Biomarkers and Mechanisms of Disease Progression and Outcome of Aortic Stenosis in Humans

Sponsor

Heinrich-Heine University, Duesseldorf (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05851209

Collaborator

German Research Foundation (Other), University Bonn (Other), University Cologne (Other), Collaborative Research Center (Other)

938

Enrollment

Locations

Anticipated Duration (Months)

312.7

Patients Per Site

3.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Aortic Stenosis Imaging Pathogenesis Disease Progression Aortic Valve Calcification Genetics

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

938 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2031

Outcome Measures

Primary Outcome Measures

progress of aortic stenosis [5 years]
Prevalence (number of participants) measured by transthoracic echocardiography

Secondary Outcome Measures

hospitalization [5 years]
Rate of patients (%) being hospitalized due to a progress of aortic stenois
death [5 years]
occurence of myocardial infarction [5 years]
occurence of stroke [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University-Hospital Bonn	Bonn	Germany	53127
2	University Hospital Cologne	Cologne	Germany	50937
3	University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine	Düsseldorf	Germany	40225

Sponsors and Collaborators

Heinrich-Heine University, Duesseldorf
German Research Foundation
University Bonn
University Cologne
Collaborative Research Center

Investigators

Study Chair: Malte Kelm, Prof., Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf
Study Chair: Georg Nickenig, Prof., University Bonn
Study Chair: Stephan Baldus, Prof., University Cologne