Abstract 12075: Extracellular Vesicle Cargo Long-Noncoding RNAs Are Dynamic Biomarkers in Acute Decompensated Heart Failure

Abstract

Introduction: Acute decompensation is associated with increased long-term mortality in patients with heart failure (HF). Biomarkers of acute HF that are dynamic during decongestion may provide physiologic insight for this observation. We hypothesized that long-noncoding RNAs (lncRNAs) and mRNAs in extracellular vesicles (EVs) not only mark different types of HF, but also may be dynamically altered with decongestion across physiologically important pathways. Methods: RNA sequencing was performed on plasma-derived EVs in acute HF patients (7 HFpEF; 7 HFrEF) at hospital admission (V1) and at discharge (V2) along with 9 controls without HF. Differential expression analysis was performed using DESeq2 across groups and time-points. Transcripts were prioritized by fold change (±1.5) and statistical significance (<5% FDR). We subsequently validated targets in EVs from 182 additional patients (24 control; 86 HFpEF; 72 HFrEF). Results: Between HF and control patients, 138 lncRNAs and 147 mRNAs were different (Fig a,b). LncRNAs were confirmed to be exclusively present in EVs. Of 13 targets investigated in our validation cohort, 5 lncRNAs and 6 mRNAs were significantly different between control and HF (age, sex-adjusted; Fig c). Pairwise comparisons between EV RNAs at hospital admission versus decongestion revealed a significant change in 4 lncRNAs (Fig d,e ) that was independent of weight change during hospitalization. Notably, distinct fragments derived from these transcripts were noted in HF versus control groups. Conclusions: The plasma EV transcriptome is significantly altered in patients with acute HF. Plasma EV-derived lncRNA fragments demarcate congestion and decongestion better than mRNAs, may be markers for pathophysiologically relevant pathways independent of volume status, and may provide additional prognostic information.