Biomarkers of myocardial fibrosis predict sustained mitral regurgitation reduction after transcatheter edge-to-edge mitral valve repair

Left-ventricular reverse remodeling occurs frequently after transcatheter edge-to-edge mitral valve repair (M-TEER) and may be beneficial for sustained long-term reduction of mitral regurgitation (MR). We hypothesized an interplay of myocardial fibrosis with sustained MR reduction and that biomarkers of fibrosis can predict long-term procedural success. 

 

We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural peripheral blood samples for biomarker analysis. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression of 92 defined biomarkers. We analyzed differences in biomarker expression levels between patients that had sustained procedural success (absolute MR reduction of ≥2 grades compared to baseline) at the latest available follow-up after M-TEER and patients that had not. 59 patients were excluded due to a) inability of device placement during the index procedure, b) in-hospital death within the index hospitalization c) device detachment during follow-up or d) lack of available follow-up echocardiography.

 

183 patients were included in the final analysis of which 166 (90.7%) had sustained procedural success at a latest available follow-up of median 502.0 days (interquartile range 150.0 – 1174.0 days). Patients with sustained MR reduction had a higher prevalence of coronary artery disease (65.1 vs. 35.3%, p = 0.016) whereas patients with inferior long-term results more often had dilated cardiomyopathy (35.3 vs. 16.3%, p = 0.052). No other differences in terms of baseline characteristics were seen, especially regarding etiology of MR (secondary MR in 60.8% of patients with sustained procedural success vs. 52.9%, p = 0.53) or residual MR grade at discharge (residual MR grade ≥III+ in 5.4 vs. 11.8%, p = 0.30). 

Median expression of 3 biomarkers associated with myocardial fibrosis was significantly higher in patients, in which long-term MR reduction was not achieved: (Matrix-metalloproteinase 9 (MMP-9) 1.4-fold, p = 0.012; Matrix-metalloproteinase 2 (MMP-2) 1.2-fold, p = 0.041 and Platelet-derived growth factor subunit A (PDGFA) 2.3-fold, p = 0.022). Other significantly regulated biomarkers were Chitotriosidase-1 (CHIT-1; 0.6-fold, p = 0.041) and Contactin-1 (CNTN-1; 1.3-fold, p = 0.027). 

Biomarkers of fibrosis showed a robust prognostic value regarding long-term procedural success: area under the curve (AUC) for MMP-9 0.684 (95% confidence interval (CI) 0.563 – 0.806, p = 0.012), for MMP-2 0.651 (95% CI 0.504 – 0.798, p = 0.041) and for PDGFA 0.668 (95% CI 0.517 – 0.820, p = 0.022). 

 

Higher expression levels of biomarkers of myocardial fibrosis (MMP-9, MMP-2, PDGFA) are predictors of non-sustained MR reduction after M-TEER.