Login Register Cart 0
Generic placeholder image

Current Cardiology Reviews

Editor-in-Chief

ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Cardiac Amyloidosis: A Contemporary Review of Medical and Surgical Therapy

Author(s): Drew Brownell, Aiswarya J. Pillai and Nandini Nair*

Volume 20, Issue 2, 2024

Published on: 04 October, 2023

Article ID: e041023221736 Pages: 10

DOI: 10.2174/011573403X240302230925043500

Price: $65

Abstract

Amyloidosis is a systemic disease initiated by deposition of misfolded proteins in the extracellular space, due to which multiple organs may be affected concomitantly. Cardiac amyloidosis, however, remains a major cause of morbidity and mortality in this population due to infiltrative /restrictive cardiomyopathy. This review attempts to focus on contemporary medical and surgical therapies for the different types of cardiac amyloidosis. Amyloidosis affecting the heart are predominantly of the transthyretin type (acquired in the older or genetic in the younger patients), and the monoclonal immunoglobulin light chain (AL) type which is solely acquired. A rare form of secondary amyloidosis AA type can also affect the heart due to excessive production and accumulation of the acute-phase protein called Serum Amyloid A” (SAA) in the setting of chronic inflammation, cancers or autoinflammatory disease. More commonly AA amyloidosis is seen in the liver and kidney. Other rare types are Apo A1 and Isolated Atrial Amyloidosis (AANF). Medical therapies have made important strides in the clinical management of the two common types of cardiac amyloidosis. Surgical therapies such as mechanical circulatory support and cardiac transplantation should be considered in appropriate patients. Future research using AI driven algorithms for early diagnosis and treatment as well as development of newer genetic engineering technologies will drive improvements in diagnosis, treatment and patient outcomes.

Keywords: Cardiac amyloidosis, mechanical circulatory support, ATTR, cardiac transplantation, cardiomyopathy.

Graphical Abstract

[1]
Sipe JD, Benson MD, Buxbaum JN, et al. Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 2014; 21(4): 221-4.
[http://dx.doi.org/10.3109/13506129.2014.964858] [PMID: 25263598]
[2]
Chamling B, Drakos S, Bietenbeck M, Klingel K, Meier C, Yilmaz A. Diagnosis of cardiac involvement in amyloid A amyloidosis by cardiovascular magnetic resonance imaging. Front Cardiovasc Med 2021; 8: 757642.
[http://dx.doi.org/10.3389/fcvm.2021.757642] [PMID: 34646875]
[3]
Pinney JH, Hawkins PN. Amyloidosis. Ann Clin Biochem 2012; 49(3): 229-41.
[http://dx.doi.org/10.1258/acb.2011.011225] [PMID: 22402917]
[4]
Spoladore R, Falasconi G, Marcatti M, et al. Advances in pharmacotherapy for cardiac amyloidosis. Expert Opin Pharmacother 2021; 22(4): 469-81.
[http://dx.doi.org/10.1080/14656566.2020.1836159] [PMID: 33043721]
[5]
Witteles RM. Cardiac transplantation and mechanical circulatory support in amyloidosis. JACC: CardioOncology 2021; 3(4): 516-21.
[http://dx.doi.org/10.1016/j.jaccao.2021.05.007] [PMID: 34729523]
[6]
Frumkin D, Taube ET, Stangl K, Knebel F. Rapid progression of aortic and mitral stenosis in a patient with AA amyloidosis: A case report. Eur Heart J Case Rep 2019; 3(2): ytz051.
[http://dx.doi.org/10.1093/ehjcr/ytz051] [PMID: 31449604]
[7]
Alkhawam H, Patel D, Nguyen J, et al. Cardiac amyloidosis: Pathogenesis, clinical context, diagnosis and management options. Acta Cardiol 2017; 72(4): 380-9.
[http://dx.doi.org/10.1080/00015385.2017.1335034] [PMID: 28705053]
[8]
Saleem M, Balla S, Amin MS, et al. Hereditary apolipoprotein A-I–associated cardiac amyloidosis. JACC Case Rep 2021; 3(7): 1032-7.
[http://dx.doi.org/10.1016/j.jaccas.2021.02.016] [PMID: 34317679]
[9]
Shah KB, Inoue Y, Mehra MR. Amyloidosis and the heart. Arch Intern Med 2006; 166(17): 1805-13.
[http://dx.doi.org/10.1001/archinte.166.17.1805] [PMID: 17000935]
[10]
Röcken C, Peters B, Juenemann G, et al. Atrial amyloidosis. Circulation 2002; 106(16): 2091-7.
[http://dx.doi.org/10.1161/01.CIR.0000034511.06350.DF] [PMID: 12379579]
[11]
Martinez-Naharro A, Hawkins PN, Fontana M. Cardiac amyloidosis. Clin Med 2018; 18 (Suppl. 2): s30-5.
[http://dx.doi.org/10.7861/clinmedicine.18-2-s30] [PMID: 29700090]
[12]
Adam RD, Coriu D, Jercan A, et al. Progress and challenges in the treatment of cardiac amyloidosis: A review of the literature. ESC Heart Fail 2021; 8(4): 2380-96.
[http://dx.doi.org/10.1002/ehf2.13443] [PMID: 34089308]
[13]
Griffin JM, Maurer MS. Transthyretin cardiac amyloidosis: A treatable form of heart failure with a preserved ejection fraction. Trends Cardiovasc Med 2021; 31(1): 59-66.
[http://dx.doi.org/10.1016/j.tcm.2019.12.003] [PMID: 31889610]
[14]
Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med 2018; 379(11): 1007-16.
[http://dx.doi.org/10.1056/NEJMoa1805689] [PMID: 30145929]
[15]
Elliott P, Drachman BM, Gottlieb SS, et al. Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circ Heart Fail 2022; 15(1): e008193.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.008193] [PMID: 34923848]
[16]
Ibrahim M, Saint Croix GR, Lacy S, et al. The use of diflunisal for transthyretin cardiac amyloidosis: A review. Heart Fail Rev 2022; 27(2): 517-24.
[http://dx.doi.org/10.1007/s10741-021-10143-4] [PMID: 34272629]
[17]
Siddiqi OK, Mints YY, Berk JL, et al. Diflunisal treatment is associated with improved survival for patients with early stage wild-type transthyretin (ATTR) amyloid cardiomyopathy: The Boston University Amyloidosis Center experience. Amyloid 2022; 29(2): 71-8.
[http://dx.doi.org/10.1080/13506129.2021.2000388] [PMID: 35083944]
[18]
Benbrahim M, Norman K, Sanchorawala V, Siddiqi OK, Hughes D. A review of novel agents and clinical considerations in patients with ATTR cardiac amyloidosis. J Cardiovasc Pharmacol 2021; (5): 544-8.
[http://dx.doi.org/10.1097/FJC.0000000000001004] [PMID: 33657048]
[19]
Judge DP, Heitner SB, Falk RH, et al. Transthyretin stabilization by AG10 in symptomatic transthyretin amyloid cardiomyopathy. J Am Coll Cardiol 2019; 74(3): 285-95.
[http://dx.doi.org/10.1016/j.jacc.2019.03.012] [PMID: 30885685]
[20]
Hanson JLS, Arvanitis M, Koch CM, et al. Use of serum transthyretin as a prognostic indicator and predictor of outcome in cardiac amyloid disease associated with wild-type transthyretin. Circ Heart Fail 2018; 11(2): e004000.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.117.004000] [PMID: 29449366]
[21]
Cappelli F, Martone R, Taborchi G, et al. Epigallocatechin-3-gallate tolerability and impact on survival in a cohort of patients with transthyretin-related cardiac amyloidosis. A single-center retrospective study. Intern Emerg Med 2018; 13(6): 873-80.
[http://dx.doi.org/10.1007/s11739-018-1887-x] [PMID: 29882023]
[22]
Yamamoto H, Yokochi T. Transthyretin cardiac amyloidosis: An update on diagnosis and treatment. ESC Heart Fail 2019; 6(6): 1128-39.
[http://dx.doi.org/10.1002/ehf2.12518] [PMID: 31553132]
[23]
Gamez J, Salvadó M, Reig N, et al. Transthyretin stabilization activity of the catechol- O -methyltransferase inhibitor tolcapone (SOM0226) in hereditary ATTR amyloidosis patients and asymptomatic carriers: Proof-of-concept study. Amyloid 2019; 26(2): 74-84.
[http://dx.doi.org/10.1080/13506129.2019.1597702] [PMID: 31119947]
[24]
Miller M, Pal A, Albusairi W, et al. Enthalpy-driven stabilization of transthyretin by AG10 mimics a naturally occurring genetic variant that protects from transthyretin amyloidosis. J Med Chem 2018; 61(17): 7862-76.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00817] [PMID: 30133284]
[25]
Fernandes L, Cardim-Pires TR, Foguel D, Palhano FL. Green tea polyphenol epigallocatechin-gallate in amyloid aggregation and neurodegenerative diseases. Front Neurosci 2021; 15: 718188.
[http://dx.doi.org/10.3389/fnins.2021.718188] [PMID: 34594185]
[26]
Yadav JD, Othee H, Chan KA, Man DC, Belliveau PP, Towle J. Transthyretin amyloid cardiomyopathy—current and future therapies. Ann Pharmacother 2021; 55(12): 1502-14.
[http://dx.doi.org/10.1177/10600280211000351] [PMID: 33685242]
[27]
Pinheiro F, Varejão N, Esperante S, et al. Tolcapone, a potent aggregation inhibitor for the treatment of familial leptomeningeal amyloidosis. FEBS J 2021; 288(1): 310-24.
[http://dx.doi.org/10.1111/febs.15339] [PMID: 32324953]
[28]
Nelson LT, Paxman RJ, Xu J, Webb B, Powers ET, Kelly JW. Blinded potency comparison of transthyretin kinetic stabilisers by subunit exchange in human plasma. Amyloid 2021; 28(1): 24-9.
[http://dx.doi.org/10.1080/13506129.2020.1808783] [PMID: 32811187]
[29]
Rubin J, Maurer MS. Cardiac amyloidosis: Overlooked, underappreciated, and treatable. Annu Rev Med 2020; 71(1): 203-19.
[http://dx.doi.org/10.1146/annurev-med-052918-020140] [PMID: 31986086]
[30]
Griffin JM, Rosenblum H, Maurer MS. Pathophysiology and therapeutic approaches to cardiac amyloidosis. Circ Res 2021; 128(10): 1554-75.
[http://dx.doi.org/10.1161/CIRCRESAHA.121.318187] [PMID: 33983835]
[31]
Solomon SD, Adams D, Kristen A, et al. Effects of patisiran, an RNA interference therapeutic, on cardiac parameters in patients with hereditary transthyretin-mediated amyloidosis. Circulation 2019; 139(4): 431-43.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.118.035831] [PMID: 30586695]
[32]
Antonopoulos AS, Panagiotopoulos I, Kouroutzoglou A, et al. Prevalence and clinical outcomes of transthyretin amyloidosis: A systematic review and meta‐analysis. Eur J Heart Fail 2022; 24(9): 1677-96.
[http://dx.doi.org/10.1002/ejhf.2589] [PMID: 35730461]
[33]
Koike H, Okumura T, Murohara T, Katsuno M. Multidisciplinary approaches for transthyretin amyloidosis. Cardiol Ther 2021; 10(2): 289-311.
[http://dx.doi.org/10.1007/s40119-021-00222-w] [PMID: 34089151]
[34]
Judge DP, Kristen AV, Grogan M, et al. Phase 3 multicenter study of revusiran in patients with hereditary transthyretin-mediated (hATTR) amyloidosis with cardiomyopathy (ENDEAVOUR). Cardiovasc Drugs Ther 2020; 34(3): 357-70.
[http://dx.doi.org/10.1007/s10557-019-06919-4] [PMID: 32062791]
[35]
Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: A randomized clinical trial. Amyloid 2023; 30(1): 18-26.
[http://dx.doi.org/10.1080/13506129.2022.2091985] [PMID: 35875890]
[36]
Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen treatment for, patients with hereditary transthyretin amyloidosis. N Engl J Med 2018; 379(1): 22-31.
[http://dx.doi.org/10.1056/NEJMoa1716793] [PMID: 29972757]
[37]
Cornell RF, Fraser R, Costa L, et al. Bortezomib-based induction is associated with superior outcomes in light chain amyloidosis patients treated with autologous hematopoietic cell transplantation regardless of plasma cell burden. Transplant Cell Ther 2021; 27(3): 264.e1-7.
[http://dx.doi.org/10.1016/j.jtct.2020.11.018] [PMID: 33781533]
[38]
Kennedy VE, Natsuhara K, Maringanti SA, et al. Daratumumab plus bortezomib and dexamethasone in newly diagnosed systemic light chain amyloidosis. Curr Probl Cancer 2023; 47(3): 100953.
[http://dx.doi.org/10.1016/j.currproblcancer.2023.100953] [PMID: 36807996]
[39]
Liu B, Wang Y, Ning X, et al. A comparative study of cyclophosphamide, thalidomide and dexamethasone (CTD) versus bortezomib and dexamethasone (BDex) in light-chain amyloidosis. Curr Probl Cancer 2021; 45(2): 100669.
[http://dx.doi.org/10.1016/j.currproblcancer.2020.100669] [PMID: 33127168]
[40]
Aimo A, Castiglione V, Rapezzi C, et al. RNA-targeting and gene editing therapies for transthyretin amyloidosis. Nat Rev Cardiol 2022; 19(10): 655-67.
[http://dx.doi.org/10.1038/s41569-022-00683-z] [PMID: 35322226]
[41]
Siddiqi OK, Ruberg FL. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment. Trends Cardiovasc Med 2018; 28(1): 10-21.
[http://dx.doi.org/10.1016/j.tcm.2017.07.004] [PMID: 28739313]
[42]
Bustamante JG, Zaidi SRH. Amyloidosis. StatPearls. Treasure Island, FL: StatPearls Publishing 2021.
[43]
Chaulagain CP, Herlitz LC, Fu J, Bilani N, Lucitt C, Comenzo RL. How we manage systemic immunoglobulin heavy chain amyloidosis (AH amyloidosis) and immunoglobulin heavy-and-light-chain amyloidosis (AH/AL Amyloidosis). Clin Lymphoma Myeloma Leuk 2020; 20(11): e826-31.
[http://dx.doi.org/10.1016/j.clml.2020.06.017] [PMID: 32703752]
[44]
Papa R, Lachmann HJ. Secondary, AA, amyloidosis. Rheum Dis Clin North Am 2018; 44(4): 585-603.
[http://dx.doi.org/10.1016/j.rdc.2018.06.004] [PMID: 30274625]
[45]
Yilmaz A, Bauersachs J, Bengel F, et al. Diagnosis and treatment of cardiac amyloidosis: Position statement of the German Cardiac Society (DGK). Clin Res Cardiol 2021; 110(4): 479-506.
[http://dx.doi.org/10.1007/s00392-020-01799-3] [PMID: 33459839]
[46]
Westermark GT, Fändrich M, Westermark P. AA amyloidosis: Pathogenesis and targeted therapy. Annu Rev Pathol 2015; 10(1): 321-44.
[http://dx.doi.org/10.1146/annurev-pathol-020712-163913] [PMID: 25387054]
[47]
Muchtar E, Dispenzieri A, Magen H, et al. Systemic amyloidosis from A (AA) to T (ATTR): A review. J Intern Med 2021; 289(3): 268-92.
[http://dx.doi.org/10.1111/joim.13169] [PMID: 32929754]
[48]
Moutafi M, Ziogas DC, Michopoulos S, et al. A new genetic variant of hereditary apolipoprotein A-I amyloidosis: A case-report followed by discussion of diagnostic challenges and therapeutic options. BMC Med Genet 2019; 20(1): 23.
[http://dx.doi.org/10.1186/s12881-019-0755-5] [PMID: 30665372]
[49]
Hyer C, Campbell C, Kahwash R. Clinical implications of atrial natriuretic peptide amyloidosis. BMJ Case Rep 2021; 14(6): e242856.
[http://dx.doi.org/10.1136/bcr-2021-242856] [PMID: 34155027]
[50]
Esplin BL, Gertz MA. Current trends in diagnosis and management of cardiac amyloidosis. Curr Probl Cardiol 2013; 38(2): 53-96.
[http://dx.doi.org/10.1016/j.cpcardiol.2012.11.002] [PMID: 23337445]
[51]
Aimo A, Vergaro G, Castiglione V, Rapezzi C, Emdin M. Safety and tolerability of neurohormonal antagonism in cardiac amyloidosis. Eur J Intern Med 2020; 80: 66-72.
[http://dx.doi.org/10.1016/j.ejim.2020.05.015] [PMID: 32475765]
[52]
van den Berg MP, Mulder BA, Klaassen SHC, et al. Heart failure with preserved ejection fraction, atrial fibrillation, and the role of senile amyloidosis. Eur Heart J 2019; 40(16): 1287-93.
[http://dx.doi.org/10.1093/eurheartj/ehz057] [PMID: 30753432]
[53]
Grupper A, Park SJ, Pereira NL, et al. Role of ventricular assist therapy for patients with heart failure and restrictive physiology: Improving outcomes for a lethal disease. J Heart Lung Transplant 2015; 34(8): 1042-9.
[http://dx.doi.org/10.1016/j.healun.2015.03.012] [PMID: 25940074]
[54]
Kittleson MM, Cole RM, Patel J, et al. Mechanical circulatory support for cardiac amyloidosis. Clin Transplant 2019; 33(10): e13663.
[http://dx.doi.org/10.1111/ctr.13663] [PMID: 31309629]
[55]
Michelis KC, Zhong L, Tang WHW, et al. Durable mechanical circulatory support in patients with amyloid cardiomyopathy. Circ Heart Fail 2020; 13(12): e007931.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.120.007931] [PMID: 33164568]
[56]
Davis MK, Lee PHU, Witteles RM. Changing outcomes after heart transplantation in patients with amyloid cardiomyopathy. J Heart Lung Transplant 2015; 34(5): 658-66.
[http://dx.doi.org/10.1016/j.healun.2014.09.006] [PMID: 25444369]
[57]
Grogan M, Gertz M, McCurdy A, et al. Long term outcomes of cardiac transplant for immunoglobulin light chain amyloidosis: The Mayo Clinic experience. World J Transplant 2016; 6(2): 380-8.
[http://dx.doi.org/10.5500/wjt.v6.i2.380] [PMID: 27358783]
[58]
Rosenbaum AN, AbouEzzeddine OF, Grogan M, et al. Outcomes after cardiac transplant for wild type transthyretin amyloidosis. Transplantation 2018; 102(11): 1909-13.
[http://dx.doi.org/10.1097/TP.0000000000002240] [PMID: 29677073]
[59]
Kristen AV, Kreusser MM, Blum P, et al. Improved outcomes after heart transplantation for cardiac amyloidosis in the modern era. J Heart Lung Transplant 2018; 37(5): 611-8.
[http://dx.doi.org/10.1016/j.healun.2017.11.015] [PMID: 29217108]
[60]
Griffin JM, Chiu L, Axsom KM, et al. Outcomes after heart transplantation for al compared to ATTR cardiac amyloidosis. Clin Transplant 2020; 34(10): e14028.
[http://dx.doi.org/10.1111/ctr.14028] [PMID: 32623785]
[61]
Barrett CD, Alexander KM, Zhao H, et al. Outcomes in patients with cardiac amyloidosis undergoing heart transplantation. JACC Heart Fail 2020; 8(6): 461-8.
[http://dx.doi.org/10.1016/j.jchf.2019.12.013] [PMID: 32387068]
[62]
Chen Q, Moriguchi J, Levine R, et al. Outcomes of heart transplantation in cardiac amyloidosis patients: A single center experience. Transplant Proc 2021; 53(1): 329-34.
[http://dx.doi.org/10.1016/j.transproceed.2020.08.020] [PMID: 32917391]
[63]
Ohiomoba RO, Youmans QR, Ezema A, et al. Cardiac transplantation outcomes in patients with amyloid cardiomyopathy. Am Heart J 2021; 236: 13-21.
[http://dx.doi.org/10.1016/j.ahj.2021.02.016] [PMID: 33621542]
[64]
Qualls DA, Lewis GD, Sanchorawala V, Staron A. Orthotopic heart transplant rejection in association with immunomodulatory therapy for AL amyloidosis: A case series and review of the literature. Am J Transplant 2019; 19(11): 3185-90.
[http://dx.doi.org/10.1111/ajt.15499] [PMID: 31207062]
[65]
García-García E, González-Romero GM, Martín-Pérez EM, Zapata Cornejo ED, Escobar-Aguilar G, Cárdenas Bonnet MF. Real-world data and machine learning to predict cardiac amyloidosis. Int J Environ Res Public Health 2021; 18(3): 908.
[http://dx.doi.org/10.3390/ijerph18030908] [PMID: 33494357]
[66]
Schrutka L, Anner P, Agibetov A, et al. Machine learning-derived electrocardiographic algorithm for the detection of cardiac amyloidosis. Heart 2022; 108(14): 1137-47.
[http://dx.doi.org/10.1136/heartjnl-2021-319846] [PMID: 34716183]
[67]
Agibetov A, Seirer B, Dachs TM, et al. Machine learning enables prediction of cardiac amyloidosis by routine laboratory parameters: A proof-of-concept study. J Clin Med 2020; 9(5): 1334.
[http://dx.doi.org/10.3390/jcm9051334] [PMID: 32375287]
[68]
Lacy MQ, Dispenzieri A, Hayman SR, et al. Autologous stem cell transplant after heart transplant for light chain (Al) amyloid cardiomyopathy. J Heart Lung Transplant 2008; 27(8): 823-9.
[http://dx.doi.org/10.1016/j.healun.2008.05.016] [PMID: 18656793]
[69]
Gillmore JD, Gane E, Taubel J, et al. CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis. N Engl J Med 2021; 385(6): 493-502.
[http://dx.doi.org/10.1056/NEJMoa2107454] [PMID: 34215024]
[70]
Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 2012; 337(6096): 816-21.
[http://dx.doi.org/10.1126/science.1225829] [PMID: 22745249]
[71]
Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 2014; 157(6): 1262-78.
[http://dx.doi.org/10.1016/j.cell.2014.05.010] [PMID: 24906146]
[72]
Li H, Yang Y, Hong W, Huang M, Wu M, Zhao X. Applications of genome editing technology in the targeted therapy of human diseases: Mechanisms, advances and prospects. Signal Transduct Target Ther 2020; 5(1): 1.
[http://dx.doi.org/10.1038/s41392-019-0089-y] [PMID: 32296011]
[73]
Dasgupta I, Flotte TR, Keeler AM. CRISPR/Cas-dependent and nuclease-free in vivo therapeutic gene editing. Hum Gene Ther 2021; 32(5-6): 275-93.
[http://dx.doi.org/10.1089/hum.2021.013] [PMID: 33750221]

Rights & Permissions Print Cite
Article Metrics
13
© 2024 Bentham Science Publishers | Privacy Policy