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Eur J Heart Fail. 2018 Jan;20(1):67-75. doi: 10.1002/ejhf.984. Epub 2017 Sep 26.

Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients.

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Heart Failure Unit, Germans Trias i Pujol Hospital, Badalona, Spain.
Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Henry Ford Hospital, Heart and Vascular Institute, Detroit, MI, USA.
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
ACS Biomarker BV, Amsterdam, The Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Heart Failure Research Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.



Small studies suggested circulating microRNAs (miRNAs) as biomarkers for heart failure (HF). However, standardized approaches and quality assessment for measuring circulating miRNAs are not uniformly established, and most studies have been small, so that results are inconsistent. We used a standardized data handling protocol, optimized for circulating miRNA qPCRs to remove noise and used it to assess which circulating miRNAs robustly add prognostic information in patients with HF.


We measured 12 miRNAs in two independent cohorts totalling 2203 subjects. Cohort I (Barcelona) comprised 834 chronic HF patients. Cohort II (Detroit) comprised 1369 chronic HF patients. Each sample was measured in duplicate, and normalized to a very abundant and stable miRNA (miR-486-5p). We used a multistep algorithm to distinguish false amplification signals and thus classify each miRNA measurement as 'valid', 'undetectable' or 'invalid'. Higher levels of miR-1254 and miR-1306-5p were significantly associated with risk of the combined endpoint of all-cause mortality and HF hospitalization in both cohorts, with hazard ratios ranging from 1.11 to 1.21 per log increase (P-values 0.004 to 0.009). However, adding these miRNAs to established predictors (age, sex, haemoglobin, renal function, and NT-proBNP) did not further augment the c-statistic beyond 0.69 (cohort I) or 0.70 (cohort II).


We used a stringent quality assessment for miRNA testing, and were able to replicate the association of miR-1254 and miR-1306-5p with risk of death and HF hospitalization in HF patients of two independent cohorts. However, these two circulating miRNAs failed to improve prognostication over established predictors.


Heart failure; Risk stratification; microRNAs

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