Abstract 14959: RNA-Seq Analysis of Peripheral Blood Monocyte Gene Expression Before and After Cardiac Resynchronization Therapy
Introduction: Cardiac resynchronization therapy (CRT) management could be improved with a better understanding of physiological pathways associated with improved responses, but routine myocardial tissue assessment is not feasible because of risks associated with cardiac biopsies. RNA analysis of peripheral blood monocytes (PBMCs) may be a promising alternative.
Hypothesis: CRT responders have a unique gene expression profile in circulating PBMCs compared with nonresponders.
Methods: RNA-Seq analysis of PBMCs was performed in n=14 patients before CRT and at a median 2.05 years after initial CRT implantation in responders and surviving nonresponders. Responders had at least a 15% reduction in left ventricular end-systolic volume and at least a 2 ml/kg/minute improvement in peak VO2 after CRT. Polymerase chain reaction (PCR) was used to confirm changes in selected genes of interest.
Results: Responders exhibited many changes not seen in nonresponders, particularly in key pathways including immune system and cytokine signaling; apoptosis and the cell cycle; phospholipid metabolism; glucose metabolism including glycolysis; gluconeogenesis and pyruvate metabolism including the tricarboxylic acid (TCA) cycle; NF kappa beta signaling; tubular function; transforming growth factor-beta signaling; and the response to oxidative stress. 2,365 genes had significant changes in responders (p<0.05 after adjustment for multiple comparisons) but not nonresponders. Of these genes, 413 had at least a 2-fold change post-CRT, 322 had fold changes between 2 and 4, 88 had fold changes between 4 and 8, and 3 had fold changes greater than 8. PCR of a selected set of these genes linked to improved cardiac function confirmed RNA-Seq results.
Conclusions: RNA-Seq analysis of PBMCs after CRT demonstrates many genes in key pathways with significant changes in responders but not nonresponders. These methods may be particularly useful in assessing prognosis after CRT.
Author Disclosures: K.C. Bilchick: None. L. Meng: None. J. Garmey: None. C.A. McNamara: None.
- © 2015 by American Heart Association, Inc.