Relationship between Pre-Implant Interleukin-6 Levels, Inflammatory Response, and Early Outcome in Patients Supported by Left Ventricular Assist Device: A Prospective Study

Caruso, Raffaele; Botta, Luca; Verde, Alessandro; Milazzo, Filippo; Vecchi, Irene; Trivella, Maria Giovanna; Martinelli, Luigi; Paino, Roberto; Frigerio, Maria; Parodi, Oberdan

doi:10.1371/journal.pone.0090802

Cited by 31 publications

(30 citation statements)

References 21 publications

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“…Increasing our understanding of shear‐dependent blood trauma is important to the development of safer VADs as high shear stresses within the pumps causes hemolysis, platelet activation, leukocyte damage, and degradation of vWF. Heart failure is an inflammatory disorder which greatly affects leukocyte responses and patient outcomes, making leukocytes critical to the success of VAD therapy. In vitro testing of shear stress on different blood components can aid in the design of VADs, especially if consideration of the impact of biomaterials in this setting can be incorporated.…”

Section: Discussionmentioning

confidence: 99%

Artificial shear stress effects on leukocytes at a biomaterial interface

et al. 2019

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Medical devices, such as ventricular assist devices (VADs), introduce both foreign materials and artificial shear stress to the circulatory system. The effects these have on leukocytes and the immune response are not well understood. Understanding how these two elements combine to affect leukocytes may reveal why some patients are susceptible to recurrent device‐related infections and provide insight into the development of pump thrombosis. Biomaterials—DLC: diamond‐like carbon‐coated stainless steel; Sap: single‐crystal sapphire; and Ti: titanium alloy (Ti6Al4V) were attached to the parallel plates of a rheometer. Whole human blood was left between the two discs for 5 minutes at +37°C with or without the application of shear stress (0 s–1 or 1000 s–1). Blood was removed and used for complete blood cell counts, flow cytometry (leukocyte activation, cell death, microparticle generation, phagocytic ability, and reactive oxygen species [ROS] production), and the production of pro‐inflammatory cytokines. L‐selectin expression on monocytes was decreased when blood was exposed to the biomaterials both with and without shear. Applying shear stress to blood on a Sap and Ti surface led to activation of neutrophils shown as decreased L‐selectin expression. Sap and Ti blunted the LPS‐stimulated macrophage migration inhibitory factor (MIF) production, most notably when sheared on Ti. The biomaterials used here have been shown to activate leukocytes in a static environment. The introduction of shear appears to exacerbate this activation. Interestingly, a widely accepted biocompatible material (Ti) utilized in many different types of devices has the capacity for immune cell activation and inhibition of MIF secretion when combined with shear stress. These findings contribute to our understanding of the contribution of biomaterials and shear stress to recurrent infections and vulnerability to sepsis in some VAD patients as well as pump thrombosis.

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Section: Discussionmentioning

confidence: 99%

Artificial shear stress effects on leukocytes at a biomaterial interface

et al. 2019

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“…With regard to risk stratification in ESHF-patients, little is known about remodeling/inflammatory profiles and their impact on clinical outcome and prognosis, and it's reasonable to speculate a role of inflammatory system on the outcome of these fragile patients. The findings of this study underscore the importance to consider the remodeling/inflammatory parameters to deepen the knowledge of features of HF patients and better stratify the operative risk, and the risk of death after LVAD implantation [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation

et al. 2014

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BackgroundIn end-stage heart failure (HF), the implantation of a left ventricular assist device (LVAD) is able to induce reverse remodeling. Cellular proteases, such as cathepsins, are involved in the progression of HF. The aim of this study was to evaluate the role of cathepsin system in HF patients supported by LVAD, in order to determine their involvement in cardiac remodeling.MethodsThe expression of cysteine (CatB, CatK, CatL, CatS) and serine cathepsin (CatG), and relative inhibitors (Cystatin B, C and SerpinA3, respectively) was determined in cardiac biopsies of 22 patients submitted to LVAD (pre-LVAD) and compared with: 1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior LVAD (HT, n = 7); 2) patients supported by LVAD at the moment of transplantation (post-LVAD, n = 6).ResultsThe expression of cathepsins and their inhibitors was significantly higher in pre-LVAD compared to the HT group and LVAD induced a further increase in the cathepsin system. Significant positive correlations were observed between cardiac expression of cathepsins and their inhibitors as well as inflammatory cytokines. In the pre-LVAD group, a relationship of cathepsins with dilatative etiology and length of hospitalization was found.ConclusionsA parallel activation of cathepsins and their inhibitors was observed after LVAD support. The possible clinical importance of these modifications is confirmed by their relation with patients’ outcome. A better discovery of these pathways could add more insights into the cardiac remodeling during HF.

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“…Activation of the systemic inflammatory response pre-implant, represented by levels of circulating IL-6, has previously been associated with worse INTERMACS profiles, poor early outcomes, and longer hospital stays in LVAD recipients (27, 28). However, little is known about the effect of baseline inflammatory profiles on RVF and long-term survival in these patients.…”

Section: Discussionmentioning

confidence: 99%

Chemokine receptor patterns and right heart failure in mechanical circulatory support

Nayak

Neill

Kormos

et al. 2017

The Journal of Heart and Lung Transplantation

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Background Right Ventricular failure (RVF) complicates 9–44% of LVAD implants postoperatively. Current prediction scores perform only modestly in validation studies, and do not include immune markers. Chemokines are inflammatory signaling molecules with a fundamental role in cardiac physiology and stress adaptation. We aimed to study chemokine receptor regulation in LVAD recipients who develop RVF. Methods Expression of chemokine receptor genes 3–8 was examined in the peripheral blood of 111 LVAD patients, collected 24 hours prior to implant. RNA was isolated using a PAXgene protocol. Gene expression was assessed using a targeted microarray (RT2 Profiler PCR array, Qiagen). Results were expressed as PCR cycles to threshold and normalized to the average of 3 control genes- GAPDH, HPRT1 and B2M. Secondary outcomes studied were 1 year mortality and long-term RV failure (RVF-LT). Results Chemokine receptors CCR3, CCR4, CCR6, CCR7 and CCR8 were down regulated in LVAD recipients who had RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further down regulated in those that required mechanical support of their RV. Additionally, under-expression of CCR3–8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. Chemokine receptor expression did not predict RVF-LT in our patient cohort. Conclusions Pre-LVAD chemokine receptor down regulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play an important role in prognostication in this patient population.

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Relationship between Pre-Implant Interleukin-6 Levels, Inflammatory Response, and Early Outcome in Patients Supported by Left Ventricular Assist Device: A Prospective Study

Cited by 31 publications

References 21 publications

Artificial shear stress effects on leukocytes at a biomaterial interface

Artificial shear stress effects on leukocytes at a biomaterial interface

Uncovering the cathepsin system in heart failure patients submitted to Left Ventricular Assist Device (LVAD) implantation

Chemokine receptor patterns and right heart failure in mechanical circulatory support

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