Mitral valve leaflet tissue plasticity following transcatheter edge-to-edge repair in humans

Abstract

Transcatheter edge-to-edge repair (TEER) is a promising minimally invasive approach for the treatment of mitral valve (MV) regurgitation (MR). However, long-term outcomes have been suboptimal in several recent clinical trials, likely complicated by the substantial heterogeneity of MR presentations and the combinatorial nature of the procedure itself. Moreover, the long-term consequences of MV TEER on the leaflet tissue itself have never been studied, and represent a key target for procedural optimization. As a first step in addressing these deficiencies, we conducted a novel study to investigate the effects of TEER-induced MV shape and strain at several months after implantation. We first acquired and analyzed longitudinal echocardiographic imaging data from five patients pre, post, and at 3-month follow-up post-TEER. We then quantified TEER-induced time-evolving changes in MV diastolic shape and systolic leaflet strains using a computational in vivo geometry recovery method. In the ED state we found evidence of substantial MV leaflet \textit{plasticity} (defined here as permanent changes MV leaflet geometry) at the 3 month time point. Though the patterns of plasticity were generally heterogeneous, the highest regions of plasticity consistently corresponded to the position of the TEER device. Moreover, the first principal direction field consistently converged onto the position(s) of the clip(s) in all cases, further suggesting that the clip is the primary driver of the observed plasticity. This result emphasized the fact that the MV leaflets are not dimensionally stable post-TEER, and instead continue to remodel. To evaluate the potential confounding effects of concomitant changes in ventricular shape, we also quantified changes in annular and left ventricular dimensions and found no significant changes over time. These observations support our hypothesis that the focal stress concentrations induced by the clip drive MV leaflet tissue remodeling at 3 months. In summary these novel results confirm that TEER has effects beyond those observed immediately post-operation. These unique findings underscore a mechanism for long-term repair failure and constitute a potential key target for patient-specific procedural optimization.