Mechanisms Of Disease Progression in Aortic Stenosis - the MODAS Study

Evaluation of Immunologic and Image Morphologic Parameters to Predict Disease Progression in Patients With Moderate Aortic Valve Stenosis

Biomarkers and mechanisms in the progression of aortic valve stenosis are sometimes not sufficiently understood. The current project will take into account image morphological and immunological aspects that predict the development of hemodynamically relevant aortic valve stenosis in order to identify high-risk patients and to develop further therapeutic options.

Early recognition and management of aortic stenosis (AS) are substantial to avoid life threatening events during the clinical course. Multi-factorial complex mechanisms including fibrosis, oxidative stress, inflammation, angiogenesis, osteogenic differentiation and the effect of genetic risk variants have been proposed to be involved mechanistically in the pathogenesis of degenerative AS. It is crucial to identify the potentially involved mechanisms of AS progression in order to 1) identify patients at risk for pronounced cardiac damage and adverse outcomes that might benefit from early aortic valve replacement and 2) to discover treatment options that might slow down progression and lower adverse clinical events.

The consortium´s work has revealed that various inflammatory events play a substantial role for the onset and progression of aortic valve calcification and stenosis in cell culture and small animal experiments We hypothesize that patients with and without rapid progress to severe aortic stenosis differ in terms of genetic, immunological and imaging parameters early in the disease course, and that these parameters can be combined to create strong and reliable predictors of disease progression. Hence, we plan to assess multiple morphological, functional, genetic and immunological readouts and investigate their capacity to predict disease progression in AS in a clinical observational cohort of 938 patients with moderate AS.

This project is a working package as part of TRR259, which is a collaborative project between the three universities: Bonn, Cologne and Düsseldorf.

Inclusion Criteria:

• The patient has an acquired (tricuspid) moderate aortic valve stenosis, which is the reason for regular outpatient cardiological care.
• The subject has been informed verbally and in writing about the study and has given written consent to participate in this study.
• Age > 18 years

Exclusion Criteria:

• The subject has contraindications for the performance of a magnetic resonance imaging or computed tomography (e.g., severe arrhythmias , contrast agent intolerance, a pacemaker, or severe renal insufficiency or severe renal insufficiency or claustrophobia).
• Presence of only mild or already high-grade acquired tricuspid Aortic valve stenosis
• Patient with bicuspid aortic valve
• Inability to follow the instructions of study personnel
• Lack of written informed consent