Transcatheter mitral valve implantation (TMVI) represent a new treatment option in patients with degenerated bioprostheses, failed annuloplasty rings, and severe mitral annular calcification at high risk for conventional mitral valve surgery [1, 2]. Among them, the transcatheter mitral valve-in-valve implantation (TMViV) is the most matured strategy which has obtained US Food and Drug Administration approval and European Union CE Mark and may be considered as an alternative to surgery in patients at high or inoperable surgical risk according to current guidelines [3, 4]. The most frequently used transcatheter heart valves (THVs) are the balloon expandable valves during the TMViV procedures. Cheung et al. [5] performed the first successful human implantation of a THV in a degenerated bioprosthetic mitral valve via transapical approach in 2009. And the delivery approach in most patients had been transapical in early stage due to its technical easiness [6]. However, transapical approach has been associated with an increased risk for periprocedural complications and mortality and a slower recovery [1, 2, 7, 8, 9]. Over the past few years, the transseptal approach has been increasingly adopted by more operators. This fully percutaneous approach has shown a safe and effective procedure with rapid recovery. Additionally, preliminary data from the VIVID registry showed that left ventricular function in patients with ejection fraction 50% at baseline had greater improvement in patients treated with transseptal versus transapical TMViV [10, 11]. The transseptal procedure, however, is technically challenging.

The two main technical challenges of transseptal approach are the pursuit of proper transseptal puncture position [12] and ideal coaxiality for THV system delivery [13, 14]. Some patients have an atrial septal incision during the first mitral valve surgery. These patients generally have a scarred or thickened septum due to the prior surgery, which makes it difficult to puncture the atrial septum. In this case, the septum could be punctured with radiofrequency transmitted through the transseptal needle. Then, atrial septostomy with large peripheral balloon expanding are also required to obtain sufficient septal defect [15, 16, 17]. Even so, mounted valve crossing the septum may be a challenging step, and even serious troublesome situations such as valve displacement and support guide wire detachment into the left atrium. Addressing these issues may prolong the procedure and make it more difficult. Meanwhile, the crossing of the mitral orifice may be more challenging because the THV may block against the bioprosthetic ring or calcific bulks of the mitral annulus because of the obliquity of the THV regarding the mitral orifice. Poor coaxiality may also lead to THV migration or paravalvular leaks post deployment [18]. These problems may eventually require more complicated strategy or even open surgery to resolve.

Our team used a long pre-curved sheath in TMViV procedure, which significantly simplified the procedures. This method avoids difficulties when the loaded THV passes through the atrial septum and mitral valve. At the same time, it can effectively avoid large iatrogenic atrial septal defect, and the delivery system can easily reach the optimal anchoring zone and achieve ideal catheter coaxiality. If the delivery system is difficult to reach the desired deployment position, it can also be fully retracted into the long sheath. This method is expected to improve the efficiency of procedure and reduce the difficulty of procedure. The objective of this study was to evaluate the effectiveness of long pre-curved sheath techniques in TMViV procedures.

Bioprosthetic valves are increasingly preferred over mechanical valves, due to avoiding lifelong anticoagulation and the lower risk of thromboembolic complications [20]. At the same time, the aging of the population has led to an increase in elderly patients with valvular disease, and the amount of bioprosthetic valves will further increase. However, bioprosthetic valves have a limited durability and valve deterioration is frequently observed [21, 22]. It is estimated that the number of patients requiring re-treatment for bioprosthesis failure is likely to rise within the next years. Redo open heart surgery for bioprosthetic valve failure is associated with significant risks, particularly in patients with comorbidities, including advanced age [23]. It is not only a challenge of surgical techniques and prognosis, but also a huge challenge of patient psychological acceptance. TMVI has been investigated in 4 different settings: valve in native, valve-in-valve (VIV), ViR and ViMAC. VIV is the most promising setting for TMVI [24, 25]. Over the past decade less invasive transcatheter valve-in-valve (VIV) procedures have been increasingly utilized in the aortic, mitral, pulmonary, and tricuspid positions [26, 27, 28, 29, 30, 31]. It has been considered as an alternative to surgery in patients at high or prohibitive surgical risk according to latest guidelines. Transcatheter valve-in-valve procedure is a revolutionary technological innovation. This treatment has the obvious advantages of not requiring open chest, cardiopulmonary bypass, cardiac arrest, and short procedural time, minimal trauma, and fast recovery [29, 32, 33]. In this cohort of patients, all 27 cases achieved procedural success. The procedural duration is only about 90 minutes, and the postoperative hospital stay is only less than 5 days. There are even patients who complete all treatments within 24 hours and are safely discharged after receiving day surgery. At the same time, the follow-up results are encouraging. Except for one patient who died of non-cardiac-related causes six months after procedure, all other patients survived at 1 year follow-up. And there were no re-hospitalizations for serious complications in the whole group. The postoperative recovery of cardiac function in this cohort is also encouraging. 92.6% of patients had a postoperative improvement by $\ge$1 New York Heart Association (NYHA) functional class. This result is similar to those of the other previous studies [30, 31, 33, 34, 35], reflecting the significant advantages of TMViV procedure as a minimally invasive treatment technique in the perioperative period. At the same time, the results of short-term follow-up are not inferior to those of traditional surgery. Moreover, the medium-term clinical outcome of this technology is also not inferior to redo surgery according to the 3-year follow-up data from the VIVID Registry [30]. Therefore, both the 2020 ACC/AHA Valvular Disease Management Guidelines and the 2021 ESC/EACTS Guidelines suggested the treatment of transcatheter valve-in-valve (VIV) procedures as class IIa recommendation for patients at high or prohibitive surgical risk [3, 4].

TMViV procedure was first implemented by transapical approach [5], and most patients underwent transapical procedures in the early stages [6]. This approach facilitates coaxial delivery of the THV across the failed bioprosthesis and is technically less challenging than the transseptal alternative [36, 37, 38, 39]. And many centers are familiar with this technique due to their experience in transapical TAVR. There were also a few case reports in which THVs were implanted via trans-atrial approach with left minimal thoracotomy. Although the transapical approach is most commonly used previously due to its technical easiness, it has been associated with an increased risk for periprocedural complications and mortality and a slower recovery. Therefore, TMViV via the transseptal approach might be a better option for this high-risk population. At present, percutaneous transseptal TMViV has become the preferred least invasive treatment choice for patients with degenerated mitral bioprosthesis [40, 41]. However, it must be noted that the transseptal approach is more technically challenging than transapical approach. Therefore, guidelines also explicitly recommend that such treatment be done in experienced institutions [3].

Transseptal TMViV procedure has two technical challenges. One is transseptal puncture technique at scarred and calcified atrial septum and choosing the appropriate puncture position. The other is to establish an ideal delivery track that facilitates the THV system to across the atrial septum and failed bioprothesis, and reach the perfect release position. The key point of transseptal puncture technique is to choose the appropriate puncture position, which facilitates the ideal delivery track. Under TEE and fluoroscopic guidance, transeptal puncture is usually performed at the predetermined location from CT measurements. TMViV procedures generally prefer transseptal puncture in the inferoposterior portion of atrial septum instead of superoposterior location of septostomy similar to the transseptal puncture for MitraClip procedures. The puncture is usually located in the middle of the fossa ovalis and approximately 3 cm high from the mitral valve plane at a TEE four-chamber view. This location is similar to transseptal access for percutaneous mitral balloon commissurotomy. Our institution usually uses the center of the mitral prosthesis as a marker of puncture height on fluoroscopy in the projection perpendicular to the plane of the mitral bioprosthesis. It is more difficult to navigate the septum and deliver the THV with superior punctures. And the inferior puncture is not conducive to the ideal coaxiality of the catheter in the mitral prothesis [9, 12, 13]. The other technical challenge of transeptal puncture is resistant septum. It might be difficult for some patients to succeed in routine puncture. These patients generally have a scarred or thickened septum from the prior surgery. If resistance to crossing the septum with the needle occurs, pressure must be continuously applied until crossing. When crossing is still not possible, radiofrequency may be used by a standard electrosurgical cautery generator via the puncture needle, brief pulses being applied to the hub of the needle by direct contact [12, 13]. If these methods are still ineffective, you may need to re-select the puncture position. Once the transseptal puncture succeed, it is necessary to apply a sufficiently large balloon for atrial septostomy multiple times in order to obtain a sufficiently loose transseptal channel. Therefore, many patients will have obvious residual iatrogenic atrial septal defects after procedures.

Even if the balloon dilatation of atrial septum is successfully completed, it may still be challenging for the THVs delivery system to pass through the septum. Such a situation is not uncommon in transseptal TMViV procedures. The edge of scarred and calcified septum may lead to entrapment and blockage of the THV. If some resistance occurs, pushing catheter forcefully is a very dangerous, which may lead to valve dismounting/deformation, or ventricular rupture caused by excessive force of the stiff support guide wire, or guide wire inadvertent pullback into the left atrium or even loses of the established transseptal access. Addressing these situations requires a wealth of experience from the operator. The operator should carefully manipulate the catheter by torquing the system and adjusting the flexion angle until crossing the scarred atrial septum. If crossing is still not possible or guide wire pullback into the left atrium, the THV should be reintegrated into the sheath and removed and started all over again. At this point, complete withdrawal of the THV may also encounter greater difficulties, as balloon expanding valves are often difficult to retract into the regular delivery sheath. In addition, even if the THV successfully crosses the atrial septum, the crossing of the mitral orifice may be more challenging because the THV may block against the bioprosthetic ring or calcific bulks of the mitral annulus, or in severely stenotic orifices. In most cases, the undesirable catheter coaxiality and the obliquity of the THV with regard to the mitral orifice is the main cause of blockage. These will cause great difficulties in the continuation of the procedure.

The long pre-curved sheath we used in this study can effectively solve the above technical difficulties. After successfully transeptal puncturing and establishing a track to left ventricular apex, the long pre-curved sheath was advanced directly into the left ventricle along the stiff guide wire. Once the long sheath crossed the septum and bioprosthetic ring, the ideal THV delivery track was already established. Thereafter, the mounted THV system was advanced smoothly through the atrial septum and bioprosthetic ring within the long sheath, so that no blockage occurred in the atrial septum and bioprosthetic ring. At the same time, due to the strong support of the long pre-curved sheath, the coaxiality of the delivery track will be more stable. And it is easier to manipulate the optimal orientation of the catheter by rotating sheath. Before THV deployment, the retracted long sheath can still support the delivery system to position the THV appropriately. The curvature at the tip of the long sheath helped to maintain the sagittal position coaxiality of the THV within the bioprosthetic ring. Even in cases where a complete withdrawal of THV delivery system is required, it can be easily retracted into the 22F sheath, avoiding the irreversible condition of unsheathed procedure. In addition, there is no need to dilate atrial septal with an oversized balloon after puncture. It is relatively easy for the long sheath system with dilator to cross the calcified atrial septum under the support of stiff guide wire. For patients who had not undergone atrial septal incision and suturing in the previous surgery, even balloon dilatation is not required, which is similar to the Mitraclip procedure. Therefore, there is generally no excessive iatrogenic atrial septal defect after procedure, and there is no need for closure. In this study, the long pre-curved sheaths were used in the TMViV procedures for the later 17 patients. Compared with previous procedures done with regular sheaths, this technique significantly saved procedural time and fluoroscopic time, and improved surgical efficiency. And none of the patients required postoperative closure of the atrial septal defect. However, in the first 10 patients with regular expandable sheaths, two had transcatheter atrial septal defect closure due to large iatrogenic interatrial shunt. This increases the procedural duration and medical costs with more implanted intracardiac devices.

One of the most important features limiting the use of TMVI is LVOT obstruction. The structure of Prizvalve™ valve is similar to that of other commercial spherical expansion valves, and the screening criteria are also similar. In this study, we have followed the consensus standards of the past. The number of cases enrolled in our study was small, and most of them were mainly reflux cases. The patients had large left ventricle. The assessment before intervention showed that there was no risk of left ventricular outflow tract obstruction. All patients successfully received valve in valve implantation, and no such complication occurred after TMVI.

The present series is a retrospective, non-randomized study in a single center with its inherent limitations. The relatively small number of patients did not allow us to find more convincing conclusions.

TMViV procedure is currently an alternative treatment for patients with degenerated mitral bioprothesis at high or inoperable surgical risk. The advantages of this minimally invasive treatment reflect the revolutionary technological innovation of transcatheter valvular therapy. Transseptal TMViV procedure with a long pre-curved sheath avoids the blockage of the THV delivery system in the scarred and calcified atrial septum and bioprothesis ring, and facilitates the ideal coaxiality required for deployment. The application of long pre-curved sheath in TMViV procedure simplifies transseptal approach and saves procedural time.

Data and materials are available on request.

YL, MZ and CX contributed equally to this work. YL acquired and analyzed data and wrote the manuscript. MZ and CX acquired, analyzed, and interpreted data and revised the manuscript. JY designed the study and acquired, analyzed, and interpreted the data. PJ, YM, LL, WX and YYM revised the manuscript and acquired the data. All authors read and approved the final manuscript.

The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). All patients provided written informed consent and the study protocol was approved by the institutional ethics review board of Xijing Hospital (Approval Number: QX20191018-1).

Not applicable.

This study was supported by funding from Innovation Capability Support Plan of Shaanxi Province - Science and technology innovation team project (S2020TD-034), the Distinguished Young Scholar Cultivation Project of Xijing Hospital (XJZT14J03 and XJZT15ZL01), the National Key Research and Development Program of China (2020YFC2008100), and National Natural Science Foundation of China (82000373, 82100513).

The authors declare no conflict of interest.