Targeted proteomic profiling of transcatheter edge-to-edge repair failure in patients with mitral regurgitation and heart failure

Aims: To assess the changes in circulating biomarkers concentrations after mitral valve transcatheter edge-to-edge repair (M-TEER) and their relationship with procedural success vs. failure in patients with severe mitral regurgitation (MR) and heart failure (HF). Methods and results: Pre-procedural, post-intervention, and 30 days post-intervention plasma samples were analyzed for 266 different proteins using the Olink Proseek® Multiplex cardiovascular (CVD) II, CVD III, and inflammation panels, in patients with MR undergoing M-TEER. Multiple biomarkers showed a differential expression 30 days after M-TEER in patients with procedural failure vs. those with a successful evolution. The proteins upregulated in patients with procedural failure were functionally enriched in pathways related to immune regulation, inflammation, extracellular matrix organization, and cellular structures. After adjustment for confounding variables, increases in IL2RA, RAGE, IGFBP2, and COL1A1 values at 30 days post-intervention were associated with procedural failure. Changes in IGFBP2 and IL2RA values were also independently associated with pulmonary artery systolic pressure (PASP) increases after M-TEER. Conclusion: In a cohort of patients with severe MR undergoing M-TEER, differences in circulating biomarkers concentrations related to inflammation and fibrosis were observed between patients with procedural success as compared to those with procedural failure. Biomarkers known to be associated with HF severity were over-expressed in patients with procedural failure, compared with those with procedural success, after M-TEER.