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Maja-Theresa Dieterlen,&ast; Eva Katharina Messer,&ast; Kristin Klaeske, Franz Sieg, Sandra Eifert, Josephina Haunschild, Khalil Jawad, Diyar Saeed, Alexey Dashkevich,&ast; Michael Andrew Borger&ast; University Clinic of Cardiac Surgery, Leipzig Heart Center, HELIOS Clinic, Leipzig, Germany&ast;These authors contributed equally to this workCorrespondence: Maja-Theresa Dieterlen, University Department for Cardiac Surgery, Heart Center Leipzig, University Hospital, HELIOS Clinic, Strümpellstraße 39, Leipzig, 04289, Germany, Tel +49 – 341 865 1651, Fax +49 – 341 865 1452, Email mdieterlen@web.dePurpose: Infection is the most common complication after left ventricular assist device (LVAD) implantation. The immune status of LVAD patients is relevant for the incidence and severity of infection, but it is unknown if there is a predisposing immune status prior to LVAD implantation that contributes to an increased risk for infection in the post-implant period. We analyzed the pre-LVAD immune status in patients with infection within 3 months after LVAD implantation in comparison to infection-free patients.Patients and Methods: Fifty-four consecutive LVAD patients were included in this study. According to their infectious history in the first 3 months after LVAD implantation, these patients were grouped into an infection (n=23) and an infection-free group (n=31). Pre-LVAD blood samples were obtained for flow cytometric analysis of immunological parameters including B cells, subsets of T, dendritic and natural killer cells. Patient-specific, clinical and laboratory data were recorded.Results: Blood count analysis prior to LVAD implantation showed comparable counts of erythrocytes (p=0.19), platelets (p=0.33) and leukocytes (p=0.50) between patients with infection and infection-free patients in the post-implant period. Patients with infection in the first 3 months after LVAD implantation had lower concentrations of lymphocytes (p=0.02). Forty percent of the patients with infection showed more often pre-LVAD neutrophil-to-lymphocyte ratios (NLR) > 7 than patients without infection in the first 3 months after LVAD implantation (14%, p=0.05). Patients with infection already had lower percentages of CD3+ T cells (p=0.03), CD19+ B cells (p< 0.01), BDCA2+ pDCs (p=0.03) and BDCA4+ plasmacytoid DCs (pDCs) (p=0.05) prior to LVAD implantation than infection-free patients.Conclusion: Our results demonstrated that patients with infection in the early post-implant period showed lower concentrations of lymphocytes, especially of CD3+ T cells and CD19+ B cells, decreased percentages of BDCA2+ and BDCA4+ pDCs, and had more often NLRs > 7 indicating moderate-to-severe inflammation. Thus, we identified specific immunological changes pre-LVAD that could help to identify patients at risk for infection in the early post-implant period.Keywords: LVAD, immune system, T cells, B cells, plasmacytoid dendritic cells, neutrophil–lymphocyte ratio

Purpose: Infection is a common complication following left ventricular assist device (LVAD) implantation. Patients with obesity are particularly at risk due to their high percentage of adipose tissue and the resulting chronic inflammatory state and resulting immunological changes. This study investigated changes of immunological parameters in relation to body mass index (BMI) during the first year after LVAD implantation., Methods: Blood samples were obtained prior to LVAD implantation and at 3 (1 st FU), 6 (2 nd FU) and 12 mo (3 rd FU) after LVAD implantation. Patients were divided into three groups (normal weight: BMI of 18.5-24.9 kg/m 2 ; n=12; pre-obesity: 25.0-29.9 kg/m 2 ; n=15; obesity: ≥ 30.0 kg/m 2 ; n=17) based on their BMI at the time of LVAD implantation. Flow cytometric analyses for CD4 + and CD8 + T cells, regulatory T cells (T regs ), B cells as well as dendritic cells (DCs) were performed., Results: After LVAD implantation, obese patients (0.51 ± 0.20%) showed a higher proportion of overall DCs than normal-weight (0.28 ± 0.10%) and pre-obese patients (0.32 ± 0.11%, p<0.01) at 3 rd FU. The proportion of BDCA3 + myeloid DCs was lower in obese patients (64.3 ± 26.5%) compared to normal-weight patients (82.7 ± 10.0%, p normal-weight vs. obesity =0.05) at 2 nd FU after LVAD implantation. The analysis of BDCA4 + plasmacytoid DCs revealed a reduced proportion in pre-obese (21.1 ± 9.8%, p normal-weight vs. pre-obesity =0.01) and obese patients (23.7 ± 10.6%, p normal-weight vs. obesity =0.05) compared to normal-weight patients (33.1 ± 8.2%) in the 1 st FU. T cell analysis showed that CD4 + T cells of obese patients (62.4 ± 9.0%) significantly increased in comparison to pre-obese patients (52.7 ± 10.0%, p pre-obesity vs. obesity =0.05) and CD8 + T cells were lower in obese patients (31.8 ± 8.5%) than in normal-weight patients (42.4 ± 14.2%; p normal-weight vs. obesity =0.04) at the 3 rd FU. Furthermore, we observed significantly reduced proportions of T regs in pre-obese patients compared to normal-weight and obese patients at 2 nd FU (p=0.02) and 3 rd FU (p=0.01) after LVAD implantation., Conclusion: This study reported changes of the innate and adaptive immune system of pre-obese and obese compared to normal-weight patients one year after LVAD implantation. DCs and their subsets, CD8 + T cells and T regs were affected immune cell populations that indicate immunological changes which might increase the incidence of postoperative infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Klaeske, Messer, Klein, Sieg, Eifert, Haunschild, Jawad, Saeed, Dashkevich, Borger and Dieterlen.)

Introduction: Infections are a major problem after left ventricular assist device (LVAD) implantation that affects morbidity, mortality, and the quality of life. Obesity often increases the risk for infection. In the cohort of LVAD patients, it is unknown if obesity affects the immunological parameters involved in viral defense. Therefore, this study investigated whether overweight or obesity affects immunological parameters such as CD8+ T cells and natural killer (NK) cells., Methods: Immune cell subsets of CD8+ T cells and NK cells were compared between normal-weight (BMI 18.5-24.9 kg/m2, n = 17), pre-obese (BMI 25.0-29.9 kg/m2, n = 24), and obese (BMI ≥30 kg/m2, n = 27) patients. Cell subsets and cytokine serum levels were quantified prior to LVAD implantation and at 3, 6, and 12 months after LVAD implantation., Results: At the end of the first postoperative year, obese patients (31.8% ± 2.1%) had a lower proportion of CD8+ T cells than normal-weight patients (42.4% ± 4.1%; p = 0.04), and the percentage of CD8+ T cells was negatively correlated with BMI (p = 0.03; r = -0.329). The proportion of circulating NK cells increased after LVAD implantation patients in normal-weight (p = 0.01) and obese patients (p &lt; 0.01). Patients with pre-obesity showed a delayed increase (p &lt; 0.01) 12 months after LVAD implantation. Further, obese patients showed an increase in the percentage of CD57+ NK cells after 6 and 12 months (p = 0.01) of treatment, higher proportions of CD56bright NK cells (p = 0.01), and lower proportions of CD56dim/neg NK cells (p = 0.03) 3 months after LVAD implantation than normal-weight patients. The proportion of CD56bright NK cells positively correlated with BMI (p &lt; 0.01, r = 0.403) 1 year after LVAD implantation., Conclusions: This study documented that obesity affects CD8+ T cells and subsets of NK cells in patients with LVAD in the first year after LVAD implantation. Lower proportions of CD8+ T cells and CD56dim/neg NK cells and higher proportion of CD56bright NK cells were detected in obese but not in pre-obese and normal-weight LVAD patients during the first year after LVAD implantation. The induced immunological imbalance and phenotypic changes of T and NK cells may influence viral and bacterial immunoreactivity., (© 2023 The Author(s). Published by S. Karger AG, Basel.)