Abstract 4360: Blood Gene Expression Signatures Associated with the Severity and Mortality of Heart Failure
Background: Leukocyte gene expression signatures have been correlated with specific pathologic conditions and may be a valuable diagnostic and prognostic tool. We sought to determine whether leukocyte gene expression signatures in patients with heart failure (HF) correlates with disease severity and prognosis.
Methods and Results: HF subjects were identified from our clinical service and their functional status (New York Heart Association [NYHA] class) was recorded. Control subjects were recruited from those referred for cardiac stress imaging. These subjects had atypical or non-cardiac chest pain, no prior diagnosis of cardiac disease, and determined to have normal myocardial function and perfusion. Blood was collected after overnight fast. Total RNA was extracted from leukocytes. Microarray hybridization was performed with the use of whole-genome GeneChip U133Plus2 from Affymetrix in accordance with established protocols. Subjects were categorized into three groups; compensated heart failure (NYHA class I and II; n=32), decompensated heart failure (NYHA class III and IV; n=40), and controls. Survival analysis and subsequent multi-test correction identified a total 197 genes significantly (q<0.2) associated with survival. Functional categorization demonstrated that genes involved in T-cell receptor signaling were most significantly over-presented in patients with HF. Cluster analysis of these genes identified three groups. Survival of HF patients correlated positively with NYHA classification as well as with the three groups defined by the ten T cell receptor signaling related genes. The T cell receptor gene classes were more strongly (p=0.0067) associated with survival than NYHA status (p=0.040).
Conclusions: The sympathetic nerve system in heart failure interacts with the immune system by suppressing T cell and NK cell activities; we suggest that our observation of down-regulation of T cell and NK cell signaling pathways in HF maybe the result of such interactions. Furthermore, our results suggest that leukocyte gene expression profiling may aid in delineating risk of mortality in patients with HF. If these results are confirmed with larger studies, they may represent a novel tool to assess prognosis and guide therapy.