Percutaneous edge‐to‐edge repair of severe mitral regurgitation using the MitraClip XTR versus NTR system

Abstract Background Transcatheter mitral valve repair (TMVR) has shown to improve symptoms and functional capacity in patients with severe mitral valve regurgitation (MR). Novel device developments provide the technology to treat patients with complex anatomies and large coaptation gaps. Nevertheless, the question of superiority of one device remains unanswered. We aimed to compare the MitraClip XTR and MitraClip NTR system in a real world setting. Hypothesis TMVR with the MitraClip XTR system is equally effective, but associated with a higher risk of leaflet injury. Methods We retrospectively analyzed peri‐procedural and mid‐term clinical and echocardiographic outcomes of 113 patients treated for severe MR between March 2018 and August 2019 at the University Hospital of Munich. Results Postprocedural MR reduction to ≤2+ was comparable in both groups (XTR: 96.1% vs. NTR: 97.6%, p = .38). There was a significant difference in a composite safety endpoint of periprocedural Major adverse cardiac and cerebrovascular events (MACCE) including leaflet injury between groups (XTR 14.6% vs. NTR 1.7%, 95% CI [2.7, 24.6], p = .012). After a median follow‐up of 8.5 (4.4, 14.0) months, durable reduction of MR was confirmed (XTR: in 91.9% vs. NTR: 96.8%, p = .31) and clinical and symptomatic improvement was comparable in both groups accordingly. Conclusion While efficacy was comparable in both treatment groups, patients treated with the MitraClip XTR systems showed more events of acute leaflet tear and single leaflet device attachment (SLDA). A detailed echocardiographic assessment should be done to identify risk candidates for acute leaflet injury.


| INTRODUCTION
Heart failure (HF) and related symptoms often originate from severe MR. Being the second most frequent heart valve disease in our society, MR represents an important health challenge. 1,2 It is acknowledged that two different entities of MR should be distinguished: Primary MR (degenerative) and secondary (functional) MR. 3 Given these different etiologies, a precise characterization of the disease is mandatory to decide on an adequate treatment approach. 4 Surgical mitral valve repair remains the gold-standard treatment for patients with primary MR and acceptable operative risk. [5][6][7] For patients with a highly elevated perioperative risk of mortality the MitraClip system (Abbott Vascular, Abbott Park, Illinois) for transcatheter mitral valve repair (TMVR) has emerged as an alternative treatment approach. 8,9 Surgical results frequently show suboptimal results with recurrence of MR after surgical mitral valve repair for secondary MR. 10 Therefore, a large proportion of patients with severe secondary MR are currently treated by edge-to-edge-repair. Patients with secondary MR seem to benefit from TMVR in terms of mortality and reduction of HF hospitalizations. 8,11,12 Despite the fact that TMVR showed an effective and durable reduction of MR severity with concomitant symptomatic improvement, the presence of complex anatomic settings including patients with large flails and significant coaptation gaps or patients with significant annulus dilatation and restrictive leaflets complicate leaflet grasping.
The introduction of the new generation MitraClip XTR system with 3 mm longer clip arms enables the treatment of many of these anatomically challenging cases. 13 Moreover, the availability of the MitraClip XTR system might improve the annuloplasty effect of edgeto-edge treatment and might reduce the need of multiple clip interventions by grasping a larger proportion of the mitral leaflets.
However, some authors hypothesized that these adjustments result in increased tension on the leaflets and therefore elevated risk of acute leaflet injury. [13][14][15]  All patients showed heart-failure related symptoms (NYHA II-IV) despite optimal medical therapy. An interdisciplinary heart team consensus was obtained before TMVR in order to evaluate the best treatment option for each individual.

| Echocardiography and procedural techniques
All echocardiographies were performed and analyzed by experienced physicians. Baseline and follow-up MR severity was assessed according to current recommendations of the American Society of Echocardiography. 16 Right ventricular parameters were assessed in an apical four-chamber view. [17][18][19] The TMVR procedures were performed under general anesthesia with two-and three-dimensional transesophageal echocardiography as well as fluoroscopic guidance as previously described. 20 The decision of using either the MitraClip XTR or the MitraClip NTR system was up to the preference of the interventional cardiologist. After TMVR, routine clinical follow-up was assessed at 30 days, 3, 6, and 12 months. Last available follow-up was used to analyze mid-term follow-up. Survival information was collected via medical records, telephone calls and the local residents' registration office.     Figure S1).

| DISCUSSION
This study systematically analyses and compares the efficacy and safety of two MitraClip-devices, the MitraClip XTR and NTR system. In this study, both groups showed significant and persistent reduction of MR at follow-up assessed by echocardiographic imaging.
Acute procedural success in this study (96.7% MR ≤ II, 74.2% MR ≤ I) was similar to the results reported in MITRA-FR (76% MR ≤ I) and COAPT trial (95% ≤ II). Despite being higher than reported by registries and retrospective studies (37-43%), 12,13 the proportion of patients with multiple device implantations in this study (55%) appears Both, XTR and NTR system managed to provide mid-term reduction of heart-failure related symptoms assessed by NYHA functional class and additional echocardiographic imaging confirmed durable MR reduction. Previous in vitro and in vivo assessments of the MitraClip system and especially a recent study on the XTR system reported few incidents of leaflet injuries requiring surgical intervention. 13,25,26 These few events often led to SLDA. 14 Limitations are the retrospective nature of this study leading to imbalanced baseline characteristics, low patient number as well as the incomplete follow-up. Furthermore, there was no independent echo core lab analysis. However, to the best of our knowledge, this is the first study comparing different device sizes for edge-to-edge mitral valve therapy. Further multicenter studies are on the way to define the optimal device selection for TMVR. In this context the recently introduced PASCAL system (Edwards Lifesciences, Irvine, CA) as well as the next generation of MitraClips, that have the capability to perform independent grasping, need to be taken in consideration. This study highlights the necessity of a careful and individual patient selection by an interdisciplinary heart team to assure an optimal treatment approach.

| CONCLUSION
TMVR with both, MitraClip XTR and MitraClip NTR, appears to be effective and durable. Moreover, TMVR reduces HF related symptoms and improves functional capacity. In a real-world setting, the MitraClip XTR system appears to have higher rates of device-associated complications than the NTR system. The increased amount of tissue grasping by the XTR system may increase the risk of acute leaflet injury. Therefore, the MitraClip XTR system should primarily be used in selected patients with complex anatomies.

ACKNOWLEDGMENT
Open access funding enabled and organized by Projekt DEAL.