Liver-specific microRNA-122 as prognostic biomarker in patients with chronic systolic heart failure.

ABSTRACT

BACKGROUND: Circulating microRNAs (miRs) have been proposed as potential diagnostic biomarkers in heart failure. Studies investigating the prognostic value of circulating miRs in patients with chronic systolic heart failure (HFrEF) are scarce. The aim of this study was to investigate the prognostic value of circulating miRs in patients with HFrEF. METHODS AND RESULTS: A pathway-focused microRNA array was performed in derivation case-control cohort of 40 patients with HFrEF who died during the follow-up (cases) and 36 survivors (controls). MicroRNA expression profiling revealed significant differential expression of miR-122, miR-126 and miR-423 between cases and controls. In a validation cohort, circulating levels of these 3 miRs were assessed using qPCR in 234 patients with HFrEF. Primary study endpoints were all-cause and cardiovascular mortality. During a median follow-up time of 3.2 years, 76 patients (32.5%) died. Only miR-122 and miR-423 were independent predictors of the primary endpoint with respective hazard ratios per increase of one standard deviation (HR per 1-SD) of 1.14 (95% CI 1.02-1.29, p = 0.021) and 1.24 (95% CI 1.09-1.41, p = 0.001). Adding miR-122 to multivariable model including clinical risk factors and NT-proBNP improved net reclassification index (NRI) by 40.4% (p = 0.004), whereas miR-423 improved NRI by 35.3% (p = 0.012). Adding miR-122, but not miR-423, to the same model improved Harrell's C index from 0.78 (95% CI 0.73-0.83) to 0.81 (95% CI 0.76-0.86, p = 0.030). CONCLUSION: Circulating miR-122 as a biomarker is predicting all-cause and cardiovascular mortality and improved risk stratification of HFrEF patients. Thus, miR-122 might be a new biomarker for risk assessment in HFrEF.