Whole Blood Gene Expression of Multiorgan Dysfunction (MOD) after LVAD Implantation

Abstract

Purpose Early recognition of MOD has important implications in diagnosis and treatment of patients with advanced heart failure (AdHF) undergoing implantation of mechanical circulatory support devices (MCSD). We hypothesized that whole blood (WB) mRNA gene expression can be linked to systemic inflammatory response as evaluated by SOFA score. Methods and Materials We collected WB from 29 AdHF patients undergoing MCSD implantation between 3/2010 and 5/2011 and 8 age matched controls. MOD was defined by SOFA score, with patients divided into low (≤ 4) (n=8), intermediate (5-11) (n=13), and high (≥12) (n=8) risk groups at median 8 days (IQR 7 - 14) postoperatively. After globin reduction, total mRNA was purified, amplified and hybridized on Illumina Whole Genome Expression Chips. Expression data was extracted and analyzed using GeneSpring GX 12 (Agilent). Results Mean age was 57±15 years. After normalization with Kruskal-Wallis testing, 440 transcripts were differentially expressed ( Figure B ) (Benjamini-Hochberg correction, FDR 0.05, fold change 1.5). Hierarchical clustering (A, C) (Pearson absolute distance) organized samples in ascending SOFA risk groups. Gene ontology and pathway analysis revealed significant enrichment of genes representing regulation of immune response including pathways of innate and adaptive immunity. Comparison with PBMC showed >75% overlapping genes (D). Conclusions WB transcriptome analysis can be used to evaluate the inflammatory response after MCSD. The use of WB without need for PBMC extraction provides a rapid tool that may eventually be performed close to bedside for early prediction of MOD.