The association of biological markers with echocardiographic indices in patients with myocardial infarction with ST segment elevation and preserved left ventricular ejection fraction

Aim. To compare dynamics of biological marker concentrations with echocardiographic data in patients with ST elevation myocardial infarction (STEMI) and preserved LV function during the hospitalization period. Materials and methods. The study successively included 100 patients with diagnosis of STEMI and LV ejection fraction <40%. Revascularization of the symptom-related artery was performed for all patients. Echocardiography was performed for all patients on days 1 and 10-12. Serum concentrations of the following markers were measured for all patients on admission and followed up on days 10-12 of disease onset: matrix metalloprotein-ases 1, 2, and 3 (MMP), tissue inhibitor of matrix metalloproteinases 1 (TIMP1), galectin 3; N-terminal fragment of pro-B natriuretic peptide (NT-proBNP); and soluble IL-1 receptor family member (sST2). Results. The following indexes tended to increase (р<0.05) by days 10-12 of myocardial infarction: LV ejection fraction, stroke volume, E/е’, and early mitral flow propagation velocity (EMFPV). In contrst, end-diastolic volume, end-systolic volume, DT, ET, Em, Em/EMFPV were decreased (р<0.05). The MMP 3 concentration measured on days 10-12 of myocardial infarction was 1.62 times higher than the value obtained on day 1 whereas the soluble ST2 receptor concentration measured on days 10-12 was, in contrast, almost half as high as the values determined on day 1. Also, statistically significant changes during the hospitalization period were observed for galectin-3 (p=0.0001), MMP 2 (p=0.0003), and NT-proBNP (p=0.0361). According to results of the correlation analysis most of the studied markers correlated with indexes of LV systolic and diastolic function both on day 1 and day 10. Conclusion. In the group of patients with STEMI with preserved LV function, consistent dynamics (days 1 and 10-12) of most of the studied markers, including galectine-3, MMP 2, MMP 3, sST2, and NT-proBNP was observed. On day 1 of STEMI, levels of biological markers statistically significantly correlated with echocardio-graphic indexes of systolic and diastolic function.

биологические маркеры, инфаркт миокарда, сохранная функция левого желудочка, biological markers, myocardial infarction, preserved left ventricular function

1. Johansson S/, Rosengren A/, Young K/, Jennings E. Mortality and morbidity trends after the first year in survivors of acute myocardial infarction: a systematic review. BMC Cardiovascular Disorders [Internet]. 2017 [cited 2018]; 17 (1). DOI: 10.1186/s12872-017-0482-9

2. Оганов Р.Г., Погосова Г.В. Современные стратегии профилактики и лечения ССЗ. Кардиология. 2007; 47 (12): 1-10. [Oganov R. G., Pogosova G. V. Contemporary strategies of prevention and treatment of cardiovascular diseases. Kardiologiia. 2007; 47 (12): 1-10.]

3. Рагино Ю.И., Чернявский А.М., Полонская Я.В., Волков А.М., Каштанова Е.В., Цымбал С. Ю. Воспалительно-деструктивные биомаркеры нестабильности атеросклеротических бляшек: исследования сосудистой стенки и крови. Кардиология. 2012; 52 (5): 37-41. [Ragino Yu. I., Chernjavski A. M., Polonskaya Ya. V., Volkov A. M., Kashtanova E. V., Tcimbal S. Yu., Polovnikova E. M. Inflammatory-destructive biomarkers of instability of atherosclerotic plaques: studies of the vascular wall and blood. Kardiologiia. 2012; 52 (5): 37-41.]

4. Von Lueder T.G., Wang B.H., Kompa A.R., Huang L., Webb R., Jordaan P. et al. Angiotensin receptor neprilysin inhibitor LCZ696 attenuates cardiac remodeling and dysfunction after myocardial infarction by reducing cardiac fibrosis and hypertrophy. Circulation: Heart Failure. 2015; 8 (1): 71-8. DOI: 10.1161/CIRCHEARTFAILURE.114.001785

5. French B.A., Kramer C.M. Mechanisms of postinfarct left ventricular remodeling. Drug Discovery Today: Disease Mechanisms. 2007; 4 (3): 185-96. DOI: 10.1016/j. ddmec. 2007.12.006

6. Galli A., Lombardi F. Postinfarct Left Ventricular Remodelling: A Prevailing Cause of Heart Failure. Cardiology Research and Practice. 2016; 2016: 1-12. DOI: 10.1155/2016/2579832

7. Carrick D., Haig C., Rauhalammi S., Ahmed N., Mordi I., McEntegart M. et al. Pathophysiology of LV Remodeling in Survivors of STEMI. JACC: Cardiovascular Imaging. 2015; 8 (7): 779-89. DOI: 10.1016/j.jcmg. 2015.03.007

8. Marshall R.P., Simpson J.K., Lukey P.T. Strategies for biomarker discovery in fibrotic disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2013; 1832 (7): 1079-87. DOI: 10.1016/j.bbadis. 2013.01.018

9. Zile M.R., Baicu C.F., Ikonomidis J.S., Stroud R.E., Nietert P.J., Bradshaw A.D. et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and ti-tin. Circulation. 2015; 131 (14): 1247-59. DOI: 10.1161/CIRCU-LATIONAHA. 114.013215

10. Rogers F.J., Gundala T., Ramos J.E., Serajian A. Heart Failure With Preserved Ejection Fraction. The Journal of the American Osteopathic Association. 2015; 115 (7): 432. DOI: 10.7556 /jaoa.2015.089

11. Prevalence, clinical characteristics and outcomes of HF with preserved versus reduced ejection fraction. British Journal of Cardiology [Internet]. 2016 [cited 2018]; DOI: 10.5837/bjc.2016.005

12. Chu J.W., Jones G.T., Tarr G.P., Phillips L.V., Wilkins G.T., van Rij AM et al. Plasma active matrix metalloproteinase 9 and indices of diastolic function in patients with preserved systolic function. International Journal of Cardiology. 2013; 167 (4): 1242-6. DOI: 10.1016/j.ij-card. 2012.03.147

13. O’Donoghue M.L., Morrow D.A., Cannon C.P., Jarolim P., Desai N.R., Sherwood MW et al. Multimarker Risk Stratification in Patients With Acute Myocardial Infarction. J Am Heart Assoc. 2016; 5 (5). DOI: 10.1161/JAHA.115.002586

14. Bartunek J., Delrue L., Van Durme F., Muller O., Casselman F., De Wiest B. et al. Nonmyocardial Production of ST2 Protein in Human Hypertrophy and Failure Is Related to Diastolic Load. Journal of the American College of Cardiology. 2008; 52 (25): 2166-74. DOI: 10.1016/j.jacc.2008.09.027

15. Wang Y.-C., Yu C.-C., Chiu F.-C., Tsai C.-T., Lai L.-P., Hwang J.-J. et al. Soluble ST2 as a Biomarker for Detecting Stable Heart Failure With a Normal Ejection Fraction in Hypertensive Patients. Journal of Cardiac Failure. 2013; 19 (3): 163-8. DOI: 10.1016/j.cardfail. 2013.01.010

16. Ponikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G.F., Coats A.J.S. et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016; 37 (27): 2129-200. DOI: 10.1093/eurheartj/ehw128

17. Huttin O., Coiro S., Selton-Suty C., Juillière Y., Donal E., Magne J. et al. Prediction of Left Ventricular Remodeling after a Myocardial Infarction: Role of Myocardial Deformation: A Systematic Review and Meta-Analysis. Rouet P, editor. PLOS ONE. 2016; 11 (12): e0168349. DOI: 10.1371/journal.pone.0168349

18. Reis Filho J.R. de A.R., Cardoso J.N., Cardoso C.M. dos R., Pereira-Barretto A.C. Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure. Arquivos Brasileiros de Cardiologia [Internet]. 2015 [cited 2018]; DOI: 10.5935/abc.20150025

19. Zouein F.A., Zgheib C., Liechty K.W., Booz G.W. Post-Infarct Biomaterials, Left Ventricular Remodeling, and Heart Failure: Is Good Good Enough?: acellular biopolymers to limit cardiac remodeling. Congestive Heart Failure. 2012; 18 (5): 284-90. DOI: 10.1111/j.1751-7133.2012.00298.

20. Maries L, Manitiu I. Diagnostic and prognostic values of B-type natriuretic peptides (BNP) and N-terminal fragment brain natriuretic peptides (NT-pro-BNP): review article. Cardiovascular Journal Of Africa. 2013; 24 (7): 286-9. DOI: 10.5830/CVJA-2013-055

21. Vardeny O., Miller R., Solomon S.D. Combined Neprilysin and Renin-Angiotensin System Inhibition for the Treatment of Heart Fail- 36. ure. JACC: Heart Failure. 2014; 2 (6): 663-70. DOI: 10.1016/j.jchf. 2014.09.001

22. Johnson J. Matrix metalloproteinases and their inhibitors in cardiovascular pathologies: current knowledge and clinical potential. Metalloproteinases In Medicine. 2014; 21. DOI: 10.2147/MNM.S50999

23. Orn S., Manhenke C., Squire I.B., Ng L, Anand I., Dickstein K. Plasma MMP-2, MMP-9 and N-BNP in Long-Term Survivors Following Complicated Myocardial Infarction: Relation to Cardiac Magnetic Resonance Imaging Measures of Left Ventricular Structure and Function. Journal of Cardiac Failure. 2007; 13 (10): 843-9. DOI: 10.1016/j.cardfail. 2007.07.006

24. Jordan A., Roldan V., Garcia M., Monmeneu J., de Burgos F.G., Lip G.Y.H. et al. Matrix metalloproteinase-1 and its inhibitor, TIMP-1, in systolic heart failure: relation to functional data and prognosis. Journal of Internal Medicine. 2007; 262 (3): 385-92. DOI: 10.1111/j.1365-2796.2007.01823.x

25. Creemers E.E.J.M., Davis J.N., Parkhurst A.M., Leenders P., Dowdy K.B., Hapke E. et al. Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice. American Journal of Physiology-Heart and Circulatory Physiology. 2003; 284 (1): H364-71. DOI: 10.1152/ajpheart.00511.2002

26. Kelly D., Khan S.Q., Thompson M., Cockerill G., Ng L.L., Samani N. et al. Plasma tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9: novel indicators of left ventricular remodelling and prognosis after acute myocardial infarction. European Heart Journal. 2008; 29 (17): 2116-24. DOI: 10.1093/eurheartj/ehn315

27. Sundstrom J. Relations of Plasma Matrix Metalloproteinase-9 to Clinical Cardiovascular Risk Factors and Echocardiogra-phic Left Ventricular Measures: The Framingham Heart Study. Circulation. 2004; 109 (23): 2850-6. DOI: 10.1161/01.CIR. 0000129318.79570.84

28. Ohtsuka T., Nishimura K., Kurata A., Ogimoto A., Okayama H., Higaki J. Serum Matrix Metalloproteinase-3 as a Novel Marker for Risk Stratification of Patients With Nonischemic Dilated Cardiomyopathy. Journal of Cardiac Failure. 2007; 13 (9): 752-8. DOI: 10.1016/j.cardfail.2007.06.730

29. Ho J.E., Liu C., Lyass A., Courchesne P., Pencina M.J., Vasan R.S. et al. Galectin-3, a Marker of Cardiac Fibrosis, Predicts Incident Heart Failure in the Community. Journal of the American College of Cardiology. 2012; 60 (14): 1249-56. DOI: 10.1016/j.jacc. 2012.04.053

30. Di Tano G., Caretta G., De Maria R., Parolini M., Bassi L., Testa S. et al. Galectin-3 predicts left ventricular remodelling after anterior-wall myocardial infarction treated by primary percutaneous coronary intervention. Heart. 2017; 103 (1): 71-7. DOI: 10.1136/heartjnl-2016-309673

31. Felker G.M., Fiuzat M., Shaw L.K., Clare R., Whellan D.J., Bettari L. et al. Galectin-3 in Ambulatory Patients With Heart Failure: Results From the HF-ACTION Study. Circulation: Heart Failure. 2012; 5 (1): 72-8. DOI: 10.1161/CIRCHEARTFAILURE. 111.963637

32. Gonzalez A., Lopez B., Ravassa S., Beaumont J., Arias T., Hermida N. et al. Biochemical markers of myocardial remodelling in hypertensive heart disease. Cardiovascular Research. 2008; 81 (3): 509-18. DOI: 10.1093/cvr/cvn235

33. Cardiac biomarkers: expert advice for clinicians. 1st ed. Maisel AS, editor. - New Delhi: Jaypee Bros. Medical Pub; 2012. 239 p. ISBN: 978-93-5025-564-3

34. Zhang., Zhang X., Mi Y., Liu J. Predicting value of serum soluble ST2 and interleukin-33 for risk stratification and prognosis in patients with acute myocardial infarction. Chin Med J. 2013; 126 (19): 3628-31.

35. Santhanakrishnan R., Chong J.P.C., Ng T.P., Ling L.H., Sim D., Toh G. Leong K et al. Growth differentiation factor 15, ST2, high-sensitivity troponin T, and N-terminal pro brain natriuretic peptide in heart failure with preserved vs. reduced ejection fraction. European Journal of Heart Failure. 2012; 14 (12): 1338-47. DOI: 10.1093/eurjhf/hfs130

36. Bhatia R.S., Tu J.V., Lee D.S., Austin P.C., Fang J., Haouzi A. et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006; 355 (3): 260-9. DOI: 10.1056/NEJMoa051530

37. Owan T.E., Hodge D.O., Herges R.M., Jacobsen S.J., Roger V.L., Redfield M.M. Trends in prevalence and outcome of heart failure with preserved ejection fraction. New England Journal of Medicine. 2006; 355 (3): 251-9. DOI: 10.1056/NEJMoa052256

38. Meluzin J., Tomandl J. Can Biomarkers Help to Diagnose Early Heart Failure with Preserved Ejection Fraction? Disease Markers. 2015; 2015: 1-9. DOI: 10.1155/2015/426045

39. Paulus W.J., Tschöpe C., Sanderson J.E., Rusconi C., Flachskampf F.A., Rademakers F.E. et al. How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. European Heart Journal. 2007; 28 (20): 2539-50. DOI: 10.1093/eurheartj/ehm037