Inflammation, fibrosis and cardiovascular hemodynamics: a potential interaction to prevent Fontan circulatory failure.

The Fontan operation has become the final step in the palliation of most patients with single ventricle disease. Nevertheless, late failure is common and difficult to treat. The exact mechanism of diastolic dysfunction, commongly observed in failing Fontan patients, is poorly understood and may relate to accelerated ageing of the ventricle. Better evaluation of Fontan hemodynamics by modulating preload and insights in the pathways causing increased stiffness, such as inflammation and fibrosis would help to identify therapeutic targets. Within this project, we aim to assess Fontan hemodynamics by simultaneously assessing ventricular volumes and pressures whilst modulating preload using a CMR compatible lower body negative pressure chamber. Assessment of biomarkers related to RAAS activation, inflammation and fibrosis will increase knowledge on pathways causing adverse cardiovascular remodeling. Finally, we will test the acute effects of a loop diuretic on hemodynamcs and the chronic effects of spironolactone on neurohumoral activation and fibrotic remodeling.

Keywords:Univentricular heart, Fontan, Heart failure, Cardiac magnetic resonance imaging, Inflammation, Fibrosis

Disciplines:Cardiology