Early Expression of Pro- and Anti-Inflammatory Cytokines in Left Ventricular Assist Device Recipients With Multiple Organ Failure Syndrome RAFFAELE CARUSO,* SALVATORE TRUNFIO,† FILIPPO MILAZZO,† JONICA CAMPOLO,* RENATA DE MARIA,* TIZIANO COLOMBO,† MARINA PAROLINI,* ALDO CANNATA,† CLAUDIO RUSSO,† ROBERTO PAINO,† MARIA FRIGERIO,† LUIGI MARTINELLI,† AND OBERDAN PARODI* To assess whether the combined evaluation of total Sequen- tial Organ Failure Assessment (t-SOFA) score and pro- and anti-inflammatory cytokine profiles early after left ventricular assist device (LVAD) implant discriminates patients at high risk for multiple organ failure syndrome (MOFS) in the first month post-LVAD, we analyzed plasma interleukin (IL)-6, IL-8, IL-10, IL-1ra, IL-1, tumor necrosis factor- (TNF-), and urine neopterin levels before (day 0) and at 4 hours, 1, 3, 7, 14, and 30 days after LVAD implant in 23 recipients. Eight patients died of MOFS between days 7 and 30 (nonsurvivors). At preimplant, only blood urea nitrogen and age were higher in nonsurvivors than survivors. At 4 hours, IL-8, IL-10, and IL1-ra levels were higher in nonsurvivors than in survivors; t-SOFA was also higher and peaked on day 3 in nonsurvivors. Only IL-8 levels on day 1 were significantly associated with a t-SOFA >10 on day 3 (odds ratio 1.10, 95% confidence interval 1.01–1.21, p  0.04). Neopterin, marker of monocyte activa- tion, increased significantly only in nonsurvivors (p < 0.001). These findings suggest that an activated inflammatory system soon after LVAD implant is implicated in MOFS development. Early monitoring of inflammatory mediators and t-SOFA score may be a valuable tool for outcome prediction in LVAD recip- ients. ASAIO Journal 2010; 56:313–318. L eft ventricular assist device (LVAD) implant in end-stage heart failure (ESHF) has proven effective as bridge to heart transplantation (HT) by allowing recovery of adequate cardio- vascular hemodynamic function. However, current 1-year sur- vival rates of LVAD patients range approximately from 50% to 80%. 1–3 The death hazard is highest during the first month after LVAD implant, multiple organ failure syndrome (MOFS) being the major cause of death. The development of MOFS and its impact on the risk of mortality in the intensive care unit (ICU) after cardiac surgery have been described using the Sequential Organ Failure As- sessment (SOFA) scoring system. 4,5 Multiple organ failure syn- drome is influenced by the degree of the immunoinflammatory response, independent of the presence of infection. In LVAD patients, liver dysfunction was shown to be associated to the progressive release of inflammatory mediators, 6 such as inter- leukin (IL)-6, IL-8, and C-reactive protein (CRP). In the setting of trauma or severe acute pancreatitis, early release of anti- inflammatory cytokines has been detected in patients at high risk for MOFS development. 7,8 The impact of an early inflam- matory response on MOFS development after LVAD implant still needs to be elucidated. To assess whether the early postimplant release of pro- and anti-inflammatory cytokines would discriminate LVAD recipi- ents at high risk for MOFS at 1 month, we assessed the profiles of pro- and anti-inflammatory mediators by serial postopera- tive monitoring and the changes in total SOFA (t-SOFA) score in LVAD recipients during the first postoperative month. Materials and Methods In the study, we included 23 patients with ESHF, not ame- nable to recovery by pharmacological or conventional surgical therapy, who underwent LVAD implantation as bridge to HT according to guideline indications for mechanical support. 9 In 22 patients, continuous flow pumps were implanted: 8 De Bakey (MicroMed, Houston, TX), 6 Incor (Berlin Heart GmbH, Berlin, Germany), 4 HeartMateII (Thoratec, Pleasanton, CA), and 4 Levitronix (Levitronix LLC, Waltham, MA) LVADs. A pulsatile flow pump Novacor LVAD (World Heart Inc., Oak- land, CA) was implanted in one patient. The hemodynamic parameters, cardiac index, pulmonary capillary wedge pressure, right atrial pressure, and mixed ve- nous oxygen saturation, were measured by pulmonary artery Swan-Ganz catheter. Left ventricular ejection fraction was quan- tified by transesophageal echocardiography. Hemodynamic and echocardiography were assessed preoperatively, before anesthe- sia induction, at 4 hours and 1, 3, and 7 days after weaning from cardiopulmonary bypass (CPB). We calculated the t- SOFA score according to Pa ¨tila ¨ et al. 4 from preimplant to 1 week after surgery. In sedated patients, the neurological score was computed retrospectively, when sedatives were stopped or alternatively, after their temporary discontinuation. We measured plasma IL-6, IL-8, IL-10, IL-1, tumor necrosis factor- (TNF-), IL-1 receptor antagonist (IL-1ra), serum CRP (sCRP), and urine neopterin concentrations serially from day 0 to day 7 and subsequently at 14 and 30 days since LVAD implant. Plasma cytokine levels were measured according to From the *CNR Clinical Physiology Institute-Milan, and †Cardiovas- cular Department, Niguarda Ca’ Granda Hospital, Milan, Italy. Submitted for consideration January 2010; accepted for publication in revised form March 2010. Reprint Requests: Oberdan Parodi, MD, CNR Clinical Physiology Institute-Milan, Niguarda Ca ` Granda Hospital, Piazza Ospedale Mag- giore 3, 20162 Milan, Italy. Email: ifcnig@tin.it. DOI: 10.1097/MAT.0b013e3181de3049 ASAIO Journal 2010 313