Calcification in TAVI Prostheses: Correlation of Calcification Hotspots with Mechanical Stress and Thrombotic Deposits

• Applicants: Dr. Mareike Barth; Dr. Johanna Clauser
• Subject Area: Cardiac and Vascular Surgery ; Biomedical Systems Technology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 556971496

Transcatheter aortic valve implantation (TAVI) has emerged as a widely accepted alternative to traditional surgical valve replacement. Due to the rising numbers of TAVI procedures, the durability of prostheses becomes more important. However, durability analyses are limited to a follow-up period of 8 years in most reports. Thus, long-term durability of TAVI valves focusing on structural valve deterioration and especially on calcific degeneration is understudied to date. Two of the main durability limitations are leaflet thrombosis and deterioration due to calcification. The possible triggers for calcification are manifold, reaching from an outbalanced calcification inducer-inhibitor ratio, blood cell migration into the valve material, protein adhesion on the material, to shear stresses during crimping and resheathing. To date, the reasons for impaired durability in TAVI valves are far from understood. Therefore, we will evaluate calcification onset in TAVI valves due to mechanical load and interactions with blood. In-house produced TAVI valve prototypes are used to perform comprehensive in-vitro calcification tests with crimped, resheathed, and non-crimped valves in combination with analyses of tissue integrity, spatial and quantitative calcification deposition. Differences between the groups are evaluated, correlated with hotspots of mechanical load, and validated by means of clinical image data at the timepoint before vale-in-TAVI procedure. Further, pericardium patches are incubated with human whole blood in a Chanler Loop setup to evaluate blood cell interaction and migration. Blood and material samples are analyzed in terms of blood cell numbers, protein concentrations and histology over the course of experiments. Afterwards, patch samples are directly transferred to a calcification test to account for the impact of blood-material interactions on calcification. Calcification is analyzed as before and compared to reference materials without prior blood contact. Finally, crimped and non-crimped heart valve prototypes are subjected to a full in-vitro thrombogenicity test under physiological flow and pressure conditions, followed by a calcification test. The combination of both, mechanical load and previous blood contact allows for the final analysis of calcification onset in TAVI valves. Again, results are compared to clinical image data to validate calcification hotspots and their causes with the clinical situation. At the end of the project, the correlation between mechanical stress, thrombogenicity, and the calcification origin of TAVI valves is enrolled. With this new knowledge, heart valve prostheses can be specifically designed and tested to avoid calcification hotspots. Future projects might include the development of specific anti-calcification coatings, refinement of crimping and resheathing protocols and the evaluation of further influencing factors such as valve-in-valve procedures or alternative materials for TAVI prostheses.

• DFG Programme: Research Grants