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      Perioperative management and inflammatory marker monitoring in a cardiac surgery patient treated with tocilizumab: a case report of successful surgical aortic valve replacement

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          Abstract

          Background

          Interleukin (IL)-6 is associated with wound healing and infection response. Tocilizumab (TCZ) is a monoclonal antibody against the IL-6 receptor, interfering with its signalling pathway. However, reports on patients treated with TCZ undergoing cardiac surgery are limited.

          Case summary

          A 73-year-old man with Castleman disease, treated with TCZ, underwent surgical aortic valve replacement via median sternotomy for aortic valve regurgitation with exertional shortness of breath. Comprehensive measures for preventing surgical site infection along with close examination were implemented during the perioperative period. Tocilizumab was discontinued 26 days before surgery and resumed 30 days after surgery, during which plasma IL-6 levels decreased. There was no evidence of infection or exacerbation of Castleman disease. Vascular endothelial growth factor levels increased before an increase in C-reactive protein levels following hospital discharge and prior to TCZ resumption.

          Discussion

          Meticulous perioperative management with a multi-disciplinary approach is crucial during the cessation of TCZ for cardiac surgery. Changes in vascular endothelial growth factor levels may serve as an early predictor of underlying disease exacerbation after TCZ cessation for surgery.

          Graphical Abstract

          Graphical Abstract

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          Most cited references15

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          2021 ESC/EACTS Guidelines for the management of valvular heart disease

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            Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease.

            Interleukin-6 (IL-6) plays pathologic roles in immune-inflammatory diseases such as rheumatoid arthritis (RA) and Castleman disease. By inhibiting IL-6 receptors (IL-6Rs), tocilizumab (a humanized anti-IL-6R antibody) ameliorates the symptoms of these diseases and normalizes acute-phase proteins, including C-reactive protein (CRP). We found that tocilizumab treatment increased serum levels of IL-6 and soluble IL-6R (sIL-6R). To investigate the pathologic significance of these increases, we analyzed the kinetics of serum IL-6 and sIL-6R and the proportion of sIL-6R saturated with tocilizumab after tocilizumab administration in patients with RA and Castleman disease and then compared the results with the CRP values. Serum IL-6 and sIL-6R markedly increased after tocilizumab administration in both RA and Castleman disease. As long as free tocilizumab was detectable, sIL-6R was saturated with tocilizumab and IL-6 signaling was completely inhibited. We concluded that it is likely that sIL-6R increased because its elimination half-life was prolonged by the formation of tocilizumab/sIL-6R immune complex, and that free serum IL-6 increased because IL-6R-mediated consumption of IL-6 was inhibited by the unavailability of tocilizumab-free IL-6R. We also concluded that the increased level of free IL-6 during tocilizumab treatment closely reflects the actual endogenous IL-6 production and true disease activity.
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              Interleukin-6 Signaling and Anti-Interleukin-6 Therapeutics in Cardiovascular Disease

              IL (interleukin)-6 is a pivotal cytokine of innate immunity, which enacts a broad set of physiological functions traditionally associated with host defense, immune cell regulation, proliferation, and differentiation. Following recognition of innate immune pathways leading from the NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasome to IL-1 to IL-6 and on to the hepatically derived clinical biomarker CRP (C-reactive protein), an expanding literature has led to understanding of the proatherogenic role for IL-6 in cardiovascular disease and thus the potential for IL-6 inhibition as a novel method for vascular protection. In this review, we provide an overview of the mechanisms by which IL-6 signaling occurs and how that impacts upon pharmacological inhibition; describe murine models of IL-6 and atherogenesis; summarize human epidemiological data outlining the utility of IL-6 as a biomarker of vascular risk; outline genetic data suggesting a causal role for IL-6 in systemic atherothrombosis and aneurysm formation; and then detail the potential role of IL-6 inhibition in stable coronary disease, acute coronary syndromes, heart failure, and the atherothrombotic complications associated with chronic kidney disease and end-stage renal failure. Finally, we review anti-inflammatory and antithrombotic findings for ziltivekimab, a novel IL-6 ligand inhibitor being developed specifically for use in atherosclerotic disease and poised to be tested formally in a large-scale cardiovascular outcomes trial focused on individuals with chronic kidney disease and elevated levels of CRP, a population at high residual atherothrombotic risk, high residual inflammatory risk, and considerable unmet clinical need.
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                Author and article information

                Contributors
                Role: Handling Editor
                Role: Editor
                Role: Editor
                Role: Editor
                Journal
                Eur Heart J Case Rep
                Eur Heart J Case Rep
                ehjcr
                European Heart Journal. Case Reports
                Oxford University Press (UK )
                2514-2119
                March 2025
                24 February 2025
                24 February 2025
                : 9
                : 3
                : ytaf085
                Affiliations
                Department of Cardiovascular Surgery, Toyohashi Municipal Hospital , 50 Hachikenn-nishi, Aotake-cho, Toyohashi 441-8570, Japan
                Department of Cardiovascular Surgery, Toyohashi Municipal Hospital , 50 Hachikenn-nishi, Aotake-cho, Toyohashi 441-8570, Japan
                Department of Cardiac Surgery, Nagoya University Hospital , Nagoya, Japan
                Department of Haematology and Oncology, Toyohashi Municipal Hospital , Toyohashi, Japan
                Department of Cardiology, Toyohashi Municipal Hospital , Toyohashi, Japan
                Author notes
                Corresponding author. Tel: +81 532 33 6111, Fax: +81 532 33 6177, Email: machapon@ 123456icloud.com

                Conflict of interest: None declared.

                Author information
                https://orcid.org/0000-0003-3599-4626
                Article
                ytaf085
                10.1093/ehjcr/ytaf085
                11911119
                40098608
                e67be0e8-53a3-46fd-9a83-2526857d3aca
                © The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 September 2024
                : 27 December 2024
                : 06 February 2025
                : 17 March 2025
                Page count
                Pages: 5
                Categories
                Case Report
                AcademicSubjects/MED00200
                Eurheartj/42
                Eurheartj/43
                Eurheartj/12
                Eurheartj/48
                Eurheartj/55

                case report,perioperative management,tocilizumab,interleukin-6,vascular endothelial growth factor,surgical site infection

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