KEYNOTE: In vivo remodeling of mitral valve leaflet following transcatheter edge-to-edge repair in humans

Abstract

Mitral regurgitation (MR) is the most common valvular disease in the United States affecting over 2% of the population and is expected to double by 2030 due to population aging. MR of any type is a major prognostic factor of mortality: the risk of mortality with severe MR at five years is 36% and even moderate MR nearly doubles the risk of mortality in patients with multiple cardiac comorbidities. In this context, image-based computational simulations can play a key role in understanding MV disease and optimizing transcatheter edge-to-edge repair (TEER) procedures. Moreover, TEER presents a unique challenge in that the device imparts a sustained focal stress on the MV leaflets. Although the long-term consequences of MV TEER is a prevailing clinical concern, these effects have never been studied. For example, we have previously demonstrated that the MV leaflet tissue plastically deforms after myocardial infarction through annular dilation and chordal tethering. These changes in altered mechanical loading have been shown to stimulate shifts in MV biosynthesis at the cellular and molecular levels. Therefore, as TEER induces pronounced focal stress concentrations, we hypothesize that the MV leaflets will undergo substantial plastic deformation post-TEER. To address this hypothesis, we acquired TEE imaging data of patients’ MVs before, immediately after, and 3 months after treatment with TEER to quantify the effects of TEER-induced plastic deformation on MV leaflet function. Our findings not only confirmed the presence of plastic deformation but also offer strong evidence that this plasticity is primarily driven by the TEER procedure itself, rather than other organ-level shifts in loading or boundary conditions. This study emphasizes once again the importance of an individualized approach to MV treatment optimization, but with a holistic focus on all aspects of MV function, with the objective to ensure the best possible long-term outcomes for each patient.