Abstract 16518: Gene Expression Analysis of Patients After Mechanical Circulatory Support Implantation with High Sequential Organ Failure Assessment Score Identifies Altered Regulation of Innate and Cellular Immunity, Programmed Cell Death, and Coagulation Pathways
Introduction: The cause of multiorgan dysfunction syndrome (MOD) after mechanical circulatory support device (MCSD) implantation in patients with advanced heart failure is not well understood. We hypothesized that different degrees of MOD, as quantified by the Sequential Organ Failure Assessment (SOFA) score, correlate with progressive changes in specific immunological processes governed by leukocyte biology.
Methods: We enrolled 29 consecutive patients undergoing MCSD implantation at a single institution between March 2010 and May 2011, and 8 healthy age matched controls. Patients were divided into low (≤ 4) (n=8), intermediate (5-11) (n=13), and high (≥ 12) (n=8) SOFA-score groups at median 8 days (25-75% IQR 7 - 14) postoperatively. Blood samples were collected and processed for peripheral blood mononuclear cell (PBMC) separation. Total RNA was purified, amplified and hybridized on Illumina Whole Genome Expression Chips. The expression data was extracted and analyzed using GeneSpring GX 12 (Agilent).
Results: The mean age of the patients was 57±15 years. Using Kruskal-Wallis test, 2444 unique transcripts were differentially expressed across groups (Benjamini-Hochberg correction, false discovery rate (FDR) 0.05, fold change 1.5). Based on these genes, hierarchical clustering (Pearson absolute distance) separated the high-SOFA groups from all other groups. Gene ontology and pathway analysis revealed significant enrichment of gene ontology categories and regulation of immune related pathways including the innate and adaptive immune responses (Figure) overlapping with those observed in major trauma or sepsis. Specifically, there was disregulation of pathways involved with programmed cell death and coagulation.
Conclusions: MOD after MCSD surgery is linked to major inflammatory response integrated pathway mechanisms of infection, programmed cell death, and coagulation. Gene expression is a strong predictor of associated MOD risk. .
- © 2012 by American Heart Association, Inc.