Clinical trial NCT05851209: Biomarkers and Mechanisms of Disease Progression and Outcome of Aortic Stenosis in Humans
Official title: Evaluation of Immunologic and Image Morphologic Parameters to Predict Disease Progression in Patients With Moderate Aortic Valve Stenosis
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Aortic Stenosis
Imaging
Pathogenesis
Disease Progression
Aortic Valve Calcification
Genetics
Keywords: severe aortic stenosis
disease progression
pathogenesis of degenerative aortic stenosis
early detection
Cardiovascular magnet resonance
Transthoracal echocardiography
computertomography
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
Collaborators: name: German Research Foundation
name: University Bonn
name: University Cologne
name: Collaborative Research Center
First posted: 2023-05-09
Enrollment: 938
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a moderate aortic valve stenosis

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: progress of aortic stenosis
timeFrame: 5 years
Secondary outcomes:
measure: hospitalization
timeFrame: 5 years
measure: death
timeFrame: 5 years
measure: occurence of myocardial infarction
timeFrame: 5 years
measure: occurence of stroke
timeFrame: 5 years
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University-Hospital Bonn
city: Cologne
country: Germany
facility: University Hospital Cologne
city: Düsseldorf
country: Germany
facility: University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine
Study officials:
affiliation: Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf
name: Malte Kelm, Prof.
role: STUDY_CHAIR
affiliation: University Bonn
name: Georg Nickenig, Prof.
role: STUDY_CHAIR
affiliation: University Cologne
name: Stephan Baldus, Prof.
role: STUDY_CHAIR
References: