Abstract P2089: Myocardial Long Non-Coding RNAs Expression Signatures In Heart Failure With Preserved Ejection Fraction

Abstract

Heart failure with preserved ejection fraction (HFpEF) accounts for greater than half of all HF cases and has 5 year mortality rates on par with HF with reduced ejection fraction (HFrEF). Unlike HFrEF, however, HFpEF patients have limited therapeutic options. Improved understanding of myocardial epigenetics are needed to develop novel therapeutics. We have previously conducted myocardial transcriptomics in HFpEF and found several thousand differentially expressed genes between HFpEF vs Controls. Targeting a single gene or pathway will likely not address the many abnormalities seen in HFpEF, highlighting the need for epigenetic approaches. Long non-coding RNAs (lncRNAs) exert epigenetic control over large numbers of transcripts and represent potential therapeutic targets in HFpEF.We measured lncRNA expression from myocardial tissue from HFpEF (n=41), HFrEF (n=30), and control (CON, n=24). Agnostic principal component and hierarchical gene clustering analyses separated HFpEF, HFrEF and CON with minimal overlap. LncRNA’s differentially expressed in HFpEF were predicted to control pathways related to neurotransmitter release, cytoskeleton, and muscle cell development. Three lncRNA-derived HFpEF subgroups were identified with distinct clinical correlates and clinical outcomes, and a subset of these predicted a poor prognosis. Differential expression analysis using DESeq2 revealed 95 upregulated and 342 downregulated lncRNAs.Our findings suggest that HFpEF has a lncRNA profile distinct from HFrEF and controls, highlighting potential epigenetic therapeutic targets for HFpEF.