Systemic ATTR-amyloidosis, a Rare Form of Internal Organ Damage

The article presents the case report of a rare hereditary form of systemic ATTR-amyloidosis in Russian patient with a discussion of approaches to the diagnosis and treatment of this form, also based on the own experience in the management of such patients. Modern ideas about the pathogenesis of the disease as well as detailed information about the clinical manifestations of amyloid cardiopathy and of other organs are presented. The nature of structural and hemodynamic changes in the heart is discussed on the basis of experience, including own, ultrasound examination of the heart in patients with amyloidosis, especially the article focuses the reader's attention on the true infiltrative nature of transtiretin amyloid cardiopathy in contrast to AL-amyloidosis, in which there is a significant inflammatory component that determines a more unfavorable natural course of AL-amyloidosis of the heart. The article discusses the differential diagnosis of different types of amyloidosis, the diagnostic difficulties associated with weak congophilia of transtiretin amyloidosis and at the same time substantiates the need for morphological verification of the diagnosis. Modern methods of treatment of ATTR-amyloidosis are discussed.

1. Association of Nephrologists, Scientific Society of Nephrologists of Russia. Diagnosis and treatment of AA- and AL-amyloidosis. Clinical recommendations, 2014. [cited by Jun 06, 2019]. Available from: http://nonr.ru/wp-content/uploads/2013/11/National-Clinical-Recommendations- “Diagnosisand Treatment” AA--AL- amyloidosis “.pdf (In Russ).

2. Wechalekar A.D., Gillmore J.D., Hawkins P.N. Systemicamyloidosis. Lancet. 2016;387(10038):2641-54. DOI:10.1016/S0140-6736(15)01274-X.

3. Kelly J.J., Kyle R.A., O'Brien P.C., et al. The natural history of peripheral neuropathy in primary systemic amyloidosis. Annals of Neurology. 1979;6(1):1-7. DOI:10.1002/ana.410060102.

4. Kyle R., Gertz M. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol.1995;32(1):45-59.

5. Garcia-Pavia P., Comín-Colet J., Barriales-Villa R., et al. Comments on the 2014 ESC Guidelines on the diagnosis and management of hypertrophic cardiomyopathy. A critical view from the perspective of Spanish cardiology. Rev Esp Cardiol. 2015;68:4-9. DOI:10.1016/j.rec.2014.10.011.

6. Rapezzi C., Merlini G., Quarta C., et al. Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203-12. DOI: 10.1161/CIRCULATIONAHA.108.843334.

7. Falk R., Alexander K., Liao R., et al. AL (Light-Chain) Cardiac Amyloidosis: A Review of Diagnosis and Therapy. J Am Coll Cardiol. 2016;20;68(12):1323-41. DOI:10.1016/j.jacc.2016.06.053.

8. Falk R., Quarta C., Dorbala S. How to Image Cardiac Amyloidosis: A Focused Practical Review. Circ Cardiovasc Imaging. 2014;7(3):552-62. DOI:10.1161/CIRCIMAGING.113.001396.

9. Maceira A., Joshi J., Prasad S., et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation. 2005;111(2):186-93. DOI:10.1161/01.CIR.0000152819.97857.9D.

10. Sinitsyn V.E., Mershina E.A., Larina O.M. The possibilities of magnetic resonance imaging in the diagnosis of cardiomyopathy. Clinical and Experimental Surgery. 2014;1:54-63 (In Russ.)

11. Syed I.S., Glockner J.F., Feng D., et al. Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis. JACC Cardiovasc Imaging. 2010;3(2):155-64. DOI:10.1016/j.jcmg.2009.09.023.

12. Roller F.C., Harth S., Schneider C., et al. T1, T2 Mapping and Extracellular Volume Fraction (ECV): Application, Value and Further Perspectives in Myocardial Inflammation and Cardiomyopathies. Rofo. 2015;187(9):760-70. DOI:10.1055/s-0034-1399546.

13. Karamitsos T.D., Piechnik S.K., Banypersad S.M., et al. Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. JACC Cardiovasc Imaging. 2013;6(4):488-97. DOI:10.1016/j.jcmg.2012.11.013.

14. Fontana M., Banypersad S.M., Treibel T.A., et al. Native T1 mapping in transthyretin amyloidosis. JACC Cardiovasc Imaging. 2014;7(2):157-65. DOI:10.1016/j.jcmg.2013.10.008.

15. Banypersad S.M., Sado D.M., Flett A.S., et al. Quantification of myocardial extracellular volume fraction in systemic AL amyloidosis: an equilibrium contrast cardiovascular magnetic resonance study. Circ Cardiovasc Imaging. 2013;6(1):34-9. DOI:10.1161/CIRCIMAGING.112.978627.

16. Bokhari S., Castano A., Pozniakoff T., et al. (99m)Tc-pyrophosphate scintigraphy for differentiating light chain cardac amyloidosis from the transthyret in related familial and senile cardiac amyloidoses. Circ Cardiovasc Imaging. 2013;6(2):195-201. DOI:10.1161/CIRCIMAGING.112.000132.

17. Rapezzi C., Quarta C.C., Guidalotti P.L., et al. Usefulness and limitations of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in the aetiological diagnosis of amyloidotic cardiomyopathy. Eur J Nucl Med Mol Imaging. 2011;38(3):470-8. DOI:10.1007/s00259-010-1642-7.

18. Quarta C.C., Obici L., Guidalotti P.L., et al. High 99mTc-DPD myocardial uptake in a patient with apolipoprotein AI-related amyloidotic cardiomyopathy. Amyloid. 2013;20(1):48-51. DOI:10.3109/13506129.2012.746938.

19. Hutt D.F., Quigley A.M., Page J., et al. Utility and limitations of 3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy in systemic amyloidosis. Eur Heart J Cardiovasc Imaging. 2014;15(11):1289-98. DOI:10.1093/ehjci/jeu107.

20. Patel K.S., Hawkins P.N. Cardiac amyloidosis: where are we today? J Intern Med. 2015;278(2):126-44. DOI:10.1111/joim.12383.

21. Ternacle J., Bodez D., Guellich A., et al. Causes and consequences of longitudinal LV dysfunction assessed by 2D strain echocardiography in cardiac amyloidosis. JACC Cardiovasc Imaging. 2016;9(2):126-38. DOI:10.1016/j.jcmg.2015.05.014.

22. Grossman W., Jones D., McLaurin L.P. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest. 1975; 56(1):56-64. DOI:10.1172/JCI108079.

23. Jiang L., Huang Y., Hunyor S., et al. Cardiomyocyte apoptosis is associated with increased wall stress in chronic failing left ventricle. Eur Heart J. 2003;24:742-51. DOI:10.1016/s0195-668x(02)00655-3.

24. Bellavia D., Pellikka P.A., Abraham T.P., et al. Evidence of impaired left ventricular systolic function by Doppler myocardial imaging in patients with systemic amyloidosis and no evidence of cardiac involvement by standard two dimensional and Doppler echocardiography. Am J Cardiol. 2008;101(7):1039-45. DOI:10.1016/j.amjcard.2007.11.047.

25. Buchalter M.B., Weiss J.L., Rogers W.J., et al. Noninvasive quantification of left ventricular rotation deformation in normal human using magnetic resonance imaging myocardial tagging. Circulation. 1990;81(4):1236-44.

26. Torrent-Guasp F. Structure and function of the heart. Rev Esp Cardiol. 1998;51(2):91-102.

27. Phelan D., Collier P., Thavendiranathan P., et al. Relative apical sparing of longitudinal strain using two-dimensional speckle-tracking echocardiography is both sensitive and specific for the diagnosis of cardiac amyloidosis. Heart. 2012;98(19):1442-8. DOI:10.1136/heartjnl-2012-302353.

28. Phelan, D., Thavendiranathan, P., Popovic, Z., et al. Application of a parametric display of two-dimensional speckle-tracking longitudinal strain to improve the etiologic diagnosis of mild to moderate left ventricular hypertrophy. J Am Soc Echocardiogr. 2014;27(8):888-95. DOI:10.1016/j.echo.2014.04.015.

29. Pandey T., Alapati S., Wadhwa V., et al. Evaluation of myocardial strain in patients with amyloidosis using cardiac magnetic resonance feature tracking. Current Problems in Diagnostic Radiology. 2016;46(4):288-294. DOI:10.1067/j.cpradiol.2016.11.008.

30. Sengupta P.P., Tajik A.J., Chandrasekaran K., et al. Twist mechanics of the left ventricle: principles and application. JACC Cardiovasc Imaging. 2008;1(3):366-76. DOI:10.1016/j.jcmg.2008.02.006.

31. Pavlyukova E.N., Kuzhel D.A., Matyushin G.V., et al. Left ventricular rotation, twist and untwist: physiological role and clinical relevance. Rational Pharmacotherapy in Cardiology. 2015;11(1):68-78. (In Russ.) DOI:10.20996/1819-6446-2015-11-1-68-78.

32. Nucifora G., Muser D., Morocutti G., et al. Disease-specific differences of left ventricular rotational mechanics between cardiac amyloidosis and hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2014;307(5):H680-8. DOI:10.1152/ajpheart.00251.2014.

33. Takemura G., Takatsu Y., Doyama K., et al. Expression of atrial and brain natriuretic peptides and their genes in hearts of patients with cardiac amyloidosis. J Am Coll Cardiol. 1998;31(4):754-65.

34. Shi J., Guan J., Jiang B., et al. Amyloidogenic light chains induce cardiomyocyte contractile dysfunction and apoptosis via a noncanonical p38 MAPK pathway. Proc Natl Acad Sci U S A. 2010;107(9):4188-93. DOI:10.1073/pnas.0912263107.

35. Gertz M.A., Merlini G. Definition of organ involvement and response to treatment in AL amyloidosis: an updated consensus opinionfrom the 10th International Symposium on Amyloid and Amyloidosis, Tours, France, 18-22 April 2004. Am J Hematol. 2005;79(4):319-28. DOI: 10.1002/ajh.20381.

36. Palladini G., Foli A., Milani P., et al. Best use of cardiac biomarkers in patients with AL amyloidosis and renal failure. Am J Hematol. 2012;87(5):465-71. DOI:10.1002/ajh.23141.

37. Zhdanova E.A., Rameev V.V., Moiseev S.V., et al. Cardiac amyloidosis. Clinical Pharmacology & Therapeutics. 2011;20(5):44-50 (In Russ.)

38. Zhdanov E.A., Gudkov K.V., Rameev V.V., et al. Modern ideas about amyloidosis of the heart. Cardiology. 2013;53(12):70-8. (In Russ)

39. Alyokhin M.N. Tissue doppler in clinical echocardiography. Moscow: OOO Insvazizdat; 2006 (In Russ).

40. Koyama J., Ray-Sequin P.A., Falk R.H. Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis. Circulation. 2003;107(19):2446-52 DOI: 10.1161/01.CIR.0000068313.67758.4F.

41. Liu Dan, Hu Kai, Nordbeck P., et al. Longitudinal strain bull’s eye plot patterns in patients with cardiomyopathy and concentric left ventricular hypertrophy. Eur J Med Res. 2016;21:21. DOI:10.1186/s40001-016-0216-y.

42. Nikiforov V.S., Nikishchenkova I.V. Modern Possibilities of Speckle Tracking Echocardiography in Clinical Practice. Rational Pharmacotherapy in Cardiology. 2017;13(2):248-55 (In Russ). DOI: 10.20996/1819-6446-2017-13-2-248-255.

43. Sipe J., Benson M., Buxbaum J., et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-213. DOI:10.1080/13506129.2016.1257986

44. Holmgren G., Steen L., Ekstedt J., et al. Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30). Clin Genet. 1991;40(3):242-6.

45. Maurer M., Schwartz J., Gundapaneni B., et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2018;379(11):1007-16. DOI: 10.1056/NEJMoa1805689.