MicroRNA signatures differentiate preserved from reduced ejection fraction heart failure.
OBJECTIVE
Differentiation of heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction independent of echocardiography is challenging in the community. Diagnostic strategies based on monitoring circulating microRNA (miRNA) levels may prove to be of clinical value in the near future. The aim of this study was to identify a novel miRNA signature that could be a useful HF diagnostic tool and provide valuable clinical information on whether a patient has HFrEF or HFpEF.


RESULTS
MiRNA biomarker discovery was carried out on three patient cohorts, no heart failure (no-HF), HFrEF, and HFpEF, using Taqman miRNA arrays. The top five miRNA candidates were selected based on differential expression in HFpEF and HFrEF (miR-30c, -146a, -221, -328, and -375), and their expression levels were also different between HF and no-HF. These selected miRNAs were further verified and validated in an independent cohort consisting of 225 patients. The discriminative value of BNP as a HF diagnostic could be improved by use in combination with any of the miRNA candidates alone or in a panel. Combinations of two or more miRNA candidates with BNP had the ability to improve significantly predictive models to distinguish HFpEF from HFrEF compared with using BNP alone (area under the receiver operating characteristic curve >0.82).


CONCLUSIONS
This study has shown for the first time that various miRNA combinations are useful biomarkers for HF, and also in the differentiation of HFpEF from HFrEF. The utility of these biomarker combinations can be altered by inclusion of natriuretic peptide. MiRNA biomarkers may support diagnostic strategies in subpopulations of patients with HF.
Experimental & Clinical Cardiology Group, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin, Ireland; Chronic Cardiovascular Disease Management Group, St Vincent's Healthcare Group/St Michael's Hospital, Dublin, Ireland.
Chris J
CJ
Watson
Shashi K
SK
Gupta
Eoin
E
O'Connell
Sabrina
S
Thum
Nadezhda
N
Glezeva
Jasmin
J
Fendrich
Joe
J
Gallagher
Mark
M
Ledwidge
Lea
L
Grote-Levi
Kenneth
K
McDonald
Thomas
T
Thum
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000503:physiopathology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D045265:Natriuretic Peptides; D013318:Stroke Volume / Q000502:physiology*; D018754:Ventricular Dysfunction / Q000503:physiopathology*
D015415:Biomarkers; D035683:MicroRNAs; D045265:Natriuretic Peptides
Biomarker; Diagnosis; Ejection fraction; Heart failure; MicroRNA; Natriuretic peptide