Microvascular dysfunction in adults with a congenital heart disease and the effect of exercise training (MICONEX)

It has been shown that adults with congenital heart disease (ACHD) have a lower functional capacity, reduced quality of life and worse prognosis compared to healthy individuals. ACHD and patients with heart failure induced by other etiologies share many characteristics, including exercise intolerance, left and/or right ventricular dysfunction and increased inflammatory cytokine levels. Among the pathophysiological changes in heart failure, microvascular dysfunction is highlighted. However, unlike in heart failure, the presence of microvascular dysfunction in ACHD is currently unknown as literature is limited and conflicting. 

In this project, we will test the hypothesis that microvascular dysfunction (MVD) is important in the pathophysiology of ACHD. We believe that multiple factors including genetics, underlying cardiac abnormality, history of cardiac surgery and RV overload, further aggravated by classical acquired risk factors (including overweight, hypertension and sedentary lifestyle), alter shear stress and promote systemic inflammation and endothelial oxidative stress in ACHD leading to a reduced nitric oxide bioavailability and endothelial dysfunction. As such, we hypothesize that coronary microvascular dysfunction (CMD) is present in ACHD patients (1) and that it is closely correlated with peripheral endothelial dysfunction (2), reflecting CMD as part of a systemic microvascular disorder. Moreover, we are convinced that detecting CMD is important to allow identification of ACHD with an unfavorable prognosis and that this CMD can easily be identified with adenosine-based Doppler echocardiography. Therefore, we will validate this technique, which has never been performed before in ACHD, as a non-invasive method with the invasive coronary reactivity testing as “gold standard” (1*). We will also explore the clinical significance of this MVD (3). For this aim, we will determine the correlations of the microvascular function measurements with clinical characteristics, laboratory data and echocardiographic measures. Finally, the potential therapeutic effect of exercise training will be investigated (4). Therefore, patients will be randomized into usual care versus a medically guided sixteen-week home-based aerobic exercise training program. If successful, identification of ACHD patients with microvascular dysfunction will allow better risk stratification and patient selection for intervention. Long term prognostic impact will be explored in future projects.

Funding: FWO

Researcher: Vanreusel Inne

Promotor: Van Berendoncks An

Co-promotor: Van Craenenbroeck Emeline

Co-promotor: Segers Vincent

Co-promotor: Hens Wendy