title: Chemokine receptor patterns and right heart failure in mechanical circulatory support.
abstract: BACKGROUND
  Right ventricular failure (RVF) complicates 9% to 44% of left ventricular assist device (LVAD) implants post-operatively. 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. In this study we investigated chemokine receptor regulation in LVAD recipients who develop RVF.
  
  
  METHODS
  Expression of chemokine receptor (CCR) genes 3 to 8 were examined in the peripheral blood of 111 LVAD patients, collected 24 hours before 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 polymerase chain reaction (PCR) cycles to threshold and normalized to the average of 3 control genes, glyceraldehyde phosphate dehydrogenase (GAPDH), hypoxanthine phosphoribosyltransferase 1 (HPRT1) and β2-microglobulin (B2M). Secondary outcomes studied were 1-year mortality and long-term RV failure (RVF-LT).
  
  
  RESULTS
  CCR3, CCR4, CCR6, CCR7 and CCR8 were downregulated in LVAD recipients with RVF. Within this cohort of patients, CCR4, CCR7 and CCR8 were further downregulated in those who required RV mechanical support. In addition, under-expression of CCR3 to CCR8 was independently associated with an increased risk of mortality at 1 year, even after adjusting for RVF. CCR expression did not predict RVF-LT in our patient cohort.
  
  
  CONCLUSIONS
  Pre-LVAD CCR downregulation is associated with RVF and increased mortality after implant. Inflammatory signatures may play a major role in prognostication in this patient population.
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Nayak
authors.affiliation: School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Neill
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Kormos
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Lagazzi
authors.affiliation: Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Indrani
authors.initials: I
authors.lastname: Halder
authors.affiliation: Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: McTiernan
authors.affiliation: School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Larsen
authors.affiliation: Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Inashvili
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Teuteberg
authors.affiliation: Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Timothy N
authors.initials: TN
authors.lastname: Bachman
authors.affiliation: Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Hanley-Yanez
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
authors.affiliation: Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: simonma@upmc.edu.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Simon
mesh_terms: D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000401:mortality / Q000601:surgery; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D010414:Pennsylvania / Q000453:epidemiology; D019707:Receptors, Chemokine / Q000097:blood*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends; D013997:Time Factors; D018497:Ventricular Dysfunction, Right / Q000097:blood* / Q000401:mortality / Q000601:surgery
chemical_list: D015415:Biomarkers; D019707:Receptors, Chemokine
keywords: chemokine receptor; inflammation; left ventricular assist device; prognostication; right ventricular failure; survival