Abstract 19762: MicroRNAs Predict Left Ventricular Reverse Remodeling in Chronic Systolic Heart Failure
Background: Current strategies to identify individuals who have LV reverse remodeling (LVRR) for subsequent treatment are limited. Plasma circulating microRNAs (miRNAs) represent an emerging area of epigenetic regulation of LVRR in animal models.
Hypothesis: Circulating miRNAs are associated with LVRR in chronic systolic heart failure (HF).
Methods: A bioluminescence point-of-care assay (Abcam Firefly) was used to quantify candidate plasma circulating miRNAs in 64 individuals with systolic HF and serial echocardiographic data over 10 months. Logistic regression was used to estimate association of patterns of circulating miRNAs (by principal component analysis) with LVRR. In vivo validation of selected miRNAs was performed in a mouse model of pressure-overload HF.
Results: Of 64 individuals, 26 experienced LVRR (15% reduction in LV end-systolic volume index). Relative to a clinical model comprised of clinical markers of HF-related risk (age, sex, NT-proBNP, and echocardiographic LV ejection fraction), addition of a principal component score from 11 miRNAs, (including 423, 212, and 29a) was associated with LVRR (OR=6.84, 95% CI 1.81-25.80, P=0.005) with significant improvement in discrimination for LVRR (C-statistic clinical: 0.66: C-statistic clinical + miRNAs: 0.82, P=0.008) In vivo validation of these miRNAs and their targets shows changes in expression of several miRNAs implicated in HF and changes in putative miRNA targets in the MAPK and IL-2 signaling pathways.
Conclusions: A signature of plasma miRNAs associated with LVRR that improved discrimination was identified; these miRNAs are also involved in pathways of LV remodeling and myocardial biology in mice. Together, these results suggest a prognosticative and functional role for circulating miRNAs in LV remodeling.
Author Disclosures: O. Ziegler: None. R. Shah: None. K. Danielson: None. K. Hanspers: None. M. Tackett: Employment; Significant; Dr. Tackett is an employee of Abcam (the platform used in this study).. A. Pico: None. S. Das: None. J. Januzzi: None.
- © 2016 by American Heart Association, Inc.