Coronary artery disease and microvascular dysfunction in aortic valve stenosis.

Aortic valve stenosis is the most frequent valve pathology in the Western world and its incidence is increasing in a continuously ageing population. Aortic valve stenosis is associated with coronary microvascular dysfunction (MVD), a pathophysiological entity that is receiving more attention lately, since it is a major cause of angina pectoris and has been shown to negatively affect patients prognosis. Many aspects of MVD remain unclear and current research has been hampered by the absence of a recognised animal model. The present research project aims to establish an appropriate sheep model of aortic valve stenosis and microvascular dysfunction, allowing a detailed evaluation of microvascular changes over time and their relation to the cardiac function. It will also allow us to standardize the use of cutting edge clinically approved technology to measure the evolution of the microvascular function after induction of aortic valve stenosis. Moreover, MVD interferes with the current assessment of intermediate coronary artery stenotic lesions, potentially leading to misclassification of their severity. This animal model will allow the study of the complex interactions between MVD and coronary artery stenosis. Finally, these insights will be substantiated in a clinical trial to calculate a correcting factor to improve the assessment of coronary artery stenotic lesion severity and guide appropriate revascularisation treatment in conjunction with aortic valve replacement.