More to Come

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In this issue of JACC: Asia, Zhong et al¹ report the 2-year pivotal trial outcomes of the Neonova transcatheter edge-to-edge repair (TEER) system (Hangzhou Duanyou Medical Technology) in 123 high-risk Chinese patients with symptomatic moderate-to-severe or severe primary mitral regurgitation (MR) enrolled across 23 centers. The principal contribution of this work is its demonstration of not only the comparable procedural outcomes of a newcomer TEER device but also the durable efficacy of TEER through 2 years in an Asian patient population.

Unmet Needs for Mitral Regurgitation Treatment in the Asia-Pacific Region

MR is the most prevalent valvular heart disease worldwide, and its disease burden continues to climb as populations age. The Asia-Pacific (APAC) region is now catching up rapidly. Single-center Chinese data suggest that as many as 10 million patients may carry severe MR, and similar trajectories have been observed in Japan and Korea as life expectancy lengthens and echocardiographic surveillance broadens.

Despite this recognition, intervention rates for MR remain suboptimal, particularly in older patients, owing to elevated operative risk and the presence of multiple comorbidities. Although TEER has become the standard of care for high-risk or inoperable patients, access remains limited by regional disparities in health care infrastructure and reimbursement. Consequently, the disease burden of MR among untreated patients appears more pronounced in the APAC region than in Western countries.

Two decades after the first MitraClip (Abbott) implant, and following pivotal evidence from the 2 globally established devices—MitraClip and PASCAL Precision (Edwards)—in the EVEREST II, COAPT, EXPAND G4, and CLASP IID trials,^2,3 TEER now carries a higher level of recommendation in the 2025 European Society of Cardiology/European Association for Cardio-Thoracic Surgery valvular heart disease guidelines⁴ for selected patients with both primary (class IIa) and secondary (class I) MR.

Even though the guidelines endorse TEER as a therapeutic concept rather than a device-specific recommendation, most clinical trials—particularly randomized controlled studies—have used a particular device platform. Careful evaluation of procedural performance across different devices is therefore an important issue as TEER is expanded into broader regions to alleviate the MR disease burden.

Although the present study is a single-arm, performance-goal trial, the authors demonstrated an immediate procedural success rate of 98.4%, a 1-year event-free survival of 92.7% (well above the prespecified 60% performance goal), and sustained efficacy at 2 years, with 95.4% of patients maintaining MR ≤ 2+ and an all-cause mortality of only 4.1%. Reverse left ventricular remodeling and durable NYHA functional class improvement further reinforce the clinical implications of the Neonova TEER system.

Anatomical Considerations in the Asia-Pacific Population and the Case for Dedicated TEER Design

Asian patients, on average, have smaller left atrial dimensions, smaller mitral annular dimensions, and smaller mitral valve area than Western populations. These anatomical differences directly contribute to potential procedural challenges, including inadequate trans-septal height that leads to aortic hugging along the device trajectory, and inadequate residual mitral valve area after placement of multiple clips. Moreover, Asian patients tend to be older at presentation, with a heavier burden of mitral annular calcification, a higher proportion of fragile or thinned leaflets after years of unrepaired prolapse, and an increasing proportion of atrial secondary MR driven by long-standing atrial fibrillation. Collectively, these features increase the risk of single-leaflet device attachment, leaflet tear, inadequate MR reduction, elevated transmitral pressure gradient, and impaired procedural durability following the index procedure.

Each of the contemporary platforms answers some of these challenges. MitraClip's² evolution through the G4 generation introduced 4 clip sizes (longer vs standard arm length and wider vs standard width), independent gripper actuation, and continuous left atrial pressure monitoring, all of which are refinements that are particularly important for tailoring device selection to individual anatomical considerations. Beyond independent grasping, PASCAL Precision³ addresses the gap-and-fill problem by deploying broad nitinol paddles around a central spacer that mechanically occupies the regurgitant orifice and redistributes leaflet stress. By this special design, the risk of leaflet injury could be minimized. DragonFly-M⁵ takes the spacer concept further with a compressible nitinol filler that distends laterally on closure and offers 270° arm reversion to facilitate atraumatic retrieval. The Neonova system¹ represents yet another design philosophy: a 10-mm linear clip with an automatic elastic clamping mechanism and a deliberately shallow (approximately 2-3 mm) left ventricular intrusion depth, intended to minimize subvalvular interaction, chordal entanglement, and induced mitral stenosis. The similarities and differences across these 4 TEER devices are summarized in Figure 1. Whether any of these design choices translates into superior clinical outcomes in a head-to-head comparison remains unanswered. What can be learned from each unique design is that every iteration is dedicated to addressing a clinically relevant and as-yet unresolved problem.

Figure 1.

Comparison of Currently Available Transcatheter Mitral Edge-to-Edge Repair Devices

The figure summarizes regulatory status, available models, key device-design parameters (clip width, graspable length, independent leaflet grasping, and central spacer), major trial evidence, and 1-year clinical outcomes (procedural success, residual MR ≤ 2+, all-cause mortality, leaflet adverse events) for MitraClip G4/G5 (Abbott),² PASCAL Precision (Edwards Lifesciences),³ DragonFly-M (Valgen Medtech),⁵ and the Neonova system (Hangzhou Duanyou Medical Technology).¹ The Neonova leaflet adverse event represents a single anterior leaflet clip dislodgement during second-clip implantation in 1 of 123 patients, an acute intraprocedural event rather than single leaflet device attachment as conventionally defined (≥30 days).

Morikawa et al⁶ recently investigated procedural differences in the EXPAND G4 study by comparing the Japanese and overall cohorts. Not surprisingly, despite the smaller cardiac dimensions and mitral valve areas of Asian patients, a 100% implant rate was achieved with the latest G4 system. Wider clips were used most often, with the XTW used in 29% and the NTW in 39% of subjects. Similarly, a wider version of the TMrCLAMP was used most commonly (62%) in the present Neonova 2-year study. When additional clips were required, the smaller TMrCLAMP-S was applied in up to 82% of cases. With regard to one of the Achilles’ heels of the TEER procedure, leaflet injury, both studies demonstrated comparable rates of approximately 1% in the EXPAND G4 Japan cohort and 0.8% in the Neonova study. Interestingly, the mean transmitral pressure gradient appeared higher in the EXPAND G4 Japan cohort compared with the Neonova study (2.9 mm Hg vs 2.2 mm Hg). This finding may reflect a double-edged consequence of the absence of a central spacer in the MitraClip design: greater leaflet tension on the one hand, but more pronounced annular reduction on the other.

Future Directions and Remaining Challenges

The 2-year Neonova trial demonstrates the feasibility and safety of this novel device in a carefully selected primary-MR cohort with anatomically favorable lesions concentrated in A2/P2 (60% central pathology); 60% of patients required only a single clip. Whether the favorable signal extends to secondary MR, particularly atrial secondary MR, as well as commissural lesions or calcified annuli, remains unknown. Head-to-head randomized studies comparing market-leading devices within the APAC region will ultimately be required, and the field would benefit from building evidence collaboratively. Studies exploring issues such as endothelialization, mechanical stress distribution, or preprocedural prediction of clip number and size using artificial intelligence–based software across different TEER platforms are likewise promising and of clinical value. Ultimately, integration of a multidisciplinary heart-team approach in treating patients with severe MR remains the cornerstone of delivering high-quality transcatheter valvular intervention.

Funding Support and Author Disclosures

Drs Lee and Sung are the proctors of Abbott and Edwards. Dr Chang has reported that he has no relationships relevant to the contents of this paper to disclose.