CD8⁺CD28^null T Lymphocytes are Associated with the Development of Atrial Fibrillation after Elective Cardiac Surgery

Abstract

Background Postoperative atrial fibrillation (POAF) is assumed as a complex and multifactorial interaction of different pathogenic factors. Data suggests an inflammatory process as the main trigger of this specific type of atrial fibrillation. CD8⁺ T lymphocytes that lack the surface protein CD28 were found to be crucially involved in chronic inflammatory processes within the cardiovascular system. Of utmost interest, these so-called CD8⁺CD28^null T cells are known to present with autoaggressive behavior and deleterious cytotoxic effects on human tissue.

Methods A total of 129 patients undergoing elective cardiac valve and/or coronary artery bypass graft surgery were enrolled. Fluorescence-activated cell sorting was performed to investigate lymphocyte subsets. Patients were stratified in two subgroups according to patients developing POAF (n = 60) and individuals free of POAF (n = 69).

Results Comparing patients developing POAF to individuals free of POAF, the fraction of CD8⁺ lymphocytes was significantly higher in individuals developing POAF (30.5% [POAF] vs. 25.7% [no-POAF]; p = 0.021). Interestingly, also the fraction of CD8⁺CD28^null T lymphocytes was significantly higher in the POAF subgroup (66.7% [POAF] vs. 61.6% [non-POAF]; p = 0.043). Multivariate logistic regression proved that the fraction of CD8⁺CD28^null cells is a strong and independent prognosticator for the development of POAF with an adjusted odds ratio per 1 standard deviation of 3.21 (95% confidence interval 1.01–10.18; p = 0.048).

Conclusion We found that cytotoxic CD8⁺CD28^null T lymphocytes proved to be a strong and independent predictor for the development of POAF after elective cardiac surgery. Our results potentially indicate an autoimmune impact of this preexisting, highly cytotoxic T cell subset in the pathogenesis of POAF.

Keywords

postoperative - atrial fibrillation - CD8 + CD28null - T lymphocytes - cardiac surgery

Publikationsverlauf

Eingereicht: 26. Februar 2020

Angenommen: 01. Mai 2020

Artikel online veröffentlicht:
28. Juni 2020

• References

• 1 Chugh SS, Havmoeller R, Narayanan K. , et al. Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study. Circulation 2014; 129 (08) 837-847
• 2 Krijthe BP, Kunst A, Benjamin EJ. , et al. Projections on the number of individuals with atrial fibrillation in the European Union, from 2000 to 2060. Eur Heart J 2013; 34 (35) 2746-2751
• 3 Maesen B, Nijs J, Maessen J, Allessie M, Schotten U. Post-operative atrial fibrillation: a maze of mechanisms. Europace 2012; 14 (02) 159-174
• 4 Li T, Sun Z-L, Xie Q-Y. Meta-analysis identifies serum C-reactive protein as an indicator of atrial fibrillation risk after coronary artery bypass graft. Am J Ther 2016; 23 (06) e1586-e1596
• 5 Paschalis A, Tousoulis D, Demosthenous M. , et al. Pre-operative inflammation and post-operative atrial fibrillation in coronary artery bypass surgery. Int J Cardiol 2014; 173 (02) 327-328
• 6 Wu Z-K, Laurikka J, Vikman S, Nieminen R, Moilanen E, Tarkka MR. High postoperative interleukin-8 levels related to atrial fibrillation in patients undergoing coronary artery bypass surgery. World J Surg 2008; 32 (12) 2643-2649
• 7 Abdelhadi RH, Gurm HS, Van Wagoner DR, Chung MK. Relation of an exaggerated rise in white blood cells after coronary bypass or cardiac valve surgery to development of atrial fibrillation postoperatively. Am J Cardiol 2004; 93 (09) 1176-1178
• 8 Jacob KA, Nathoe HM, Dieleman JM, van Osch D, Kluin J, van Dijk D. Inflammation in new-onset atrial fibrillation after cardiac surgery: a systematic review. Eur J Clin Invest 2014; 44 (04) 402-428
• 9 Weng NP, Akbar AN, Goronzy J. CD28(-) T cells: their role in the age-associated decline of immune function. Trends Immunol 2009; 30 (07) 306-312
• 10 Sulzgruber P, Koller L, Winter M-P. , et al. The impact of CD4⁺CD28^null T-lymphocytes on atrial fibrillation and mortality in patients with chronic heart failure. Thromb Haemost 2017; 117 (02) 349-356
• 11 Kirchhof P, Benussi S, Kotecha D. , et al. 2016 ESC guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur J Cardiothorac Surg 2016; 50 (05) e1-e88
• 12 Tousoulis D, Zisimos K, Antoniades C. , et al. Oxidative stress and inflammatory process in patients with atrial fibrillation: the role of left atrium distension. Int J Cardiol 2009; 136 (03) 258-262
• 13 Fagnoni FF, Vescovini R, Mazzola M. , et al. Expansion of cytotoxic CD8+ CD28- T cells in healthy ageing people, including centenarians. Immunology 1996; 88 (04) 501-507
• 14 Patti G, Chello M, Candura D. , et al. Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. Circulation 2006; 114 (14) 1455-1461
• 15 Kuhn EW, Liakopoulos OJ, Stange S. , et al. Preoperative statin therapy in cardiac surgery: a meta-analysis of 90,000 patients. Eur J Cardiothorac Surg 2014; 45 (01) 17-26
• 16 Reimann KA, Chernoff M, Wilkening CL, Nickerson CE, Landay AL. ; The ACTG Immunology Advanced Technology Laboratories. Preservation of lymphocyte immunophenotype and proliferative responses in cryopreserved peripheral blood mononuclear cells from human immunodeficiency virus type 1-infected donors: implications for multicenter clinical trials. Clin Diagn Lab Immunol 2000; 7 (03) 352-359