Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients

Caruso, Raffaele; Verde, Alessandro; Cabiati, Manuela; Milazzo, Filippo; Boroni, Chiara; Ry, Silvia Del; Parolini, Marina; Vittori, Claudia; Paino, Roberto; Martinelli, Luigi; Giannessi, Daniela; Frigerio, Maria; Parodi, Oberdan

doi:10.1016/j.healun.2012.02.006

Cited by 40 publications

(30 citation statements)

References 26 publications

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“…The levels of interleukin (IL)-6 and IL-8, crucial cytokines for the activation of systemic inflammatory pathways, and neopterin, a marker reflecting monocyte activation, are found to increase after LVAD implantation, particularly in patients affected by MOF [7], the main cause of death during the early phase of MCS [8]. Moreover, pre-implant levels of IL-6 have been associated with hemodynamic status, as defined by Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles, with higher levels in patients presenting critical INTERMACS profiles [9]. Since the signal pathways, IL-6-dependent, and specific monocyte attracting chemokines, such as IL-8, are proposed as crucial triggers in controlling monocyte activation, an important condition in the development of MOF and of haemostatic complications [10], it can be assumed that they play a critical role in affecting outcomes during the early phase of LVAD support.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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PurposeThe immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among pre-implant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients.MethodsIn 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA ≥11 was considered as main adverse outcome. Length of ICU-stay, 1 week-tSOFA score, hospitalisation and 3-month survival were considered additional end-points.ResultsDuring ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score ≥11. Pre-implant level of IL-6 ≥ 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p = 0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2–6.1) pg/mL] and B [24.6 (16.4–38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004–2.217, p = 0.048). The ICU-stay and hospitalisation resulted longer in B-group (p = 0.001 and p = 0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group.ConclusionsLVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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“…Furthermore, they have shown that the increase in inflammation may persist in the early postoperative period (first few weeks) and may be associated with multiorgan dysfunction and length of ICU stay. In a second study by Caruso et al [32], inflammation correlated with the INTERMACS profiles, supporting the concept that inflammation could contribute to poor outcome following LVAD therapy. The role of inflammation in modulating RVF in LVAD recipients still requires further study.…”

Section: Postoperative Factors Contributing To Rightventricular Failurementioning

confidence: 71%

Right-ventricular failure following left ventricle assist device implantation

Patlolla

Beygui²,

Haddad³

2013

Current Opinion in Cardiology

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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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Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients

Cited by 40 publications

References 26 publications

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

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

Right-ventricular failure following left ventricle assist device implantation

Chemokine receptor patterns and right heart failure in mechanical circulatory support

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