Circulating microRNAs and Outcome in Patients with Acute Heart Failure

Abstract

Background: The biomarker value of circulating microRNAs (miRNAs) has been extensively addressed in patients with acute coronary syndrome. However, prognostic performances of miRNAs in patients with acute heart failure (AHF) has received less attention.

Methods: A test cohort of 294 patients with acute dyspnea (236 AHF and 58 non-AHF) and 44 patients with stable chronic heart failure (CHF), and an independent validation cohort of 711 AHF patients, were used. Admission levels of miR-1/-21/-23/-126/-423-5p were assessed in plasma samples.

Results: In the test cohort, admission levels of miR-1 were lower in AHF and stable CHF patients compared to non-AHF patients (p = 0.0016). Levels of miR-126 and miR-423-5p were lower in AHF and in non-AHF patients compared to stable CHF patients (both p<0.001). Interestingly, admission levels of miR-423-5p were lower in patients who were re-admitted to the hospital in the year following the index hospitalization compared to patients who were not (p = 0.0001). Adjusted odds ratio [95% confidence interval] for one-year readmission was 0.70 [0.53-0.93] for miR-423-5p (p = 0.01). In the validation cohort, admission levels of miR-423-5p predicted 1-year mortality with an adjusted odds ratio [95% confidence interval] of 0.54 [0.36-0.82], p = 0.004. Patients within the lowest quartile of miR-423-5p were at high risk of long-term mortality (p = 0.02).

Conclusions: In AHF patients, low circulating levels of miR-423-5p at presentation are associated with a poor long-term outcome. This study supports the value of miR-423-5p as a prognostic biomarker of AHF.

Fig 1. Flow chart of the study population.

Fig 2. Admission levels of miRNAs.

Levels of 5 miRNAs were assessed in plasma samples obtained at admission in 236 AHF patients 58 non-AHF patients, and 44 CHF patients. Between-group comparisons were performed and corresponding p values are indicated.

Fig 3. Time-course of plasma miRNA levels.

The change between miRNA levels at admission and day 5 was calculated and compared between AHF patients (n = 51) and non-AHF patients (n = 13). P values for comparison between levels at admission and at day 5 are indicated for non-AHF. For AHF patients, all p values are > 0.05.

Fig 4. Association between miRNA levels and hospital readmission using multivariable analyses.

Odds ratios (OR) [95% confidence interval] are shown for biological parameters, including miRNAs for the risk of hospital readmission during the first year following initial presentation. ORs have been adjusted for age, gender, heart rate, systolic and diastolic blood pressure, history of atrial fibrillation and of HF, LVEF, BNP, sodium, creatinine, proteins and hemoglobin.

Fig 5. Association between miR-423-5p levels and mortality in the validation cohort (n = 711).

The cohort was divided in quartiles of miR-423-5p values and Kaplan-Meier analysis was performed with calculation of the log rank to assess statistical significance. Q denotes quartile and p values from log rank test are displayed.