100 patients (50 men and 50 women including 25% with a history of pregnancy) aged 18-45 years with moderate and severe CHD (Fallot, systemic RV, and single ventricle), where fibrosis has been identified as a risk factor for heart failure, will be included. A control group of 50 patients (25 men and 25 women) were matched on age and sex.~The main objective of the study is to study the difference in NET activation between men and women with complex congenital heart disease.~Secondary objectives are:~To compare the NET activity between healthy subjects vs. patients at inclusion.~To compare male vs. female NET activity in healthy subjects at inclusion.~To study the existence of associations of NET with biomarkers of fibrosis (biological and imaging) at baseline in men and women with complex congenital heart disease.~To study the protective value of pregnancy on inflammatory mechanisms and the formation of fibrosis involved in impaired ventricular function and heart failure in these patients.~The enrolled patients will have blood samples collected for analysis of PAD4/NETs biomarkers, and fibrosis markers. NET/fibrosis markers will be correlated with clinical/laboratory parameters, notably NET/PAD4 levels with markers of fibrosis such as collagen biomarkers, ECG, echocardiographic, and cardiac magnetic resonance imaging biomarkers.
Neutrophil hyperactivation has detrimental effects on cardiac tissue after injuries, leading to fibrosis lesions and cardiac dysfunction. It is now well-established that women present with different clinical symptoms in cardiovascular disease compared to men. A cardioprotective effect in women has been suggested in some studies including patients with congenital heart disease (CHD) and heart failure. Our hypothesis is that estrogen protects the hearts of female patients aged 18-45 with CHD. There is no information available as to the involvement of neutrophils in heart failure in females compared to male patients, and therefore this study will provide important information for both the CHD and neutrophil biology fields comparing NET activation in women and men with severe CHD.