Retrospective analysis of cardiovascular involvement in patients with systemic amyloidosis

Amyloidosis is a heterogeneous group of the diseases caused by the extracellular deposition of amyloid in various organs including a cardiovascular system.

Aim. To study the cardiovascular damage in patients with systemic amyloidosis.

Material and methods. A retrospective assessment of 38 cases of systemic amyloidosis was carried out. Diagnosis was verified by biopsy in 57,9% (27,3% of these cases were then confirmed by autopsy) and autopsy in 42,1% of patients. Congo red stain and polarized-light microscopy were used. The systemic nature of lesion was diagnosed in the positive biopsies of two or more localizations or in the positive biopsy of one localization in the combination with the clinical picture of amyloidosis at least one organ. Median (interquartile range) of age was 72,5 (64-84) years (women, 65,8%; men, 34,2%).

Results. In the medical history, 81,6% of patients with systemic amyloidosis had hypertension, 52,6% — coronary artery disease, 34,2% — myocardial infarction, 36,8% — type 2 diabetes, 44,7% — atrial fibrillation, 26,3% — conduction disorders. Also 13,2% of patients had an implanted pacemaker. According to the electrocardiography, 42,3% of patients had a low QRS voltage. According to echocardiography, left ventricular (LV) hypertrophy was detected in 94,7% of patients. In addition, 31,6% of patients had signs of granular sparkling myocardial appearance, 20% — impaired local LV contractility, 77,8% — increased pulmonary artery reassure, 28,6% — LV diastolic dysfunction, 14,3% — normal diastolic function. LV ejection fraction (LVEF) was 55 (44,5-55)%. LVEF <40% was detected in 15%, 4050% — in 20%, >50% — in 65% of patients. Heart failure was indicated in 71,1% of patients with systemic amyloidosis, chronic kidney disease (CKD) — in 95% of patients. The estimated glomerular filtration rate (CKD-EPI) was 21,2 (13,1-40) ml/min/1,73 m². Proteinuria (1,1 (0,5-3,0) g/l) was detected in 88,9% of patients. Nephrotic syndrome occurred in 27,8% of patients.

Conclusion. Patients with cardiovascular lesions of unclear etiology, especially in the presence of LV wall thickening, preserved LVEF, stage 4-5 CKD and proteinuria, require screening for systemic amyloidosis.

1. Lysenko (Kozlovskaya) LV, Rameev VV, Moiseev S, et al. Clinical guidelines for diagnosis and treatment of systemic amyloidosis. Klinicheskaya farmakologiya i terapiya = Clin Pharmacol Therapy. 2020;29(1):13-24. (In Russ.) doi:10.32756/0869-5490-2020-1-13-24.

2. Sipe JD, Benson MD, Buxbaum JN, et al. Amyloid fibril proteins and amyloidosis: chemical identification and clinical classification International Society of Amyloidosis 2016 Nomenclature Guidelines. Amyloid. 2016;23(4):209-13. doi:10.1080/13506129.2016.1257986.

3. Oerlemans MIFJ, Rutten KHG, Minnema MC, et al. Cardiac amyloidosis: the need for early diagnosis. Neth Heart J. 2019;27(11):525-36. doi:10.1007/s12471-019-1299-1.

4. Manolis AS, Manolis AA, Manolis TA, Melita H. Cardiac amyloidosis: An underdiagnosed/underappreciated disease. Eur J Intern Med. 2019;67:1-13. doi:10.1016/j.ejim.2019.07.022.

5. Sperry BW, Tang WHW. Amyloid heart disease: genetics translated into disease-modifying therapy. Heart. 2017;103(11):812-7. doi:10.1136/heartjnl-2016-309914.

6. Maleszewski JJ. Cardiac amyloidosis: pathology, nomenclature, and typing. Cardiovasc Pathol. 2015;24(6):343-50. doi:10.1016/j.carpath.2015.07.008.

7. Seferovic PM, Ponikowski P, Anker SD, 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; 21(10):1169-86. doi:10.1002/ejhf.1531.

8. Lopez-Sainz A, de Haro-Del Moral FJ, Dominguez F, et al. Prevalence of cardiac amyloidosis among elderly patients with systolic heart failure or conduction disorders. Amyloid. 2019;26(3):156-63. doi:10.1080/13506129.2019.1625322.

9. Gilstrap LG, Dominici F, Wang Y, et al. Epidemiology of Cardiac Amyloidosis-Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States. Circ Heart Fail. 2019;12(6):e005407. doi:10.1161/CIRCHEARTFAILURE.118.005407.

10. Fajardo J, Cummings A, Brown E, et al. Clinical pathway to screen for cardiac amyloidosis in heart failure with preserved ejection fraction. Amyloid. 2019;26(sup1):166-7. doi:10.1080/13506129.2019.1583178.

11. Murtagh B, Hammill SC, Gertz MA, et al. Electrocardiographic findings in primary systemic amyloidosis and biopsy-proven cardiac involvement. Am J Cardiol. 2005;95(4):535-7. doi:10.1016/j.amjcard.2004.10.028.

12. Mareev YV, Fomin IV, Ageev FT, et al. Clinical guidelines OSSN-RKO-RNMOT. Heart failure: chronic (CHF) and acute decompensated (ODSF). Diagnostics, prevention and treatment. Kardiologiia. 2018;8-164. (In Russ.) doi:10.18087/cardio.2475.

13. Rebrova OYu. Statistical analysis of medical data. Application of the STATISTICA application package. 2006, Mediasphere: Moscow. p. 305. (In Russ.) ISBN: 5-89084-013-4.

14. Mohammed SF, Mirzoyev SA, Edwards WD, et al. Left ventri -cular amyloid deposition in patients with heart failure and preserved ejection fraction. JACC Heart Fail. 2014;2(2):113-22. doi:10.1016/j.jchf.2013.11.004.

15. 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 Heart J. 2015;36(38):2585-94. doi:10.1093/eurheartj/ehv338.

16. Pinney JH, Smith CJ, Taube JB, et al. Systemic amyloidosis in England: an epidemiological study. Br J Haematol. 2013;161(4):525-32. doi:10.1111/bjh.12286.

17. Reznik EV, Nguyen TL, Stepanova EA, et al. Cardiac Amyloidosis: Internist and Cardiologist Insight. The Russian Archives of Internal Medicine. 2020;10(6):430-57. (In Russ.) doi:10.20514/2226-6704-2020-10-6-430-457.

18. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2020. doi:10.1093/eurheartj/ehaa612.

19. Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation. 2005;112(13):2047-60. doi:10.1161/CIRCULATIONAHA.104.489187.

20. Shalnova SA, Deev AD., Kapustina AV, et al. Coronary heart disease in persons older than 55 years. Prevalence and prognosis. Cardiovascular Therapy and Prevention. 2014;13(4):21-8. (In Russ.) doi:10.15829/1728-8800-2014-4-21-28.

21. Neben-Wittich MA, Wittich CM, Mueller PS, et al. Obstructive intramural coronary amyloidosis and myocardial ischemia are common in primary amyloidosis. Am J Med. 2005;118(11):1287. doi:10.1016/j.amjmed.2005.06.017.

22. Reznik EV, Nikitin IG. Cardiorenal syndrome in patients with heart failure as a stage of the cardiorenal Continuum (part 2): prognosis, prevention and treatment. The Russian Archives of Internal Medicine. 2019;9(2):93-106. (In Russ.). doi:10.20514/2226-6704-2019-9-2-93-106.

23. Reznik EV, Nikitin IG. Cardiorenal syndrome in patients with chronic heart failure as a stage of the cardiorenal Continuum (part 1): definition, classification, pathogenesis, diagnosis, epidemiology. The Russian Archives of Internal Medicine. 2019;9(1): 5-22. (In Russ.) doi:10.20514/2226-6704-2019-9-1-5-22.

24. 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.

25. Sekijima Y, Mundayat R, Ishii T, Ando Y. 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.

26. Rysava R. AL amyloidosis: advances in diagnostics and treatment. Nephrol Dial Transplant. 2019;34(9):1460-6. doi:10.1093/ndt/gfy291.

27. Damy T, Kristen AV, Suhr OB, et al. Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS). Eur Heart J. 2019;ehz173. doi:10.1093/eurheartj/ehz173.