Abstract 13840: Leukocyte Gene Expression Signatures of MultiOrgan Dysfunction After Mechanical Circulatory Support Device Implantation in Patients with Heart Failure
Background: The Multiorgan dysfunction syndrome (MOD) is a major cause of morbidity and mortality after mechanical circulatory support device (MCSD) implantation in patients with advanced heart failure (AHF). Since MOD is a condition with aberrant leukocyte activation/suppression, we hypothesized that MOD is associated with specific leukocyte gene expression profiles (GEP) which may help detect/predict risk of MOD.
Methods: We enrolled 9 consecutive HF patients undergoing MCSD implantation at Columbia University Medical Center between March 5th 2010 and May 18th 2010, and 3 healthy age-matched controls. MOD was defined by Sequential Organ Failure Assessment (SOFA) score. Patients were divided into low (≤4), intermediate (5–11), and high (≥12) SOFA-score groups. 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. Expression data was extracted and analyzed using GeneSpring GX 11. Biological interpretation of the signatures was performed using High-Throughput GoMiner.
Results: The mean age of the patients was 51±7 years. Using Kruskal-Wallis testing, 1438 unique transcripts were differentially expressed across groups (false discovery rate (FDR) ≤0.02, fold change≥1.5). Based on these genes, hierarchical clustering using Pearson distance metrics separated the high-SOFA groups from all other groups (Figure 1). Gene Ontology analysis (FDR≤0.02) revealed enrichment of 80 categories including “immune response”, “defense response”, “lymphocyte activation”, and “regulation of cell death”.
Conclusions: AHF patients undergoing MCSD surgery who develop postoperative MOD have unique leukocyte gene expression signatures. If confirmed in larger studies, leukocyte gene expression signatures can be used to develop a genomic classifier to detect/predict MOD in heart failure patients undergoing MCSD implantation.
- © 2010 by American Heart Association, Inc.