Clin Res Cardiol (2025). DOI 10.1007/s00392-025-02737-x
1Universitätsklinikum Schleswig-Holstein Innere Medizin III mit den Schwerpunkten Kardiologie, Angiologie und internistische Intensivmedizin Kiel, Deutschland; 2Internal Medicine V, Department of Angiology University Hospital Schleswig Holstein 24105, Deutschland; 3Universitätsmedizin der Johannes Gutenberg-Universität Mainz Präventive Kardiologie und Medizinische Prävention Mainz, Deutschland
Background and Aims:
Transcatheter Aortic Valve Implantation (TAVI) reduces left ventricular afterload and induces immediate myocardial adaptation, potentially contributing to cardiac remodelling. To gain mechanistic insights into these adaptation processes and identify novel targets for pharmacological intervention, we conducted a longitudinal proteomic analysis using the Olink Explore HT platform for a proteomics analysis in patients undergoing TAVI.
Methods:
Plasma samples were collected from patients undergoing TAVI via the biobank of the Clinic for Cardiology, UKSH Campus Kiel. Samples were obtained immediately before and approximately three months after the procedure. Proteomic profiling was performed using Olink® technology, and statistical significance was adjusted using the Benjamini–Hochberg method. Gene ontology enrichment was used to interpret the biological significance of regulated proteins.
Results:
Paired plasma samples from 58 patients (median age 80 years [IQR 75–84]; 55% female) were analyzed. Baseline aortic valve area (AVA) averaged 0.8 cm², and 33% had a reduced ejection fraction. TAVI was performed using third-generation CoreValve (52%), Sapien (37%), or Navitor (11%) prostheses.
Proteomic analysis identified 560 significantly regulated proteins (235 upregulated) from 5416 targets post-TAVI. Among the regulated proteins were expected proteins such as nt-proBNP, other known targets such as Troponin T or I, GDF15 or TIMP1 were not significantly altered. Enriched gene ontology terms included “cell adhesion” and “wound healing,” suggesting active tissue repair and remodeling. The most directly cardiac-related term enriched was “cardiac septum development,” (including e.g. the proteins HEG1,CCN1,NOTCH2,NOTCH1,TGFBR3) indicating the anticipated structural and developmental signaling responses in the myocardium.
Conclusion:
TAVI induces significant changes in the circulating proteome, particularly in pathways related to tissue remodeling. In this context, the proteins involved in the development of the cardiac septum pathway are exciting targets for linking data from other omics levels of the same cohort and further validation.