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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Disease Progression; Aortic Stenosis; Genetics; Pathogenesis; Aortic Valve Calcification; Imaging

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 Type: Observational
• Enrollment (Anticipated): 938

Contacts and Locations

• Study Contact: Name: Lisa Dannenberg, MD; Phone Number: +49211811800; Email: lisa.dannenberg@med.uni-duesseldorf.de
• Study Contact Backup: Name: Verena Veulemans, MD; Phone Number: +4921118800; Email: verena.veulemans@med.uni-duesseldorf.de

Study Locations

• Germany
  • Bonn, Germany, 53127
    • University-Hospital Bonn
    • Contact: Bernando S Franklin, Prof.; Email: ranklin@uni-bonn.de
    • Contact: Julian Luetkens, MD; Email: julian.luetkens@ukbonn.de
    • Principal Investigator: Bernando S Franklin, Prof.
    • Principal Investigator: Julian Luetkens, MD
    • Principal Investigator: Jasmin Shameki, MD
  • Cologne, Germany, 50937
    • University Hospital Cologne
    • Contact: Victor Mauri, MD; Email: victor.mauri@uk-koeln.de
    • Principal Investigator: Victor Maudi, MD
  • Düsseldorf, Germany, 40225
    • University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine
    • Contact: Verena Veulemans, MD; Phone Number: +4921118800; Email: verena.veulemans@med.uni-duesseldorf.de
    • Contact: Clinical Trial Unit; Phone Number: +49211811800; Email: ctu@med.uni-duesseldorf.de
    • Principal Investigator: Verena Veulemans, MD
    • Principal Investigator: Malte Kelm, Prof, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with a moderate aortic valve stenosis

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progress of aortic stenosis	Prevalence (number of participants) measured by transthoracic echocardiography	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death		5 years
hospitalization	Rate of patients (%) being hospitalized due to a progress of aortic stenois	5 years
occurence of myocardial infarction		5 years
occurence of stroke		5 years

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Collaborators: 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

Publications and helpful links

Helpful Links

• Website of TRR259

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2023
• Primary Completion (Anticipated): July 1, 2026
• Study Completion (Anticipated): July 1, 2031

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: May 5, 2023
• First Posted (Actual): May 9, 2023

Study Record Updates

• Last Update Posted (Actual): May 9, 2023
• Last Update Submitted That Met QC Criteria: May 5, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: early detection; severe aortic stenosis; disease progression; pathogenesis of degenerative aortic stenosis; Cardiovascular magnet resonance; Transthoracal echocardiography; computertomography
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Disease Progression; Aortic Valve Stenosis; Constriction, Pathologic
• Other Study ID Numbers: TRR259 C06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No