Abstract
The use of transcatheter edge-to-edge mitral valve repair (TEER) in symptomatic patients with severe mitral regurgitation (MR) has dramatically increased over the last few years. Current guidelines consider TEER as a reasonable option in symptomatic patients with primary or chronic secondary severe MR with high or prohibitive surgical risk and favorable anatomy. However, several anatomical and morphological mitral features have restricted the use of this mini-invasive technique in its early experience. The latest fourth generation (G4) of the MitraClip system has been recently introduced and includes the possibility of independent leaflet grasping and 4 different sizes. This technical update offers the possibility of selecting and combining multiple devices for complex mitral valve anatomies and challenging procedures, which helps expand the applications of TEER. The present review describes the potential advantages and the help of the MitraClip G4 devices to overcome various anatomic and morphologic issues in challenging cases with complex primary and secondary MR procedures.
Keywords: Echocardiography, Mitral regurgitation, Transcatheter edge-to-edge repair
Introduction
Since the first experience of transcatheter edge-to-edge mitral valve repair (TEER) in the single-arm Endovascular Valve Edge-to-Edge Repair Study (EVEREST),1 several randomized trials have clarified the role of the MitraClip (Abbott, Santa Clara, California) system in the management of primary (EVEREST II randomized trial)2 and secondary (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation [COAPT] and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation [MITRA-FR] trials)3,4 mitral regurgitation (MR). Currently, the 2020 American College of Cardiology/American Heart Association (ACC/AHA) guidelines of valvular heart disease consider TEER as a reasonable option in symptomatic patients with chronic primary or secondary severe MR with high or prohibitive surgical risk and favorable anatomical features.5 Therefore, comprehensive echocardiographic analysis remains the cornerstone for the assessment of MR in patients referred for TEER. Challenging procedures,6 such as those including commissural prolapses, Barlow’s valve disease, large gaps, prior TEER, small valve areas, organic fibro-calcific mitral disease, or complex secondary MR features are considered unfavorable. However, the latest generation of the MitraClip system, named G4 (Figure 1), facilitates TEER in complex mitral valve anatomies.
Figure 1.
Percutaneous transcatheter edge-to-edge mitral valve repair in the era of MitraClip G4. Legends: Complete arsenal and technical update of the MitraClip G4 system (top left). Choice of each device based on anatomical and morphological characteristics (top central). Spectrum of the primary MR etiologies from fibroelastic deficiency (FED) to Barlow's disease (bottom left). Spectrum of the secondary MR etiologies (bottom central). Key points of TEER with the MitraClip G4 system (right column).
Abbreviations: FED, fibroelastic deficiency; FMR, functional mitral regurgitation; TEE, transesophageal echocardiography; TEER, transcatheter edge-to-edge repair.
This article illustrates, by showing cases of challenging MR, the new frontiers of TEER and the potential advantages of the MitraClip G4 system.
Technical Advances of the G4 MitraClip System (Figure 1)
The G4 MitraClip system succeeds the previous ones (Classic, NT, NTR, XTR) and offers 4 different clip sizes: the NT and XT (similar in sizes to NTR and XTR) and the NTW and XTW, which have 50% wider arms. The previous generations were limited in the leaflet tissue insertion in certain anatomies (wide coaptation gaps, large redundant tissue, large flail gap), while the new technical iteration may offer a 50% wider insertion in the grasping area. This expanded portfolio of clips gives physicians the ability to choose a clip size or combination of clips based on each patient’s mitral valve anatomy. Moreover, the 2 graspers on the clip arms of the MitraClip NTR/XTR did not move independently, while the G4 clips are capable of grasping the anterior and posterior mitral leaflets separately, which is a significant benefit in different challenging anatomies (i.e., large flail gap, functional MR with large coaptation depth, and very restricted posterior leaflet). Finally, the delivery system is improved in order to provide more precise and controlled steering and offers the ability to continuously monitor left atrial pressure for real-time hemodynamic monitoring during the procedure.
Wide Jet of MR and Risk of Iatrogenic Mitral Stenosis: NTW as a Solution
Several anatomical or technical issues, such as preintervention small valve area (<4cm2), significant mitral annular calcification, short and restricted leaflets, and redo-TEER, are at high risk of iatrogenic stenosis when considering TEER, especially in cases with wide or adjacent jet(s) suggesting the need for multi-clip implantation. Moreover, primary MR related to leaflet thickening and leaflet/subvalvular fibro-calcific remodeling remains a scenario where TEER has traditionally obtained suboptimal MR reduction. Consequently, this option is not always considered in the presence of any of these issues. However, as shown in Figure 2, in the setting of fibro-calcific valve remodeling, small valve area, and mitral annular calcification, the new NTW clip allows capture of a wider area of the A2-P2 segments compared to the narrower NT clip while limiting the risk for significant stenosis associated with the use of multiple clips or devices with longer arms.
Figure 2.
Complex mixed mitral regurgitation with small valve surface area. (a) Severe MR with complex anatomic valve features. Mitral leaflets were thickened and moderately hyperechogenic, there was fibro-calcific remodeling of the subvalvular apparatus, and the mitral annulus was moderately calcified (Supplemental Video 3 and 4). The 3D diastolic mitral valve area was small (3.2 cm2) and the transvalvular mean gradient mildly increased (3 mmHg). The MR jet had a wide origin at the A2-P2 level. The MR mechanism was mixed including the presence of a short and restricted posterior leaflet (9 mm in length) with anterior leaflet pseudo-prolapse. (b) An NTW clip was implanted in the central A2-P2 area with a stable grasp of both leaflets (green star) and residual trace-to-mild MR (Supplemental Video 5). Normalization of the pulmonary veins flow was observed. The postprocedural mean gradient was deemed acceptable (5 mmHg) in this particular case.
Abbreviations: LVOT, left ventricular outflow tract; MR, mitral regurgitation; PVF, pulmonary vein flow; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
Redo-TEER is another scenario where iatrogenic residual mitral stenosis is concerning. Beyond the risk of clip detachment, progression of the mitral disease may lead to recurrent MR despite a prior successful TEER, and this issue is frequently at risk of stenosis by adding clips in a redo-TEER procedure. However, considering the residual length of the leaflets, the size of the jet(s), as well as their relation with the tissue bridge formed in the first procedure, the MitraClip G4 system offers new tailored technical solutions. Indeed, the NTW device may be considered advantageous in redo-TEER depending on the mechanism of the recurrent jet(s), residual 3-dimensional diastolic area of each orifice, and residual mean gradient. In Figure 3, we illustrate a case of recurrent severe secondary MR lateral to a prior NTR device successfully implanted 3 years before. Considering the limited valve area remaining after the first procedure, an NT clip was chosen as the larger XT clip may lead to higher residual gradients. The need to treat and secure the whole A2-P2 area to prevent future MR recurrence favored the selection of the wider NTW devices over the NT.
Figure 3.
Redo transcatheter edge-to-edge mitral valve repair of recurrent secondary mitral regurgitation. (a) Posterior leaflet tethering and anterior pseudo-prolapse causing severe MR before the first TEER procedure. One NTR clip implantation with only mild residual MR (Supplemental Video 6). (b) Three years later, severe MR was observed laterally to the previous clip due to increased posterior tethering with anterior pseudo-prolapse (Supplemental Video 7), without clip detachment (white asterisk). The medial and lateral orifices were 0.5 cm2 and 2.4 cm2, respectively. (c) A first NTW was implanted laterally (light green star). Subsequently, 3 residual jets of MR were seen: one trace-to-mild jet medial to the prior clip, a second trace-to-mild jet through the NTW clip, and a mild-to-moderate jet lateral to the NTW clip. The mean gradient was 2 mmHg at that point. (d) Another lateral NTW was implanted (green star). Finally, only the 2 previously described trace-to-mild jets persisted (Supplemental Video 8), the mean gradient was 3 mmHg, and PVF improved.
Abbreviations: LVOT, left ventricular outflow tract; MR, mitral regurgitation; PVF, pulmonary vein flow; TEER, transcatheter edge-to-edge repair.
The Longer and Wider Clip XTW in Complex Primary Mitral Diseases
Complex primary MR, including commissural lesions and Barlow’s valve disease, are considered more difficult to treat with TEER compared to central location or less extensive organic pathologies.
In regard to commissural lesions, TEER is limited by several factors: i. more challenging steering, navigation, and positioning of the delivery system; ii. difficulty in obtaining an optimal perpendicular approach to the valvular plane from the interatrial septum; iii. the risk of clip entrapment in the subvalvular apparatus, especially at the medial scallops; and iv. no guarantee of getting optimal echocardiographic images for procedural guidance. Although there is still a risk of entrapment in the subvalvular apparatus, the improvement in the precision of the steering catheter along with the new grasping technology (simultaneous or independent) offered by the MitraClip G4 system could facilitate the treatment of these eccentric lesions. Indeed, although commissural disease is preferably addressed with shorter-arm devices (NT or NTW), challenging cases such as those with large flails may be addressed with the devices with longer arms (Figure 4). Independent grasping and the use of devices with wider arms may reduce the number of maneuvers per procedure by decreasing the number of grasping attempts and clips. The simultaneous bi-plane tool during the echocardiographic guidance is paramount to obtain the optimal orthogonal left ventriclar outflow tract view to guide the procedure.
Figure 4.
Large medial commissural prolapse with eccentric severe mitral regurgitation. (a) Severe primary MR with a large medial commissural flail and a small chordae rupture causing a very eccentric jet (Supplemental Video 9). (b) Despite the commissural location, an XTW device was used because of the large flail (flail width = 16 mm, flail gap = 11 mm). The clip was implanted at the A3-P3 level (green star), and mild lateral MR remained (dotted blue line). No residual prolapse was observed (Supplemental Video 10). The mean gradient was measured at 2 mmHg, and the pulmonary veins flow was normalized.
Abbreviations: LVOT, left ventricular outflow tract; MR, mitral regurgitation; PVF, pulmonary vein flow.
The complex anatomy of Barlow’s valve disease implies the following features: i. multi-segment involvement and frequently multiples jets; ii. dilatation and dynamic systolic distortion of the mitral annulus; and iii. redundant valvular tissue and excess leaflet billowing motion. These patients were excluded from the initial TEER studies,1,2 and the few data reported by experienced teams suggest the need for more devices, longer procedural times, and a higher risk of recurrent MR and hospitalization for heart failure at 3 years in this setting.7 However, the use of the XTW device is a new weapon aiming to improve the restoration of leaflet coaptation in these valves with diffuse redundant tissue and multi-scallop prolapse (Figure 5). Aside from the procedural MR reduction, a multi-clip strategy using XTW clips is required in Barlow’s disease in order to stabilize the valve repair and to prevent future recurrences of leaflet prolapse (Figure 5).
Figure 5.
MitraClip G4 in Barlow’s mitral valve disease. (a) Classical Barlow’s disease associating bileaflet prolapse and mitral annular disjunction (Supplemental Video 11 and 12). Severe MR with 2 jets (Supplemental Video 13): the main one at the lateral A2-P2 (dotted red line), and the second one at the medial A2-P2. Mitral valve area and posterior leaflet length were 6 cm2 and 12 mm, respectively. (b) A first XTW clip was implanted at the lateral A2-P2 (main jet) (light green star), leaving trace-to-mild MR lateral to the clip. However, 2 other jets were observed medially. At that point, the mean gradient was measured at 1 mmHg. (c) A second XTW clip was implanted medially to the first one (green star). Finally, only the trace-to-mild jet lateral to the first clip and a trace jet medial to the second clip were observed, with mild overall MR (Supplemental Video 14). The remaining area and mean gradient were 2.1 cm2 (lateral = 1.2 cm2, medial = 0.9 cm2) and 2 mmHg, respectively.
Abbreviations: LVOT, left ventricular outflow tract; MR, mitral regurgitation; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
Multi-Clip Strategy and Combination of G4 Devices in Complex Secondary MR
Two features are essential when considering TEER in severe secondary MR; i. the hemodynamic left ventricle (LV) conditions; and ii. the mitral anatomic accessibility.
On the one hand, MR severity and LV dimensions and function should be in line with disproportionate rather than proportionate MR. Indeed, MITRA-FR-like patients3 with typically less severe MR but very severe LV dilatation did not benefit from TEER; while COAPT-like patients4 with more severe MR but less advanced LV disease had better outcomes with TEER compared to optimal guideline-directed medical therapy. On the other hand, all patients should have a favorable mitral anatomy that anticipates satisfactory results post-TEER, that is, significant reduction of MR without significant mitral stenosis.
However, the anatomic substrate in secondary MR depends on the different mechanisms involved in the balance between closing and tethering forces. For instance, the mechanism may rely either on asymmetric tethering of one single leaflet or on well-balanced tenting of both leaflets. These mechanisms may be combined in a single valve and lead to several separate jets (Figure 6). In other cases, the tethering and closure forces are imbalanced in a large part of the coaptation area, hence requiring large edge-to-edge repair with multiple clips. When this wide “Alfieri stitch” is performed, each implanted clip should be adapted to the leaflet’s length at its grasping zone (Figure 7). Thus, the use and combination of the whole spectrum of G4 devices help to overcome various anatomic issues in complex secondary MR, by limiting the strain on the leaflets and thus the stenotic phenomenon, and also by optimizing the reduction of the jet(s). The possibility to use the independent grasping is also a valuable tool for improving the restoration of the leaflet coaptation when marked posterior tethering and/or wide gaps are present.
Figure 6.
Triple orifice strategy in asymmetric secondary mitral regurgitation. (a) Ischemic MR with 2 different jets: a severe medial jet [posterior tethering and anterior pseudo-prolapse (red dotted-line, box and arrow)] and a mild-to-moderate lateral jet [well-balanced bileaflet tenting (blue dotted-line, box and arrow)]. Both jets were separated, on both sides of A2-P2 (Supplemental Video 15). (b) First, an XTW was implanted in the main (medial) jet (light green star). Significant MR reduction with only trace MR medial to the clip and the previously mild-to-moderate lateral jet (blue dotted line). The medial orifice was 1 cm2, and it was decided to treat the lateral jet. (c) Given the relatively small lateral orifice (2 cm2) and the mechanism of the lateral jet, an NT device was implanted (green star). The result was a triple-orifice repair (Supplemental Video 16, medial = 1 cm2, central = 0.3 cm2, lateral = 0.8 cm2) with a mean gradient of 3 mmHg, and trace-to-mild MR. The PVF normalized.
Abbreviations: LVOT, left ventricular outflow tract; MR, mitral regurgitation; PVF, pulmonary vein flow.
Figure 7.
Concomitant use of different MitraClip G4 devices in a wide secondary mitral regurgitation. (a) Severe ischemic MR with 3 jets related to diffuse A2-P2 tenting, severe tethering of posterior leaflet, and anterior pseudo-prolapse (Supplemental Video 17). (b) An NTW clip was implanted in the medial A2-P2 (light green star). As expected, the severe central jet persisted (red dotted line). (c) Given the central location of the remaining jet with a posterior leaflet ≥9 mm, an XTW was chosen (green star). After this second implantation, a moderate lateral jet (diffuse bileaflet tenting) was confirmed and the mean gradient was 4 mmHg. (d) To optimize the coaptation while avoiding mitral stenosis, a second NTW (third clip) was implanted laterally (dark green star). After the third clip, spontaneous echo contrast (“smoke sign”) was observed, which is related to the dramatic decrease in MR. Final result: trace MR valve area of 1.6 cm2 (Supplemental Video 18, lateral = 0.7 cm2, medial = 0.9 cm2) and mean gradient of 5 mmHg.
Abbreviations: LVOT, left ventricular outflow tract; MR, mitral regurgitation; PVF, pulmonary vein flow.
Conclusion
In the era of the latest MitraClip G4 system, the technical innovations and the wide spectrum of sizes along with the growing experience of the Heart Valve Team offer the possibility to select and combine multiple devices for complex mitral valve anatomies, therefore expanding the potential applications of TEER. The preprocedural planning and a comprehensive step-by-step and clip-by-clip intraprocedural guidance remain paramount to ensure optimal results in challenging anatomies.
The advancements of the MitraClip system associated with the emergence of new TEER devices (such as PASCAL devices) and the emulation around transcatheter mitral valve replacement, make it possible to consider treating percutaneously an increasingly large population of patients. Achieving optimal results requires deep involvement and continuous investment from the Heart Valve Teams in this field in order to maintain optimal expertise.
Funding
The authors have no funding to report.
Disclosure Statement
Dr I. Silva is supported by a grant from the Martin Escudero Foundation (Madrid, Spain). Vassili Panagides has received institutional research grants from Medtronic, Boston Scientific and Microport. Dr J. Ternacle is a proctor for Abbott. Dr Clavel has core laboratory contracts with Edwards Lifesciences, for which she receives no direct compensation and has received research grants from Medtronic. P Pibarot received funding from Edwards Lifesciences, Medtronic, Pi-Cardia, and Phoenix Cardiac Devices for echocardiography core laboratory analyses in the field of transcatheter valve therapies with no personal compensation.
Review Statement
Given his role as an editor, Philippe Pibarot, DVM, PhD, had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Neal S. Kleiman, MD.
Guest Editor: Neal S. Kleiman, MD
Footnotes
Supplemental data for this article can be accessed on the publisher’s website.
Supplementary Material
Transesophageal echocardiography – 3D view of the clip with independent movement of the posterior gripper.
Transesophageal echocardiography – X-plan view of an independent grasping of the posterior leaflet.
Transthoracic echocardiography – Parasternal short axis view on the mitral valve with moderate mitral annular calcification.
Transesophageal echocardiography – Bicommissural view with color doppler showing severe mitral regurgitation.
Transthoracic echocardiography – Apical 2 chambers view with color Doppler after the clip implantation.
Transesophageal echocardiography – Bicommissural view with color Doppler after the first transcatheter edge-to-edge procedure (one clip).
Transesophageal echocardiography – New posterior leaflet tethering with anterior leaflet pseudo-prolapse and significant mitral regurgitation 3 years later.
Transesophageal echocardiography – Bicommissural view with color Doppler after the second transcatheter edge-to-edge procedure (2 new clips).
Transthoracic echocardiography – Apical 2 chambers view without color Doppler with zoom on the medial large prolapse.
Transthoracic echocardiography – Apical 2 chambers view without color Doppler after the clip implantation.
Transthoracic echocardiography – Parasternal long axis view showing Barlow’s mitral valve disease with bileaflet prolapse and systolic annular disjunction.
Transesophageal echocardiography – 3D view showing Barlow’s mitral valve disease with bileaflet prolapse and systolic annular disjunction.
Transthoracic echocardiography – Apical 2 chambers view with color Doppler showing severe mitral regurgitation.
Transthoracic echocardiography – Apical 2 chambers view with color Doppler showing trace-to-mild mitral regurgitation after 2 clips implantation.
Transesophageal echocardiography – 3D view with color Doppler showing 2 jets of mitral regurgitation (severe mitral valve regurgitation).
Transesophageal echocardiography – 3D view of the mitral with triple diastolic orifices after 2 clips implantation.
Transesophageal echocardiography – 3D view showing diffuse A2-P2 tenting, severe central tethering of the posterior leaflet, and anterior pseudo-prolapse.
Transesophageal echocardiography – 3D view of the mitral after 3 clips implantation.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Transesophageal echocardiography – 3D view of the clip with independent movement of the posterior gripper.
Transesophageal echocardiography – X-plan view of an independent grasping of the posterior leaflet.
Transthoracic echocardiography – Parasternal short axis view on the mitral valve with moderate mitral annular calcification.
Transesophageal echocardiography – Bicommissural view with color doppler showing severe mitral regurgitation.
Transthoracic echocardiography – Apical 2 chambers view with color Doppler after the clip implantation.
Transesophageal echocardiography – Bicommissural view with color Doppler after the first transcatheter edge-to-edge procedure (one clip).
Transesophageal echocardiography – New posterior leaflet tethering with anterior leaflet pseudo-prolapse and significant mitral regurgitation 3 years later.
Transesophageal echocardiography – Bicommissural view with color Doppler after the second transcatheter edge-to-edge procedure (2 new clips).
Transthoracic echocardiography – Apical 2 chambers view without color Doppler with zoom on the medial large prolapse.
Transthoracic echocardiography – Apical 2 chambers view without color Doppler after the clip implantation.
Transthoracic echocardiography – Parasternal long axis view showing Barlow’s mitral valve disease with bileaflet prolapse and systolic annular disjunction.
Transesophageal echocardiography – 3D view showing Barlow’s mitral valve disease with bileaflet prolapse and systolic annular disjunction.
Transthoracic echocardiography – Apical 2 chambers view with color Doppler showing severe mitral regurgitation.
Transthoracic echocardiography – Apical 2 chambers view with color Doppler showing trace-to-mild mitral regurgitation after 2 clips implantation.
Transesophageal echocardiography – 3D view with color Doppler showing 2 jets of mitral regurgitation (severe mitral valve regurgitation).
Transesophageal echocardiography – 3D view of the mitral with triple diastolic orifices after 2 clips implantation.
Transesophageal echocardiography – 3D view showing diffuse A2-P2 tenting, severe central tethering of the posterior leaflet, and anterior pseudo-prolapse.
Transesophageal echocardiography – 3D view of the mitral after 3 clips implantation.