In this case series, we used MSCT-derived 3D modelling and simulations for TMVR planning with transcatheter balloon-expandable valves in ViMAC, MViR, and MViV and found that: 1) many patients were deemed ineligible for TMVR based on 3D modelling and simulations because of issues related to sizing, anchoring or expected neo-LVOTO; 2) neo-LVOTO still occurred in one-fourth of patients despite advanced imaging planning, and 3 out of 4 cases occurred in ViMAC patients; 3) most neo-LVOTO cases resulted from a too deep valve implant depth and could be resolved with alcohol septal ablation; and 4) procedure-related mortality was substantial in this early experience, particularly with ViMAC.

Our observation of high procedure-related mortality with TMVR using transcatheter balloon expandable valves in ViMAC, MViR and MViV is consistent with previous registries. Clinical outcomes after TMVR are also highly variable among various patient categories. ViMAC emerged as a higher risk phenotype in our series. The MITRAL trial displayed a 30-day mortality of 21.8% with ViMAC, 11.5% with MViR and 8.1% with MViV [4]. Yoon et al. also found higher all-cause mortality after ViMAC (34.5%) compared with MViR (9.9%) and MViV (6.2%) at 30 days [7].

LVOTO was highest in our ViMAC group, which is concordant with previous studies, and has a multifactorial aetiology [9, 11]. Posterior MAC may preferentially pivot the transcatheter valve into an anterior direction towards the LVOT [15]. Furthermore, systolic anterior motion of the AML may contribute to LVOTO in these patients [16].

Four patients in our case series still developed LVOTO despite our simulations. There are several reasons why simulations may be inadequate [17]. First, this series included the early experience with simulations. The simulations were improved along the course of the study by doing more simulations per patient, including multiple transcatheter valve sizes and implant depths and at different systolic phases. However, digital simulations do not appreciate device/host interactions including heterogeneous MAC, frame deformation and frame or AML displacement. Finally, it may be difficult to accurately duplicate the simulated implantation depth in the cathlab. These intrinsic limitations of 3D simulation are relevant to all subgroups but appear more prominent with ViMAC as illustrated by the actual LVOTO rates that refuted the prior simulations.

In 2 patients with deeper than planned implantation who received a follow-up MSCT, the neo-LVOTO could be reproduced when the actual THV implantation depth was used. Therefore, more simulations including a greater variation of implant depths may be warranted to better appreciate the effects of deeper than intended THV implantations. Unexpected THV frame displacement and deformation also contributed to neo-LVOTO. Figure 4b illustrates how posterior MAC pushed the THV frame more anteriorly towards the LVOT than simulated.

Neo-LVOTO could be resolved by alcohol septal ablation in all but 1 patient in our study. This is consistent with previous research by Guerrero et al., which demonstrated that alcohol septal ablation is an effective and safe therapeutic option in TMVR-induced LVOTO [18]. Other percutaneous LVOT modification techniques have emerged over the last years (e.g. LAMPOON or SESAME) but were not applied in our centres [19, 20].

The high rate of screening failures due to anatomical causes and the relatively high procedure-related complication rate illustrate the need for further planning optimisation, dedicated transcatheter mitral valve platforms and ancillary techniques to enhance procedure safety in the context of ViMAC, MViR, and MViV.

Dedicated TMVR valve technologies are tested in ViMAC. The ViMAC arm of the Tendyne registry (Abbott Vascular, Illinois, United States), for instance, found a low rate of LVOTO (1 out of 20 patients) and complete elimination of mitral regurgitation in all patients [21]. Furthermore, the ENCIRCLE study (M3 platform, Edwards LifeSciences Corp., Irvine, USA) and the APOLLO study (Intrepid system, Medtronic, Minneapolis, USA) have also initiated ViMAC substudies. (Clinicaltrials.gov ID NCT04153292; NCT05496998). Nevertheless, LVOTO remains a significant risk and acknowledged reason for screen failure with all dedicated mitral valve technologies.

The findings of these case series should be interpreted while taking into account the relatively small sample size and against the background of existing larger series that also included the early experience with 3D modelling and simulation for ViMAC, MViR and MViV.