*2.2.3.1. Carillon®*

*2.2.1.3.4. Effect on heart remodeling: mitral annulus and left ventricle*

best timing for PMVR.

124 Interventional Cardiology

("valve-in-ring" procedure).

*2.2.2. Percutaneous chordal replacement: Neochord®*

Reverse LV remodeling is the 'holy grail' of PMVR. Reported results from surgical series of primary MR have been linked to better prognosis [61]. Echo reports from EVEREST trial have demonstrated that there is an inverse remodeling after a successful MitraClip® procedure involving both the left chambers (ventricle and atrium) [62]. Interestingly, the magnitude of the reverse remodeling is greater with greater reduction in MR and this positive effect is maintained at 5 years follow-up [28]. Similar findings were reported in the EVEREST highrisk cohort [55, 57], although, in these series, patients with LVEF below 25% and severe LV dilation (LV end-systolic diameter > 55 mm) were excluded. By contrast, real-world FMR patients treated with MitraClip® tend to exhibit poor or no remodeling at all [32]. One possible explanation for these conflicting results is that real-world patients are treated too late in the natural history of the chronic HF disease, when the LV is largely dilated and LVEF is severely depressed. These patients are less likely to show reverse remodeling and this is a hint for the

Although PMVR with MitraClip® reproduces somehow the Alfieri procedure, traction forces within MV may also favor MA remodeling. Recent studies have demonstrated that in FMR, the MA size (anteroposterior diameter), the MA area and the tenting area are significantly reduced after device implantation [63]. Furthermore, this reduction is associated with an improved functional status at 6 month after the procedure [64]. Conversely, in primary MR, MA parameters remain stable after clipping. Therefore, the potential association of an indirect annuloplasty-like effect may improve mid-term results of this therapy in patients with FMR.

Neochord® (Neochord, Minnesota, MN) are the first ePTFE chordal loops conceived to be implanted on the MV leaflets to correct flail or prolapse [65]. Colli et al. reported the results of transapical off-pump mitral valve implantation of Neochord in 62 patients with MV prolapse [66]. Thirty-day major adverse events included one acute myocardial infarction (2%) and two

Annuloplasty is the most common surgical repair performed to treat MR [47]. This technique is widely used as a stand-alone procedure to enhance MV coaptation in FMR or added to leaflet repair in degenerative MR in order to improve durability [67]. Based on prior large surgical experience, some percutaneous novel devices have tried to reproduce undersized MV annuloplasty to address dilatation of the MA. A reliable TMVA has the potential to improve outcomes in combination with edge-to-edge repair in selected patients and to increase therapeutic alternatives in patients with anatomic ineligibility for MitraClip®. As a further potential advantage, unlike the MitraClip®, this approach preserves the native valve anatomy, thus keeping the option for future valve implantation open. In fact, some of the annuloplasty rings may actually serve as a dock for the anchoring of available transcatheter aortic valves

cases of sepsis (3%). MR at 30 days was grade 1+ or 2+ in 55 patients (88.7%).

*2.2.3. Transcatheter mitral valve annuloplasty (TMVA): Carillon®, Cardioband®, Mitralign®*

The coronary sinus (CS) encircles approximately two-thirds of the MA, in close relation to the posterior and anterior MV leaflets. This was the rationale for the first catheter-based devices that aim to achieve an indirect annuloplasty through the cannulation of the CS. The Carillon® Mitral Contour System (Cardiac Dimension, Inc., Kirkland, WA, USA) obtained the CE mark in 2011. This deformable annular system is implanted in the CS and can reduce the septolateral diameter of the MA by postimplant cinching [68]. The procedure can be easily performed under fluoroscopic guidance through a jugular vein access and without general anesthesia. Nevertheless, some limitations have hampered the development of this technique. Advance imaging studies have demonstrated that the location of the CS is no coplanar to the MA, but basally displaced into the LA [69]. Moreover, potentially serious complications have also been reported, including compression of the circumflex artery or damage of the septal conduction system [70]. Finally, the lack of prior surgical background for the CS approach may be a concern as regards the long-term outcomes of this procedure.

To date, published evidence is limited to a couple observational studies. In the Titan trial, only 36 of 53 (67.9%) patients underwent permanent system implantation due to transient coronary compromise or reduction of MR < 1+ (recapture of the device was carried out in those cases) [71]. Rates of death at 1 and 12 months in this study were 1.9 and 22.6%. In the TITAN II trial, the system was successfully implanted in 30 of 36 (83.3%) patients, and 30-day and 1-year reported mortality were 2.8 and 23%, respectively. Both trials showed that device implantation was related to a significant reduction in MR, and to clinical improvement and reverse LV remodeling in patients with FMR and HF during up to 24-month follow-up. Ongoing REDUCE trial will compare the device to OMT in HF subjects with FMR, thus, providing further evidence of the potential benefits of this technology.

#### *2.2.3.2. Cardioband®*

Cardioband® (Valtech, Inc, Or Yehuda, Israel) is the transcatheter device that most closely resembles surgical direct annuloplasty technique. The system consists of a flexible annuloplasty band that is delivered from a transseptal approach and implanted onto the atrial side of the MA. This incomplete Dacron ring is attached in a supraannular position with multiple spiral anchors from commissure to commissure under transesophageal echo and fluoroscopic guidance. After implantation, the Cardioband® length can be shortened in order to improve leaflet coaptation and reduce MR.

Although flexible partial rings have failed in this sort of patients when implanted surgically [72], initial clinical experiences with Cardioband® are promising, confirming the feasibility and safety of the device implantation [73]. The CE Mark Trial has enrolled high-risk subjects with symptomatic FMR despite OMT. Early outcomes of this trial in 31 patients at 1 month showed a significant reduction in the septolateral dimension of the MA in all but two patients (36.8 ± 4.8 vs. 29 ± 5.5 mm, *p* < 0.01) and an increased leaflet coaptation surface [74]. Following Cardioband® adjustment (29 of 31 patients), MR was none or trace in 6 (21%), mild in 21 (72%) and moderate in 2 (7%) cases. Procedural mortality was zero and in-hospital mortality was 6.5% (2 of 31 patients, neither procedure nor device-related). At 30 days, 22 of the 25 patients (88%) had MR grade ≤ 2+. Following results of this trial showed persistent reduction in MR (92% MR ≤ 2+) and improvement in functional class (77% NYHA I–II) at 24-month follow up. Reported procedural success rate (reduction in at least one grade in MR at discharge) was 86%. In 2017, an RCT comparing Cardioband® versus stand-alone OMT will start recruiting in the USA.
