Generic placeholder image

Current Medical Imaging


ISSN (Print): 1573-4056
ISSN (Online): 1875-6603

Mini-Review Article

Role of Nuclear Imaging in Cardiac Amyloidosis Management: Clinical Evidence and Review of Literature

Author(s): Viviana Frantellizzi*, Laura Cosma, Arianna Pani, Mariano Pontico, Miriam Conte, Cristina De Angelis and Giuseppe De Vincentis

Volume 16, Issue 8, 2020

Page: [957 - 966] Pages: 10

DOI: 10.2174/1573405615666191210103452

Price: $65


Cardiac amyloidosis (CA) is an infiltrative disease characterized by the extracellular deposition of fibrils, amyloid, in the heart. The vast majority of patients with CA has one of two types between transthyretin amyloid (ATTR) and immunoglobulin light chain associated amyloid (AL), that have different prognosis and therapeutic options. CA is often underdiagnosed. The histological analysis of endomyocardial tissue is the gold standard for the diagnosis, although it has its limitations due to its invasive nature. Nuclear medicine now plays a key role in the early and accurate diagnosis of this disease, and in the ability to distinguish between the two forms. Recent several studies support the potential advantage of bone-seeking radionuclides as a screening technique for the most common types of amyloidosis, in particular ATTR form. This review presents noninvasive modalities to diagnose CA and focuses on the radionuclide imaging techniques (bone-seeking agents scintigraphy, cardiac sympathetic innervation and positron emission tomography studies) available to visualize myocardial amyloid involvement. Furthermore, we report the case of an 83-year old male with a history of prostate cancer, carcinoma of the cecum and kidney cancer, submitted to bone scan to detect bone metastasis, that revealed a myocardial uptake of 99mTC-HMPD suggestive of ATTR CA. An accurate and early diagnosis of CA able to distinguish beyween AL and ATTR CA combined to the improving therapies could improve the survival of patients with this disease.

Keywords: Cardiac amyloidosis, transthyretin amyloid, MIBG Scan, PET radiotracers, myocardial SPECT, cancer and amyloidosis.

Graphical Abstract
Izumiya Y, Takashio S, Oda S, Yamashita Y, Tsujita K. Recent advances in diagnosis and treatment of cardiac amyloidosis. J Cardiol 2018; 71(2): 135-43.
[ ] [PMID: 29113705]
Maleszewski JJ. Cardiac amyloidosis: Pathology, nomenclature, and typing. Cardiovasc Pathol 2015; 24(6): 343-50.
[ ] [PMID: 26361138]
Giorgetti A, Genovesi D, Milan E, et al. Cardiac amyloidosis. Clin Transl Imaging 2019; 7(1): 21-32.
Hassan W, Al-Sergani H, Mourad W, Tabbaa R. Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Tex Heart Inst J 2005; 32(2): 178-84.
[PMID: 16107109]
González-López E, López-Sainz Á, Garcia-Pavia P. Diagnosis and treatment of transthyretin cardiac amyloidosis. Progress and hope. Rev Esp Cardiol (Engl Ed) 2017; 70(11): 991-1004.
[ ] [PMID: 28870641]
Promislow SJ, Ruddy TD. The evolving landscape of nuclear imaging in cardiac amyloidosis. J Nucl Cardiol 2020; 27(1): 202-9.
[ ] [PMID: 29777480]
Andrikopoulou E, Bhambhvani P. Nuclear imaging of cardiac amyloidosis. J Nucl Cardiol 2019; 26(2): 505-8.
[ ] [PMID: 28822085]
Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016; 133(24): 2404-12.
[ ] [PMID: 27143678]
Glaudemans AWJM, van Rheenen RWJ, van den Berg MP, et al. Bone scintigraphy with (99m)technetium-hydroxymethylene diphosphonate allows early diagnosis of cardiac involvement in patients with transthyretin-derived systemic amyloidosis. Amyloid 2014; 21(1): 35-44.
[ ] [PMID: 24455993]
Kyriakou P, Mouselimis D, Tsarouchas A, et al. Diagnosis of cardiac amyloidosis: A systematic review on the role of imaging and biomarkers. BMC Cardiovasc Disord 2018; 18(1): 221.
[ ] [PMID: 30509186]
Bhogal S, Ladia V, Sitwala P, et al. Cardiac amyloidosis: An updated review with emphasis on diagnosis and future directions. Curr Probl Cardiol 2018; 43(1): 10-34.
[ ] [PMID: 29173805]
Alkhawam H, Patel D, Nguyen J, et al. Cardiac amyloidosis: pathogenesis, clinical context, diagnosis and management options. Acta Cardiol 2017; 72(4): 380-9.
[ ] [PMID: 28705053]
Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med 2018; 28(1): 10-21.
[ ] [PMID: 28739313]
Agha AM, Parwani P, Guha A, et al. Role of cardiovascular imaging for the diagnosis and prognosis of cardiac amyloidosis. Open Heart 2018; 5(2), e000881.
[ ] [PMID: 30305910]
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): 1022-30.
[ ] [PMID: 18325442]
Aljaroudi WA, Desai MY, Tang WHW, Phelan D, Cerqueira MD, Jaber WA. Role of imaging in the diagnosis and management of patients with cardiac amyloidosis: state of the art review and focus on emerging nuclear techniques. J Nucl Cardiol 2014; 21(2): 271-83.
[ ] [PMID: 24347127]
Noordzij W, Glaudemans AWJM, Longhi S, et al. Nuclear imaging for cardiac amyloidosis. Heart Fail Rev 2015; 20(2): 145-54.
[ ] [PMID: 25424887]
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(2): 195-201.
[ ] [PMID: 23400849]
Castano A, Haq M, Narotsky DL, et al. Multicenter study of planar Technetium 99m Pyrophosphate Cardiac imaging: predicting survival for patients with ATTR cardiac amyloidosis. JAMA Cardiol 2016; 1(8): 880-9.
[ ] [PMID: 27557400]
Yamamoto Y, Onoguchi M, Haramoto M, Kodani N, Komatsu A, Kitagaki H, et al. Novel method for quantitative evaluation of cardiac amyloidosis using (201)TlCl and (99m)Tc-PYP SPECT. Ann Nucl Med 2012; 26(8): 634-43.
[ ] [PMID: 22777859]
Papantoniou V, Valsamaki P, Kastritis S, Tsiouris S, Delichas Z, Papantoniou Y, et al. Imaging of cardiac amyloidosis by (99m)Tc-PYP scintigraphy. Hell J Nucl Med 2015; 18(Suppl. 1): 42-50.
[PMID: 26665211]
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(6): 1355-63.
[ ] [PMID: 26453570]
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(6): 1076-84.
[ ] [PMID: 16168294]
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(6): 659-70.
[ ] [PMID: 21679902]
Longhi S, Guidalotti PL, Quarta CC, et al. Identification of TTR-related subclinical amyloidosis with 99mTc-DPD scintigraphy. JACC Cardiovasc Imaging 2014; 7(5): 531-2.
[ ] [PMID: 24831216]
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(1): 17-24.
[ ] [PMID: 26849806]
Minutoli F, Di Bella G, Mazzeo A, et al. Comparison between (99m)Tc-diphosphonate imaging and MRI with late gadolinium enhancement in evaluating cardiac involvement in patients with transthyretin familial amyloid polyneuropathy. AJR Am J Roentgenol 2013; 200(3), W256-65.
[ ] [PMID: 23436870]
Cappelli F, Gallini C, Di Mario C, et al. Accuracy of 99mTc-Hydroxymethylene diphosphonate scintigraphy for diagnosis of transthyretin cardiac amyloidosis. J Nucl Cardiol 2019; 26(2): 497-504.
[ ] [PMID: 28537040]
Abulizi M, Cottereau A-S, Guellich A, et al. Early-phase myocardial uptake intensity of 99mTc-HMDP vs 99mTc-DPD in patients with hereditary transthyretin-related cardiac amyloidosis. J Nucl Cardiol 2018; 25(1): 217-22.
[ ] [PMID: 27804073]
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(4): 210-20.
[ ] [PMID: 26465835]
De Vincentis G, Frantellizzi V, Fedele F, et al. Role of cardiac 123I-mIBG imaging in predicting arrhythmic events in stable chronic heart failure patients with an ICD. J Nucl Cardiol 2018.
[ ] [PMID: 29594915]
Slart RHJA, Glaudemans AWJM, Hazenberg BPC, Noordzij W. Imaging cardiac innervation in amyloidosis. J Nucl Cardiol 2019; 26(1): 174-87.
[ ] [PMID: 28887775]
Coutinho MCA, 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(5): 627-36.
[ ] [PMID: 23833285]
Piekarski E, Chequer R, Algalarrondo V, 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(7): 1108-18.
[ ] [PMID: 29511839]
Sachchithanantham S, Wechalekar AD. Imaging in systemic amyloidosis. Br Med Bull 2013; 107(1): 41-56.
[ ] [PMID: 23896486]
Kim YJ, Ha S, Kim YI. Cardiac amyloidosis imaging with amyloid positron emission tomography: A systematic review and meta-analysis. J Nucl Cardiol 2018.
[ ] [PMID: 30022405]
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(9): 1652-62.
[ ] [PMID: 24841414]
Osborne DR, Acuff SN, Stuckey A, Wall JS. A routine PET/CT protocol with streamlined calculations for assessing cardiac amyloidosis using 18F-Florbetapir. Front Cardiovasc Med 2015; 2: 23.
[ ] [PMID: 26664895]
Park M-A, 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(8), e002954.
[ ] [PMID: 26259579]
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(2): 213-20.
[ ] [PMID: 23238792]
Lee S-P, Lee ES, Choi H, et al. 11C-Pittsburgh B PET imaging in cardiac amyloidosis. JACC Cardiovasc Imaging 2015; 8(1): 50-9.
[ ] [PMID: 25499132]
Pilebro B, Arvidsson S, Lindqvist P, et al. Positron emission tomography (PET) utilizing Pittsburgh compound B (PIB) for detection of amyloid heart deposits in hereditary transthyretin amyloidosis (ATTR). J Nucl Cardiol 2018; 25(1): 240-8.
[ ] [PMID: 27645889]
Van Der Gucht A, Galat A, Rosso J, et al. [18F]-NaF PET/CT imaging in cardiac amyloidosis. J Nucl Cardiol 2016; 23(4): 846-9.
[ ] [PMID: 26403145]
Morgenstern R, Yeh R, Castano A, Maurer MS, Bokhari S. 18Fluorine sodium fluoride positron emission tomography, a potential biomarker of transthyretin cardiac amyloidosis. J Nucl Cardiol 2018; 25(5): 1559-67.
[ ] [PMID: 28176254]
Gagliardi C, Tabacchi E, Bonfiglioli R, et al. Does the etiology of cardiac amyloidosis determine the myocardial uptake of [18F]-NaF PET/CT? J Nucl Cardiol 2017; 24(2): 746-9.
[ ] [PMID: 26976144]
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(11): 1733-9.
[ ] [PMID: 27307344]
Mekinian A, Jaccard A, Soussan M, et al. 18F-FDG PET/CT in patients with amyloid light-chain amyloidosis: Case-series and literature review. Amyloid 2012; 19(2): 94-8.
[ ] [PMID: 22587492]
Sharma M, Koman E, Ledley GS, Cho SH. Revisiting transthyretin related cardiac amyloidosis: Case report and review of literature. Clin Pract 2018; 8(2): 1054.
[ ] [PMID: 30069298]
Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med 2018; 28(1): 10-21.
[ ] [PMID: 28739313]
Alkhawam H, Patel D, Nguyen J, et al. Cardiac amyloidosis: Pathogenesis, clinical context, diagnosis and management options. Acta Cardiol 2017; 72(4): 380-9.
[ ] [PMID: 28705053]
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): 2872-91.
[ ] [PMID: 31171094]
Rigopoulos AG, Ali M, Abate E, et al. Advances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement. Heart Fail Rev 2019; 24(4): 521-33.
[ ] [PMID: 30790171]
Emdin M, Aimo A, Rapezzi C, et al. Treatment of cardiac transthyretin amyloidosis: An update. Eur Heart J 2019., ehz298.
[ ] [PMID: 31111153]
Ricci M, Frantellizzi V, Bulzonetti N, De Vincentis G. Reversibility of castration resistance status after Radium-223 dichloride treatment: Clinical evidence and Review of the literature. Int J Radiat Biol 2018; 1-29.
[ ] [PMID: 30557063]
De Vincentis G, Follacchio GA, Frantellizzi V, et al. 223Ra-dichloride therapy in an elderly bone metastatic castration-resistant prostate cancer patient: A case report presentation and comparison with existing literature. Aging Clin Exp Res 2018; 30(6): 677-80.
[ ] [PMID: 28856577]
Prelaj A, Rebuzzi SE, Buzzacchino F, et al. Radium-223 in patients with metastatic castration-resistant prostate cancer: Efficacy and safety in clinical practice. Oncol Lett 2019; 17(2): 1467-76.
[ ] [PMID: 30675201]
De Vincentis G, Monari F, Baldari S, et al. Narrative medicine in metastatic prostate cancer reveals ways to improve patient awareness & quality of care. Future Oncol 2018; 14(27): 2821-32.
[ ] [PMID: 29905090]
Sciarra A, Gentilucci A, Salciccia S, et al. Psychological and functional effect of different primary treatments for prostate cancer: A comparative prospective analysis. Urologic Oncol 2018; 36(7): 340-e7-.e21.

Rights & Permissions Print Export Cite as
© 2023 Bentham Science Publishers | Privacy Policy