Mitral valve disease is the most prevalent form of valvular disease, affecting 10% of patients over the age of 75 years (1). Bioprosthetic valves have become more common in the treatment of mitral valve disease. Consequently, structural valve deterioration is the most prevalent problem and reoperation is required in as many as 35% of patients within the first 10 years after mitral valve surgery (2). Redo mitral valve surgery is associated with high perioperative morbidity and mortality (3, 4) due to repeat sternotomy, cardiopulmonary bypass, the older age of patients, and severe comorbidities. Nevertheless, transcatheter mitral valve-in-valve (TMVIV) implantation has been developed as a feasible and safe treatment for high-risk and inoperable patients (5–7). In TMVIV, an oversizing strategy is preferred due to the risk of embolization resulting from high gradient pressure between the ventricle and atrium. However, excessive oversizing may be unfavorable, as it leads to under expansion of the transcatheter heart valve (THV) device, which increases the risk of leaflet pin-wheeling, device thrombosis, and decreased durability (8).

The J-Valve System (JieCheng Medical Technology Corporation Ltd., Suzhou, China) is a low-profile, self-expanding THV (Figures 1A,B). Excellent short-term outcomes, such as 4.7% all-cause mortality, 2% new permanent pacemaker implantation, 0% coronary artery obstruction, and 0% myocardial infarction at the 1-year follow-up, have demonstrated the efficacy and safety of the J-Valve in the treatment of patients with aortic stenosis and/or insufficiency (9–12). While the J-Valve was originally designed to treat aortic stenosis and/or insufficiency (12), its specific self-positioning design is also favorable in TMVIV implantation. Inspired by the Sapien prosthesis (Edwards Lifesciences Incorporation, Irvine, California, USA) to initially perform transapical mitral valve-in-valve by crimping the valve into the delivery catheter in the opposite direction, we attempted to treat high-risk or inoperable patients with degenerative mitral bioprostheses using the J-Valve System.

This study demonstrates the feasibility of the J-Valve for use in TMVIV in patients with degenerated mitral bioprostheses to treat mitral regurgitation, mitral stenosis, or a combination of the two. The MVARC-defined technical success rate with the J-Valve was 96.2%, which is comparable to that reported in the TMVIV multicenter registry study of 94.6% (7). TMVIV using the J-Valve was also associated with good short-term outcomes. This study showed 3.8% all-cause mortality at the 30-day follow-up and 16.0% at 1-year follow-up, whereas the 30-day and 1-year all-cause mortality in the Transcatheter Valve Therapy Registry (5) were 5.4 and 16.7%, respectively. The stroke rates were 0 and 12.0% at the 30-day and 1-year follow-ups, respectively, and 1.1 and 3.3% in the previous report (5). No device-related death, device embolization, or LVOT obstruction occurred. All the patients experienced a clinically important improvement in heart failure symptoms during follow-up. The hemodynamic performance was acceptable after the TMVIV procedure with the J-Valve. The mean MVG was 5.8 mm Hg and 6.4 mm Hg at the 30-day and 1-year follow-ups, respectively, which is comparable to those in the TMVIV multicenter registry study of 7.3 mm Hg and 7.0 mm Hg, respectively (7). No patient had more than mild mitral regurgitation or required valve-related reintervention after TMVIV during follow-up.

In the TAVR procedure, the J-Valve System can fix the native aortic valves in the middle of its locators and frame, which can offer robust support to reduce the risk of left ventricular dislocation (10, 11). In addition, the J-Valve is the low-profile THV that is suitable for TMVIV implantation. In in vitro test, the locators could be deployed in the “sinuses” of the SHVs (Figure 3). The construction of the J-Valve with the locators could also reduce the risk of embolization, as it works in the aortic position. Inspired by these features, we initially applied the J-Valve in the TMVIV procedure as a second choice in the treatment of high-risk surgical patients with mitral bioprosthetic deterioration.

Currently, the Sapien 3 (Edwards Lifesciences Incorporation, Irvine, California, USA) is used as the standard THV for most TMVIV interventions with good short-term outcomes (7, 15). To avoid embolization, it is important to avoid parallel deployment and achieve conical deployment with an oversizing strategy (8). Unlike with the Sapien XT (Edwards Lifesciences Incorporation, Irvine, California, USA) (16), interventionists tend to select the proper Sapien 3 size selection following a slightly oversizing principle for its favorable extensibility. In the early exploration of the J-Valve system, interventionalists also performed the TMVIV procedure using an oversizing strategy that would lead to under expansion of the leaflets (Figure 5). Nevertheless, the J-Valve can be sized according to the ID of the SHV for the robust fixation of locators to reduce the risk of dislocation (Figures 6A–P). In this analysis cohort, 34.6% of patients underwent TMVIV according to the principle of “true sizing.” Notably, 13 of the deteriorated SHVs in these patients were the Hancock II (Medtronic, Minneapolis, Minnesota, USA) whose label sizes of 29, 27, and 25 mm were corresponded to IDs of 24, 22, and 20.5 mm, respectively. Therefore, “true sizing” was unlikely to occur in patients with a Hancock II (Table 2). When the SHVs of the Hancock II were excluded, nine of 13 patients (69.2%) underwent TMVIV with the principle of “true sizing” (Table 2). No patient had experienced valve dislocation by the last follow-up. Therefore, TMVIV with a J-Valve system of “true sizing” may be feasible and would theoretically result in fully unfolded leaflets (Figures 6A,I,M), a lower gradient, and longer durability.

Left ventricular outflow tract obstruction is a potentially disastrous complication of TMVIV and predicting this condition still poses a challenge. The expected neo-LVOT area measured from cardiac CT is used to assess the risk of LVOT obstruction caused by transcatheter mitral valve replacement (17, 18). All the patients in this study underwent multislice CT to evaluate the risk of LVOT obstruction and no patient in this study had a predicted neo-LVOT area <200 mm² (Figures 2A,B).

At the time of surgical implantation, most surgeons prefer orienting SHVs such that two posts straddle the LVOT rather than the posterior annulus so that there is no strut occluding the LVOT. However, the SHV orientation does not influence the risk of LVOT obstruction during a TMVIV procedure with Sapien valves because the height of the skirt is lower than the leaflets of the SHV (19). In contrast, the frame and skirt of the J-Valve are wavelike (Figure 1A) and with the fixation of the locators, the struts of the J-Valve usually overlap the struts of the SHV (Figures 6B,F,J,N). This characteristic would not increase the risk of LVOT obstruction. However, the length of the bovine pericardial leaflets of the Perimount (SHV; Edwards Lifesciences Incorporation, Irvine, California, USA) is longer than J-Valve's frame (Figure 6B) or the other THVs, which might increase the risk of LVOT obstruction.

Previous studies have demonstrated transfemoral MVIV to be safer than transapical implantation with fewer complications and lower mortality (7, 15). The J-Valve system was primarily designed for transapical TAVR and the transfemoral J-Valve system is still under clinical trials. We had to perform the procedure via transapical access rather than transvenous access. Similar to transapical aortic valve replacement, transapical TMVIV offers short and straight access to the degenerated SHV with good coaxial alignment. However, the transapical approach in this study still promoted less safe 30-day outcomes than the transfemoral approach in a large TMVIV study (7).

A previous study by Sung-Han Yoon et al. showed a high incidence of valve thrombosis after TMVIV (15). Nevertheless, anticoagulation therapy after TMVIV surgery is still controversial. Given the high proportion of atrial fibrillation (65.4%) in this cohort and the complex configuration of valve-in-valve, anticoagulation with warfarin was recommended for these patients for at least 6 months. However, two patients had a hemorrhagic stroke and one patient had an ischemic stroke during a 1-year follow-up. A retrospective review of the visit data of the three patients revealed that the two patients with hemorrhagic stroke both failed to regularly monitor prothrombin time. This may be the main reason why the stroke rate is obviously higher than that reported in other studies (7, 15) and it also suggests that anticoagulation education for the elderly should be improved.

Although TMVIV is becoming a promising therapy in high-risk patients with mitral bioprosthetic dysfunction and should be considered a therapeutic option (7), patients with small SHVs or low-risk patients may likely undergo redo surgical mitral valve replacement. This is because elevated valve gradients, the durability of the THVs, the optimal management of concomitant TR, and optimal anticoagulation strategies are still unknown and require further study (20).

In addition to the inherent bias of observational studies, the major limitation was that this study had a small sample size and short-term follow-up, as it included only 26 patients with a median follow-up time of 370 days (range, 8–762 days). Moreover, the leaflets of the surgical valves in Figure 4 did not deteriorate. Thus, these simulations could not authentically represent valve-in-valve implantation in vivo.

Transcatheter implantation of the J-Valve system within a degenerated mitral bioprosthesis via the transapical route is feasible and associated with good short-term outcomes in high-risk surgical patients. All the patients experienced improvements in heart failure after discharge. Owing to the locator units, the J-Valve system may be a good alternative to the TMVIV procedure and its use may shed light on new devices customized for valve-in-valve procedures.

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding authors.

The studies involving human participants were reviewed and approved by Ethics Committee of Zhongshan Hospital, Fudan University. The patients/participants provided their written informed consent to participate in this study.

YL, YY, WW, JC, CW, and LW contributed to the study conception and design. MY, LH, and LD performed material preparation, data collection, and analysis. YL, YY, and JC wrote the draft of the manuscript. All the authors have read and approved the final version of the manuscript.

This study was supported by the National Natural Science Foundation of China (Grant Number: 81974272) and Shanghai Engineering Technology Research Center for Cardiac Intervention (Grant Number: 19DZ2250300).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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