|
|
转甲状腺素蛋白淀粉样变心肌病的研究现状
|
Abstract:
转甲状腺素蛋白淀粉样变心肌病(ATTR-CM)是一种罕见的进行性衰弱性疾病。ATTR-CM主要是由于TTR淀粉样蛋白在心肌中的积聚而引起的。然而，ATTR-CM的临床表现多样且缺乏特异性，因此很容易被误诊或漏诊。目前有多种辅助检查可用于更准确地诊断该病，但它们的临床价值各不相同。尽管该病的整体预后不佳，但随着对该病的深入研究，越来越多的治疗方案正在被探索并进行临床实验。本文对转甲状腺素蛋白淀粉样变心肌病的研究现状进行了综述。
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, progressive and debilitating disease. ATTR-CM is mainly caused by the accumulation of TTR amyloid protein in the myocardium. Howev-er, the clinical manifestations of ATTR-CM are diverse and lack specificity, so it is easily misdiag-nosed or missed. There are a variety of tests available to more accurately diagnose the disease, but their clinical value varies. Despite the overall poor prognosis of the disease, more and more treat-ment options are being explored and undergoing clinical trials as the disease is further studied. This article reviews the research status in transthyretin amyloid cardiomyopathy.
| [1] | Gillmore, J.D. and Hawkins, P.N. (2013) Pathophysiology and Treatment of Systemic Amyloidosis. Nature Reviews Nephrology, 9, 574-586. https://doi.org/10.1038/nrneph.2013.171 |
| [2] | Donnelly, J.P. and Hanna, M. (2017) Car-diac Amyloidosis: An Update on Diagnosis and Treatment. Cleveland Clinic Journal of Medicine, 84, 12-26. https://doi.org/10.3949/ccjm.84.s3.02 |
| [3] | Kholova, I. and Niessen, H.W.M. (2005) Amyloid in the Cardiovascular System: A Review. Journal of Clinical Pathology, 58, 125-133. https://doi.org/10.1136/jcp.2004.017293 |
| [4] | Rowczenio, D.M., Noor, I., Gillmore, J.D., et al. (2014) Online Registry for Mutations in Hereditary Amyloidosis Including Nomenclature Recommendations. Human Mutation, 35, E2403-E2412. https://doi.org/10.1002/humu.22619 |
| [5] | Maurer, M.S., Hanna, M., Grogan, M., et al. (2016) Gen-otype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). Journal of the American College of Cardiology, 68, 161-172.
https://doi.org/10.1016/j.jacc.2016.03.596 |
| [6] | Coelho, T., Maurer, M.S. and Suhr, O.B. (2013) THAOS—The Transthyretin Amyloidosis Outcomes Survey: Initial Report on Clinical Manifestations in Patients with Hereditary and Wild-Type Transthyretin Amyloidosis. Current Medical Research and Opinion, 29, 63-76. https://doi.org/10.1185/03007995.2012.754348 |
| [7] | Rapezzi, C., Quarta, C.C., Obici, L., et al. (2013) Disease Profile and Differential Diagnosis of Hereditary Transthyretin-Related Amyloidosis with Exclusively Cardiac Phenotype: An Italian Perspective. European Heart Journal, 34, 520-528. https://doi.org/10.1093/eurheartj/ehs123 |
| [8] | Grogan, M., Scott, C.G., Kyle, R.A., et al. (2016) Natural History of Wild-Type Transthyretin Cardiac Amyloidosis and Risk Stratification Using a Novel Staging System. Journal of the American College of Cardiology, 68, 1014-1020.
https://doi.org/10.1016/j.jacc.2016.06.033 |
| [9] | Tanskanen, M., Peuralinna, T., Polvikoski, T., et al. (2008) Senile Systemic Amyloidosis Affects 25% of the Very Aged and Associates with Genetic Variation in alpha2-Macroglobulin and Tau: A Population-Based Autopsy Study. Annals of Medicine, 40, 232-239. https://doi.org/10.1080/07853890701842988 |
| [10] | Scully, P.R., Treibel, T.A., Fontana, M., et al. (2018) Prevalence of Cardiac Amyloidosis in Patients Referred for Transcatheter Aortic Valve Replacement. Journal of the American Col-lege of Cardiology, 71, 463-464.
https://doi.org/10.1016/j.jacc.2017.11.037 |
| [11] | Miyamoto, M., Nakamura, K., Nakagawa, K., et al. (2023) Preva-lence and Treatment of Arrhythmias in Patients with Transthyretin and Light-Chain Cardiac Amyloidosis. Circulation Reports, 5, 298-305.
https://doi.org/10.1253/circrep.CR-23-0022 |
| [12] | 中华医学会心血管病学分会心力衰竭学组, 中华心血管病杂志编辑委员会. 转甲状腺素蛋白心脏淀粉样变诊断与治疗中国专家共识[J]. 中华心血管病杂志, 2021, 49(4): 324-332. |
| [13] | Murtagh, B., Hammill, S.C., Gertz, M.A., et al. (2005) Electrocardiographic Findings in Primary Sys-temic Amyloidosis and Biopsy-Proven Cardiac Involvement. American Journal of Cardiology, 95, 535-537.
https://doi.org/10.1016/j.amjcard.2004.10.028 |
| [14] | Gertz, M.A., Benson, M.D., Dyck, P.J., et al. (2015) Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis. Journal of the American College of Cardiology, 66, 2451-2466. https://doi.org/10.1016/j.jacc.2015.09.075 |
| [15] | Liu, D., Hu, K., Niemann, M., et al. (2013) Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis from Other Causes of Concentric Left Ventricular Hypertrophy. Circulation: Cardiovascular Imaging, 6, 1066-1072. https://doi.org/10.1161/CIRCIMAGING.113.000683 |
| [16] | Phelan, D., Collier, P., Thavendiranathan, P., et al. (2012) Relative Apical Sparing of Longitudinal Strain Using Two-Dimensional Speckle-Tracking Echocardiography Is both Sensitive and Specific for the Diagnosis of Cardiac Amyloidosis. Heart, 98, 1442-1448. https://doi.org/10.1136/heartjnl-2012-302353 |
| [17] | Casella, M., Compagnucci, P., Ciliberti, G., et al. (2023) Char-acteristics and Clinical Value of Electroanatomical Voltage Mapping in Cardiac Amyloidosis. Canadian Journal of Car-diology. https://doi.org/10.1016/j.cjca.2023.10.022 |
| [18] | Zhao, L., Tian, Z. and Fang, Q. (2016) Diagnostic Accu-racy of Cardiovascular Magnetic Resonance for Patients with Suspected Cardiac Amyloidosis: A Systematic Review and Meta-Analysis. BMC Cardiovascular Disorders, 16, Article No. 129. https://doi.org/10.1186/s12872-016-0311-6 |
| [19] | Messroghli, D.R., Moon, J.C., Ferreira, V.M., et al. (2017) Clin-ical 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 Asso-ciation for Cardiovascular Imaging (EACVI). Journal of Cardiovascular Magnetic Resonance, 19, Article No. 75. https://doi.org/10.1186/s12968-017-0389-8 |
| [20] | Pan, J.A., Kerwin, M.J. and Salerno, M. (2020) Native T1 Map-ping, Extracellular Volume Mapping, and Late Gadolinium Enhancement in Cardiac Amyloidosis: A Meta-Analysis. JACC: Cardiovascular Imaging, 13, 1299-1310.
https://doi.org/10.1016/j.jcmg.2020.03.010 |
| [21] | Rapezzi, C., Quarta, C.C., Guidalotti, P.L., et al. (2011) Useful-ness and Limitations of 99mTc-3,3-Diphosphono-1,2- propanodicarboxylic Acid Scintigraphy in the Aetiological Diag-nosis of Amyloidotic Cardiomyopathy. European Journal of Nuclear Medicine and Molecular Imaging, 38, 470-478.
https://doi.org/10.1007/s00259-010-1642-7 |
| [22] | Bokhari, S., Casta？o, A., Pozniakoff, T., et al. (2013) 99mTc-Pyrophosphate Scintigraphy for Differentiating Light-Chain Cardiac Amyloidosis from the Transthyretin-Related Familial and Senile Cardiac Amyloidoses. Circulation: Cardiovascular Imaging, 6, 195-201. https://doi.org/10.1161/CIRCIMAGING.112.000132 |
| [23] | Gillmore, J.D., Maurer, M.S., Falk, R.H., et al. (2016) Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation, 133, 2404-2412. https://doi.org/10.1161/CIRCULATIONAHA.116.021612 |
| [24] | Garcia-Pavia, P., Rapezzi, C., Adler, Y., et al. (2021) Diagnosis and Treatment of Cardiac Amyloidosis: A Position Statement of the ESC Working Group on Myocar-dial and Pericardial Diseases. European Heart Journal, 42, 1554-1568.
https://doi.org/10.1093/eurheartj/ehab072 |
| [25] | Cimiotti, D., Budde, H., Hassoun, R., et al. (2021) Genetic Restric-tive Cardiomyopathy: Causes and Consequences— An Integrative Approach. International Journal of Molecular Sci-ences, 22, Article No. 558.
https://doi.org/10.3390/ijms22020558 |
| [26] | Brown, E.E., Lee, Y.Z.J., Halushka, M.K., et al. (2017) Genetic Testing Improves Identification of Transthyretin Amyloid (ATTR) Subtype in Cardiac Amyloidosis. Amyloid, 24, 92-95.
https://doi.org/10.1080/13506129.2017.1324418 |
| [27] | Saelices, L., Chung, K., Lee, J.H., et al. (2018) Amyloid Seeding of Transthyretin by ex Vivo Cardiac Fibrils and Its Inhibition. Proceedings of the National Academy of Sciences of the United States of America, 115, E6741-E6750.
https://doi.org/10.1073/pnas.1805131115 |
| [28] | Nelson, L.M., Penninga, L., Sander, K., et al. (2013) Long-Term Outcome in Patients Treated with Combined Heart and Liver Transplantation for Familial Amyloidotic Cardiomyopathy. Clinical Transplantation, 27, 203-209.
https://doi.org/10.1111/ctr.12053 |
| [29] | Maurer, M.S., Schwartz, J.H., Gundapaneni, B., et al. (2018) Tafamidis Treatment for Patients with Trans-Thyretin Amyloid Cardiomyopathy. The New England Journal of Medicine, 379, 1007-1016.
https://doi.org/10.1056/NEJMoa1805689 |
| [30] | Shah, S.J., Fine, N., Garcia-Pavia, P., et al. (2023) Effect of Ta-famidis on Cardiac Function in Patients with Transthyretin Amyloid Cardiomyopathy: A Post Hoc Analysis of the ATTR-ACT Randomized Clinical Trial. JAMA Cardiology, 8, e234147. https://doi.org/10.1001/jamacardio.2023.4147 |
| [31] | Miller, M., Pal, A., Albusairi, W., et al. (2018) Enthalpy-Driven Stabilization of Transthyretin by AG10 Mimics a Naturally Occurring Genetic Variant That Protects from Transthyretin Amyloidosis. Journal of Medicinal Chemistry, 61, 7862-7876. https://doi.org/10.1021/acs.jmedchem.8b00817 |
| [32] | Nelson, L.T., Paxman, R.J., Xu, J., et al. (2021) Blinded Po-tency Comparison of Transthyretin Kinetic Stabilisers by Subunit Exchange in Human Plasma. Amyloid, 28, 24-29. https://doi.org/10.1080/13506129.2020.1808783 |
| [33] | Judge, D.P., Heitner, S.B., Falk, R.H., et al. (2019) Trans-thyretin Stabilization by AG10 in Symptomatic Transthyretin Amyloid Cardiomyopathy. Journal of the American College of Cardiology, 74, 285-295.
https://doi.org/10.1016/j.jacc.2019.03.012 |
| [34] | Almeida, M.R., Gales, L., Damas, A.M., et al. (2005) Small Trans-thyretin (TTR) Ligands as Possible Therapeutic Agents in TTR Amyloidoses. Current Drug Targets—CNS & Neuro-logical Disorders, 4, 587-596.
https://doi.org/10.2174/156800705774322076 |
| [35] | Berk, J.L., Suhr, O.B., Obici, L., et al. (2013) Repurposing Diflunisal for Familial Amyloid Polyneuropathy: A Randomized Clinical Trial. JAMA, 310, 2658-2667. https://doi.org/10.1001/jama.2013.283815 |
| [36] | Wixner, J., Westermark, P., Ihse, E., et al. (2019) The Swedish Open-Label Diflunisal Trial (DFNS01) on Hereditary Transthyretin Amyloidosis and the Impact of Amyloid Fibril Composition. Amyloid, 26, 39-40.
https://doi.org/10.1080/13506129.2019.1593133 |
| [37] | Lohrmann, G., Pipilas, A., Mussinelli, R., et al. (2020) Sta-bilization of Cardiac Function with Diflunisal in Transthyretin (ATTR) Cardiac Amyloidosis. Journal of Cardiac Failure, 26, 753-759.
https://doi.org/10.1016/j.cardfail.2019.11.024 |
| [38] | Almeida, M.R., Macedo, B., Cardoso, I., et al. (2004) Selective Binding to Transthyretin and Tetramer Stabilization in Serum from Patients with Familial Amyloidotic Polyneuropathy by an Iodinated Diflunisal Derivative. Biochemical Journal, 381, 351-356. https://doi.org/10.1042/BJ20040011 |
| [39] | Gamez, J., Salvadó, M., Reig, N., et al. (2019) Transthyretin Stabilization Activity of the Catechol-O-Methyltransferase Inhibitor Tolcapone (SOM0226) in Hereditary ATTR Amyloidosis Patients and Asymptomatic Carriers: Proof-of- Concept Study. Amyloid, 26, 74-84. https://doi.org/10.1080/13506129.2019.1597702 |
| [40] | Corazza, A., Verona, G., Waudby, C.A., et al. (2019) Bind-ing of Monovalent and Bivalent Ligands by Trans-Thyretin Causes Different Short- and Long-Distance Conformational Changes. Journal of Medicinal Chemistry, 62, 8274-8283.
https://doi.org/10.1021/acs.jmedchem.9b01037 |
| [41] | Verona, G., Mangione, P.P., Raimondi, S., et al. (2017) Inhi-bition of the Mechano-Enzymatic Amyloidogenesis of Transthyretin: Role of Ligand Affinity, Binding Cooperativity and Occupancy of the Inner Channel. Scientific Reports, 7, Article No. 182. https://doi.org/10.1038/s41598-017-00338-x |
| [42] | Pinheiro, F., Varej？o, N., Sánchez-Morales, A., et al. (2023) PITB: A High Affinity Transthyretin Aggregation Inhibitor with Optimal Pharmacokinetic Properties. European Journal of Medicinal Chemistry, 261, Article ID: 115837.
https://doi.org/10.1016/j.ejmech.2023.115837 |
| [43] | Penchala, S.C., Connelly, S., Wang, Y., et al. (2013) AG10 In-hibits Amyloidogenesis and Cellular Toxicity of the Familial Amyloid Cardiomyopathy-Associated V122I Transthyretin. Proceedings of the National Academy of Sciences of the United States of America, 110, 9992-9997. https://doi.org/10.1073/pnas.1300761110 |
| [44] | Liu, Y.T., Yen, Y.J., Ricardo, F., et al. (2019) Biophysical Charac-terization and Modulation of Transthyretin Ala97Ser. Annals of Clinical and Translational Neurology, 6, 1961-1970. https://doi.org/10.1002/acn3.50887 |
| [45] | Suhr, O.B., Coelho, T., Buades, J., et al. (2015) Efficacy and Safety of Patisiran for Familial Amyloidotic Polyneuropathy: A Phase II Multi-Dose Study. Orphanet Journal of Rare Diseases, 10, Article No. 109.
https://doi.org/10.1186/s13023-015-0326-6 |
| [46] | Coelho, T., Adams, D., Concei？？o, I., et al. (2020) A Phase II, Open-Label, Extension Study of Long-Term Patisiran Treatment in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis. Orphanet Journal of Rare Diseases, 15, Article No. 179. https://doi.org/10.1186/s13023-020-01399-4 |
| [47] | Adams, D., Gonzalez-Duarte, A., O’Riordan, W.D., et al. (2018) Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. The New England Journal of Medicine, 379, 11-21.
https://doi.org/10.1056/NEJMoa1716153 |
| [48] | Fontana, M., Martinez-Naharro, A., Chacko, L., et al. (2021) Re-duction in CMR Derived Extracellular Volume with Patisiran Indicates Cardiac Amyloid Regression. JACC: Cardiovas-cular Imaging, 14, 189-199.
https://doi.org/10.1016/j.jcmg.2020.07.043 |
| [49] | Maurer, M.S., Kale, P., Fontana, M., et al. (2023) Patisiran Treat-ment in Patients with Transthyretin Cardiac Amyloidosis. The New England Journal of Medicine, 389, 1553-1565. https://doi.org/10.1056/NEJMoa2300757 |
| [50] | Ando, Y., Adams, D., Benson, M.D., et al. (2022) Guidelines and New Directions in the Therapy and Monitoring of ATTRv Amyloidosis. Amyloid, 29, 143-155. https://doi.org/10.1080/13506129.2022.2052838 |
| [51] | Habtemariam, B.A., Karsten, V., Attarwala, H., et al. (2021) Single-Dose Pharmacokinetics and Pharmaco-Dynamics of Transthyretin Targeting N-Acetylgalactosamine-Small Inter-fering Ribonucleic Acid Conjugate, Vutrisiran, in Healthy Subjects. Clinical Pharmacology & Therapeutics, 109, 372-382. https://doi.org/10.1002/cpt.1974 |
| [52] | Adams, D., Tournev, I.L., Taylor, M.S., et al. (2023) Efficacy and Safety of Vutrisiran for Patients with Hereditary Transthyretin-Mediated Amyloidosis with Polyneuropathy: A Random-ized Clinical Trial. Amyloid, 30, 18-26.
https://doi.org/10.1080/13506129.2022.2091985 |
| [53] | Zimmermann, T.S., Karsten, V., Chan, A., et al. (2017) Clinical Proof of Concept for a Novel Hepatocyte-Targeting GalNAc-siRNA Conjugate. Molecular Therapy, 25, 71-78. https://doi.org/10.1016/j.ymthe.2016.10.019 |
| [54] | Judge, D.P., Kristen, A.V., Grogan, M., et al. (2020) Phase 3 Multicenter Study of Revusiran in Patients with Hereditary Transthyretin-Mediated (hATTR) Amyloidosis with Cardio-myopathy (ENDEAVOUR). Cardiovascular Drugs and Therapy, 34, 357-370. https://doi.org/10.1007/s10557-019-06919-4 |
| [55] | Hawkins, P.N., Ando, Y., Dispenzeri, A., et al. (2015) Evolving Landscape in the Management of Transthyretin Amyloidosis. Annals of Medicine, 47, 625-638. https://doi.org/10.3109/07853890.2015.1068949 |
| [56] | Dasgupta, N.R., Rissing, S.M., Smith, J., et al. (2020) In-otersen Therapy of Transthyretin Amyloid Cardiomyopathy. Amyloid, 27, 52-58. https://doi.org/10.1080/13506129.2019.1685487 |
| [57] | Benson, M.D., Waddington-Cruz, M., Berk, J.L., et al. (2018) Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. The New England Journal of Medi-cine, 379, 22-31. https://doi.org/10.1056/NEJMoa1716793 |
| [58] | Viney, N.J., Guo, S., Tai, L.J., et al. (2021) Lig-and Conjugated Antisense Oligonucleotide for the Treatment of Transthyretin Amyloidosis: Preclinical and Phase 1 Data. ESC Heart Failure, 8, 652-661. https://doi.org/10.1002/ehf2.13154 |
| [59] | Coelho, T., Marques, W., Dasgupta, N.R., et al. (2023) Eplontersen for Hereditary Transthyretin Amyloidosis with Polyneuropathy. JAMA, 330, 1448-1458. https://doi.org/10.1001/jama.2023.18688 |
| [60] | Maurer, M.S. (2021) Gene Editing—A Cure for Transthyretin Am-yloidosis? The New England Journal of Medicine, 385, 558-559. https://doi.org/10.1056/NEJMe2110557 |
| [61] | Finn, J.D., Smith, A.R., Patel, M.C., et al. (2018) A Single Admin-istration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent in Vivo Genome Editing. Cell Reports, 22, 2227-2235.
https://doi.org/10.1016/j.celrep.2018.02.014 |
| [62] | Gillmore, J.D., Gane, E., Taubel, J., et al. (2021) CRISPR-Cas9 in Vivo Gene Editing for Transthyretin Amyloidosis. The New England Journal of Medicine, 385, 493-502. https://doi.org/10.1056/NEJMoa2107454 |
| [63] | Chukwudi, C.U. (2016) rRNA Binding Sites and the Molecular Mechanism of Action of the Tetracyclines. Antimicrobial Agents and Chemotherapy, 60, 4433-4441. https://doi.org/10.1128/AAC.00594-16 |
| [64] | Medina, L., González-Lizárraga, F., Dominguez-Meijide, A., et al. (2021) Doxycycline Interferes with Tau Aggregation and Reduces Its Neuronal Toxicity. Frontiers in Aging Neurosci-ence, 13, Article ID: 635760.
https://doi.org/10.3389/fnagi.2021.635760 |
| [65] | Cardoso, I., Martins, D., Ribeiro, T., et al. (2010) Synergy of Combined Doxycycline/TUDCA Treatment in Lowering Transthyretin Deposition and Associated Biomarkers: Studies in FAP Mouse Models. Journal of Translational Medicine, 8, Article No. 74. https://doi.org/10.1186/1479-5876-8-74 |
| [66] | Obici, L., Cortese, A., Lozza, A., et al. (2012) Doxycycline plus Tauroursodeoxycholic Acid for Transthyretin Amyloidosis: A Phase II Study. Amyloid, 19, 34-36. https://doi.org/10.3109/13506129.2012.678508 |
| [67] | Wixner, J., Pilebro, B., Lundgren, H.E., et al. (2017) Effect of Doxycycline and Ursodeoxycholic Acid on Transthyretin Amyloidosis. Amyloid, 24, 78-79. https://doi.org/10.1080/13506129.2016.1269739 |
| [68] | Karlstedt, E., Jimenez-Zepeda, V., Howlett, J.G., et al. (2019) Clinical Experience with the Use of Doxycycline and Ursodeoxycholic Acid for the Treatment of Transthyretin Cardiac Amyloidosis. Journal of Cardiac Failure, 25, 147-153. https://doi.org/10.1016/j.cardfail.2019.01.006 |
| [69] | Higaki, J.N., Chakrabartty, A., Galant, N.J., et al. (2016) Novel Conformation-Specific Monoclonal Antibodies against Amyloi-dogenic Forms of Transthyretin. Amyloid, 23, 86-97. https://doi.org/10.3109/13506129.2016.1148025 |
| [70] | Michalon, A., Hagenbuch, A., Huy, C., et al. (2021) A Hu-man Antibody Selective for Transthyretin Amyloid Removes Cardiac Amyloid through Phagocytic Immune Cells. Nature Communications, 12, Article No. 3142.
https://doi.org/10.1038/s41467-021-23274-x |
| [71] | Garcia-Pavia, P., Aus Dem Siepen, F., Donal, E., et al. (2023) Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid. The New England Journal of Medicine, 389, 239-250.
https://doi.org/10.1056/NEJMoa2303765 |
| [72] | Campbell, C.M., Baiyee, C., Almaani, S., et al. (2023) Targeted Therapeutics for Transthyretin Amyloid Cardiomyopathy. American Journal of Therapeutics, 30, e447-e453. https://doi.org/10.1097/MJT.0000000000001296 |
