Google Scholar
  • 20 Galat A, Rosso J, Guellich A. et al. Usefulness of (99m)Tc-HMDP scintigraphy for the etiologic diagnosis and prognosis of cardiac amyloidosis. Amyloid 2015; 22 (04) 210-220
    CrossrefPubMedSearch in Google Scholar
  • 21 Hutt DF, Quigley AM, Page J. et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging 2014; 15 (11) 1289-1298
    CrossrefPubMedSearch in Google Scholar
  • 22 Gillmore JD, Maurer MS, Falk RH. et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016; 133 (24) 2404-2412
    CrossrefPubMedSearch in Google Scholar
  • 23 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 (02) 195-201
    CrossrefPubMedSearch in Google Scholar
  • 24 Rapezzi C, Quarta CC, Guidalotti PL. et al. Role of (99m)Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging 2011; 4 (06) 659-670
    CrossrefPubMedSearch in Google Scholar
  • 25 Gerber J, Miller EJ. Optimal interpretation of Tc99m PYP in 2020: avoiding the million-dollar mistake. J Nucl Cardiol 2021; 28 (02) 503-506
    CrossrefPubMedSearch in Google Scholar
  • 26 Dorbala S, Bokhari S, Miller E, Bullock-Palmer R, Soman P, Thompson R. ASNC practice points: 99m-technetium-pyrophosphate imaging for transthyretin cardiac amyloidosis. 2019 (American society of nuclear cardiology website). Accessed September 2021 at: https://www.asnc.org/Files/Amyloid/ASNC%20Practice%20Point-99mTechnetium-Pyrophosphate.2019.pdf
  • 27 Masri A, Bukhari S, Ahmad S. et al. Efficient 1-hour technetium-99 m pyrophosphate imaging protocol for the diagnosis of transthyretin cardiac amyloidosis. Circ Cardiovasc Imaging 2020; 13 (02) e010249
    CrossrefPubMedSearch in Google Scholar
  • 28 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 (06) 1076-1084
    CrossrefPubMedSearch in Google Scholar
  • 29 Noordzij W, Glaudemans AW, van Rheenen RW. 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 (10) 1609-1617
    CrossrefPubMedSearch in Google Scholar
  • 30 Nagahara D, Nakata T, Hashimoto A. et al. Predicting the need for an implantable cardioverter defibrillator using cardiac metaiodobenzylguanidine activity together with plasma natriuretic peptide concentration or left ventricular function. J Nucl Med 2008; 49 (02) 225-233
    CrossrefPubMedSearch in Google Scholar
  • 31 Coutinho MC, Cortez-Dias N, Cantinho G. et al. Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy. Circ Cardiovasc Imaging 2013; 6 (05) 627-636
    CrossrefPubMedSearch in Google Scholar
  • 32 Lee JH, Lee GY, Kim SJ. et al. Imaging findings and literature review of (18)F-FDG PET/CT in primary systemic AL amyloidosis. Nucl Med Mol Imaging 2015; 49 (03) 182-190
    CrossrefPubMedSearch in Google Scholar
  • 33 Antoni G, Lubberink M, Estrada S. et al. In vivo visualization of amyloid deposits in the heart with 11C-PIB and PET. J Nucl Med 2013; 54 (02) 213-220
    CrossrefPubMedSearch in Google Scholar
  • 34 Dorbala S, Vangala D, Semer J. et al. Imaging cardiac amyloidosis: a pilot study using 18F-florbetapir positron emission tomography. Eur J Nucl Med Mol Imaging 2014; 41 (09) 1652-1662
    CrossrefPubMedSearch in Google Scholar
  • 35 Park MA, Padera RF, Belanger A. et al. 18F-florbetapir binds specifically to myocardial light chain and transthyretin amyloid deposits: autoradiography study. Circ Cardiovasc Imaging 2015; 8 (08) e002954
    CrossrefPubMedSearch in Google Scholar
  • 36 Law WP, Wang W, Moore P, Mollee P, Ng A. Cardiac amyloid imaging with 18F-florbetaben positron emission tomography: a pilot study. Amyloid 2017; 24 (Suppl. 01) 162
    CrossrefPubMedSearch in Google Scholar
  • 37 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 (08) 508-513
    CrossrefPubMedSearch in Google Scholar
  • 38 Hazenberg BP, van Rijswijk MH, Piers DA. et al. Diagnostic performance of 123I-labeled serum amyloid P component scintigraphy in patients with amyloidosis. Am J Med 2006; 119 (04) 355.e15-355.e24
    CrossrefPubMedSearch in Google Scholar
  • 39 Bokhari S, Shahzad R, Castaño A, Maurer MS. Nuclear imaging modalities for cardiac amyloidosis. J Nucl Cardiol 2014; 21 (01) 175-184
    CrossrefPubMedSearch in Google Scholar
  • 40 Schaadt BK, Hendel HW, Gimsing P, Jønsson V, Pedersen H, Hesse B. 99mTc-aprotinin scintigraphy in amyloidosis. J Nucl Med 2003; 44 (02) 177-183
    PubMedSearch in Google Scholar
  • 41 Ordovas KG, Higgins CB. Delayed contrast enhancement on MR images of myocardium: past, present, future. Radiology 2011; 261 (02) 358-374
    CrossrefPubMedSearch in Google Scholar
  • 42 Syed IS, Glockner JF, Feng D. et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging 2010; 3 (02) 155-164
    CrossrefPubMedSearch in Google Scholar
  • 43 Boynton SJ, Geske JB, Dispenzieri A. et al. LGE provides incremental prognostic information over serum biomarkers in AL cardiac amyloidosis. JACC Cardiovasc Imaging 2016; 9 (06) 680-686
    CrossrefPubMedSearch in Google Scholar
  • 44 Maceira AM, Joshi J, Prasad SK. et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 2005; 111 (02) 186-193
    CrossrefPubMedSearch in Google Scholar
  • 45 Vogelsberg H, Mahrholdt H, Deluigi CC. et al. Cardiovascular magnetic resonance in clinically suspected cardiac amyloidosis: noninvasive imaging compared to endomyocardial biopsy. J Am Coll Cardiol 2008; 51 (10) 1022-1030
    CrossrefPubMedSearch in Google Scholar
  • 46 Austin BA, Tang WH, Rodriguez ER. et al. Delayed hyper-enhancement magnetic resonance imaging provides incremental diagnostic and prognostic utility in suspected cardiac amyloidosis. JACC Cardiovasc Imaging 2009; 2 (12) 1369-1377
    CrossrefPubMedSearch in Google Scholar
  • 47 Dungu JN, Valencia O, Pinney JH. et al. CMR-based differentiation of AL and ATTR cardiac amyloidosis. JACC Cardiovasc Imaging 2014; 7 (02) 133-142
    CrossrefPubMedSearch in Google Scholar
  • 48 Wan K, Sun J, Han Y. et al. Increased prognostic value of query amyloid late enhancement score in light-chain cardiac amyloidosis. Circ J 2018; 82 (03) 739-746
    CrossrefPubMedSearch in Google Scholar
  • 49 Kramer CM, Barkhausen J, Flamm SD, Kim RJ, Nagel E. Society for Cardiovascular Magnetic Resonance Board of Trustees Task Force on Standardized Protocols. Standardized cardiovascular magnetic resonance (CMR) protocols 2013 update. J Cardiovasc Magn Reson 2013; 15 (01) 91
    CrossrefPubMedSearch in Google Scholar
  • 50 White JA, Kim HW, Shah D. et al. CMR imaging with rapid visual T1 assessment predicts mortality in patients suspected of cardiac amyloidosis. JACC Cardiovasc Imaging 2014; 7 (02) 143-156
    CrossrefPubMedSearch in Google Scholar
  • 51 Pandey T, Jambhekar K, Shaikh R, Lensing S, Viswamitra S. Utility of the inversion scout sequence (TI scout) in diagnosing myocardial amyloid infiltration. Int J Cardiovasc Imaging 2013; 29 (01) 103-112
    CrossrefPubMedSearch in Google Scholar
  • 52 Hamlin SA, Henry TS, Little BP, Lerakis S, Stillman AE. Mapping the future of cardiac MR imaging: case-based review of T1 and T2 mapping techniques. Radiographics 2014; 34 (06) 1594-1611
    CrossrefPubMedSearch in Google Scholar
  • 53 Moon JC, Messroghli DR, Kellman P. et al; Society for Cardiovascular Magnetic Resonance Imaging, Cardiovascular Magnetic Resonance Working Group of the European Society of Cardiology. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson 2013; 15 (01) 92
    CrossrefPubMedSearch in Google Scholar
  • 54 Messroghli DR, Moon JC, Ferreira VM. et al. Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: a consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). J Cardiovasc Magn Reson 2017; 19 (01) 75
    CrossrefPubMedSearch in Google Scholar
  • 55 Jellis CL, Kwon DH. Myocardial T1 mapping: modalities and clinical applications. Cardiovasc Diagn Ther 2014; 4 (02) 126-137
    PubMedSearch in Google Scholar
  • 56 Burt JR, Zimmerman SL, Kamel IR, Halushka M, Bluemke DA. Myocardial T1 mapping: techniques and potential applications. Radiographics 2014; 34 (02) 377-395
    CrossrefPubMedSearch in Google Scholar
  • 57 Treibel TA, Bandula S, Fontana M. et al. Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis. J Cardiovasc Comput Tomogr 2015; 9 (06) 585-592
    CrossrefPubMedSearch in Google Scholar
  • 58 Karamitsos TD, Piechnik SK, Banypersad SM. et al. Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. JACC Cardiovasc Imaging 2013; 6 (04) 488-497
    CrossrefPubMedSearch in Google Scholar
  • 59 Fontana M, Banypersad SM, Treibel TA. et al. Native T1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging 2014; 7 (02) 157-165
    CrossrefPubMedSearch in Google Scholar
  • 60 Liu JM, Liu A, Leal J. et al. Measurement of myocardial native T1 in cardiovascular diseases and norm in 1291 subjects. J Cardiovasc Magn Reson 2017; 19 (01) 74
    CrossrefPubMedSearch in Google Scholar
  • 61 Fontana M, Banypersad SM, Treibel TA. et al. Differential myocyte responses in patients with cardiac transthyretin amyloidosis and light-chain amyloidosis: a cardiac MR imaging study. Radiology 2015; 277 (02) 388-397
    CrossrefPubMedSearch in Google Scholar
  • 62 Kotecha T, Martinez-Naharro A, Treibel TA. et al. Myocardial edema and prognosis in amyloidosis. J Am Coll Cardiol 2018; 71 (25) 2919-2931
    CrossrefPubMedSearch in Google Scholar
  • 63 Jeung MY, Germain P, Croisille P, El ghannudi S, Roy C, Gangi A. Myocardial tagging with MR imaging: overview of normal and pathologic findings. Radiographics 2012; 32 (05) 1381-1398
    CrossrefPubMedSearch in Google Scholar
  • 64 Williams LK, Forero JF, Popovic ZB. et al. Patterns of CMR measured longitudinal strain and its association with late gadolinium enhancement in patients with cardiac amyloidosis and its mimics. J Cardiovasc Magn Reson 2017; 19 (01) 61
    CrossrefPubMedSearch in Google Scholar
  • 65 Oda S, Utsunomiya D, Nakaura T. et al. Identification and assessment of cardiac amyloidosis by myocardial strain analysis of cardiac magnetic resonance imaging. Circ J 2017; 81 (07) 1014-1021
    CrossrefPubMedSearch in Google Scholar
  • 66 Deux JF, Mihalache CI, Legou F. et al. Noninvasive detection of cardiac amyloidosis using delayed enhanced MDCT: a pilot study. Eur Radiol 2015; 25 (08) 2291-2297
    CrossrefPubMedSearch in Google Scholar
  • 67 Lee HJ, Im DJ, Youn JC. et al. Myocardial extracellular volume fraction with dual-energy equilibrium contrast-enhanced cardiac CT in nonischemic cardiomyopathy: a prospective comparison with cardiac MR imaging. Radiology 2016; 280 (01) 49-57
    CrossrefPubMedSearch in Google Scholar
  • 68 Scully PR, Bastarrika G, Moon JC, Treibel TA. Myocardial extracellular volume quantification by cardiovascular magnetic resonance and computed tomography. Curr Cardiol Rep 2018; 20 (03) 15
    CrossrefPubMedSearch in Google Scholar