Predictors of myocardial fibrosis and loss of epicardial adipose tissue volume in the long-term period after myocardial infarction

Aim. To assess the changes of biochemical markers in hospitalization, the relationship with the severity of myocardial fibrosis and the epicardial adipose tissue (EAT) thickness one year after myocardial infarction (MI).

Material and methods. A total of 88 patients (65 men and 23 women) with MI were examined. The percentage of cicatricial changes in the myocardium and the EAT thickness were measured using the magnetic resonance imaging (MRI) one year after MI. In the hospitalization (days 1 and 12) and 1 year after MI, the concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), stimulating growth factor (ST2), interleukin-33 (IL-33) and type I collagen (COL-1). The data were analyzed using descriptive statistics, correlation and ROC analysis, and logistic regression (Statistica 9.0).

Results. One year after MI, cicatricial changes were detected in 68 (77%) patients: 27 people had myocardial fibrosis <5%, 22 patients — 5-15%, and 19 patients >15%. We established that myocardial fibrosis after MI is associated with unfavorable medical history, a complicated course during in-hospital period and higher concentrations of ST2, NT-proBNP, COL-1 compared with patients without myocardial fibrosis. High levels of ST2, NT-proBNP increase the risk of myocardial fibrosis by 1,2 and 1,8 times after hospitalization, respectively. In patients with myocardial fibrosis >15%, IL-33 level was significantly lower in the 1st day of MI. It was found that the EAT thickness increases with fibrosis of 5-15%. An increase in the left (LV) and right ventricular (RV) EAT thickness by 1,33 times and 1,34 times, respectively, increases the risk of myocardial fibrosis (LV EAT thickness, mm (OR 1,33; 95% CI (1,08-1,4), AUC 0,75; RV EAT thickness, mm (OR 1,34; 95% CI (1,15-1,43), AUC 0,79). In patients with myocardial fibrosis >15%, EAT thickness decreases and correlates with NT-proBNP increase in the acute period and a one year after MI.

Conclusion. The development of myocardial fibrosis one year after MI is associated with an increase in ST2, NT-proBNP, COL-1, both in the hospitalization and 1 year after MI. The decrease in IL-33 concentration during hospitalization with MI is accompanied by the development of fibrosis >15% of the myocardium.

1. Ambale-Venkatesh B, Liu CY, Liu YC, et al. Association of myocardial fibrosis and cardiovascular events: the multi-ethnic study of atherosclerosis. European Heart JournalCardiovascular Imaging. 2018;20(2):168-76. doi:10.1093/ehjci/jey140.

2. Segura AM, Frazier OH, Buja LM. Fibrosis and heart failure. Heart failure reviews. 2014;19(2):173-85. doi:10.1007/s10741-012-9365-4.

3. Dyleva YA, Gruzdeva OV, Uchasova EG, et al. Stimulating growth factor ST2 in cardiology: present and future. Lechashchij vrach. 2017;11:65-71. (In Russ.)

4. Gruzdeva OV, Akbasheva OE, Dyleva YA, et al. Adipokine and cytokine profiles of epicardial and subcutaneous adipose tissue in patients with coronary heart disease. Bulletin of experimental biology and medicine. 2017;163(5):608-11. (In Russ.) doi:10.1007/s10517-017-3860-5.

5. Fitzgibbons TP, Czech MP. Epicardial and perivascular adipose tissues and their influence on cardiovascular disease: basic mechanisms and clinical associations. Journal of the American Heart Association. 2014;3(2):e000582. doi:10.1161/jaha.113.000582.

6. Cai R, Gu J, Sunet H, et al. Induction of SENP1 in myocardium contributes to abnormities of mitochondria and cardiomyopathy. Journal of molecular and cellular cardiology. 2015;79:115-22. doi:10.1016/j.yjmcc.2014.11.014.

7. Seki K, Sanada S, Kudinova AY, et al. Interleukin-33 prevents apoptosis and improves survival after experimental myocardial infarction through ST2 signaling. Circ. Heart Fail. 2009;2:684-91. doi:10.1161/circheartfailure.109.873240.

8. Guzel S, Serin O, Guzel EC, et al. Interleukin-33, мatrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 in myocardial infarction. Korean J. Intern. Med. 2013;28:165-73. doi:10.3904/kjim.2013.28.2.165.

9. Wang TD, Lee WJ, Shih FY, et al. Association of epicardial adipose tissue with coronary atherosclerosis is region-specific and independent of conventional risk factors and intra-abdominal adiposity. Atherosclerosis. 2010;213(1):279-87. doi:10.1016/j.atherosclerosis.2010.07.055.

10. Barbarash OL, Usoltseva EN. Heart failure treatment under control of natriuretic peptides concentration. Kompleksnye problemy serdečno-sosudistyh zabolevanij. 2014;(1):67-74. (In Russ.) doi:10.17802/2306-1278-2014-1.

11. Sengenes C, Berlan M, De Glisezinski I, et al. Natriuretic peptides: a new lipolytic pathway in human adipocytes. FASEB J. 2000;14:1345-51. doi:10.1096/fasebj.14.10.1345.

12. Valero-Munoz M, Li S, Wilson RM, et al. Heart failure with preserved ejection fraction induces beiging in adipose tissue. Circ Heart Fail. 2016;9:e002724. doi:10.1161/CIRCHEARTFAILURE.115.002724.

13. Lafontan M, Moro C, Berlan M, et al. Control of lipolysis by natriuretic peptides and cyclic GMP. Trends Endocrinol Metab. 2008;19:130-7. doi:10.1016/j.tem.2007.11.006.

14. Austin S, St-Pierre J. PGC1alpha and mitochondrial metabolism–emerging concepts and relevance in ageing and neurodegenerative disorders. J Cell Sci. 2012;125(Pt 21):496371. doi:10.1242/jcs.113662.

15. Barbarash OL, Gruzdeva OV, Akbasheva OE, et al. Clinical and biochemical predictors of diabetes mellitus manifestation after myocardial infarction. Russian Journal of Cardiology. 2014;(3):87-94. (In Russ.) doi:10.15829/1560-4071-2014-3-87-94.