Abstract
Aims: Heart failure is a clinical syndrome characterized by subclinical systemic inflammation and immune system activation associated with iron deficiency. No data exist on the various activations of immune-mediated mechanisms of inflammation in heart failure patients with reduced/preserved ejection fraction. We aimed to (1) investigate possible differences in inflammatory parameters and oxidative stress, and (2) detect a different iron status between groups.Materials and Methods: We enrolled 50 consecutive Caucasian outpatients with heart failure. All patients underwent echocardiographic measurements, laboratory determinations, evaluation of iron status and Toll-like receptors, and NF-κB expression in peripheral blood mononuclear cells, as well as pro-inflammatory cytokines. All statistical calculations were made using SPSS for Mac version 21.0.Results: Patients with reduced ejection fraction showed significantly lower hemoglobin levels (12.3 ± 1.4 vs. 13.6 ± 1.4 g/dl), serum iron (61.4 ± 18.3 vs. 93.7 ± 33.7 mcg/dl), transferrin iron binding capacity (20.7 ± 8.4 vs. 31.1 ± 15.6 %), and e-GFR values (78.1 ± 36.1 vs. 118.1 ± 33.9 ml/min/1.73 m2) in comparison to patients with preserved ejection fraction, while unsaturated iron binding capacity (272.6 ± 74.9 vs. 221.7 ± 61.4 mcg/dl), hepcidin (4.61 ± 0.89 vs. 3.28 ± 0.69 ng/ml), and creatinine (1.34 ± 0.55 vs. 1.03 ± 0.25 mg/dl) were significantly higher in the same group. When considering inflammatory parameters, patients with reduced ejection fraction showed significantly higher expression of both Toll-like receptors-2 (1.90 ± 0.97 vs. 1.25 ± 0.76 MFI) and Toll-like receptors-4 (4.54 ± 1.32 vs. 3.38 ± 1.62 MFI), respectively, as well as a significantly higher activity of NF-κB (2.67 ± 0.60 vs. 1.07 ± 0.30). Furthermore, pro-inflammatory cytokines, interleukin-1, and interleukin-6, was significantly higher in patients with reduced ejection fraction, while the protective cytokine interleukin-10 was significantly lower in the same group. Correlational analyses demonstrated a significant and inverse relationship between left ventricular function and inflammatory parameters in patients with reduced ejection fraction, as well as a direct correlation between ferritin and inflammatory parameters.Conclusions: Our data demonstrate a different immune-mediated inflammatory burden in heart failure patients with reduced or preserved ejection fraction, as well as significant differences in iron status. These data contribute to further elucidate pathophysiologic mechanisms leading to cardiac dysfunction.
Highlights
Heart failure (HF) is a complex clinical syndrome, characterized by impairment of both the cardiac structure and function leading to left ventricle filling or ejection abnormalities
On the basis of their ejection fraction (EF), patients were divided into HF with reduced EF (HF-rEF) and HF-pEF groups
The mean NHYA functional class was significantly different between the groups (2.9 ± 0.5 vs. 2.2 ± 0.5 in the HF-rEF and in the HF-pEF group, respectively)
Summary
Heart failure (HF) is a complex clinical syndrome, characterized by impairment of both the cardiac structure and function leading to left ventricle filling or ejection abnormalities. It is well established that HF patients, independent from prevalent systolic or diastolic dysfunction, show increased levels of pro-inflammatory cytokines, associated to adverse clinical outcomes [3, 4]. This inflammatory status, probably driven by the coexistence of traditional cardiovascular (CV) risk factors, is maintained by other mechanisms such as immune system activation [3, 4]. Randomized trials [8,9,10] of intravenous ferric carboxymaltose in the treatment of ID in HFrEF patients demonstrated an improvement of symptoms, and this therapeutic approach should be considered when treating ID in this setting of patients, in order to alleviate symptoms
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