The impact of decreased left ventricular ejection fraction on neutrophil extracellular trap (NET) formation measured
Tomasz Urbanowicz1, Beata Krasińska2, Ievgen Spasenenko2
1Cardiac Surgery and Transplantology Department, Poznan University of Medical Sciences, Długa ½ Street, Poznan, 61-848, Poland. turbanowicz@ump.edu.pl.
Insights
Heart failure patients show increased neutrophil extracellular trap (NET) formation, a marker of NETs. Higher NET levels correlate with reduced left ventricular ejection fraction, suggesting a pro-thrombotic state and potential therapeutic target.
Area of Science:
- Cardiology
- Immunology
Background:
- Heart failure (HF) is associated with pro-coagulative characteristics, but specific therapeutic targets remain elusive.
- Neutrophil extracellular traps (NETs), formed by neutrophils, are implicated in various inflammatory and thrombotic conditions.
Purpose of the Study:
- To investigate the association between peripheral blood citrullinated histone 3 (CitH_3), a marker of NET formation, and left ventricular ejection fraction (LVEF) in patients with de novo congestive heart failure.
- To explore NETs as a potential therapeutic target in HF management.
Main Methods:
- Prospective study of 88 de novo congestive HF patients.
- Comparison of comorbidities, laboratory tests, and imaging results with peripheral blood CitH_3 concentrations on admission.
- Patients divided into HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) groups based on LVEF.
Main Results:
- Significantly higher CitH_3 serum concentrations in the HFrEF group compared to the HFpEF group (p=0.019).
- A significant negative correlation between LVEF and CitH_3 concentration (r=-0.444, p=0.005).
- A significant negative correlation between LVEF and serum NT-pro-BNP (r=-0.435, p<0.001).
Conclusions:
- Patients with reduced LVEF in heart failure exhibit increased NET formation.
- Elevated CitH_3 levels suggest an increased pro-thrombotic state in HF patients.
- NETs represent a potential therapeutic target for improving clinical outcomes in heart failure.
Abstract:
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.
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