Catheter-based innovations in mitral valve surgery

Valvular heart disease (VHD) accounts for approximately 20% of all cardiac surgical procedures in western countries. Due to effective rheumatic fever preventive measures, degenerative and congenital conditions are the main aetiologies of VHD in the USA and Europe. Although medical management plays an important role, surgical treatment remains the cornerstone of VHD treatment. Surgical intervention on the mitral valve accounts for 5–10% of all surgical procedures [1–3]. Transcatheter treatment of mitral VHD is not new. Percutaneous mitral commissurotomy with the Inoué-type balloon technique has been the main interventional treatment for mitral stenosis for more than 20 years [4]. Percutaneous mitral commissurotomy, in selected patients, is preferred to open surgery in interventional guidelines because of its effectiveness, low procedural morbidity and mortality as well as the possibility of reintervention. Only an unfavourable anatomy would see open surgery to be chosen as first line therapy [5]. However, the story of transcatheter treatment of mitral regurgitation (MR) is very different. Recent evidence has shown that surgical correction of moderate or severe MR is performed in less than one-third of patients despite favourable impact on patient survival [6]. Perceived invasiveness of open surgery and insufficient consideration of MR to have a genuine impact on patient survival and symptoms might constitute some of the reasons of this unmet need, and as such possible targets for research. After the success of percutaneous mitral commissurotomy for mitral stenosis and transcatheter aortic valve implantation (TAVI) for aortic stenosis, MR seems to be the new focus of contemporary research and industrial development in structural interventional cardiology [7]. Interestingly, devices designed for transcatheter treatment of MR are often directly inspired from open surgical techniques, the only difference being the approach and the devices used. The techniques of tissue manipulation that were performed using metallic surgical pliers with direct vision of the valve anatomy are now replaced with plastic and metallic pliers introduced percutaneously through the vessels with indirect vision by fluoroscopy and imaging. Similar to open surgery, transcatheter devices can be divided into repair and replacement groups [8]. Interestingly, the debate opposing repair and replacement in cardiovascular surgery is being transposed to transcatheter therapies [7]. The popularity of surgical mitral valve repair at the beginning of the 21st century encouraged the development of numerous percutaneous mitral plasty devices [9, 10]. Despite its limitations, the MitraClip™ transcatheter repair device has recently demonstrated its survival benefit [hazard ratio (HR) 0.62, 95% confidence interval (95% CI) 0.46–0.82; P < 0.001) and rehospitalization reduction (HR 0.53; 95% CI 0.40–0.70; P < 0.001) as opposed to medical treatment alone in very selected patients with secondary MR in the COAPT trial [11, 12]. The MitraClip was the first transcatheter mitral valve intervention device to be developed. It aims to percutaneously reproduce the surgical Alfieri-technique, and has known several iterations since its inception (NT, NTR, XTR) aiming at increasing its manoeuverability [13]. The similarly designed Pascal™ device has been studied and just received CE mark [10]. The valvular repair systems were later completed by the development of percutaneous annuloplasty (such as CardioBand™) and chordal replacement (such as NeoChord™ or Harpoon™) systems [14, 15]. However, a difficult learning curve as well as lack of efficiency on resolution of the MR are among the main limitations of these devices [14, 16–18] and might be viewed as inherited from the surgical repair techniques that inspired them. Combining the techniques of transcatheter repair has been proposed to mitigate the lack of efficacy on MR resolution; however, this poses increased complication risk and costs [19] (Fig. 1). Perhaps, valve replacement could be a better option. Mitral transcatheter repair devices. Mitral transcatheter repair devices. Mitral repair is favoured over replacement by open surgical treatment of MR in the international guidelines [5]. However, the recommendation is based on observational data that showed repair to be superior to replacement regarding early survival, for primary as well as secondary MR, in patients in whom repair was possible and was performed in experienced centres [20, 21]. This tendency persists in recent literature [22]. However, randomized data showed that replacement nearly eliminated the risk of long-term recurrent significant secondary MR at 2 years (58.8% after repair versus 3.8% after replacement) [23] which could lead to higher long-term mortality of repair. By avoiding cardiopulmonary bypass, mechanical ventilation and access site infectious complications, transcatheter mitral valve replacement (TMVR) could improve perioperative mortality while preserving late outcomes by drastically reducing the risk of MR persistence or recurrence. Based on experience with open surgery, transcatheter replacement has a shorter learning curve and allows broader implementation of the technique beyond expert centres, thus allowing more patients to have interventional correction of MR. This hypothesis drives the development of TMVR systems (Fig. 2). Mitral transcatheter heart valves. Mitral transcatheter heart valves. The first-in-human TMVR was performed with the CardiAQ valve in 2012 [24]. Recently published observational data with the Tendyne™ and Intrepid™ devices implanted transapically in very high surgical risk patients are encouraging. The 30-day mortality was high (1/30 in the Tendyne and 7/50 in the Intrepid studies) but significant MR elimination was constant after the intervention [25, 26]. Following the example of PARTNER and CoreValve trials with TAVI, the first trial comparing TMVR with the Intrepid or Tendyne devices to open surgery is already in progress (APOLLO trial, NCT03242642; SUMMIT trial, NCT03433274) (Table 1). The principal limitation of these systems was their transapical delivery, a major setback when TMVR is opposed to trans-septally deployed repair systems such as MitraClip. Indeed, experience with TAVI showed that the transapical approach is associated with higher tamponade and bleeding risk, as well as residual left ventricle apex dysfunction [27, 28]. Ongoing randomized controlled trials on transcatheter mitral intervention CV: cardiovascular; MR: mitral regurgitation; OMT: optimal medical therapy; TMVR: transcatheter mitral valve replacement. Ongoing randomized controlled trials on transcatheter mitral intervention CV: cardiovascular; MR: mitral regurgitation; OMT: optimal medical therapy; TMVR: transcatheter mitral valve replacement. As the portfolio will further expand with the recent successful first-in-man implantation of Abbott CEPHEA™ and CardioValve Mitral Tech™ [both trans-septal transcatheter heart valves (THVs)], and numerous feasibility and safety single-arm studies with other transapical and transseptal TMVR devices are underway (Edwards EVOQUE™ NCT02718001; HighLife™ NCT02974881; Neovasc Tiara™ NCT02276547), Webb et al. recently published their short, although favourable experience with trans-septally implanted Edwards Sapien M3 (Edwards Lifesciences, Irvine, CA, USA), which was implanted in 10 patients presenting primary or secondary MR. The M3 is the mitral derivative of the Sapien 3 balloon-expandable device, which is one of the two dominant devices used for TAVI. The MVARC-defined technical success rate was 90% and authors did not observe stroke or death during the short 30-day follow-up. The devices used an expandable polytetrafluoroethylene–covered nitinol ‘dock’ which allows stabilizing of the THV. Such ‘docking’ systems recall the challenge for mitral THV developers to design devices that are to remain stable in the mitral annulus despite the absence of a solid armature. This is one of the major differences when TMVR is compared with TAVI where THVs are implanted in calcified stenotic aortic valves. Mitral annular calcification is infrequently associated with significant mitral dysfunction; however, even in those patients who have this native calcification armature the results of TMVR (with TAVI devices) in mitral annular calcification are unfavourable, with technical success achieved only in two-thirds of patients [17]. By comparison, ‘valve in valve’ and ‘valve in ring’ (TMVR with TAVI devices in degenerated mitral bioprostheses and annuloplasty rings respectively) yield better results with approximatively 95% and 80% technical success rates [17]. However, THVs designed for the mitral valve might yield better results, as supported by the recent use of Tendyne in mitral annular calcification which yielded encouraging results in compassionate cases and is under clinical investigation. Despite the popularity and active development of transcatheter mitral therapies, these therapies present several limitations and risks. Limitations include vascular complications due to large delivery systems, bleeding and stroke. Indications can be limited by stringent anatomical compatibility characteristics (e.g. for MitraClip those are flail gap and width, coaptation length and depth) or the risk of left ventricle outflow tract obstruction by a novel mitral THV. Furthermore, some conditions still demand an open surgery such as endocarditis and severe complications of non-invasive interventions. Transcatheter therapies can be viewed as a natural evolution towards minimizing invasive interventional procedures. In recent years, mini-invasive mitral surgery has further reduced incision sizes by using miniature instruments, and allowed indirect visualization by endoscopy and remotelly controlled robots. Contemporary improvement in interventional cardiology allowed the development of intravascular approaches and encouraged hybrid strategies such as bypass grafting associated with percutaneous coronary intervention leading to improved outcomes. As such transcatheter therapies offer an opportunity for inter-disciplinary collaboration [8], excellence centres have already adopted state-of-the-art hybrid approaches, and offer education for endovascular, transcatheter, mini-invasive and hybrid techniques. However, a revolution is yet to happen through artificial intelligence and automatized and semi-automatized robotic intervention that could further reduce morbidity in patients. Further, artificial intelligence has the potential to improve predictive and preventive strategies, which could probably lead to ‘near-zero’ invasiveness approaches. Therefore, transcatheter therapies could be regarded as a new set of tools rather than a definitive achievement. Conflict of interest: Thomas Modine is a consultant for Boston Scientific, Medtronic, Edwards, Cephea, Microport, GE, Abbott. He received a research support grant from Edwards. Pavel Overtchouk declares no conflict of interest.