Serum Levels of Irisin Are Positively Associated with Improved Cardiac Function in Patients with Heart Failure with Reduced Ejection Fraction

The role of irisin in predicting functional cardiac recovery in patients with heart failure with reduced ejection fraction (HFrEF) retains not fully understood. The aim of the study is to determine discriminative value of irisin for improved left ventricular ejection fraction (LVEF) in discharged patients with HFrEF. We included in the study 313 patients who were discharge with HFrEF (at admission LVEF < 40%) and followed them for 3 months. HF with improved EF (HFimpEF) was defined as an increase in LVEF of more than 40% on transthoracic B-mode echocardiography within 3 months of follow-up. All individuals gave their informed consent to participate in the study and obtained optimal guideline-based management. Serum concentrations of NT-proBNP, high-sensitivity cardiac troponin T, tumor necrosis factor-alpha (TNF-alpha), high-sensitivity C-reactive protein (hs-CRP), interleukin-6, galectine-3, soluble suppression of tumorigenicity-2 and irisin were determined using commercially available enzyme-linked immunosorbent assay kits. At 3rd months 117 (37.4%) patients had improved LVEF, whereas 196 individuals were categorized as having persistent HFrEF. The proportions of current stable coronary artery disease, atrial fibrillation, chronic kidney disease grade 1-3, and percutaneous coronary intervention history were significantly higher in patients with persistent HFrEF compared with HFimpEF. We found that HFimpEF was associated with lower left ventricular end-diastolic dimension, serum levels of NT-proBNP and higher left atrial volume index (LAVI), irisin concentrations than those with persistent HFrEF, whereas the levels of other biomarkers did not significantly differ between groups. The most balanced cut-off value of irisin and NT-proBNP (improved LVEF versus non-improved LVEF) were 10.8 ng/mL (area under curve [AUC] = 0.96, sensitivity = 81.0%, specificity = 88.0%; P = 0.0001) and 1540 pmol/L (AUC = 0.79; sensitivity = 73.1%, specificity 78.5%, p = 0.0001), respectively. Using multivariate comparative analysis we established that the irisin levels ≥ 10.8 ng/mL (odds ration [OR] = 1.73; P = 0.001) and NT-proBNP < 1540 pmol/mL (OR = 1.47; P = 0.001), LAVI < 39 mL/m2 (OR = 1.23; P = 0.001), atrial fibrillation (OR = 0.95; P = 0.010) independently predicted HFimpEF. The discriminative value of irisin ≥10.8 ng/mL was better than NT-proBNP <1540 pmol/mL, but the combined model (irisin added to NT-proBNP) did not improve the predictive modality of irisin alone. In conclusion, serum irisin ≥10.8 ng/mL predicted improved LVEF in patients with HFrEF independently of NT-proBNP.