title: Relationship between pre-implant interleukin-6 levels, inflammatory response, and early outcome in patients supported by left ventricular assist device: a prospective study.
abstract: OBJECTIVE
  The 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  During 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.
  
  
  CONCLUSIONS
  LVAD-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.
authors.affiliation: CNR Institute of Clinical Physiology, CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Caruso
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Botta
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Verde
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Milazzo
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Vecchi
authors.affiliation: CNR Institute of Clinical Physiology and University of Pisa, Pisa, Italy.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Trivella
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Martinelli
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Paino
authors.affiliation: CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Frigerio
authors.affiliation: CNR Institute of Clinical Physiology, CardioThoracic and Vascular Department, Niguarda Ca' Granda Hospital, Milan, Italy.
authors.forename: Oberdan
authors.initials: O
authors.lastname: Parodi
mesh_terms: D005260:Female; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000276:immunology / Q000601:surgery*; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000276:immunology; D015850:Interleukin-6 / Q000097:blood* / Q000276:immunology; D016209:Interleukin-8 / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000097:blood / Q000276:immunology; D011446:Prospective Studies; D016019:Survival Analysis
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D019798:Neopterin