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

Abstract

Background: The purpose of the study is to investigate a possible predictive value of irisin for improved left ventricular (LV) ejection fraction (EF) in discharged patients with known heart failure with reduced ejection fraction (HFrEF). Methods: We included in the study 313 patients who were discharged with HFrEF (at admission, LVEF ≤ 40%) and monitored for 3 months. HF with improved LVEF (HFimpEF) was characterized as a >40% increase in LVEF on transthoracic B-mode echocardiography within 3 months of follow-up. Circulating biomarkers including NT-proBNP and irisin were detected at baseline and after 3 months of observation. By the third month, 117 (37.4%) patients had HFimpEF, whereas 196 individuals were categorized as having persistent HFrEF. Results: We found that HFimpEF was related to lower LV end-diastolic dimensions and concentrations of NT-proBNP and higher left atrial volume index (LAVI) and irisin concentrations than those with persistent HFrEF. The most balanced cut-offs of irisin and NT-proBNP concentrations (improved LVEF versus non-improved LVEF) were 10.8 ng/mL and 1540 pmol/L, respectively. Multivariate regression analysis showed that atrial fibrillation (odds ratio [OR] = 0.95; p = 0.010), LAVI < 39 mL/m² (OR = 1.23; p = 0.001), irisin levels ≥ 10.8 ng/mL (OR = 1.73; p = 0.001), and NT-proBNP < 1540 pmol/mL (OR = 1.47; p = 0.001) independently predicted HFimpEF. The discriminative ability of irisin ≥ 10.8 ng/mL was better than NT-proBNP < 1540 pmol/mL; the predictive ability of irisin alone was not improved by the combined model (irisin added to NT-proBNP). Conclusions: serum irisin ≥ 10.8 ng/mL predicted HFimpEF independently of natriuretic peptide in HFrEF patients.

Keywords: biomarkers; cardiac function; heart failure; improved ejection fraction; irisin; natriuretic peptides.

Figure 1

Rationale for investigating irisin in HF patients based on its biological effects. Abbreviations: BDNF, brain-derived neurotrophic factor; HF, heart failure; FNDC5, fibronectin type III domain-containing 5 protein; PGC-1α, peroxisome proliferator-activated receptor γ coactivator-1α; RANKL, receptor activator of nuclear factor -κB ligand; WAT, white adipose tissue; ↑, increase; ↓, decrease.

Figure 2

Flow chart of the study design. Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin-II receptor blockers; ARNI, angiotensin receptor neprilysin inhibitors; Echo-CG, echocardiography; ECG, electrocardiography; GLP-1-RAs, glucagon-like peptide-1 receptor agonists; IL, interleukin; LVEF, left ventricular ejection fraction; hs-CRP, high-sensitivity C-reactive protein; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFimpEF, heart failure with improved ejection fraction; MRAs, mineralocorticoid receptor antagonists; NT-proBNP, N-terminal brain natriuretic pro-peptide; TNF-alpha, tumor necrosis factor-alpha; sST2, soluble suppression of tumorigenicity-2; SGLT2, sodium–glucose co-transporter-2; TIA, transient ischemic attack.

Figure 3

An example of the determination of HFimpEF in patients with a 3-month interval between investigations. (A) Echocardiographic parameters at baseline. (B) Echocardiographic parameters in 3 months.

Figure 4

Receiver operating characteristic curves for predictive factors of HFimpHF. Abbreviations: AUC, area under curve; CI, confidence interval; hs-CRP, high-sensitivity C-reactive protein; E/e`, early diastolic blood filling to longitudinal strain ratio; LAVI, left atrial volume index; Se, sensitivity; Sp, specificity; NT-proBNP, N-terminal brain natriuretic pro-peptide; sST2, soluble suppression of tumorigenicity-2; TNF-alpha, tumor necrosis factor-alpha.

Figure 4

Receiver operating characteristic curves for predictive factors of HFimpHF. Abbreviations: AUC, area under curve; CI, confidence interval; hs-CRP, high-sensitivity C-reactive protein; E/e`, early diastolic blood filling to longitudinal strain ratio; LAVI, left atrial volume index; Se, sensitivity; Sp, specificity; NT-proBNP, N-terminal brain natriuretic pro-peptide; sST2, soluble suppression of tumorigenicity-2; TNF-alpha, tumor necrosis factor-alpha.

Figure 5

Possible predictive algorithm of HFimpEF with biomarker use. Abbreviation: HFrEF, heart failure with reduced ejection fraction; HFimpEF, heart failure with improved ejection fraction; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal brain natriuretic pro-peptide.