Screening for TMVR: A Glimpse Into the Future Technological Needs and Requirements

The development of transcatheter therapies has expanded the therapeutic reach to high-risk patients with severe mitral regurgitation (MR). In this patient population, transcatheter edge-to-edge repair (TEER) is the only clinically approved procedure, with more than 150,000 patients treated to date. Among these real-world cases, nearly one-half do not have Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (COAPT)-like enrollment criteria, and a substantial proportion is left untreated because of anatomic reasons, limiting the success of TEER.1Scotti A. Munafò A. Adamo M. et al.Transcatheter edge-to-edge repair in COAPT-ineligible patients: incidence and predictors of 2-year good outcome.Can J Cardiol. 2022; 38: 320-329Abstract Full Text Full Text PDF PubMed Scopus (10) Google Scholar In recent years, transcatheter mitral valve replacement (TMVR) is emerging as an alternative solution for these patients, promising the advantage of being “agnostic” to the underlying mitral valve pathology. Each individual TMVR device displays unique structural design features and mechanisms of delivery; thus, patient screening with multimodality imaging is a critical step in ensuring procedural suitability. The goal of preprocedural imaging is primarily to assess mitral annular sizing and morphology of surrounding tissues according to the needs of the device and to identify any other potential challenges that may affect the success of the procedure. As a result of this selective process, only a minority of the patients screened are deemed to be eligible for TMVR,2Ludwig S. Ruebsamen N. Deuschl F. et al.Screening for transcatheter mitral valve replacement: a decision tree algorithm.EuroIntervention. 2020; 16: 251-258Crossref PubMed Google Scholar slowing enrollment in clinical trials and the progress of the field. Understanding the root causes behind these rejections is fundamental to identify the ongoing clinical challenges and future design needs and to expand adoption of TMVR. In this issue of the Canadian Journal of Cardiology, Demir et al.3Demir O.M. Conradi L. Prendergast B. et al.Clinical characteristics and outcomes of patients screened for but Deemed Clinically Not Suitable for Transcatheter Mitral Valve Replacement: DECLINE-TMVR Registry.Can J Cardiol. 2023; 39: 581-589Scopus (2) Google Scholar present a multicentre experience of the screening results for TMVR trials in Europe, United States, and Canada (the Deemed Clinically Not Suitable for Transcatheter Mitral Valve Replacement [DECLINE-TMVR] study). Of 294 patients screened, 70% (n = 207) were deemed anatomically unsuitable for TMVR. The most common reasons for rejection were mitral annular size outside the therapeutic range (28%), small predicted neo-left ventricular outflow tract (LVOT) area (26%), and small ventricular size (14%). The 4 most common valves used for screening were 37% Tendyne (Abbott Vascular, Abbott Park, IL), 21% Tiara (Neovasc Inc, Vancouver, BC), 13% Intrepid (Medtronic, Minneapolis, MN), and 7% Highlife (HighLife SAS, Paris, France). Only one-third (29%) of patients were screened for a second TMVR device, and 1 of 10 (11%) for a third TMVR device. Of all the patients who failed TMVR screening, 144 (70%) were subsequently screened for TEER or surgery, and 58 (40%) of them underwent transcatheter repair procedures. In this cohort of patients, 87 (30%) were accepted for TMVR, and the transapical approach was used in almost all the procedures (91%). Although the findings are representative of a real-world experience on TMVR and support what has been already been described in other databases, there are several limitations in the study design that need to be highlighted. First, almost all the devices were transapical technologies; then, most of the anatomic exclusions are limited to the design and mechanism of delivery of these technologies. Also, additional anatomic exclusions related to the transseptal approach are not accounted for in this report. The variability in the criteria to screen and adjudicate patients seen in each TMVR program introduces significant and uncountable heterogeneity among all the centres. Each participating site decided who were the patients to be screened for TMVR and made the final decision on their clinical eligibility for the procedure. Also, the TMVR systems used for the screening process varied among centres. With most patients being screened for only 1 device, it cannot be excluded that a portion of them would have been eligible for other valves. Only 1 reason for screening failure was reported, but a combination of more than 1 characteristic might have been also present (ie, small ventricular size and risk of LVOT obstruction). Outcome results should be considered exploratory; no data are available on reduction of MR; survival analyses are biased by significant differences in patient risk profile and treatment allocation. Nonetheless, this study sheds light on the limitations of the TMVR devices used in this study and identifies potential unresolved unmet clinical needs. It is important to characterize the patient population screened for TMVR today. This study population displays a high number of comorbid conditions, a high surgical-risk profile, and is commonly rejected from surgery. One could speculate that the rates of TMVR ineligibility may improve when patients with better clinical profiles are considered for this procedure. Interestingly, patients rejected for TMVR had higher proportions of primary MR, including small left ventricles, higher left ventricular ejection fraction, and presence of mitral annular calcification. This is in line with previous reports in which larger cardiac cavities (ie, secondary MR) decreasing the potential for LVOT obstruction are predominantly favoured during the TMVR screening process. Because of the fact that primary MR is also frequently accompanied by structural leaflet abnormalities that could potentially limit TEER indications, expanding the use of indication to this type of patients is fundamental to fill this treatment gap. Patients with primary MR frequently have smaller annulus and left ventricular cavities increasing the risk of LVOT obstruction. Whether the reasons identified for TMVR ineligibility were predominantly related to primary MR cases is unclear. However, the study findings support the available literature on the TMVR screening process (Fig. 1).2Ludwig S. Ruebsamen N. Deuschl F. et al.Screening for transcatheter mitral valve replacement: a decision tree algorithm.EuroIntervention. 2020; 16: 251-258Crossref PubMed Google Scholar,4Coisne A. Pontana F. Tchétché D. et al.Transcatheter mitral valve replacement: factors associated with screening success and failure.EuroIntervention. 2019; 15: e983-e989Crossref PubMed Scopus (23) Google Scholar Mitral valve annulus dimensions and risk of LVOT obstruction are the most common reason for TMVR ineligibility, followed by mitral annular calcification, left ventricular size, and function. Identifying the limitations of the TMVR screening process is fundamental to design future TMVR devices that may be offered to a larger patient population. Rejection because of annular sizes can be easily overcome with broader availability of valve sizes, expanding the current range of treatable annulus dimensions. Similarly, the presence of mitral annular calcification requires devices with sufficient radial force to prevent the negative impact of frame deformation on valve function. Other anatomic challenges, such as LVOT obstruction risk, will require further technologic improvements in frame design or mechanisms of anchoring. On the other side, transseptal delivery will add additional anatomic challenges and exclusions requiring further design of advanced delivery systems. The DECLINE-TMVR registry provides important insights into the clinical challenges and remaining unmet needs in the TMVR field. The complexity and anatomic variability of the mitral valve apparatus makes the design of a “workhorse TMVR device” among the the greatest engineering challenges in our field. Identifying the current limitations is fundamental to continue making progress and sheds light on the future technologic requirements of the TMVR field. Small technologic improvements in valve frame design have the potential to make a big impact on patient selection and rejection rates. Some of these technological changes, already under development, promise to improve patient eligibility and accelerate the validation of a technology that promises to fill an important gap in the treatment of high-risk patients with MR. Also, it is expected that because of the less invasive nature of the procedure, new-generation transseptal TMVR systems will add momentum by allowing the inclusion of real-world patients. The biggest question is whether most of TMVR systems will become "workhorse” devices or be limited by their own designs. It is early to tell; however, it is expected that because of the complexities of the mitral anatomy, adoption of TMVR will continue to depend on the intrinsic device features and its impact on ease of use. Meanwhile, ongoing prospective clinical trials will continue to shed light regarding patient eligibility and whether TMVR has the potential to be expanded to a broader patient population. No funding was provided for this paper.