The impact of decreased left ventricular ejection fraction on neutrophil extracellular trap (NET) formation measured by citrullinated histone H3 (citH_3) concentration

The pro-coagulative characteristics of HF patients are postulated, though no specific therapeutic targets have been proposed. A total of 88 patients (17 female, 19%) with a median age of 68 years (range, 63 - 74) and a de novo congestive HF diagnosis were enrolled in the prospective study. Co-morbidities, laboratory tests, and imaging results (echocardiography, coronary angiography) were compared to the concentration of peripheral blood citrullinated histone 3 (CitH_3), a marker of neutrophil extracellular trap (NET) formation, on admission. The analyzed population was divided into two groups based on LVEF performance: HFmrEF (42 patients, 47%) and HFrEF (46 patients, 53%), with a median (Q1-Q3) age of 68 (62-74) vs. 69 (63-74) years (p = 0.789), respectively. The significant difference in CitH_3 serum concentration between the heart failure with preserved ejection fraction (HFrmEF) group (395 pg/ml [201-482]) and the heart failure with reduced ejection fraction (HFrEF) group (1941 pg/ml [405-3376]) was noted (p = 0.019). A negative correlation was noted between LVEF and citH_3 in the analyzed group (r = -0.444, p = 0.005), and with serum NT-pro-BNP (r = -0.435, p < 0.001). No correlation between citH_3 and NT-pro-BNP was found (r = 0.305, p = 0.939). Patients with heart failure and a decreased left ventricular ejection fraction can be characterized by increased neutrophil extracellular trap formation. The negative correlation between left ventricular characteristics and CitH_3 concentration suggested an increased pro-thrombotic state in HF patients. NETs could be considered a potential therapeutic target in HF patients to improve clinical outcomes. Further studies are required to confirm these findings.