Abstract 12529: Left Ventricular Gene Expression Heterogeneity in a Mouse Model of Dyssynchronous and Resynchronized Heart Failure

IntroductionCardiac resynchronization therapy improves the prognosis for patients with heart failure and left bundle branch block through cardiac reverse remodeling. The biological mechanisms governing this process remain largely unknown. In a canine model, it has been shown that dyssynchronous heart failure (DHF) induces regional heterogeneity in left ventricular gene expression which is reversed with resynchronization. We developed a mouse model of dyssynchrony and resynchronization and here use this model to test the hypothesis that DHF induces increased intra left ventricular heterogeneity in gene expression that is ameliorated with resynchronized heart failure (RHF).MethodsHeart failure was induced in mice through ischemia/reperfusion. All mice were implanted with a custom-made pacemaker. In the synchronous HF (SHF) group the pacemaker was turned off. In the DHF group the mice received right ventricular pacing (RVP) for four weeks. In the RHF group mice received RVP for two weeks, after which the pacemaker was turned off for two weeks. Heart tissue from the septum and lateral left ventricular wall was subjected to RNA sequencing.ResultsThe expression of 1923 genes differed significantly between early- and late activated left ventricular segments in DHF reflecting regional heterogeneity in gene expression, this disparity was not found in SHF or RHF hearts (Figure A). Figure B shows the ten most significantly upregulated gene ontology (GO) pathways in the lateral wall compared to septum in DHF. These pathways were predominantly associated with cell motility and extracellular matrix processing.ConclusionsDHF induces a change in gene expression between the left ventricular septum and lateral wall. This difference is absent in SHF and RHF. Our findings support that resynchronization causes a reversal in gene expression from DHF pattern to SHF pattern and may contribute to further understanding of the remodeling process in DHF and how this may be reversed.