Levels of Circulating Intermediate Monocytes Decrease after Aortic Valve Replacement in Patients with Severe Aortic Stenosis

Abstract

Aortic valve stenosis (AS) is a chronic inflammatory disease. We have previously shown that severe AS is associated with increased levels of circulating intermediate monocytes. Haemodynamics are considered to influence levels of circulating monocyte subsets; we therefore hypothesized that aortic valve replacement may result in changes in the distribution of circulating monocyte subsets. In the present study, we evaluated levels of circulating monocyte subsets in patients with severe AS undergoing surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). Levels of classical (CD14⁺⁺CD16^–), intermediate (CD14⁺⁺CD16⁺), and non-classical (CD14⁺CD16⁺⁺) CD86-positive monocytes were determined by flow cytometry in peripheral blood of patients with severe AS before (baseline) and at 3- and 6-month follow-ups (FUP) after SAVR (n = 25 patients) or TAVR (n = 44 patients). Absolute and relative levels of circulating intermediate monocytes decreased from median 39.9/µL (interquartile range [IQR]: 31.7–53.6/µL) and 6.7% (5.6–8.1%) at baseline to 31.6/µL (24.3–42.4/µL; p < 0.001) and 5.4% (4.4–6.7%; p < 0.001) at 6-month FUP after aortic valve replacement, respectively. The decrease in levels of circulating intermediate monocytes appeared earlier (between baseline and 3-month FUP) in the TAVR group compared with the SAVR group (between 3- and 6-month FUP). In conclusion, levels of circulating intermediate monocytes decrease after SAVR or TAVR in patients with severe AS.

Keywords

aortic valve stenosis - monocyte subsets - TAVR - SAVR

Funding

This work was supported by the Friede-Springer-Herz-Stiftung (Germany) and clinical internal financing. BH is a participant in the Berlin Institute of Health (BIH) Charité Clinician Scientist Program funded by the Charité-Universitätsmedizin Berlin and BIH. BH received funding by the DZHK (German Centre for Cardiovascular Research). FK is a BIH clinical fellow.

• References

• 1 Stangl V, Baldenhofer G, Knebel F. , et al. Impact of gender on three-month outcome and left ventricular remodeling after transfemoral transcatheter aortic valve implantation. Am J Cardiol 2012; 110 (06) 884-890
• 2 Galante A, Pietroiusti A, Vellini M. , et al. C-reactive protein is increased in patients with degenerative aortic valvular stenosis. J Am Coll Cardiol 2001; 38 (04) 1078-1082
• 3 Gerber IL, Stewart RA, Hammett CJ. , et al. Effect of aortic valve replacement on C-reactive protein in nonrheumatic aortic stenosis. Am J Cardiol 2003; 92 (09) 1129-1132
• 4 Freeman RV, Otto CM. Spectrum of calcific aortic valve disease: pathogenesis, disease progression, and treatment strategies. Circulation 2005; 111 (24) 3316-3326
• 5 Ziegler-Heitbrock L, Ancuta P, Crowe S. , et al. Nomenclature of monocytes and dendritic cells in blood. Blood 2010; 116 (16) e74-e80
• 6 Stansfield BK, Ingram DA. Clinical significance of monocyte heterogeneity. Clin Transl Med 2015; 4: 5
• 7 Yang J, Zhang L, Yu C, Yang XF, Wang H. Monocyte and macrophage differentiation: circulation inflammatory monocyte as biomarker for inflammatory diseases. Biomark Res 2014; 2 (01) 1
• 8 Rogacev KS, Cremers B, Zawada AM. , et al. CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 2012; 60 (16) 1512-1520
• 9 Hewing B, Au SC, Ludwig A. , et al. Severe aortic valve stenosis in adults is associated with increased levels of circulating intermediate monocytes. J Cardiovasc Transl Res 2017; 10 (01) 27-34
• 10 Spethmann S, Baldenhofer G, Dreger H. , et al. Recovery of left ventricular and left atrial mechanics in various entities of aortic stenosis 12 months after TAVI. Eur Heart J Cardiovasc Imaging 2014; 15 (04) 389-398
• 11 Lang RM, Badano LP, Mor-Avi V. , et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015; 16 (03) 233-270
• 12 Baumgartner H, Hung J, Bermejo J. , et al; EAE/ASE. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 2009; 10 (01) 1-25
• 13 Zamorano JL, Badano LP, Bruce C. , et al. EAE/ASE recommendations for the use of echocardiography in new transcatheter interventions for valvular heart disease. Eur Heart J 2011; 32 (17) 2189-2214
• 14 Lancellotti P, Tribouilloy C, Hagendorff A. , et al; Scientific Document Committee of the European Association of Cardiovascular Imaging. Recommendations for the echocardiographic assessment of native valvular regurgitation: an executive summary from the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2013; 14 (07) 611-644
• 15 Vahanian A, Alfieri O, Andreotti F. , et al; Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS). Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012; 33 (19) 2451-2496
• 16 Ziegler-Heitbrock L, Hofer TP. Toward a refined definition of monocyte subsets. Front Immunol 2013; 4: 23
• 17 Zawada AM, Rogacev KS, Schirmer SH. , et al. Monocyte heterogeneity in human cardiovascular disease. Immunobiology 2012; 217 (12) 1273-1284
• 18 Dweck MR, Boon NA, Newby DE. Calcific aortic stenosis: a disease of the valve and the myocardium. J Am Coll Cardiol 2012; 60 (19) 1854-1863
• 19 Kastellanos SS, Toumpoulis IK, Aggeli C. , et al. Time course of C-reactive protein, tumour necrosis factor-alpha and monocyte chemoattractant protein-1 following the surgical treatment of patients with aortic valve stenosis. Hellenic J Cardiol 2007; 48 (01) 5-14
• 20 Weber C, Shantsila E, Hristov M. , et al. Role and analysis of monocyte subsets in cardiovascular disease. Joint consensus document of the European Society of Cardiology (ESC) Working Groups ‘Atherosclerosis & Vascular Biology’ and ‘Thrombosis’. Thromb Haemost 2016; 116 (04) 626-637
• 21 Rogacev KS, Seiler S, Zawada AM. , et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J 2011; 32 (01) 84-92
• 22 Suzuki A, Fukuzawa K, Yamashita T. , et al. Circulating intermediate CD14++CD16+monocytes are increased in patients with atrial fibrillation and reflect the functional remodelling of the left atrium. Europace 2017; 19 (01) 40-47
• 23 Van Craenenbroeck AH, Van Ackeren K, Hoymans VY. , et al. Acute exercise-induced response of monocyte subtypes in chronic heart and renal failure. Mediators Inflamm 2014; 2014: 216534
• 24 Hong S, Mills PJ. Effects of an exercise challenge on mobilization and surface marker expression of monocyte subsets in individuals with normal vs. elevated blood pressure. Brain Behav Immun 2008; 22 (04) 590-599
• 25 Steppich B, Dayyani F, Gruber R, Lorenz R, Mack M, Ziegler-Heitbrock HW. Selective mobilization of CD14(+)CD16(+) monocytes by exercise. Am J Physiol Cell Physiol 2000; 279 (03) C578-C586
• 26 Thomas GD, Hamers AAJ, Nakao C. , et al. Human blood monocyte subsets: a new gating strategy defined using cell surface markers identified by mass cytometry. Arterioscler Thromb Vasc Biol 2017; 37 (08) 1548-1558
• 27 Jaipersad AS, Shantsila E, Blann A, Lip GY. The effect of statin therapy withdrawal on monocyte subsets. Eur J Clin Invest 2013; 43 (12) 1307-1313
• 28 Coen PM, Flynn MG, Markofski MM, Pence BD, Hannemann RE. Adding exercise to rosuvastatin treatment: influence on C-reactive protein, monocyte toll-like receptor 4 expression, and inflammatory monocyte (CD14+CD16+) population. Metabolism 2010; 59 (12) 1775-1783
• 29 Kirmizis D, Papagianni A, Dogrammatzi F. , et al. Effects of simvastatin on markers of inflammation, oxidative stress and endothelial cell apoptosis in patients on chronic hemodialysis. J Atheroscler Thromb 2010; 17 (12) 1256-1265