Abstract 15048: Circulating microRNAs as Diagnostic and Prognostic Markers for Heart Failure
Introduction: MicroRNAs have recently emerged as central players in many diseases. Their profound role in regulation of cardiac remodeling and the evolution of heart failure (HF) suggests that circulating microRNAs may have diagnostic and prognostic value. Their potential diagnostic utility in HF and/or in distinguishing HF with reduced (HFREF) versus preserved (HFPEF) left ventricular ejection fraction is not fully defined.
Hypotheses: (1) HF and the two phenotypes -HFREF and HFPEF are associated with distinct circulating microRNA signatures. (2) Plasma microRNA profiles may be prognostic in HF.
Methods and results: MicroRNA profiling was performed on plasma from 162 healthy control, 135 HFREF (with EF<40%) and 133 HFPEF (EF>50%). Eighty two microRNAs were differentially dysregulated to allow distinguishing of HF from controls with AUC>0.65, p<0.001.Twenty four microRNAs distinguished HFREF from HFPEF with AUC>0.60, p<0.001. Mir-101-3p, miR-132-3p, miR-181-5p, miR-22-3p, miR-23b-3p, miR-24-39, miR-133b, miR-24-3p and miR-21-5p, previously reported as involved in cardiac hypertrophy and fibrosis, were significantly dysregulated in HF. Specific individual microRNAs were able to distinguish HF and/or HFREF and HFPEF from control with AUC=0.90. Interestingly, we found a specific miRNA that was able to distinguish HFREF from HFPEF with AUC=0.71 as compared to NT-proBNP of AUC=0.68. Our data showed that selected microRNA panels with or without NT-proBNP improved discriminative performance achieving AUC>0.90. Furthermore, microRNAs scoring complemented NT-proBNP results by classifying NT-proBNP-assay false positive and negative results with >90% accuracy. A selected panel of microRNAs was prognostic by unadjusted Kaplan-Meier survival curve analysis. The 2 year survival rate for those with high microRNAs expression (better survival) was 95% versus 75% with low microRNA expression (p<0.001).
Conclusion: This study shows specific microRNA signatures derived from plasma may distinguish HF from controls and HFREF from HFPEF. We also identified a panel of microRNAs as a potential prognostic tool for mortality in HF. To our knowledge, this is the largest cohort study to undertake a comparison of microRNA of HF and the two phenotypes.
Author Disclosures: L. Wong: None. J. Lim: None. L. Zhou: None. R. Zou: None. M. Chan: None. C. Lam: None. H. Too: None. A.M. Richards: None.
- © 2014 by American Heart Association, Inc.