Transapical mitral valve repair procedures: Primetime for microinvasive mitral valve surgery

Abstract Introduction Nowadays micro‐invasive‐procedures (off‐pump, beating‐heart) for mitral valve repair (MVRe) are abruptly expanding with the potential to be adopted as a valuable alternative to surgery. In the present manuscript, the authors review the available technologies intended to treat mitral regurgitation (MR) through transapical approach, including annuloplasty and chordal‐repair options. Annuloplasty To date, Valcare Amend is the only transapical MV ring to have been implanted in patients. The device allows for stabilization of the annulus through a complete semirigid d‐shaped ring. The first‐in‐human successful procedure was performed in 2016 by our Group and subsequent clinical experience included a total of 14 implanted patients. Currently, the technology is under clinical trial evaluation to validate the efficacy and safety profile of the device. Chordal Repair Beating‐heart chordal implantation via transapical approach is a current feasible, safe and reproducible option. Neochord DS1000 is the most widely used technology in the field, with a solid procedural experience and good results in well‐selected patients. Its clinical use has been validated in Europe since 2012, while it is still under clinical investigation in the United States. Harpoon MVRe system is a novel technology, recently CE‐mark approved for clinical use. Discussion and Conclusions Transapical micro‐invasive technologies are current viable therapies to treat MR in selected patients. Although there are still several limitations that preclude an extensive use of such procedures, their results are promising in well‐selected patients. Embracing transcatheter MVRe therapies should guide the cardiac surgeon through the new revolution of micro‐invasive MV tailored repair.


| INTRODUCTION
Mitral valve (MV) regurgitation affects more than four million people in the United States (US) and Europe, with an incidence of 1%-2% of the western population. Its prevalence increases with age, affecting up to 10% of the population above 75 years. 1 According to current American and European guidelines, surgery is the gold standard therapy to treat mitral regurgitation (MR) in symptomatic patients, supporting surgical repair over replacement with extracorporeal circulation whenever possible. 2 Despite MR represents the most frequent valvular heart disease requiring surgery in the United States and the second most common in Europe, 3 up to onethird of patients with severe MR are never referred and nearly half are denied for surgery because of prohibitive risk due to age and comorbidities. 4 Moreover, by 2030, the increase of the population age will translate in an estimated increase of 50% in heart failure prevalence, resulting in a significantly higher rate of MR, especially due to functional mechanisms. 5 Therefore, new less-invasive therapies are needed to further expand the slice of population to be treated.
Recently the new concept of micro-invasive cardiac surgery has been introduced to identify a revolutionary group of procedures requiring neither cardiopulmonary bypass nor aortic cross-clamping. 6 This evolution in technologies allows for off-pump, beating heart procedures, with a very small skin incision or even totally percutaneously performed, often requiring local anesthesia only, with the contribution of multimodality imaging. 7 Transcatheter aortic valve replacement represents the clearest example of such micro-invasive procedures. In the very near future these emerging therapies will likely have a central role, especially in the high-risk patient population, in both degenerative and functional MR treatment, despite only weak recommendations are given for their use by current guidelines (COR IIb, LOE C). 2 Nowadays the interest of the cardiac surgeon community towards new micro-invasive procedures is abruptly expanding with the potential to be adopted as a valuable alternative to conventional surgery, even if, as far as mitral valve repair (MVRe) is concerned, there are still limitations that need to be overcame. Once the MV is reached by the use of transapical or transfemoral puncturing, these technologies can often perform just a single repair technique, acting on a specific component of the mitral apparatus (chordae OR leaflets OR annulus), in contrast to surgical repair, that allows for combined multi-target procedures (chordae AND leaflets AND annulus). Nevertheless, simultaneous implantation of different devices has already been reported in well-selected patients, even if more data are needed to validate the practice. 8 In the present manuscript, we aim to review currently available technologies intended to treat MR through a micro-invasive transapical approach, including annuloplasty and chordal repair options (Table 1).

| Annuloplasty
Transcatheter ring implantation technologies can be divided into direct and indirect annuloplasty, depending on the type of interaction with the native annulus. 9 Indirect annuloplasty devices are typically implanted into the coronary sinus and potentially are simpler for deployment, but can perform a lower grade of reduction in terms of native annular dimensions, compared to direct annuloplasty. Direct approaches can mimic a surgical annuloplasty in a more effective fashion, thus allowing for better annular stabilization and leaflet coaptation restoring.
Currently, clinical experience on transapical technologies is very limited, being Valcare Amend the only successfully implanted device in humans. 9

| Valcare Amend
The AMEND (Valcare Medical) is a transcatheter-implanting solution for direct mitral annuloplasty ( Figure 1). The device is intended to deliver a complete semirigid D-shaped ring to the left atrium (LA), to anchor it to the annulus and stabilize it, resulting in reduced antero-posterior dimensions and improved leaflet coaptation. Three ring sizes are available (34,40, and 46 mm), allowing to treat a wide range of patients, by fitting a diseased annulus ranging from 29 to 50 mm. Currently the Company developed both transapical and transseptal delivery options, through a 24 and 28 F catheter, respectively. 10 The first-in-human successful implantation was performed and described in 2016 by our Group. 11

| Procedural steps
Transapical implantation is performed in a hybrid operating room, under general anesthesia, using a conventional left anterior minithoracotomy. The entire procedure ( Figure 2)  transesophageal echocardiography (2D and 3D TEE) and fluoroscopy.
After introduction into the LV, the 28-F AMEND system is navigated over a wire through the MV into the LA. Once unsheathed, the ring adopts its closed D shape and can be appropriately oriented by the use of multiple adjustment tools of the delivery system. Once the fixation of the device to the posterior annulus. During the second step, the sheath is steered anteriorly toward the aortomitral continuity and once good contact is achieved, the anterior anchors are deployed, resulting in both complete fixation and antero-posterior diameter reduction. The device is finally released and the delivery system is retracted from the heart.

| Clinical results
Current clinical experience includes a total of 14 implanted patients. 10 Eight of them were treated for FMR as a single annuloplasty therapy, while two patients were implanted to treat degenerative mitral regurgitation (DMR) as a single therapy. In four other patients,

| Neochord DS 1000
The Neochord DS 1000 device (Neochord Inc.) is a transapical off-pump MVRe system based on expanded polytetrafluorethylene (ePTFE) chordal implantation. Currently more than 1200 patients have been already treated with Neochord in the world. 17

| Procedural steps
The procedure ( presence of significant leaflet/annular calcifications. Several studies underlined differences between these groups, reporting better results in terms of outcomes when posterior leaflet disease (A and B type) was treated, compared to more complex leaflet lesions (Type C-D). 23 , 24 The leaflet-to-annulus index (LAI) was further introduced to improve the patient-selection process. LAI was calculated by the ratio between the sum of anterior and posterior leaflet length and the anteroposterior diameter. It represents the amount of overriding tissue that is potentially responsible of coaptation, considering annular dilatation in relation to the extension of the leaflets and not as an absolute concept. An excess of leaflet tissue of at least 20% (corresponding to LAI > 1.2) has shown to be a positive predictor of MR ≤ mild at 1-year follow-up. 25 Thus, LAI can be used to identify patients without leaflet-to-annulus mismatch, who could benefit from a ringless repair procedure such as Neochord.
Since its first in human application in 2010, 26  An interesting case of MVRe through transapical artificial chords implantation in a patient affected by dextrocardia and situs-inversus, reporting no significant issues during the procedure was also described. 35 1.9 | Harpoon TDS-5 Harpoon MVReS (Edwards Lifesciences) is a novel transapical off-
Through anterior left mini-thoracotomy in the fifth intercostal space, the optimal entry site on LV apex is identified slightly more anterior than in The Harpoon Mitral Valve Repair System and procedure. A small anterolateral thoracotomy is performed in the fourth or fifth intercostal space. The valved introducer is inserted into the ventricle through a purse-string suture in a location that is 3-4 cm basal from the apex and lateral to the left anterior descending coronary artery. The TSD-5 is steered to the belly of the prolapsed leaflet at the targeted location, and once leaflet stabilization is achieved, the device is actuated, piercing the leaflet and deploying a chordal with a double-helix knotanchored on the atrial surface. The introducer is retrieved; and the chords are tensioned till the adequate coaptation is achieved, and then fixed on an epicardial Teflon pledget. Adapted from Sharma et al. 36 At 1 year, 98% of the treated patients were in New York Heart Association class I or II, and MR was none/trace in 52% (n=27), mild in 23% (n= 2), moderate in 23% (n=12) and severe in 2% (n=1). Favorable cardiac remodeling outcomes at 1 year was also reported. these procedures, might jeopardize long-term outcomes and this represents a particular concern especially in younger patients.

| DISCUSSION
On the other hand, it's important to highlight the versatility of the