A new era in treatment of cardiac amyloidosis: an overview of the Congress of cardiology

Amyloidosis is a group of diseases characterized  by accumulation of a protein of a specific fibrillar structure in the interstitium of various organs and tissues. The concept of amyloidosis  unites more than 30 different pathophysiological conditions,  each of which is based on abnormal synthesis of 30 different precursor proteins. However, 95% of amyloid cardiomyopathies are associated with just two proteins: a protein derived from light chains of immunoglobulins and a protein called transthyretin.  Determination of the precursor protein is a cornerstone of management  of patients with amyloid cardiomyopathy. Transthyretin  is a carrier protein of thyroxine, retinol and other substances, that performs vital functions. For hereditary or age-related reasons, TTR misfolding occurs in the liver. The resulting monomers, entering blood, form toxic intermediate products and amyloid fibrils. Cardiac amyloidosis (or amyloid cardiomyopathy)  used to be considered a rare disease. In the recent past, possibilities of therapy for cardiac amyloidosis were limited by prescription of diuretics, mineralocorticoid receptor antagonists and anticoagulants, since other drugs are not tolerated well by patients or are tolerated in minimal doses. Advent of the first drug specific for treatment of transthyretin amyloid cardiomyopathy in Russia increased a need of awareness of ATTR-CM among general practitioners  and cardiologists, and introduction of modern diagnostic algorithms for this disease. Timely detection and competent differential diagnosis of ATTR-CM from other types of amyloid cardiomyopathy  can play a decisive role in the prognosis of this disease. Tafamidis is a treatment that was shown to reduce mortality and CV-related hospitalization in ATTR-CM patients.

1. Donnelly J. P. , Mazen Hanna. Cardiac amyloidosis: An update on diagnosis and treatment // Cleveland Clinic Journal of Medicine. 2017; 84 (12 suppl 3): 12-26. DOI: 10.3949/ccjm.84.s3.02.

2. Siddiqi O. K., Ruberg F. L. Cardiac amyloidosis: An update on pathophysiology, diagnosis, and treatment // Trends Cardiovasc Med. 2018; 28 (1): 10-21. DOI: 10.1016/j.tcm.2017.07.004.

3. Kholová I., Niessen H. W. Amyloid in the cardiovascular system: a review // J Clin Pathol. 2005; 58 (2): 125-33. DOI: 10.1136/jcp.2004.017293. PMID: 15677530; PMCID: PMC1770576.

4. Hou X., Aguilar M.-I., Small D. H. Transthyretin and familial amyloidotic polyneuropathy // The FEBS Journal. 2007; 274: 1637-1650. https://doi.org/10.1111/j.1742-4658.2007.05712.x.

5. Ruberg F. L., Grogan M., Hanna M., Kelly J. W., Maurer M. S. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review // J Am Coll Cardiol. 2019; 73 (22): 2872-2891. DOI: 10.1016/j.jacc.2019.04.003. PMID: 31171094; PMCID: PMC6724183.

6. Maurer M. S., Elliott P., Comenzo R., Semigran M., Rapezzi C. Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis // Circulation. 2017; 135 (14): 1357-1377. DOI: 10.1161/CIRCULATIONAHA.116.024438. PMID: 28373528; PMCID: PMC5392416.

7. González-López E., López-Sainz Á., Garcia-Pavia P. Diagnosis and Treatment of Transthyretin Cardiac Amyloidosis. Progress and Hope // Rev Esp Cardiol (Engl Ed). 2017; 70 (11): 991-1004. English, Spanish. DOI: 10.1016/j.rec.2017.05.036. Epub 2017 Sep 1. PMID: 28870641.

8. Witteles R. M., Bokhari S., Damy T., Elliott P. M., Falk R. H., Fine N. M., Gospodinova M., Obici L., Rapezzi C., Garcia-Pavia P. Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice // JACC Heart Fail. 2019; 7 (8): 709-716. DOI: 10.1016/j.jchf.2019.04.010. Epub 2019 Jul 10. PMID: 31302046.

9. Geller H. I., Singh A., Alexander K. M., Mirto T. M., Falk R. H. Association Between Ruptured Distal Biceps Tendon and Wild-Type Transthyretin Cardiac Amyloidosis // JAMA. 2017; 318 (10): 962-963. DOI: 10.1001/jama.2017.9236. PMID: 28898370; PMCID: PMC5818850.

10. Clinical practice guidelines for the diagnosis and treatment of systemic amyloidosis 2020, https://clinpharm-journal.ru/articles/2020-1/klinicheskie-rekomendatsii-po-diagnostike-i-lecheniyu-sistemnogo-amiloidoza/.

11. Lousada I., Comenzo R. L., Landau H., Guthrie S., Merlini G. Light Chain Amyloidosis: Patient Experience Survey from the Amyloidosis Research Consortium // Adv Ther. 2015; 32 (10): 920-928. DOI: 10.1007/s12325-015-0250-0. Epub 2015 Oct 23. PMID: 26498944; PMCID: PMC4635176.

12. Bistola V., Parissis J., Foukarakis E., Valsamaki P. N., Anastasakis A., Koutsis G., Efthimiadis G., Kastritis E. Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis // Heart Fail Rev. 2021; 26 (4): 861-879. DOI: 10.1007/s10741-020-10062-w. Epub 2021 Jan 15. PMID: 33452596.

13. Garcia-Pavia P., Rapezzi C., Adler Y., Arad M., Basso C., Brucato A., Burazor I., Caforio A. L. P., Damy T., Eriksson U., Fontan, M., Gillmore J. D., Gonzalez-Lopez E., Grogan M., Heymans S., Imazio M., Kindermann I., Kristen A., Maurer M. S., ... Linhart A. Diagnosis and treatment of cardiac amyloidosis: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases // European Heart Journal. 2021; 42 (16): 1554-1568. https://doi.org/10.1093/eurheartj/ehab072.

14. Dorbala S., Ando Y., Bokhari S., Dispenzieri A., Falk R. H., Ferrari V. A., Fontana M., Gheysens O., Gillmore J. D., Glaudemans A. W. J. M., Hanna M. A., Hazenberg B. P. C., Kristen A. V., Kwong R. Y., Maurer M. S., Merlini G., Miller E. J., Moon J. C., Murthy V. L., Quarta C. C., Rapezzi C., Ruberg F. L., Shah S. J., Slart R. H. J. A., Verberne H. J., Bourque J. M. ASNC/AHA/ASE/EANM/HFSA/ ISA/SCMR/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: Part 1 of 2-evidence base and standardized methods of imaging // J Nucl Cardiol. 2019; 26 (6): 2065-2123. DOI: 10.1007/s12350-019-01760-6. Erratum in: J Nucl Cardiol. 2021; 28 (4): 1761-1762. PMID: 31468376.

15. Vindamex. State Register of Medicines. https://zdravmedinform.ru/grls/reg-lp-007319.html.

16. Instructions for the medical use of the drug Vindamex

17. Maurer M. S. et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy // N Engl J Med. 2018 Aug 27; [e-pub]. (https://doi.org/10.1056/NEJMoa1805689).

18. Maurer M. S., Bokhari S., Damy T., Dorbala S., Drachman B. M., Fontana M., Grogan M., Kristen A. V., Lousada I., Nativi-Nicolau J., Cristina Quarta C., Rapezzi C., Ruberg F. L., Witteles R., Merlini G. 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. Epub 2019 Sep 4. PMID: 31480867; PMCID: PMC6736650.

19. Bokhari S., Shahzad R., Castaño A., Maurer M. S. Nuclear imaging modalities for cardiac amyloidosis // J Nucl Cardiol. 2014; 21 (1): 175-184. DOI: 10.1007/s12350-013-9803-2. PMID: 24162886; PMCID: PMC4302756.

20. Adam R. D., Coriu D., Jercan A., Bădeliţă S., Popescu B. A., Damy T., Jurcuţ R. Progress and challenges in the treatment of cardiac amyloidosis: a review of the literature // ESC Heart Fail. 2021; 8 (4): 2380-2396. DOI: 10.1002/ehf2.13443. Epub 2021 Jun 5. PMID: 34089308; PMCID: PMC8318516.

21. Maurer M. S., Elliott P., Merlini G., Shah S. J., Cruz M. W., Flynn A., Gundapaneni B., Hahn C., Riley S., Schwartz J., Sultan M. B., Rapezzi C. ATTR-ACT Study Investigators. Design and Rationale of the Phase 3 ATTR-ACT Clinical Trial (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) // Circ Heart Fail. 2017; 10 (6): e003815. DOI: 10.1161/CIRCHEARTFAILURE.116.003815. PMID: 28611125.

22. Damy T., Garcia-Pavia P., Hanna M., Judge D. P., Merlini G., Gundapaneni B., Patterson T. A., Riley S., Schwartz J. H., Sultan M. B., Witteles R. Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study // Eur J Heart Fail. 2021; 23 (2): 277-285. DOI: 10.1002/ejhf.2027. Epub 2020 Nov 12. PMID: 33070419; PMCID: PMC8048553.

23. Rapezzi C., Elliott P., Damy T., Nativi-Nicolau J., Berk J. L., Velazquez E. J., Boman K., Gundapaneni B., Patterson T. A., Schwartz J. H., Sultan M. B., Maurer M. S. Efficacy of Tafamidis in Patients With Hereditary and Wild-Type Transthyretin Amyloid Cardiomyopathy: Further Analyses From ATTR-ACT // JACC Heart Fail. 2021; 9 (2): 115-123. DOI: 10.1016/j.jchf.2020.09.011. Epub 2020 Dec 9. PMID: 33309574.