A Clinical Case of the Hereditary Transthyretin Amyloidosis

Introduction: Transthyretin (ATTR) amyloidosis is a severe rare disease with wide range of characters without specific symptoms including the damage to the peripheral nervous system and cardiac involvement. Case report: A 60-year-old female patient represented with weakness and paresthesia in the distal parts of the lower limbs, impeding walking for 2 years. Initially, symptoms were considered as a manifestation of degenerative stenosis of the lumbar spine, decompressive laminectomy was performed but the symptoms after surgical treatment persisted. Based on data from clinical and electroneuromyographic examinations, axonal sensorimotor polyneuropathy was diagnosed. Genetic testing of the patient, her elder sister, son and daughter using the Sanger sequencing method detected a variant of the nucleotide sequence in the fourth exon of the transthyretin gene (Chr18: 29178562, rs148538950, NM_000371.3: c.G368A: p. Arg123His) in the heterozygous state. A subcutaneous fatty tissue biopsy of abdominal wall with a Congo red stain and polarized light examination revealed amyloid microdeposits, grade CR 1+ (minimal deposits), confirmed the diagnosis of familial ATTR-amyloidosis. Echocardiography revealed concentric left ventricular wall thickening with normal end diastolic size and volume, preserved ejection fraction, left atrial enlargement, pulmonary hypertension and type 1 diastolic dysfunction. Specific anti-amyloid therapy — tafamidis was prescribed. Conclusion: In patients with peripheral polyneuropathy and left ventricular hypertrophy of unknown etiology, a complex examination is necessary for the timely detection and treatment of amyloid polyneuropathy and cardiomyopathy.

1. Hassan W, Al-Sergani H, Mourad W, Tabbaa R. Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Texas Heart Institute journal. 2005; 32(2): 178-84. PubMed PMID: 16107109; PubMed Central PMCID: PMC1163465.

2. Резник Е.В., Нгуен Т.Л., Степанова Е.А. и др. Амилоидоз сердца: взгляд терапевта и кардиолога. Архивъ внутренней медицины. 2020; 10(6): 430-457. https://doi.org/10.20514/2226-6704-2020-10-6-430-457 Reznik E.V., Nguyen T.L., Stepanova E.A. et al. Cardiac Amyloidosis: Internist and Cardiologist Insight. The Russian Archives of Internal Medicine. 2020; 10(6): 430-457. https://doi.org/10.20514/2226-6704-2020-10-6-430-457 [in Russian].

3. Лысенко (Козловская) Л.В., Рамеев В.В., Моисеев С.В. и др. Клинические рекомендации по диагностике и лечению системного амилоидоза. Клин фармакол тер. 2020; 29(1): 13-24 Lysenko (Kozlovskaya) L.V., Rameev V.V., Moiseev S.V., et al. Clinical guidelines for diagnosis and treatment of systemic amyloidosis. Klinicheskaya farmakologiya i terapiya = Clin Pharmacol Therapy 2020; 29(1): 13-24. DOI 10.32756/0869-5490-2020-1-13-24 [in Russian]

4. Benson M.D., Buxbaum J.N., Eisenberg D.S. et al. Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2020; 27(4): 217- 22. doi: 10.1080/13506129.2020.1835263. PubMed PMID: 33100054.

5. Yamamoto H., Yokochi T. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. ESC heart failure. 2019; 6(6): 1128-39. doi: 10.1002/ehf2.12518. PubMed PMID: 31553132; PubMed Central PMCID: PMC6989279.

6. Sekijima Y., Mundayat R., Ishii T. et al. The current status of the Transthyretin Amyloidosis Outcomes Survey (THAOS) in Japan. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2019; 26(sup1): 61-2. doi: 10.1080/13506129.2019.1583182. PubMed PMID: 31343365.

7. Maurer M.S., Bokhari S., Damy T. et al. Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis. Circ Heart Fail. 2019; 12(9): e006075. doi: 10.1161/CIRCHEARTFAILURE.119.006075. PubMed PMID: 31480867; PubMed Central PMCID: PMC6736650.

8. Johnson S.M., Connelly S., Fearns C. et al. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agencyapproved drug. Journal of molecular biology. 2012; 421(2-3): 185-203. doi: 10.1016/j.jmb.2011.12.060. PubMed PMID: 22244854; PubMed Central PMCID: PMC3350832.

9. Seferovic P.M., Ponikowski P., Anker S.D. et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019. doi: 10.1002/ejhf.1531. PubMed PMID: 31129923.

10. Гудкова А.Я., Семернин Е.Н., Полякова А.А. и др. СПЕКТР МУТАЦИЙ В ГЕНЕ ТРАНСТИРЕТИНА В КОГОРТЕ ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ. Трансляционная медицина. 2016; 3(1): 34-38. https://doi.org/10.18705/2311-4495-2016-3-1-34-38 Gudkova A.Y., Semernin E.N., Polyakova A.A. et al. THE SPECTRUM OF MUTATIONS OF THE TRANSTHYRETIN GENE IN A COHORT OF PATIENTS WITH CHRONIC HEART FAILURE. Translational Medicine. 2016;3(1):34-38.. https://doi.org/10.18705/2311-4495-2016-3-1-34-38 [in Russian]

11. Nakase T., Yamashita T., Matsuo Y. et al. Hereditary ATTR Amyloidosis with Cardiomyopathy Caused by the Novel Variant Transthyretin Y114S (p.Y134S) . Internal medicine. 2019; 58(18): 2695-8. doi: 10.2169/internalmedicine.2456-18. PubMed PMID: 31178489; PubMed Central PMCID: PMC6794161.

12. Ando Y., Coelho T., Berk J.L. et al. Guideline of transthyretinrelated hereditary amyloidosis for clinicians. Orphanet journal of rare diseases. 2 013; 8: 31. doi: 10.1186/1750-1172-8-31. PubMed PMID: 23425518; PubMed Central PMCID: PMC3584981.

13. Rapezzi C., Quarta C.C., Obici L. et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusivel y cardiac phenotype: an Italian perspective. Eur Heart J. 2013; 34(7): 520-8. doi: 10.1093/eurheartj/ehs123. PubMed PMID: 22745357.

14. Damy T., Kristen A.V., Suhr O.B. et al. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amylo idosis Outcomes Survey (THAOS). Eur Heart J. 2019. doi: 10.1093/eurheartj/ehz173. PubMed PMID: 30938420.

15. Coelho T., Maurer M.S., Suhr O.B. 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. 2013; 29(1): 63-76. doi: 10.1185/03007995.2012.754348. PubMed PMID: 23193944.

16. Adams D., Ando Y., Beirao J.M. et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. Journal of neu rology. 2020. doi: 10.1007/s00415-019-09688-0. PubMed PMID: 31907599.

17. Gertz M.A. Hereditary ATTR amyloidosis: burden of illness and diagnostic challenges. The American journal of managed care. 2017; 23(7 Suppl): S107- S12. PubMed PMID: 28978215.

18. Fontana M., Banypersad S.M., Treibel T.A. et al. Differential Myocyte Responses in Patients with Cardiac Transthyretin Amyloidosis and Light-Chain Amyloidosis: A Cardiac MR Imaging Study. Radiology. 2015; 277(2): 388-97. doi: 10.1148/radiol.2015141744. PubMed PMID: 25997029.

19. Резник Е.В., Степанова E.A., Нгуен Т. и др. Ретроспективный анализ поражения сердечнососудистой системы у больных системным амилоидозом. Кардиовас кулярная терапия и профилактика. 2021; 20(1): 2496. Reznik E.V., Stepanova E.A., Nguyen T. et al. Retrospective analysis of cardiovascular involvement in patients with systemic amyloidosis. Cardiovascular Therapy and Prevention. 2021; 20(1): 2496. [in Russian].

20. Kristen A.V., Schnabel P.A., Winter B. et al. High prevalence of amyloid in 150 surgically removed heart valves-a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions. Cardiovasc Pathol. 2010; 19(4): 228-35. doi: 10.1016/j.carpath.2 009.04.005. PubMed PMID: 19502085.

21. Karafiatova L., Pika T. Amyloid cardiomyopathy. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2017; 161(2): 117-27. doi: 10.5507/bp.2017.001. PubMed PMID: 28145535.

22. Резник Е.В., Гендлин Г.Е., Сторожаков Г.И. Эхокардиография в практике кардиол ога. Москва: Практика. 2013; 212 с. Reznik E.V., Gendlin G.E., Storozhakov G.I. (2013) Echocardiography in the practice of a cardiologist. 2013; 212 p. [in Russian].

23. Carroll J.D., Gaasch W.H., McAdam K.P. Amyloi d cardiomyopathy: characterization by a distinctive voltage/ mass relation. Am J Cardiol. 1982; 49(1): 9-13. doi: 10.1016/0002-9149(82)90270-3. PubMed PMID: 6459025.

24. Park G.Y., Jamerlan A., Shim K.H., An S.S. Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases. International journal of molecula r sciences. 2019; 20(12). doi: 10.3390/ijms20122982. PubMed PMID: 31216785; PubMed Central PMCID: PMC6628571.

25. Caobelli F., Braun M., Haaf P. et al. Quantitative (99m) Tc-DPD SPECT/CT in patients with suspected A TTR cardiac amyloidosis: Feasibility and correlation with visual scores. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2020; 27(5): 1456-63. doi: 10.1007/s12350-019-01893-8. PubMed PMID: 31538322.

26. Gopal D.M., Ruberg F.L ., Siddiqi O.K. Impact of Genetic Testing in Transthyretin (ATTR) Cardiac Amyloidosis. Curr Heart Fail Rep. 2019; 16(5): 180-8. doi: 10.1007/s11897-019-00436-z. PubMed PMID: 31520266.

27. Gonzalez-Lopez E., Gallego-Delgado M., Guzzo-Merello G. et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur He art J. 2015; 36(38): 2585-94. doi: 10.1093/eurheartj/ehv338. PubMed PMID: 26224076.

28. Damy T., Costes B., Hagege A.A. et al. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopath y in patients with increased left ventricular wall thickness. Eur Heart J. 2016; 37(23): 1826-34. doi: 10.1093/eurheartj/ehv583. PubMed PMID: 26537620.

29. Scully P.R., Treibel T.A., Fontana M. et al. Prevalence of Cardiac Amyloidosis in Patients Referred for Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2018; 71(4): 463-4. doi: 10.1016/j.jacc.2017.11.037. PubMed PMID: 29389364; PubMed Central PMCID: PMC5780297.

30. Castano A., Narotsky D.L., Hamid N. et al. Unveiling transthyretin cardiac amyloidosis and its predi ctors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017; 38(38): 2879-87. doi: 10.1093/eurheartj/ehx350. PubMed PMID: 29019612; PubMed Central PMCID: PMC5837725.

31. Treibel T.A., Fontana M., Gilbertson J.A. et al. Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement. Circulation Cardiovascular imaging. 2016 Aug; 9(8): e005066.. doi: 10.1161/CIRCIMAGING.116.005066. PubMed PMID: 27511979.

32. Fajardo J., Cummings A., Brown E. et al. Clini c al pathway to screen for cardiac amyloidosis in heart failure with preserved ejection fraction. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2019; 26(sup1): 166-7. doi: 10.1080/13506129.2019.1583178. PubMed PMID: 31343333.

33. Maurer M.S., Hanna M., Grogan M. et al. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016; 68(2): 161-72. doi: 10.1016/j.jacc.2016.03.596. PubMed PMID: 27386769; PubMed Central PMCID: PMC4940135.

34. Connors L.H., Lim A., Prokaeva T. et al. Tabulation of human transthyretin (TTR) variants, 2003. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2003; 10(3): 160-84. doi: 10.3109/13506120308998998. PubMed PMID: 14640030.

35. Conceicao I., Gonzalez-Duarte A., Obici L. et al. “Re dflag” symptom clusters in transthyretin familial amyloid polyneuropathy. Journal of the peripheral nervous system : JPNS. 2016; 21(1): 5-9. doi: 10.1111/jns.12153. PubMed PMID: 26663427; PubMed Central PMCID: PMC4788142.1. Hassan W, Al-Sergani H, Mourad W, Tabbaa R. Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Texas Heart Institute journal. 2005; 32(2): 178-84. PubMed PMID: 16107109; PubMed Central PMCID: PMC1163465.

36. Резник Е.В., Нгуен Т.Л., Степанова Е.А. и др. Амилоидоз сердца: взгляд терапевта и кардиолога. Архивъ внутренней медицины. 2020; 10(6): 430-457. https://doi.org/10.20514/2226-6704-2020-10-6-430-457 Reznik E.V., Nguyen T.L., Stepanova E.A. et al. Cardiac Amyloidosis: Internist and Cardiologist Insight. The Russian Archives of Internal Medicine. 2020; 10(6): 430-457. https://doi.org/10.20514/2226-6704-2020-10-6-430-457 [in Russian].

37. Лысенко (Козловская) Л.В., Рамеев В.В., Моисеев С.В. и др. Клинические рекомендации по диагностике и лечению системного амилоидоза. Клин фармакол тер. 2020; 29(1): 13-24 Lysenko (Kozlovskaya) L.V., Rameev V.V., Moiseev S.V., et al. Clinical guidelines for diagnosis and treatment of systemic amyloidosis. Klinicheskaya farmakologiya i terapiya = Clin Pharmacol Therapy 2020; 29(1): 13-24. DOI 10.32756/0869-5490-2020-1-13-24 [in Russian]

38. Benson M.D., Buxbaum J.N., Eisenberg D.S. et al. Amyloid nomenclature 2020: update and recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2020; 27(4): 217- 22. doi: 10.1080/13506129.2020.1835263. PubMed PMID: 33100054.

39. Yamamoto H., Yokochi T. Transthyretin cardiac amyloidosis: an update on diagnosis and treatment. ESC heart failure. 2019; 6(6): 1128-39. doi: 10.1002/ehf2.12518. PubMed PMID: 31553132; PubMed Central PMCID: PMC6989279.

40. Sekijima Y., Mundayat R., Ishii T. et al. The current status of the Transthyretin Amyloidosis Outcomes Survey (THAOS) in Japan. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2019; 26(sup1): 61-2. doi: 10.1080/13506129.2019.1583182. PubMed PMID: 31343365.

41. Maurer M.S., Bokhari S., Damy T. et al. Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis. Circ Heart Fail. 2019; 12(9): e006075. doi: 10.1161/CIRCHEARTFAILURE.119.006075. PubMed PMID: 31480867; PubMed Central PMCID: PMC6736650.

42. Johnson S.M., Connelly S., Fearns C. et al. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agencyapproved drug. Journal of molecular biology. 2012; 421(2-3): 185-203. doi: 10.1016/j.jmb.2011.12.060. PubMed PMID: 22244854; PubMed Central PMCID: PMC3350832.

43. Seferovic P.M., Ponikowski P., Anker S.D. et al. Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2019. doi: 10.1002/ejhf.1531. PubMed PMID: 31129923.

44. Гудкова А.Я., Семернин Е.Н., Полякова А.А. и др. СПЕКТР МУТАЦИЙ В ГЕНЕ ТРАНСТИРЕТИНА В КОГОРТЕ ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ. Трансляционная медицина. 2016; 3(1): 34-38. https://doi.org/10.18705/2311-4495-2016-3-1-34-38 Gudkova A.Y., Semernin E.N., Polyakova A.A. et al. THE SPECTRUM OF MUTATIONS OF THE TRANSTHYRETIN GENE IN A COHORT OF PATIENTS WITH CHRONIC HEART FAILURE. Translational Medicine. 2016;3(1):34-38.. https://doi.org/10.18705/2311-4495-2016-3-1-34-38 [in Russian]

45. Nakase T., Yamashita T., Matsuo Y. et al. Hereditary ATTR Amyloidosis with Cardiomyopathy Caused by the Novel Variant Transthyretin Y114S (p.Y134S) . Internal medicine. 2019; 58(18): 2695-8. doi: 10.2169/internalmedicine.2456-18. PubMed PMID: 31178489; PubMed Central PMCID: PMC6794161.

46. Ando Y., Coelho T., Berk J.L. et al. Guideline of transthyretinrelated hereditary amyloidosis for clinicians. Orphanet journal of rare diseases. 2 013; 8: 31. doi: 10.1186/1750-1172-8-31. PubMed PMID: 23425518; PubMed Central PMCID: PMC3584981.

47. Rapezzi C., Quarta C.C., Obici L. et al. Disease profile and differential diagnosis of hereditary transthyretin-related amyloidosis with exclusivel y cardiac phenotype: an Italian perspective. Eur Heart J. 2013; 34(7): 520-8. doi: 10.1093/eurheartj/ehs123. PubMed PMID: 22745357.

48. Damy T., Kristen A.V., Suhr O.B. et al. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amylo idosis Outcomes Survey (THAOS). Eur Heart J. 2019. doi: 10.1093/eurheartj/ehz173. PubMed PMID: 30938420.

49. Coelho T., Maurer M.S., Suhr O.B. 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. 2013; 29(1): 63-76. doi: 10.1185/03007995.2012.754348. PubMed PMID: 23193944.

50. Adams D., Ando Y., Beirao J.M. et al. Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy. Journal of neu rology. 2020. doi: 10.1007/s00415-019-09688-0. PubMed PMID: 31907599.

51. Gertz M.A. Hereditary ATTR amyloidosis: burden of illness and diagnostic challenges. The American journal of managed care. 2017; 23(7 Suppl): S107- S12. PubMed PMID: 28978215.

52. Fontana M., Banypersad S.M., Treibel T.A. et al. Differential Myocyte Responses in Patients with Cardiac Transthyretin Amyloidosis and Light-Chain Amyloidosis: A Cardiac MR Imaging Study. Radiology. 2015; 277(2): 388-97. doi: 10.1148/radiol.2015141744. PubMed PMID: 25997029.

53. Резник Е.В., Степанова E.A., Нгуен Т. и др. Ретроспективный анализ поражения сердечнососудистой системы у больных системным амилоидозом. Кардиовас кулярная терапия и профилактика. 2021; 20(1): 2496. Reznik E.V., Stepanova E.A., Nguyen T. et al. Retrospective analysis of cardiovascular involvement in patients with systemic amyloidosis. Cardiovascular Therapy and Prevention. 2021; 20(1): 2496. [in Russian].

54. Kristen A.V., Schnabel P.A., Winter B. et al. High prevalence of amyloid in 150 surgically removed heart valves-a comparison of histological and clinical data reveals a correlation to atheroinflammatory conditions. Cardiovasc Pathol. 2010; 19(4): 228-35. doi: 10.1016/j.carpath.2 009.04.005. PubMed PMID: 19502085.

55. Karafiatova L., Pika T. Amyloid cardiomyopathy. Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2017; 161(2): 117-27. doi: 10.5507/bp.2017.001. PubMed PMID: 28145535.

56. Резник Е.В., Гендлин Г.Е., Сторожаков Г.И. Эхокардиография в практике кардиол ога. Москва: Практика. 2013; 212 с. Reznik E.V., Gendlin G.E., Storozhakov G.I. (2013) Echocardiography in the practice of a cardiologist. 2013; 212 p. [in Russian].

57. Carroll J.D., Gaasch W.H., McAdam K.P. Amyloi d cardiomyopathy: characterization by a distinctive voltage/ mass relation. Am J Cardiol. 1982; 49(1): 9-13. doi: 10.1016/0002-9149(82)90270-3. PubMed PMID: 6459025.

58. Park G.Y., Jamerlan A., Shim K.H., An S.S. Diagnostic and Treatment Approaches Involving Transthyretin in Amyloidogenic Diseases. International journal of molecula r sciences. 2019; 20(12). doi: 10.3390/ijms20122982. PubMed PMID: 31216785; PubMed Central PMCID: PMC6628571.

59. Caobelli F., Braun M., Haaf P. et al. Quantitative (99m) Tc-DPD SPECT/CT in patients with suspected A TTR cardiac amyloidosis: Feasibility and correlation with visual scores. Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology. 2020; 27(5): 1456-63. doi: 10.1007/s12350-019-01893-8. PubMed PMID: 31538322.

60. Gopal D.M., Ruberg F.L ., Siddiqi O.K. Impact of Genetic Testing in Transthyretin (ATTR) Cardiac Amyloidosis. Curr Heart Fail Rep. 2019; 16(5): 180-8. doi: 10.1007/s11897-019-00436-z. PubMed PMID: 31520266.

61. Gonzalez-Lopez E., Gallego-Delgado M., Guzzo-Merello G. et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur He art J. 2015; 36(38): 2585-94. doi: 10.1093/eurheartj/ehv338. PubMed PMID: 26224076.

62. Damy T., Costes B., Hagege A.A. et al. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopath y in patients with increased left ventricular wall thickness. Eur Heart J. 2016; 37(23): 1826-34. doi: 10.1093/eurheartj/ehv583. PubMed PMID: 26537620.

63. Scully P.R., Treibel T.A., Fontana M. et al. Prevalence of Cardiac Amyloidosis in Patients Referred for Transcatheter Aortic Valve Replacement. J Am Coll Cardiol. 2018; 71(4): 463-4. doi: 10.1016/j.jacc.2017.11.037. PubMed PMID: 29389364; PubMed Central PMCID: PMC5780297.

64. Castano A., Narotsky D.L., Hamid N. et al. Unveiling transthyretin cardiac amyloidosis and its predi ctors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. Eur Heart J. 2017; 38(38): 2879-87. doi: 10.1093/eurheartj/ehx350. PubMed PMID: 29019612; PubMed Central PMCID: PMC5837725.

65. Treibel T.A., Fontana M., Gilbertson J.A. et al. Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement. Circulation Cardiovascular imaging. 2016 Aug; 9(8): e005066.. doi: 10.1161/CIRCIMAGING.116.005066. PubMed PMID: 27511979.

66. Fajardo J., Cummings A., Brown E. et al. Clini c al pathway to screen for cardiac amyloidosis in heart failure with preserved ejection fraction. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2019; 26(sup1): 166-7. doi: 10.1080/13506129.2019.1583178. PubMed PMID: 31343333.

67. Maurer M.S., Hanna M., Grogan M. et al. Genotype and Phenotype of Transthyretin Cardiac Amyloidosis: THAOS (Transthyretin Amyloid Outcome Survey). J Am Coll Cardiol. 2016; 68(2): 161-72. doi: 10.1016/j.jacc.2016.03.596. PubMed PMID: 27386769; PubMed Central PMCID: PMC4940135.

68. Connors L.H., Lim A., Prokaeva T. et al. Tabulation of human transthyretin (TTR) variants, 2003. Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis. 2003; 10(3): 160-84. doi: 10.3109/13506120308998998. PubMed PMID: 14640030.

69. Conceicao I., Gonzalez-Duarte A., Obici L. et al. “Re dflag” symptom clusters in transthyretin familial amyloid polyneuropathy. Journal of the peripheral nervous system : JPNS. 2016; 21(1): 5-9. doi: 10.1111/jns.12153. PubMed PMID: 26663427; PubMed Central PMCID: PMC4788142.