Association macrophage subpopulation with cardiac biomarkers in patients with acute decompensated ischemic heart failure with reduced ejection fraction
Authors: Kruchinkina E , Suslova T E , Kzhyshkowska J G , Ryabov V V 
Published: October 2021

Abstract

Objective
To determine the association macrophage subpopulation with cardiac biomarkers (interleukin (IL)-1β, IL-6, IL-10, highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), troponin I, interferon gamma (IFN-γ), plasma brain natriuretic peptide (BNP), and N-terminal fragment of precursor protein brain-type natriuretic peptide (NT-proBNP), soluble interleukin 1 receptor-like 1 (ST2)) in patients with acute decompensated ischemic heart failure with reduced ejection fraction.

Methods
This open-label, nonrandomized, single-center, prospective trial was registered at clinicaltrials.gov (#NCT02649517) and included 25 patients (84% men, LVEF of 29.17±9.4%) with ADHF. Inclusion criteria were ADHF, not earlier than 6 months after optimal surgery (PCI or/and CABG) and optimal drug treatment for ADHF according to ESC guidelines. Invasive coronary angiography was performed in all patients to exclude the progression of coronary atherosclerosis. All patients underwent endomyocardial biopsy (EMB) with immunohistochemically analysis for diagnostic myocarditis. Macrophage infiltration in the heart was assessed by double immunofluorescence. CD68 was a marker for the cells of the macrophage lineage, CD80 was considered as M1-like macrophage and CD163, CD206, stabilin-1 were as M2-like macrophage biomarkers. Each area was evaluated in 5 random fields. On admission serum levels of IL-1β, IL-6, IL-10, hsCRP, TNF-α, troponin I, IFN-γ, ST2, BNP, and NT-proBNP were measured using enzyme-linked immunosorbent assay (ELISA). The double immunofluorescence has not been performed in 4 patients.

Results
An association was found between CD68+/CD80+ macrophages and level of TNF-α (r=0.512, p=0.042) in all patient. After EMB, all patients were divided into 2 groups. Group 1 comprised 16 patients (64%) with myocarditis; group 2 comprised 9 patients (36%) without myocarditis. In group 1 the association was found between CD68+/CD80+ macrophages and the level of troponin I (r=0.874, p=0.05). Besides, the association was revealed CD68-/CD206+ macrophages with the level of hsCRP (r= - 0.755, p=0.03), and CD163-/CD206+ macrophages with the level of IL-6 (r=0.843, p=0,009) in group 1. CD68-/stabilin-1 macrophages were in direct correlation with level of NT-proBNP (r=0.790, p=0.02) and in inverse correlation with level of troponin I (r= - 0.711, p=0.05) in group 1. In group 2 the association was found between CD68-/CD206+ macrophages and the level of ST2 (r=0.0.537, p=0.037).

Conclusion
Our data suggest that many associations identified between M1-like macrophages (CD 68+/CD 80+), M2-like macrophages (CD68-/CD206+, CD163-/CD206+) and markers of inflammation (hsCRP, IL-6) and myocardial damage (NT-proBNP, troponin I) in patients with myocarditis. Whereas in patients without myocarditis, only the association of M2-like macrophages (CD68-/CD206+) with the ST2 level was revealed, probably due to the continuing unfavorable remodeling of the heart.

Funding Acknowledgement
Type of funding sources: None.