Authors : NAVEEN V; FELIC S; ABISHEK P

Volume/Issue : Volume 9 - 2024, Issue 11 - November

Google Scholar : https://tinyurl.com/4pdwbu8t

Scribd : https://tinyurl.com/yc26bfpr

DOI : https://doi.org/10.5281/zenodo.14352136

Abstract : Transthyretin amyloid cardiomyopathy (ATTR-CM) represents a progressive and underrecognized condition driven by the deposition of misfolded transthyretin (TTR) amyloid fibrils in the heart. Through this review, we aim to explore the complexities of ATTR-CM, including its classification into wild-type (wtATTR), predominantly affecting older males, and hereditary (hATTR), linked to over 120 pathogenic TTR gene variants such as Val30Met and Val122Ile, which is notably common in individuals of African descent. The subtle and often non-specific nature of its symptoms underscores the challenges in timely diagnosis. Advances in diagnostic techniques, including Tc- 99m PYP scintigraphy and PET imaging, have transformed non-invasive detection, facilitating early identification and differentiation from other amyloidosis types. We discuss the impact of therapeutics like tafamidis, a TTR stabilizer, which has improved survival rates and reduced hospitalizations, while emphasizing the urgent need to address healthcare disparities that limit access to these advancements in certain populations. This review delves into the molecular underpinnings of ATTR-CM, highlighting the pathological progression from TTR monomer misfolding to the formation of toxic oligomers and amyloid fibrils that disrupt mitochondrial function and myocardial integrity. We evaluate emerging therapeutic approaches, such as fibril-disrupting agents and gene-editing technologies, and their potential to redefine treatment paradigms. By synthesizing the latest insights, we aim to provide a comprehensive overview of ATTR-CM, emphasizing the integration of advanced diagnostics, personalized therapeutics, and health equity to guide future research and clinical practice.

Keywords : Transthyretin Amyloid Cardiomyopathy (ATTR- CM); Amyloidosis; TTR (Transthyretin); Wild-type ATTR (wtATTR); Hereditary ATTR (hATTR); Diagnostic Imaging; Tafamidis; Gene Silencing Therapies; CRISPR-Cas9; Heart Failure with Preserved Ejection Fraction (HFpEF)

References :

1. Picken, M. M., Herrera, G. A., & Dogan, A. (2015). Amyloid and Related Disorders: Surgical Pathology and Clinical Correlations. Humana Press.
2. Conceição I, González-Duarte A, Obici L, et al. "Red-flag symptom clusters in transthyretin familial amyloid polyneuropathy." J Peripher Nerv Syst. 2016;21(1):5-9. doi:10.1111/jns.12171.
3. Wilde, A. a. M., Semsarian, C., Márquez, M. F., Shamloo, A. S., Ackerman, M. J., Ashley, E. A., Sternick, E. B., Barajas-Martinez, H., Behr, E. R., Bezzina, C. R., Breckpot, J., Charron, P., Chockalingam, P., Crotti, L., Gollob, M. H., Lubitz, S., Makita, N., Ohno, S., Ortiz-Genga, M., . . . Deneke, T. (2022). European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases. EP Europace, 24(8), 1307–1367. https://doi.org/10.1093/europace/euac030
4. Pantoni, L., & Gorelick, P. B. (2014). Cerebral Small Vessel Disease. Cambridge University Press.
5. Quarta CC, Kruger JL, Falk RH. "Cardiac amyloidosis." Circulation. 2012;126(12). doi:10.1161/CIRCULATIONAHA.111.069195.
6. Abstract proceedings of the best case report contest 2022. Clinical Cases in Internal Medicine: Learning Through Practice (7th McMaster International Review Course in Internal Medicine, September 29–October 1, 2022, Kraków, Poland, hybrid course). (2022). Polskie Archiwum Medycyny Wewnętrznej, 132(Special Issue 1). https://doi.org/10.20452/pamw.16376
7. Gillmore JD, Maurer MS, Falk RH, et al. "Nonbiopsy diagnosis of cardiac transthyretin amyloidosis." Circulation. 2016;133(24):2404-2412. doi:10.1161/CIRCULATIONAHA.116.021612.i8
8. Kristen, A.V., Dengler, T.J. and Katus, H.A. (2007) ‘Suspected cardiac amyloidosis: Endomyocardial biopsy remains the diagnostic gold‐standard’, American Journal of Hematology, 82(4), pp. 328–328. doi:10.1002/ajh.20745. 
9. Maurer MS, Schwartz JH, Gundapaneni B, et al. "Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy." N Engl J Med. 2018;379(11):1007-1016. doi:10.1056/NEJMoa1805689.
10. Crommelin, D. J. A., & Sindelar, R. D. (2002). Pharmaceutical Biotechnology: Fundamentals and Applications, Second Edition. CRC Press
11. Brito D, Albrecht FC, De Arenaza DP, Bart N, Better N, Carvajal-Juarez I, Conceição I, Damy T, Dorbala S, Fidalgo JC, Garcia-Pavia P. World heart federation consensus on transthyretin amyloidosis cardiomyopathy (ATTR-CM). Global Heart. 2023;18(1).
12. Castano A, Narotsky DL, Hamid N, et al. "Wild-type transthyretin cardiac amyloidosis: Strategies to raise awareness and aid diagnosis." JACC Heart Fail. 2017;5(7):573-581. doi:10.1016/j.jchf.2017.05.001.
13. Sabuncuoğlu, S., Yalcinkaya, A., Zhou, X., Münch, G., Chang, D., Borrelli, E., Le, N., Gangwar, B., Kumar, S., Darokar, M., Čolak, E., Žorić, L., Mirković, M., Mirković, J., Dragojević, I., Mirić, D., Kisić, B., Nikolić, L., Barderas, M., . . . González-Hernández, J. C. (2022). Importance of Oxidative Stress and Antioxidant System in Health and Disease. In Biochemistry. https://doi.org/10.5772/intechopen.100949
14. Planté-Bordeneuve, V., & Kerschen, P. (2013). Peripheral Nerve Disorders: Chapter 38. Transthyretin familial amyloid polyneuropathy. Elsevier Inc. Chapters.
15. Gertz, M. A., & Rajkumar, S. V. (2010). Amyloidosis: Diagnosis and Treatment. Springer Science & Business Media.
16. Maas, C. (2009). The Mechanism of Activation of the Contact System and Fibrinolytic System. Amyloid, 16(2), 111. https://doi.org/10.1080/13506120902879954
17. Jacobson DR, et al. "Transthyretin amyloidosis: Molecular mechanisms and clinical implications." Blood Reviews. 2020;44:100678. doi:10.1016/j.blre.2020.100678.
18. Benson MD. "The molecular basis of transthyretin amyloidosis." Clinical Chemistry and Laboratory Medicine. 2017;55(5):779-788. doi:10.1515/cclm-2016-0792.
19. Liu H, et al. "Transthyretin and the pathogenesis of amyloidosis." Journal of Molecular Medicine. 2014;92(1):23-35. doi:10.1007/s00109-013-1022-4.
20. Brodsky B, et al. "Amyloid fibril formation: A view from the bench." Nature Reviews Molecular Cell Biology. 2009;10(9):653-664. doi:10.1038/nrm2748.
21. Pensalfini, A., Albay, R., Rasool, S., Wu, J. W., Hatami, A., Arai, H., Margol, L., Milton, S., Poon, W. W., Corrada, M. M., Kawas, C. H., & Glabe, C. G. (2014). Intracellular amyloid and the neuronal origin of Alzheimer neuritic plaques. Neurobiology of Disease, 71, 53–61. https://doi.org/10.1016/j.nbd.2014.07.011
22. Wang, H., Sun, M., Li, W., Liu, X., Zhu, M., & Qin, H. (2023). Biomarkers associated with the pathogenesis of Alzheimer’s disease. Frontiers in Cellular Neuroscience, 17. https://doi.org/10.3389/fncel.2023.1279046
23. Kim, E. S., Bruinooge, S. S., Roberts, S., Ison, G., Lin, N. U., Gore, L., Uldrick, T. S., Lichtman, S. M., Roach, N., Beaver, J. A., Sridhara, R., Hesketh, P. J., Denicoff, A. M., Garrett-Mayer, E., Rubin, E., Multani, P., Prowell, T. M., Schenkel, C., Kozak, M., . . . Schilsky, R. L. (2017). Broadening Eligibility Criteria to Make Clinical Trials More Representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. Journal of Clinical Oncology, 35(33), 3737–3744. https://doi.org/10.1200/jco.2017.73.7916
24. Maurer, M. S., Elliott, P., Merlini, G., et al. (2019). Cardiac amyloidosis: Updates in pathophysiology, diagnosis, and treatment strategies. Journal of the American College of Cardiology, 73(22), 2871–2885. https://doi.org/10.1016/j.jacc.2019.04.003
25. Mattsson, G., & Magnusson, P. (2021). Cardiomyopathy: Disease of the Heart Muscle.
26. Connors, L. H., Mintz, L. J., & Weiss, M. (2016). The classification of cardiac amyloidosis. Journal of the American College of Cardiology, 67(19), 2300–2311. https://doi.org/10.1016/j.jacc.2016.02.060
27. Ruberg, F. L., & Berk, J. L. (2012). Transthyretin (TTR) cardiac amyloidosis: An infiltrative cardiomyopathy with treatment options. Journal of the American College of Cardiology, 66(1), 83–99. https://doi.org/10.1016/j.jacc.2012.06.024
28. Böhles, H., & Sewell, A. C. (2004). Metabolic Cardiomyopathy. CRC Press.
29. Cao, Q., Anderson, D., Liang, W., Chou, J., & Saelices, L. (2020). The inhibition of cellular toxicity of amyloid-β by dissociated transthyretin. Journal of Biological Chemistry, 295(41), 14015-14024. https://doi.org/10.1074/jbc.ra120.013440
30. Cioffi, C., Raja, A., Muthuraman, P., Jayaraman, A., Jayakumar, S., Váradi, A., … & Petrukhin, K. (2021). Identification of transthyretin tetramer kinetic stabilizers that are capable of inhibiting the retinol-dependent retinol binding protein 4-transthyretin interaction: potential novel therapeutics for macular degeneration, transthyretin amyloidosis, and their common age-related comorbidities. Journal of Medicinal Chemistry, 64(13), 9010-9041. https://doi.org/10.1021/acs.jmedchem.1c00099
31. Ferreira, N., Pereira-Henriques, A., & Almeida, M. (2015). Transthyretin chemical chaperoning by flavonoids: structure–activity insights towards the design of potent amyloidosis inhibitors. Biochemistry and Biophysics Reports, 3, 123-133. https://doi.org/10.1016/j.bbrep.2015.07.019
32. Ferreira, N., Saraiva, M., & Almeida, M. (2011). Natural polyphenols inhibit different steps of the process of transthyretin (ttr) amyloid fibril formation. Febs Letters, 585(15), 2424-2430. https://doi.org/10.1016/j.febslet.2011.06.030
33. Greene, M., Klimtchuk, E., Seldin, D., Berk, J., & Connors, L. (2014). Cooperative stabilization of transthyretin by clusterin and diflunisal. Biochemistry, 54(2), 268-278. https://doi.org/10.1021/bi5011249
34. Jesus, C., Almeida, Z., Vaz, D., Faria, T., & Brito, R. (2016). A new folding kinetic mechanism for human transthyretin and the influence of the amyloidogenic v30m mutation. International Journal of Molecular Sciences, 17(9), 1428. https://doi.org/10.3390/ijms17091428
35. Sun, X. (2023). Probing the dissociation pathway of a kinetically labile transthyretin mutant. Journal of the American Chemical Society, 146(1), 532-542. https://doi.org/10.1021/jacs.3c10083
36. Sun, X., Ferguson, J., Leach, B., Stanfield, R., Dyson, H., & Wright, P. (2023). Probing the dissociation pathway of a kinetically labile transthyretin mutant.. https://doi.org/10.1101/2023.06.21.545798
37. Yokoyama, T., Kosaka, Y., & Mizuguchi, M. (2014). Crystal structures of human transthyretin complexed with glabridin. Journal of Medicinal Chemistry, 57(3), 1090-1096. https://doi.org/10.1021/jm401832j
38. Patel KP, Scully PR, Saberwal B, Sinha A, Yap-Sanderson JJ, Cheasty E, Mullen M, Menezes LJ, Moon JC, Pugliese F, Klotz E. Regional distribution of extracellular volume quantified by cardiac CT in aortic stenosis: insights into disease mechanisms and impact on outcomes. Circulation: Cardiovascular Imaging. 2024 May;17(5):e015996.
39. Silva-Álvarez, C., Arrázola, M., Godoy, J., Ordenes, D., & Inestrosa, N. (2013). Canonical wnt signaling protects hippocampal neurons from aβ oligomers: role of non-canonical wnt-5a/ca2+ in mitochondrial dynamics. Frontiers in Cellular Neuroscience, 7. https://doi.org/10.3389/fncel.2013.00097
40. Rui, Y. and Zheng, J. (2016). Amyloid β oligomers elicit mitochondrial transport defects and fragmentation in a time-dependent and pathway-specific manner. Molecular Brain, 9(1). https://doi.org/10.1186/s13041-016-0261-z
41. Luth, E., Stavrovskaya, I., Bartels, T., Kristal, B., & Selkoe, D. (2014). Soluble, prefibrillar α-synuclein oligomers promote complex i-dependent, ca2+-induced mitochondrial dysfunction. Journal of Biological Chemistry, 289(31), 21490-21507. https://doi.org/10.1074/jbc.m113.545749
42. Farrugia, M., Caruana, M., Ghio, S., Camilleri, A., Farrugia, C., Cauchi, R., … & Vassallo, N. (2020). Toxic oligomers of the amyloidogenic hypf-n protein form pores in mitochondrial membranes. Scientific Reports, 10(1). https://doi.org/10.1038/s41598-020-74841-z
43. Alberdi, E., Sánchez-Gómez, M., Cavaliere, F., Pérez-Samartı́n, A., Zugaza, J., Trullás, R., … & Matute, C. (2010). Amyloid β oligomers induce ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors. Cell Calcium, 47(3), 264-272. https://doi.org/10.1016/j.ceca.2009.12.010
44. Yang, Z., Subati, T., Kim, K., Murphy, M., Dougherty, O., Christopher, I., … & Murray, K. (2022). Natriuretic peptide oligomers cause proarrhythmic metabolic and electrophysiological effects in atrial myocytes. Circulation Arrhythmia and Electrophysiology, 15(3). https://doi.org/10.1161/circep.121.010636
45. Verma, M., Vats, A., & Taneja, V. (2015). Toxic species in amyloid disorders: oligomers or mature fibrils. Annals of Indian Academy of Neurology, 18(2), 138. https://doi.org/10.4103/0972-2327.144284
46. Su, Y., Flores, S., Wang, G., Hornbeck, R. C., Speidel, B., Joseph‐Mathurin, N., … & Benzinger, T. L. (2019). Comparison of pittsburgh compound b and florbetapir in cross‐sectional and longitudinal studies. Alzheimer's &Amp; Dementia: Diagnosis, Assessment &Amp; Disease Monitoring, 11(1), 180-190. https://doi.org/10.1016/j.dadm.2018.12.008
47. Shah, J., Gao, F., Li, B., Ghisays, V., Luo, J., Chen, Y., … & Wu, T. (2022). Deep residual inception encoder‐decoder network for amyloid pet harmonization. Alzheimer S & Dementia, 18(12), 2448-2457. https://doi.org/10.1002/alz.12564
48. Chiou, A., Aman, E., & Kesarwani, M. (2020). A case report of an infiltrative cardiomyopathy in everyday practice: a specific cause that cannot be missed in the elderly. European Heart Journal - Case Reports, 4(6), 1-6. https://doi.org/10.1093/ehjcr/ytaa382
49. Treglia, G., Glaudemans, A., Bertagna, F., Hazenberg, B., Erba, P., Giubbini, R., … & Slart, R. (2018). Diagnostic accuracy of bone scintigraphy in the assessment of cardiac transthyretin-related amyloidosis: a bivariate meta-analysis. European Journal of Nuclear Medicine and Molecular Imaging, 45(11), 1945-1955. https://doi.org/10.1007/s00259-018-4013-4
50. Alexander, K., Orav, J., Singh, A., Jacob, S., Menon, A., Padera, R., … & Dorbala, S. (2018). Geographic disparities in reported us amyloidosis mortality from 1979 to 2015. Jama Cardiology, 3(9), 865. https://doi.org/10.1001/jamacardio.2018.2093
51. García‐Pavía, P., Rapezzi, C., Adler, Y., Arad, M., Basso, C., Brucato, A., … & Linhart, A. (2021). Diagnosis and treatment of cardiac amyloidosis: a position statement of the esc working group on myocardial and pericardial diseases. European Heart Journal, 42(16), 1554-1568. https://doi.org/10.1093/eurheartj/ehab072
52. Mitchell, J., Lenihan, D., Reed, C., Huda, A., Nolen, K., Bruno, M., … & Kannampallil, T. (2022). Implementing a machine-learning-adapted algorithm to identify possible transthyretin amyloid cardiomyopathy at an academic medical center. Clinical Medicine Insights Cardiology, 16. https://doi.org/10.1177/11795468221133608
53. 53.Mircsof, D. (2020). Diagnosis of amyloidosis: a survey of current awareness and clinical challenges among cardiologists in switzerland. Cardiology and Therapy, 9(1), 127-138. https://doi.org/10.1007/s40119-019-00160-8
54. Huda, A., Castaño, A., Niyogi, A., Schumacher, J., Stewart, M., Bruno, M., … & Shah, S. (2021). A machine learning model for identifying patients at risk for wild-type transthyretin amyloid cardiomyopathy. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-22876-9
55. Lau, A. (2023). Cost-effectiveness of systematic screening and treatment of transthyretin amyloid cardiomyopathy (attr-cm) in patients with heart failure with preserved ejection fraction (hfpef) in united states.. https://doi.org/10.1101/2023.08.14.23294100
56. Maurer MS, Elliott P, Comenzo R, et al. Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis. Circulation: Heart Failure. 2017.
57. Benson MD, Kincaid JC. The molecular biology and clinical features of amyloid neuropathy. Muscle & Nerve. 2007.
58. Ruberg, F. (2024). Cardiac amyloidosis due to transthyretin protein. Jama, 331(9), 778. https://doi.org/10.1001/jama.2024.0442
59. Ogieuhi, I. (2024). Tafamidis therapy in transthyretin amyloid cardiomyopathy: a narrative review from clinical trials and real-world evidence. The Egyptian Heart Journal, 76(1). https://doi.org/10.1186/s43044-024-00517-y
60. Dasgupta, N. and Rao, R. (2020). <p>diagnosis and screening of patients with hereditary transthyretin amyloidosis (hattr): current strategies and guidelines</p>. Therapeutics and Clinical Risk Management, Volume 16, 749-758. https://doi.org/10.2147/tcrm.s185677
61. .Damy, T., Kristen, A., Suhr, O., Maurer, M., Planté‐Bordeneuve, V., Yu, C., … & investigators, T. (2019). Transthyretin cardiac amyloidosis in continental western europe: an insight through the transthyretin amyloidosis outcomes survey (thaos). European Heart Journal, 43(5), 391-400. https://doi.org/10.1093/eurheartj/ehz173
62. Griffiths, D. (2020). Introduction to Elementary Particles. John Wiley & Sons.
63. Naito, T., Nakamura, K., Abe, Y., Watanabe, H., Sakuragi, S., Katayama, Y., … & Tanimoto, M. (2023). Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in japan. Esc Heart Failure, 10(3), 1896-1906. https://doi.org/10.1002/ehf2.14364
64. Madhani, A. (2023). Clinical penetrance of the transthyretin v122i variant in older black patients with heart failure: the scan‐mp (screening for cardiac amyloidosis with nuclear imaging in minority populations) study. Journal of the American Heart Association, 12(15). https://doi.org/10.1161/jaha.122.028973
65. Juarez, M., Rio‐Pertuz, G., Parmar, K., Bois, M., Shurmur, S., & Argueta-Sosa, E. (2022). A case of early hereditary transthyretin amyloid cardiomyopathy recognition with genetic screening: a case report. Journal of Primary Care & Community Health, 13. https://doi.org/10.1177/21501319211062682
66. Heart and Neurologic Disease. (2021). Elsevier.
67. Lin, W., Chattranukulchai, P., Lee, A., Lin, Y., Yu, W., Liew, H., … & Oomman, A. (2022). Clinical recommendations to diagnose and monitor patients with transthyretin amyloid cardiomyopathy in asia. Clinical Cardiology, 45(9), 898-907. https://doi.org/10.1002/clc.23882
68. amyloid cardiomyopathy: distinct from wild‐type transthyretin amyloidosis?. European Journal of Heart Failure, 26(2), 383-393. https://doi.org/10.1002/ejhf.3088
69. 69.Maestro-Benedicto, A., Vela, P., Frutos, F., Mora, N., Pomares, A., Briceño, A., … & García‐Pavía, P. (2022). Frequency of hereditary transthyretin amyloidosis among elderly patients with transthyretin cardiomyopathy. European Journal of Heart Failure, 24(12), 2367-2373. https://doi.org/10.1002/ejhf.265871
70. Dubois, J. (2024). Bone tracers for transthyretin amyloid cardiomyopathy: are [99mtc]tc-dpd and [99mtc]tc-hmdp truly equivalent?.. https://doi.org/10.1101/2024.02.14.24302851
71. Porcari, A., Razvi, Y., Masi, A., Patel, R., Rauf, M., Hutt, D., … & Gillmore, J. (2023). Prevalence, characteristics and outcomes of older patients with hereditary versus wild‐type transthyretin amyloid cardiomyopathy. European Journal of Heart Failure, 25(4), 515-524. https://doi.org/10.1002/ejhf.2776
72. Saef, J., Martyn, T., Ives, L., Roth, L., Grodin, J., Maurer, M., … & Tang, W. (2023). Predictive modeling to assess pretest probability of transthyretin gene variants based on demographic information. Circulation Heart Failure, 16(4). https://doi.org/10.1161/circheartfailure.122.009908
73. Mohty, D., Nasr, S., Ragy, H., Farhan, H., Fadel, B., Alayary, I., … & Ghoubar, M. (2023). Cardiac amyloidosis: a survey of current awareness, diagnostic modalities, treatment practices, and clinical challenges among cardiologists in selected middle eastern countries. Clinical Cardiology, 46(6), 648-655. https://doi.org/10.1002/clc.23985
74. Polimanti, R. and Nuñez, Y. (2019). Increased risk of multiple outpatient surgeries in african-american carriers of transthyretin val122ile mutation is modulated by non-coding variants. Journal of Clinical Medicine, 8(2), 269. https://doi.org/10.3390/jcm8020269
75. Razvi, Y., Porcari, A., Nora, C., Patel, R., Rauf, M., Masi, A., … & Gillmore, J. (2023). Cardiac transplantation in transthyretin amyloid cardiomyopathy: outcomes from three decades of tertiary center experience. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.1075806
76. Adams D, Gonzalez-Duarte A, O'Riordan WD, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. New England Journal of Medicine. 2018.
77. García‐Pavía, P., Bengel, F., Brito, D., Damy, T., Duca, F., Dorbala, S., … & Elliott, P. (2021). Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy. European Journal of Heart Failure, 23(6), 895-905. https://doi.org/10.1002/ejhf.2198
78. Kim, M., Prasad, M., Burton, Y., Kolseth, C., Zhao, Y., Chandrashekar, P., … & Masri, A. (2023). Comparative outcomes of a transthyretin amyloid cardiomyopathy cohort versus patients with heart failure with preserved ejection fraction enrolled in the topcat trial. Journal of the American Heart Association, 12(15). https://doi.org/10.1161/jaha.123.029705
79. Morioka, M., Takashio, S., Nishi, M., Fujiyama, A., Hirakawa, K., Hanatani, S., … & Tsujita, K. (2022). Correlation between cardiac images, biomarkers, and amyloid load in wild‐type transthyretin amyloid cardiomyopathy. Journal of the American Heart Association, 11(12). https://doi.org/10.1161/jaha.121.024717
80. García‐Pavía, P., Siepen, F., Donal, E., Lairez, O., Meer, P., Kristen, A., … & Damy, T. (2023). Phase 1 trial of antibody ni006 for depletion of cardiac transthyretin amyloid. New England Journal of Medicine, 389(3), 239-250. https://doi.org/10.1056/nejmoa2303765
81. Knight, D., Zumbo, G., Barcella, W., Steeden, J., Muthurangu, V., Martinez‐Naharro, A., … & Fontana, M. (2019). Cardiac structural and functional consequences of amyloid deposition by cardiac magnetic resonance and echocardiography and their prognostic roles. Jacc Cardiovascular Imaging, 12(5), 823-833. https://doi.org/10.1016/j.jcmg.2018.02.016
82. Tsai, C. (2023). Tafamidis decreased cardiac amyloidosis deposition in patients with ala97ser hereditary transthyretin cardiomyopathy: a 12-month follow-up cohort study. Orphanet Journal of Rare Diseases, 18(1). https://doi.org/10.1186/s13023-023-02824-0
83. Shah, S. (2024). Effect of tafamidis on cardiac function in patients with transthyretin amyloid cardiomyopathy. Jama Cardiology, 9(1), 25. https://doi.org/10.1001/jamacardio.2023.4147
84. Rettl, R., Wollenweber, T., Duca, F., Binder, C., Cherouny, B., Dachs, T., … & Binder-Rodriguez, C. (2023). Monitoring tafamidis treatment with quantitative spect/ct in transthyretin amyloid cardiomyopathy. European Heart Journal - Cardiovascular Imaging, 24(8), 1019-1030. https://doi.org/10.1093/ehjci/jead030
85. Teng, C., Li, P., Bae, J., Pan, S., Dixon, R., & Liu, Q. (2020). Diagnosis and treatment of transthyretin‐related amyloidosis cardiomyopathy. Clinical Cardiology, 43(11), 1223-1231. https://doi.org/10.1002/clc.23434
86. Elkefi, S. and Asan, O. (2023). The impact of patient-centered care on cancer patients’ qoc, self-efficacy, and trust towards doctors: analysis of a national survey. Journal of Patient Experience, 10. https://doi.org/10.1177/23743735231151533
87. Greenhalgh, J., Gooding, K., Gibbons, E., Dalkin, S., Wright, J., Valderas, J., … & Black, N. (2018). How do patient reported outcome measures (proms) support clinician-patient communication and patient care? a realist synthesis. Journal of Patient-Reported Outcomes, 2(1). https://doi.org/10.1186/s41687-018-0061-6
88. Henselmans, I., Laarhoven, H., Haes, H., Tokat, M., Engelhardt, E., Maarschalkerweerd, P., … & Smets, E. (2018). Training for medical oncologists on shared decision-making about palliative chemotherapy: a randomized controlled trial. The Oncologist, 24(2), 259-265. https://doi.org/10.1634/theoncologist.2018-0090
89. Poitras, M., Maltais, M., Bestard-Denommé, L., Stewart, M., & Fortin, M. (2018). What are the effective elements in patient-centered and multimorbidity care? a scoping review. BMC Health Services Research, 18(1). https://doi.org/10.1186/s12913-018-3213-8
90. Saul, J., Holder, S., & Lokey, J. (2018). Employing the patient-centered collaborative care approach: a case study of complex geriatric patient with psychopathalogy of treatment resistant depression and primary hyperparathyroidism.. mental-health-aging, 02(01). https://doi.org/10.35841/mental-health-aging.2.1.18-23
91. Barnes, S., Steiguer, A., Gelman, D., & Parade, S. (2020). Implementation of measurement‐based care in a child partial hospital program. The Brown University Child and Adolescent Behavior Letter, 36(7), 1-7. https://doi.org/10.1002/cbl.30475
92. Pirhonen, L., Gyllensten, H., Olofsson, E., Fors, A., Ali, L., Ekman, I., … & Bolin, K. (2020). The cost-effectiveness of person-centred care provided to patients with chronic heart failure and/or chronic obstructive pulmonary disease. Health Policy Open, 1, 100005. https://doi.org/10.1016/j.hpopen.2020.100005
93. Nagineviciute, M. (2023). Woman-centered care: standardized outcomes measure. Medicina, 59(9), 1537. https://doi.org/10.3390/medicina59091537
94. Reese, R., Duncan, B., Kodet, J., Brown, H., Meiller, C., Farook, M., … & Bohanske, R. (2018). Patient feedback as a quality improvement strategy in an acute care, inpatient unit: an investigation of outcome and readmission rates.. Psychological Services, 15(4), 470-476. https://doi.org/10.1037/ser0000163
95. Kersting, C., Kneer, M., & Barzel, A. (2020). Patient-relevant outcomes: what are we talking about? a scoping review to improve conceptual clarity. BMC Health Services Research, 20(1). https://doi.org/10.1186/s12913-020-05442-9’
96. Harris, V., Links, A., Walsh, J., Schoo, D., Lee, A., Tunkel, D., … & Boss, E. (2018). A systematic review of race/ethnicity and parental treatment decision-making. Clinical Pediatrics, 57(12), 1453-1464. https://doi.org/10.1177/0009922818788307
97. Ponti, L. (2023). Caregiver’s psychological well-being and quality of relationship with cardiac amyloidosis patients. Psychology Health & Medicine, 29(1), 66-78. https://doi.org/10.1080/13548506.2023.2280463
98. Rintell, D., Heath, D., Menendez, F., Cross, E., Cross, T., Knobell, V., … & Kalmykov, E. (2020). Patient and family experience with transthyretin amyloid cardiomyopathy (attr-cm) and polyneuropathy (attr-pn) amyloidosis: results of two focus groups.. https://doi.org/10.21203/rs.3.rs-48013/v2
99. Rintell, D., Heath, D., Mendendez, F., Cross, E., Cross, T., Knobel, V., … & Fox, J. (2021). Patient and family experience with transthyretin amyloid cardiomyopathy (attr-cm) and polyneuropathy (attr-pn) amyloidosis: results of two focus groups. Orphanet Journal of Rare Diseases, 16(1). https://doi.org/10.1186/s13023-021-01706-7
100. Ponti, L. (2023). Burden of untreated transthyretin amyloid cardiomyopathy on patients and their caregivers by disease severity: results from a multicenter, non-interventional, real-world study. Frontiers in Cardiovascular Medicine, 10. https://doi.org/10.3389/fcvm.2023.1238843
101. Saef, J., Martyn, T., Ives, L., Roth, L., Grodin, J., Maurer, M., … & Tang, W. (2023). Predictive modeling to assess pretest probability of transthyretin gene variants based on demographic information. Circulation Heart Failure, 16(4). https://doi.org/10.1161/circheartfailure.122.009908
102. Kroi, F., Fischer, N., Gezin, A., Hashim, M., & Rozenbaum, M. (2020). Estimating the gender distribution of patients with wild-type transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis. Cardiology and Therapy, 10(1), 41-55. https://doi.org/10.1007/s40119-020-00205-3
103. Maurer, M., Bokhari, S., Damy, T., Dorbala, S., Drachman, B., Fontana, M., … & Merlini, G. (2019). Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circulation Heart Failure, 12(9). https://doi.org/10.1161/circheartfailure.119.006075
104. Merino-Merino, A. (2023). Utility of genetic testing in patients with transthyretin amyloid cardiomyopathy: a brief review. Biomedicines, 12(1), 25. https://doi.org/10.3390/biomedicines12010025
105. Davies, D., Redfield, M., Scott, C., Minamisawa, M., Grogan, M., Dispenzieri, A., … & AbouEzzeddine, O. (2022). A simple score to identify increased risk of transthyretin amyloid cardiomyopathy in heart failure with preserved ejection fraction. Jama Cardiology, 7(10), 1036. https://doi.org/10.1001/jamacardio.2022.1781
106. Devesa, A., Blasco, A., Lázaro, A., Askari, E., Lapeña, G., Talavera, S., … & Aceña, Á. (2021). Prevalence of transthyretin amyloidosis in patients with heart failure and no left ventricular hypertrophy. Esc Heart Failure, 8(4), 2856-2865. https://doi.org/10.1002/ehf2.13360
107. Elliott, P., Drachman, B., Gottlieb, S., Hoffman, J., Hummel, S., Lenihan, D., … & Shah, S. (2022). Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy. Circulation Heart Failure, 15(1). https://doi.org/10.1161/circheartfailure.120.008193
108. Moya, A. (2023). Detection of transthyretin amyloid cardiomyopathy by automated data extraction from electronic health records. Esc Heart Failure, 10(6), 3483-3492. https://doi.org/10.1002/ehf2.14517
109. Rozenbaum, M., Large, S., Bhambri, R., Stewart, M., Whelan, J., Doornewaard, A., … & Nativi-Nicolau, J. (2021). Impact of delayed diagnosis and misdiagnosis for patients with transthyretin amyloid cardiomyopathy (attr-cm): a targeted literature review. Cardiology and Therapy, 10(1), 141-159. https://doi.org/10.1007/s40119-021-00219-5
110. Rio-Pertuz, G., Jenkins, L., Sethi, P., & Argueta-Sosa, E. (2022). Wild transthyretin amyloid cardiomyopathy recognition with noninvasive strategies: a case report and diagnostic approach for transthyretin-related cardiomyopathy. The Southwest Respiratory and Critical Care Chronicles, 10(42), 16-21. https://doi.org/10.12746/swrccc.v10i42.999
111. Nativi-Nicolau, J., Siu, A., Dispenzieri, A., Maurer, M., Rapezzi, C., Kristen, A., … & Mueller, C. (2021). Temporal trends of wild-type transthyretin amyloid cardiomyopathy in the transthyretin amyloidosis outcomes survey. Jacc Cardiooncology, 3(4), 537-546. https://doi.org/10.1016/j.jaccao.2021.08.009
112. Burton, A., Castaño, A., Bruno, M., Riley, S., Schumacher, J., Sultan, M., … & Patel, J. (2021). Drug discovery and development in rare diseases: taking a closer look at the tafamidis story. Drug Design Development and Therapy, Volume 15, 1225-1243. https://doi.org/10.2147/dddt.s289772
113. Yokoyama, T. and Mizuguchi, M. (2020). Transthyretin amyloidogenesis inhibitors: from discovery to current developments. Journal of Medicinal Chemistry, 63(23), 14228-14242. https://doi.org/10.1021/acs.jmedchem.0c00934
114. Shintani, Y., Okada, A., Morita, Y., Hamatani, Y., Amano, M., Takahama, H., … & Izumi, C. (2018). Monitoring treatment response to tafamidis by serial native t1 and extracellular volume in transthyretin amyloid cardiomyopathy. Esc Heart Failure, 6(1), 232-236. https://doi.org/10.1002/ehf2.12382
115. Damrauer, S., Chaudhary, K., Cho, J., Liang, L., Argulian, E., Chan, L., … & Do, R. (2019). Association of the v122i hereditary transthyretin amyloidosis genetic variant with heart failure among individuals of african or hispanic/latino ancestry. Jama, 322(22), 2191. https://doi.org/10.1001/jama.2019.17935
116. Chu, X., Wang, M., Tang, R., Huang, Y., Yu, J., Cao, Y., … & Meng, L. (2022). Clinical and biochemical characterization of hereditary transthyretin amyloidosis caused by e61k mutation. Frontiers in Molecular Neuroscience, 15. https://doi.org/10.3389/fnmol.2022.1003303
117. Müller, M., Butler, J., & Heidecker, B. (2020). Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?. European Journal of Heart Failure, 22(1), 39-53. https://doi.org/10.1002/ejhf.1695
118. Pinheiro, F., Pallarès, I., Peccati, F., Sánchez-Morales, A., Varejão, N., Bezerra, F., … & Ventura, S. (2022). Development of a highly potent transthyretin amyloidogenesis inhibitor: design, synthesis, and evaluation. Journal of Medicinal Chemistry, 65(21), 14673-14691. https://doi.org/10.1021/acs.jmedchem.2c01195
119. Eicher, J., Audia, S., & Damy, T. (2020). L'amylose cardiaque à transthyrétine. La Revue De Médecine Interne, 41(10), 673-683. https://doi.org/10.1016/j.revmed.2020.07.002
120. Mohankumar, A., Kalaiselvi, D., Thiruppathi, G., Sivaramakrishnan, M., Vijayakumar, S., Suresh, R., … & Sundararaj, P. (2022). Santalol isomers inhibit transthyretin amyloidogenesis and associated pathologies in caenorhabditis elegans. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.924862
121. Adams, D., González‐Duarte, A., O’Riordan, W., Yang, W., Ueda, M., Kristen, A., … & Suhr, O. (2018). Patisiran, an rnai therapeutic, for hereditary transthyretin amyloidosis. New England Journal of Medicine, 379(1), 11-21. https://doi.org/10.1056/nejmoa1716153
122. Dohrn, M., Ihne, S., Hegenbart, U., Medina, J., Züchner, S., Coelho, T., … & Hahn, K. (2020). Targeting transthyretin ‐ mechanism‐based treatment approaches and future perspectives in hereditary amyloidosis. Journal of Neurochemistry, 156(6), 802-818. https://doi.org/10.1111/jnc.15233
123. Joshi, P. (2023). Treating alzheimer’s and attr using crispr-cas9 to target amyloidosis. Journal of Student Research, 12(3). https://doi.org/10.47611/jsrhs.v12i3.4806
124. Aimo, A., Castiglione, V., Rapezzi, C., Franzini, M., Panichella, G., Vergaro, G., … & Emdin, M. (2022). Rna-targeting and gene editing therapies for transthyretin amyloidosis. Nature Reviews Cardiology, 19(10), 655-667. https://doi.org/10.1038/s41569-022-00683-z
125. Kotit, S. (2023). Lessons from the first-in-human in vivo crispr/cas9 editing of the ttr gene by ntla-2001 trial in patients with transthyretin amyloidosis with cardiomyopathy. Global Cardiology Science and Practice, 2023(1). https://doi.org/10.21542/gcsp.2023.4
126. Tomasoni, D., Bonfioli, G., Aimo, A., Adamo, M., Canepa, M., Lombardi, C., … & Metra, M. (2023). Treating amyloid transthyretin cardiomyopathy: lessons learned from clinical trials. Frontiers in Cardiovascular Medicine, 10. https://doi.org/10.3389/fcvm.2023.1154594