Genetic polymorphisms of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1 and development of postoperative atrial fibrillation in elderly patients

Aim. The aim of the study was to assess the association of genetic polymorphisms of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) with atrial fibrillation development in elderly patients with coronary artery disease (CAD), undergoing coronary artery bypass graft (CABG) surgery.

Material and methods. Studied were 80 patients who underwent CABG in 2015-2016 years. In all the patients routine laboratory and instrumental tests were performed. Patients also underwent genetic polymorphisms of ММР-9 А8202G and TIMP-1 C536T estimation with polymerase chain reaction. According to occurrence of postoperative atrial fibrillation (POAF) all the patients were divided into two groups: 1 group comprised 56 patients without POAF (81,8% males, mean age 65,9±4,0 years), 2 group — 24 patients with first detected episode of AF after CABG (875% males, mean age 67,7±5,4).

Results. According to results of multivariate regression analysis the odds ratio of POAF development in patients with stable angina grade III was 1,8 (95% CI 0,5-75, p=0,4), NYHA III — 0,85 (95% CI 0,2-3,5, p=0,55), history of CAD more than 20 months — 1,8 (95% CI 1,2-8,1, p=0,03), LA diameter more than 39 mm — 4,2 (95% CI 1,6-9,5, p<0,0001), allele G MMP-9 A8202G — 2,6 (95% CI 1,2-75, p=0,03).

Conclusion. In elderly patients undergoing coronary artery bypass graft surgery left atrial diameter more than 39 mm, history of coronary artery disease more than 20 months and the presence of G allele of MMP-9 A820G are significantly associated with postoperative atrial fibrillation occurrence.

1. Philip F, Becker M, Galla J, et al. Transient post-operative atrial fibrillation predicts short and long term adverse events following CABG. CardiovascDiagnTher. 2014;4(5):365-72. doi:10.3978/j.issn.2223-3652.2014.09.02.

2. Rubanenko OA, Fatenkov OV, Khokhlunov SM. Predictors of new-onset atrial fibrillation in elderly patients with coronary artery disease after coronary artery bypass graft. Journal of Geriatric Cardiology. 2016;13:444-9 doi:10.11909/j.issn.1671-5411.2016.05.017

3. Rahmutula D, Zhang H, Wilson EE, Olgin JE. Absence of NPR-C Attenuates TGF-B1 Induced Selective Atrial Fibrosis and Atrial Fibrillation. Cardiovasc Res. 2018 Sep 18. doi:10.1093/cvr/cvy224. [Epub ahead of print].

4. Huxley RR, Lopez FL, MacLehose RF, et al. Novel association between plasma matrix metalloproteinase-9 and risk of incident atrial fibrillation in a case-cohort study: the Atherosclerosis Risk in Communities study. PLoS One. 2013;8(3):e59052. doi:10.1371/journal.pone.0059052.

5. Lubitz S, Lunetta K, Lin H, et al. Novel genetic markers with atrial fibrillation in Europeans and Japanese. J Am Coll Cardiol. 2014;63(12):1200-10. doi:10.1016/j.jacc.2013.12.015.

6. Donate Puertas R, Millat G, Ernens I, et al. Atrial Structural Remodeling Gene Variants in Patients with Atrial Fibrillation. Biomed Res Int. 2018;2018:4862480. doi:10.1155/2018/4862480.eCollection2018.

7. Mayer F, Falk M, Huhn R, et al. Matrixmetalloproteinases and tissue inhibitors of metalloproteinases: Immunhistochemical markers in the diagnosis of lethal myocardial infarctions? Forensic Sci Int. 2018;288:181-8. doi:10.1016/j.forsciint.2018.04.039.

8. Thoren E, Hellgren L, Granath F, et al. Postoperative atrial fibrillation predicts cause- specific late mortality after coronary surgery. Scand Cardiovasc J. 2014;48(2):71-8. doi:10.3109/14017431.2014.880793.

9. Kotecha D, Chudasama R, Lane DA, et al. Atrial fibrillation and heart failure due to reduced versus preserved ejection fraction: A systematic review and meta-analysis of death and adverse outcomes. Int J Cardiol. 2016;203:660-6. doi:10.1016/j.ijcard.2015.10.220.

10. Parsaee M, Moradi B, Esmaeilzadeh M, et al. New onset atrial fibrillation after coronary artery bypasses grafting; an evaluation of mechanical left atrial function. Arch Iran Med. 2014;17(7):501-6. doi:0141707/AIM.0011.

11. Jakubova M, Mitro P, Stancak B, et al. The occurrence of postoperative atrial fibrillation according to different surgical settings in cardiac surgery patients. Interact Cardiovasc Thorac Surg. 2012;15:1007-12. doi:10.1093/icvts/ivs361.

12. Davoodi S, Karimi A, Ahmadi SH, et al. Early outcome of off-pump versus on-pump coronary revascularization. Pan Afr Med J. 2014;17:309. doi:10.11604/pamj.2014.17.309.1723.

13. Wittwer T, Sabashnikov A, Rahmanian PB, et al. Less invasive coronary artery revascularization with a minimized extracorporeal circulation system: preliminary results of a comparative study with off-pump-procedures. J Cardiothorac Surg. 2013;8:75. doi:10.1186/1749-8090-8-75.

14. Nattel S. Molecular and Cellular Mechanisms of Atrial Fibrosis in Atrial Fibrillation. JACC Clin Electrophysiol. 2017;3(5):425-35. doi:10.1016/j.jacep.2017.03.002.

15. Kertai MD, Li YJ, Ji Y, et al. Genome-wide association study of new-onset atrial fibrillation after coronary artery bypass grafting surgery. Am Heart J. 2015;170(3):580-90. doi:10.1016/j.ahj.2015.06.009.