Transcatheter Repair of Mitral Regurgitation: Other Devices and Novel Concepts

Abstract

Percutaneous mitral repair has been synonymous with the MitraClip device for the past several years, since no other repair therapies have been available. Over the past 2 years, three additional repair technologies have received EC approval. These four devices, MitraClip, Cardiac Dimensions Carillon, Valtech Cardioband, and Mitralign, are described in the preceding chapters. Numerous other repair devices and concepts have been described, including leaflet repair, annuloplasty, chamber remodeling, and chordal repair approaches. Some have a long history of development, while others have been described only at the concept phase and the spectrum of practical use spans from human experience, preclinical use, or only concept drawings. This review summarizes the novel mitral repair devices in these phases of early development.

1 Introduction

For many years percutaneous mitral repair was synonymous with the MitraClip device, since no other repair therapies were available. Over the past 2 years, three additional repair technologies have received EC approval. These four devices, MitraClip, Cardiac Dimensions Carillon, Valtech Cardioband, and Mitralign, are described in the preceding chapters. Numerous other repair devices and concepts have been described. The great challenges for mitral regurgitation (MR) repair devices are reflected in the fact that many novel device approaches for MR treatment have already fallen by the wayside. A variety of new device approaches are in the early stages of development. The typical sequence of development includes bench and preclinical animal testing, first in human intraoperative testing and finally percutaneous delivery for clinical use. The many other devices in the development pathway are in the earliest stages at the time of this writing. Many have been used only in preclinical or surgical applications.

The usual classification for percutaneous mitral repair devices includes leaflet repair, direct and indirect annuloplasty, chamber remodeling, and neochordal implantation. This classification includes some overlap. For example, some of the annuloplasty devices are implanted into the ventricular side of the mitral valve annulus and subannular myocardium and, therefore, may also contribute to some degree of chamber remodeling.

In addition to the complexity of creating MR repair devices that can be implanted percutaneously and also reduce MR, the appropriate patient population must be defined. Devices and approaches that may be suitable for degenerative MR may or may not also be used for functional MR. While the MitraClip device was initially intended for degenerative MR, we have found its largest application in functional MR. Neochordal implantation will clearly be used for degenerative MR. Functional MR poses a special problem since no prior surgical therapies have demonstrated important survival benefit in this population, and even the clinical impact of surgical repair for functional MR remains unclear.

This review will describe many of the devices in this area of development, some at only the concept stages, others with open surgical approaches, and some with early human transapical or percutaneous experience.

2 Leaflet Repair

The first mitral repair device with significant use in patients is the MitraClip, based on the Alfieri edge-to-edge or double-orifice surgical repair. Surgical leaflet repair has historically been used for degenerative MR, but the widespread use of MitraClip for functional MR makes it possible to consider leaflet repair devices more broadly. One leaflet approach that used a suture to create an edge-to-edge repair, the Edwards Mobius (Edwards Lifesciences, Irvine, CA) leaflet repair system, was used in a small number of patients before the effort was discontinued [1].

Cardica Mitral Repair: Edge-to-edge repair, Cardica Inc. (Redwood City, CA), sells automated stapling or anastomosis systems [2]. They have developed a concept for edge-to-edge mitral repair using a staple-like implant delivered with a transseptal catheter system (Fig. 10.1). The guide catheter has mechanisms for centering and stabilizing the delivery system. The guide catheter includes a clip channel, at least one hook channel, and at least one sling channel and a clip applier, which is movable within the clip channel. The hook and sling channels are alternately positioned and evenly spaced around the perimeter of the guide catheter. The clip or staple has at least three tines and is used to approximate or fasten the anterior and posterior mitral leaflets.

Fig. 10.1

Cardiac edge-to-edge mitral repair using a staple-like implant delivered with a transseptal catheter system. Drawing from US Patent 8,888,794, filed July 26, 2013

Cardiosolutions MitraSpacer: The MitraSpacer (West Bridgewater, MA) is a hydraulically inflated balloon that is anchored in the left ventricular apex and positioned in the regurgitant mitral orifice [3]. The device fills the space of the regurgitant orifice or malcoapting segments (Fig. 10.2). The balloon is about the size of a small chili pepper. The balloon is connected to a port just below the patient’s skin and can be inflated or deflated over time depending on the patient’s condition. A compassionate use first in human surgical implant was successfully performed in March 2015 at King’s College Hospital in London, and the results were presented at the EuroPCRLondon Valves meeting in 2015. This patient developed recurrence of MR and underwent successful addition of 2.5 mL fluid to the balloon injected through the subcutaneous port, resulting in improvement of MR.

Fig. 10.2

Cardiosolutions MitraSpacer is a hydraulic balloon that is anchored in the left ventricular apex and positioned in the regurgitant mitral orifice. The balloon, the volume of which is adjustable, fills the space of the regurgitant orifice or malcoapting segment

Middle Peak Medical: The Middle Peak (Palo Alto, California) device is an implant that functions as a posterior mitral leaflet replacement (Figs. 10.3 and 10.4). This neo-leaflet is made of dual layer ePTFE. The device is implanted directly over the existing posterior leaflet. It provides a new surface onto which the anterior leaflet can coapt. This serves several functions, including annuloplasty, by diminishing the annular area, a direct leaflet repair, and chordal support. It is intended for either surgical or transseptal delivery. Surgical implants have been performed in humans, and the transcatheter option is under development.

Fig. 10.3

The Middle Peak device is an implant that functions as a posterior mitral leaflet replacement. It provides a new surface onto which the anterior leaflet can coapt

Fig. 10.4

Intraoperative photos of Middle Peak device implantation. The Middle Peak device is implanted directly over the existing posterior leaflet. This provides several functions, including annuloplasty by diminishing the annular area, a direct leaflet repair, and chordal support. This neo-leaflet is made of dual layer ePTFE

MitraFlex: The TransCardiac Therapeutics MitraFlex (Atlanta, GA) artificial chords and leaflet plication device are designed for a direct thorascopic approach through the apex of a beating heart [4]. MitraFlex fulfills several functions, including stabilizing and centering the leaflets, automating the capture and connection of the approximate midpoint of the leaflets, implanting artificial chordae tendineae, and reducing the annulus. Figure 10.5 shows a patent drawing. There are no published reports on the use of this system.

Fig. 10.5

The TransCardiac Therapeutics MitraFlex artificial chords and leaflet plication device fulfills several functions, including stabilizing and centering the leaflets, automating the capture and connection of the approximate midpoint of the leaflets, implanting artificial chordae tendineae, and reducing the annulus

3 Indirect Annuloplasty

The only indirect annuloplasty device with EC approval and clinical use is the Cardiac Dimensions Carillon coronary sinus implant. Two indirect annuloplasty systems have previously failed, due to device fracture or coronary sinus erosion. The Edwards Monarc device (Edwards Lifesciences, Irvine, CA) used a springlike contraction band anchored with self-expanding stents at either end. The connection between the band and the stents fractured in several cases. The Viacor PTMA system (Viacor, Inc., Wilmington, MA) used nitinol rods to compress the posterior mitral annuls from within the coronary sinus, and device fractures resulted in coronary sinus perforation.

Arto-MVRx: The Arto System, by MVRx, Inc. (Belmont, California), is a permanent implantable device comprised of two anchors, deployed in the lateral wall of the left atrium and the atrial septum, respectively [5]. This was previously known as the PS3 system. A bridge between the two anchors provides a means for reduction of the minor axis of the mitral valve (Fig. 10.6). The procedure is performed under general anesthesia and fluoroscopic and transesophageal echocardiographic guidance. Using magnetically linked catheters and routine catheter exchanges, a coronary sinus anchor (T-bar) is placed and connected by an adjustable length suture to the atrial septal anchor. The suture is tensioned to indirectly decrease the anteroposterior (AP) diameter of the mitral annulus, which results in reduction of MR. Since the implant is atrial, there is no hemodynamic instability or ventricular arrhythmias. Device efficacy is seen immediately at the time of implantation. The Arto system is adjusted with tensioning or relaxing the suture prior to lock and release of the device. The system is recapturable and retrievable during the deployment.

Fig. 10.6

The Arto System implantation procedure. (a) Great cardiac vein (GCV) and left atrial (LA) MagneCaths in position and magnetically linked behind the P2 segment of the posterior mitral leaflet. (b) Close-up of magnetically linked LA and GCV MagneCaths. Each magnetic catheter has a specific shape and lumen to direct and receive the crossing wire. (c) The crossing wire (arrow) is pushed from the GCV into the LA MagneCath. The MagneCaths are aligned to direct the wire safely from the GCV to the LA through the atrial wall. (d) After using an exchange catheter, the loop guidewire in place across left atrium. This guidewire directs the placement of the GCV anchor (T-bar) and septal anchor. (e) The MVRx System in place before tensioning. T-Bar, single arrow; septal anchor, double arrow. (f) Tensioning of the bridge results in precise shortening of the mitral annulus anteroposterior diameter (arrows) and elimination of FMR; once the final position is attained, the suture is cut and secured with a suture lock

Clinical data from 11 patients implanted with the Arto system has been published in the MitrAl ValvE Repair Clinical Trial (MAVERIC Trial, clinicaltrials.gov identifier NCT02302872) [6]. All patients were deemed to be at high surgical risk by the heart team and were symptomatic, with most in NYHA Class III or IV. There were no procedural safety events and two clinical events within the 30-day follow-up period. One patient underwent uncomplicated surgical drainage of pericardial effusion without recurrence, and one patient had asymptomatic dislocation of the coronary sinus T-bar and underwent successful elective surgical MV replacement. At 6 months, MR grade, LV volumes, mitral annular dimensions, and functional status all improved. Pre-procedure FMR was grade 3–4+ in 90% and at 6 months was grade 1–2+ in 80%. EROA by PISA at baseline was 30.3 ± 11.1, decreasing at 6 months to 13.7 ± 8.6 mm². Regurgitant volumes decreased from 45.4 ± 15.0 to 19.9 ± 11.6 mL. LVESVi decreased from 77.5 ± 24.3 to 68.2 ± 28.2 mL/m² and LVEDVi 118.7 ± 28.6 to 104.9 ± 30.2 mL/m² at 6 months. Mitral annular anteroposterior diameter decreased from 45.0 ± 3.3 to 38.9 ± 2.7 mm. Functional status was NYHA Class III or IV in 81.8% and Class I/II in 18.2% at baseline, improving at 6 months to 50% Class III and 50% Class I/II. Enrollment of up to 20 additional patients at three sites (Riga, Latvia, Massy, France and London, United Kingdom) is underway in Phase II of the MAVERIC trial.

4 Direct Annuloplasty

There are two EC-approved percutaneous direct annuloplasty devices, the Valtech Cardioband (Valtech Cardio, Or Yehuda, Israel) and the Mitralign system (Mitralign, Inc., Tewksbury, MA). The Cardioband most closely resembles a surgical annuloplasty, while the Mitralign system uses pledgets to plicate the mitral annulus, similar to some established surgical suture annuloplasty procedures [7, 8]. Indirect annuloplasty has the potential to be simpler than direct annuloplasty, but direct approaches have the advantage of closer approximation of established surgical annuloplasty. Several other novel annuloplasty devices have been employed preclinically, used with surgical implants, or are in early human use.

Cerclage annuloplasty: This is a creative method for mitral annuloplasty. A wire loop is created encompassing the coronary sinus, basal myocardium, and right atrial chamber (Fig. 10.7) [9]. Annular tension is introduced through a “cerclage” suture that traverses the coronary sinus and basal septal myocardium and is secured within the right atrium. Circumferential tension is intended to reduce annular dilation and enhance mitral leaflet coaptation by introducing radial force uniformly, independent of the rotational orientation of the commissures. For cerclage, 9Fr introducer sheaths are placed percutaneously into the right jugular and femoral veins and 6Fr introducer sheaths into a femoral artery. A guidewire loop is created around the mitral annulus and LV outflow tract and then exchanged for a suture. The guidewire traverses the coronary sinus and the proximal great cardiac vein into the first septal perforator vein toward the basal interventricular septum. It is then directed across a short segment of myocardium to reenter a right heart chamber where it is snared and exchanged for a suture and tension fixation device. To conduct cerclage, a transjugular balloon-tipped guiding catheter is introduced into the coronary sinus, the occlusion balloon inflated, and a retrograde coronary contrast venogram opacifies the great cardiac vein and septal perforator veins. A stiff 0.014″ guidewire is steered into the first basal septal perforator vein. Once a right heart chamber is entered, the guidewire is snared and replaced with a braided nonabsorbable tension suture.

Fig. 10.7

Cerclage annuloplasty. A guidewire is placed via the coronary sinus and then into a coronary vein. It is passed through the septal myocardium into the right ventricular outflow tract or right atrium to encircle the mitral annulus. CS coronary sinus, LV left ventricle, MV mitral valve, PA pulmonary artery, PV pulmonic valve, RA right atrium, RV right ventricle, TV tricuspid valve

A unique feature of the cerclage procedure incorporates the use of circumflex coronary artery protection. The coronary sinus frequently crosses over the circumflex or one of its branches. The cerclage procedure utilizes a relatively rigid spacer device, shaped somewhat like a piece of elbow macaroni. This spacer protects the coronary from compression by the cerclage loop.

A single-center feasibility study is being conducted in Korea (ClinicalTrials.gov identifier NCT02471664). Inclusion criteria include NYHA Class III–IV with symptomatic severe functional MR despite optimal medical treatment. Optimal medical therapy includes an ACE inhibitor or angiotensin receptor blocker, β-blocker, and aldosterone antagonists for at least 3 months unless the patient is contraindicated or intolerant. Key exclusion criteria include LV ejection fraction lower than 25%, anomalies of the coronary sinus, or preexisting coronary sinus devices such as implantable cardioverter defibrillator or pacemaker, or 2:1 or higher grade AV block. Several patients have been treated successfully.

Micardia Encor adjustable surgical annuloplasty ring: This is currently a surgical annuloplasty ring with a percutaneous adjustment mechanism (R&D Surgical Ltd, UK) [10]. The concept is that late postoperative adjustment of the ring could be an advantage. The ring is deformable, nickel–titanium based. It is heated for 45 s, which induces a change of geometry to a preformed reduced anterior–posterior diameter.

In a clinical trial of 94 patients, a smaller ring size was implanted in patients with ischemic mitral regurgitation to “downsize” the mitral annulus [11]. A permanent lead was attached to the ring in the P2/P3 region. It was routed through the atrial wall to a subcutaneous pocket. If an adjustment was required, the lead was accessed by a small incision and connected to a generator. The ring adjusted its form during the activation procedure to a preformed shape with a reduced anterior–posterior diameter. The median age was 71 (range 64–75) years with EuroSCORE II 6.7 ± 6.3. Two-thirds were male, 48% had ischemic MR, 37% had dilated cardiomyopathy, and 15% degenerative disease. Operative mortality was 1%, and the 1-year survival was 93%. Ring adjustment was attempted in 12 patients at a mean interval of 9 ± 6 months after surgery. In three of these attempts, a technical failure occurred. In one patient, mitral regurgitation was reduced two grades, in two patients mitral regurgitation was reduced one grade, and in six patients mitral regurgitation did not change significantly. The mean grade of mitral regurgitation changed from 2.9 ± 0.9 to 2.1 ± 0.7 (P = 0.02). Five patients were reoperated after 11 ± 9 months (ring dehiscence, 2; failed adjustment, 3). Based on this early experience, the authors concluded that an adjustable ring may provide an additional option for recurrent MR. A percutaneous version, enCorTC, is under development.

Millipede: This is an annuloplasty ring that is anchored to the mitral (or tricuspid) annulus using screws and is then mechanically cinched to reduce the mitral annular circumference (Fig. 10.8). It is a complete ring (Millipede, LLC, Ann Arbor, MI) [12]. The cinching or adjustment is done in real time with echo guidance to optimize the reduction of MR. Several patients have had operative implants. A catheter system for percutaneous delivery is under development. An international trial, Annular Reshaping of the Mitral Valve for MR Using the Millipede IRIS System, for symptomatic severe MR (effective regurgitant orifice (ERO) ≥0.2 cm² for secondary MR, ERO ≥0.4 cm², for primary MR) is registered with ClinicalTrials.gov Identifier NCT02607527 anticipating enrollment of approximately ten patients beginning March 2016.

Fig. 10.8

Millipede annuloplasty ring is a complete ring that is anchored in the mitral or tricuspid annulus using screws and is then mechanically cinched to reduce the mitral annular circumference. The cinching or adjustment is done in real time with echo guidance to optimize the reduction of MR

Mitral bridge: This is a novel surgical annular repair device. Rather than encircling the mitral annulus with a ring, a nitinol bridge is sutured from the septal to the lateral annulus (Fig. 10.9). It is placed between A2 and P2 at annular level with standard sutures. It is available in five sizes from 22 to 30 mm. Thirty-four patients have been treated in an EC-approved trial. Three-quarters had Type I MR with annular dilatation, and one-quarter had Type III-b ischemic MR. Chronic AF was present in 88%. All 34 successful implants resulted in a decrease of MR to <1+. One patient developed a paravalvular leak and required reoperation at 7 months post implantation, and one developed a paravalvular leak and required catheter closure after 18 months. The device is unique in that it reduces and stabilizes the anteroposterior annular dimension without the use of annular trigone-to-trigone anchoring. It has been hypothesized that part of the mechanism of action for MitraClip is anteroposterior annular stabilization by the tissue bridge that develops after edge-to-edge repair [13].

Fig. 10.9

Mitral bridge is a novel surgical annular repair device that is sutured from the septal to the lateral annulus. It is placed between A2 and P2 at annular level with standard sutures

MitraSpan TASRA: The TASRA technique (Belmont, MA), Transapical Segmental Reduction Annuloplasty, is based on the experimental concept of septal–lateral annular cinching (SLAC). The SLAC concept was first described in adult sheep with acute ischemic MR produced by circumflex occlusion. A suture is placed from the mid-anterior annulus to the posterior LV wall (Fig. 10.10). This resulted in an anteroposterior reduction of 22% [14]. Subsequent studies found MR elimination in a chronic ischemic sheep model, with preservation of both leaflet mobility and the normal saddle shape of the mitral annulus [15, 16]. The feasibility of suture implants is generally established by the precedents of the components of the procedure, including neochordal implants, the Myocor device [17], and suture annuloplasty. There is some evidence of trigone anchoring as the most secure.

Fig. 10.10

Transapical segmental reduction annuloplasty (TASRA) is based on the experimental concept of septal–lateral annular cinching. A suture is placed from mid-anterior annulus to the posterior LV wall to accomplish annular cinching

The device system is transapical and low profile (12 F or 9 + 5 F). It allows for a direct approach to the critical locations for device implantation using short tools. Tissue crossing uses a 0.018″ wire. There are pledgeted anchors on the LV side and by the trigones. The procedure is TEE-guided, with pre-procedure planning with multi-slice CT.

The safety of implants and biocompatibility of the polyester suture and stainless steel anchors have been demonstrated in preclinical studies of 60 acute and chronic porcine implants with up to 12 weeks pathology and in 18 consecutive chronic animal implants out to 30 days. In these preclinical studies, efficacy to reduce annular diameter by 20–40% was confirmed.

A human feasibility study of the MitraSpan device (SPARE-MR) has been initiated outside the USA. The major inclusion criteria include moderate–severe, symptomatic, secondary MR with LVEF 20–50%. An IDE early feasibility study has been approved by the FDA. The long-term goal is to develop nearly percutaneous LV access with a procedure that could include both a subvalvular/papillary displacement component and an annular correction.

QuantumCor: The QuantumCor (QuantumCor, Inc., Lake Forest, CA) system uses a radiofrequency system to shrink collagen, resulting in remodeling of the annulus. The RF energy is administered with electrodes that are delivered transseptally. In preclinical work described in 2008, the device was evaluated in 16 animals [18]. Acutely, all responded appropriately with a mean septal–lateral reduction of 21.7%. Seven animals survived for 4–180 days, in which the mean septal–lateral reduction was 26.5%, with some expectation that additional remodeling might occur as the collagen matrix heals.

Valcare AMEND: Valcare (Herzliya Pituach, Israel) has developed a minimally invasive D-shaped ring technology, the AMEND device, which emulates a surgical closed, semirigid D-shaped annuloplasty ring (Fig. 10.11) [20]. The system is delivered via apical LV access into the mitral annulus. The implant is delivered under fluoroscopic and echo guidance in a linear configuration through a catheter to the target site, and as it is advanced from the guide catheter system, it changes geometry above the annulus using a series of remotely activated mechanisms. The result is a complete D-shaped ring. A series of 12 anchors in four zones that are independently deployed attach the ring into the annulus. The posterior anchors are placed first and then pulled toward the anterior side to reduce the anteroposterior dimension, thus reducing the septal–lateral dimension and mitral circumference. This technology creates an opportunity to use it as a platform for mitral valve replacement, possibly using valve prosthesis proven in aortic position. The system has been tested in preclinical models.

Fig. 10.11

The Valcare AMEND device emulates a closed surgical semirigid D-shaped annuloplasty ring. (a) The system is delivered via apical LV access into the mitral annulus in a linear configuration through a catheter to the target site. (b) As it is advanced, it changes geometry above the annulus using a series of remotely activated mechanisms [19]. (c) The result is a complete D-shaped ring. (d) A series of 12 anchors in four zones that are independently deployed attach the ring to the annulus

5 Chamber and Annular Remodeling

It has been recognized for many years that direct surgical annuloplasty is effective at reducing MR severity in functional MR but that recurrence rates are as high as almost 60% in the first 2 years after annuloplasty [21] and that annuloplasty has no direct effect on LV function, which is at the root of functional MR. Only one device has ever shown a survival advantage compared to annuloplasty for functional MR in a randomized trial, the Myocor Coapsys system (Myocor, Maple Grove, MN). This device remodeled both the mitral annulus and the LV, but unfortunately the manufacturer lost funding and went out of business in 2008. Other devices have effects on both annular and LV remodeling.

Guided Delivery Systems: The Accucinch System (Guided Delivery Systems, Santa Clara, CA) implants multiple anchors in the mitral basal annular myocardium. A tether connects the anchors, and tension of the catheter diminishes the mitral annular circumference (Fig. 10.12). This approach results in both diminution of the annular circumference and, at the same time, stabilization or remodeling of the basal LV myocardium. The concept is thus a combination of LV remodeling and annuloplasty.

Fig. 10.12

The Guided Delivery Systems Accucinch device is delivered through retrograde catheterization of the LV (a). The arrows highlight the separation of the leaflet edges, which define the regurgitant orifice. Anchors are placed in the posterior mitral annulus and connected with a “drawstring” to cinch the annular circumference. When the cord is tightened, the basilar myocardium and annulus draw the mitral leaflets together to decrease the regurgitant orifice (b); artwork by Craig Skaggs. From Feldman T, Young A. Percutaneous approaches to valve repair for mitral regurgitation. J Am Coll Cardiol. 2014;63: 2057–68

The Guided Delivery Systems Accucinch device places a delivery system below the posterior mitral leaflet on the ventricular side, through which between 10 and 20 nitinol anchors are delivered. Thus, the base of the LV is remodeled at the same time as the annulus. These anchors are tethered by a drawstring, which is tensioned to reduce the mitral annulus. An incomplete ring approach has some precedents in surgery. Surgical annular plication without placement of an annular ring has shown some efficacy in reducing MR.

Several patients have been treated over the last few years as the system has evolved, but there is no published experience. A Feasibility Study Using the Accucinch System in the Left Ventricular Reshaping of the Mitral Apparatus to Reduce Functional Mitral Regurgitation and Improve Left Ventricular Function Trial (LV RECOVER, ClinicalTrials.gov identifier NCT02153892) has been designed. The inclusion criteria include patients with severe symptomatic functional MR of ≥3+ secondary to LV or annular remodeling, as measured in accordance with the current ASE guidelines and suitable for treatment in accordance with the current AHA/ACC guidelines with LVEF ≥20% and ≤40%, stable cardiac medical regimen for heart failure for at least 1 month, and stable NYHA Classification (Class III and above) for at least 1 month. A second study, Percutaneous Left Ventricular Reshaping to Reduce Functional Mitral Regurgitation and Improve LV Function (LVRESTORESA), is also listed on the ClinicalTrials.gov web site (identifier NCT01899573). This second investigation is being conducted in Medellin, Colombia. When updated to December 1, 2015, there were ten patients enrolled in the two trials. A third study, Safety and Performance of the Accucinch System NCT02624960, apparently planned in Germany and the UK, is a single-arm, multicenter, open-label controlled study that will assess the safety and performance of the Accucinch System to induce left ventricular reverse remodeling and reduce the severity of functional mitral regurgitation in symptomatic adult patients with mitral regurgitation and left ventricular remodeling due to dilated cardiomyopathy (ischemic or nonischemic etiology) and who are at high operative risk. Enrollment has not been reported and targeted completion is set for 2019.

Mardil extracardiac annuloplasty: BACE (Basal Annuloplasty of the Cardia Externally, Mardil, Inc. Minneapolis, MN) is a tension band with inflatable silicone chambers that is wrapped around a section of the heart and is thus an extra-cardiac device (Fig. 10.13). BACE does not require open-heart surgery. The company is developing a tool to implant the BACE device through a small incision, as a minimally invasive procedure. After the device is sutured to the heart, the chambers are filled with saline via tubing connected to subcutaneous ports. The saline applies pressure at the basal LV to approximate the mitral leaflets. The saline levels can be adjusted during or after the procedure to provide the appropriate pressure needed to minimize functional MR. The pilot clinical study enrolled 11 patients at medical centers in India and showed clinical efficacy and no device-related safety concerns. Results in five patients have been published [22]. All five patients were male, NYHA Class III, with LVEF of 20–40%. Epicardial application and adjustment of the BACE device was performed on a beating heart with effective reduction in FMR to grade <1. All five patients also had three bypass grafts. Reduction in MR was sustained for at least 6 months, and there were no unanticipated or device-related adverse events. The system is being further studied in a 14-patient trial, the Evaluation of the Minimally Invasive VenTouch System in the Treatment of Functional MR (ClinicalTrials.gov Identifier NCT02671799), with centers recruiting in France and Malaysia and additional centers planned in Canada, the Czech Republic, and the Netherlands. There is also progress in a CE Mark study with 30 implants performed worldwide out of a total enrollment of 50.

Fig. 10.13

BACE (Basal Annuloplasty of the Cardia Externally) is a tension band with inflatable silicone chambers that is wrapped around a section of the heart and is thus an extra-cardiac device. After the device is sutured to the heart, the chambers are filled with saline via tubing connected to subcutaneous ports. The saline applies pressure at the basal LV to approximate the mitral leaflets. The saline levels can be adjusted during or after the procedure to provide the appropriate pressure needed to minimize functional MR

6 Chordal Repair

The use of artificial chordae tendineae is an established repair method for degenerative MR. Methods for implanting neo-chordae via transapical beating-heart approaches have been developed and commercialized, and percutaneous approaches are under development.

Harpoon: This is another transapical system for placement of ePTFE neochords. The system uses echo guidance for real-time titration of the chordal length (Fig. 10.14). The delivery system is 6F. The chords have a preformed ePTFE knot that is formed on the atrial surface of the leaflet, which securely anchors the suture. The anchoring is equivalent to that accomplished with surgical chord placement. Normal chords have a pull-out force of 0.1–0.3 N. Conventional surgical chords have a pull-out force of 8.34 ± 3.29 N, while for Harpoon chords the pull-out force measured 8.58 ± 3.34 N, tested in 11 hearts during bench testing.

Fig. 10.14

Harpoon is another transapical system for placement of ePTFE neochords. The delivery system is 6F. The chords have a preformed ePTFE knot that is formed on the atrial surface of the leaflet, which securely anchors the suture. The anchoring is equivalent to that accomplished with surgical chord placement. The system uses echo guidance for real-time titration of the chordal length

An early feasibility study was done in ten patients, in 2015, in Warsaw [23]. The population was at low risk, with normal LVEF, a mean age of 66 years, and a mean STS risk of 1.26%. Preoperative MR grade by core laboratory was severe in all patients. There was 100% procedural success. A mean of 3.6 chords per patient was placed. The introducer time was 36 min, and skin-to-skin time was 107 min. At 30-day follow-up echo, the MR grade was none or trace in most and moderate in two of the seven who had reached that time point. There was no perioperative mortality, stroke, or blood transfusion. There were two reoperations for delayed tamponade on postoperative days 5 and 13 and one late reoperation for recurrent MR on postoperative day 72.

MISTRAL: The MISTRAL Chordal repair (Mitralix Ltd, Jerusalem) uses a transseptally delivered 3D nitinol spiral-shaped atraumatic wire implant for grasping the chordae tendineae from both mitral valve leaflets in order to bring them closer together (Fig. 10.15). When the spiral is rotated, the chordae become closer, the gap between the leaflets is decreased, and coaptation is significantly improved. The system relies on a 12F off-the-shelf guide catheter (Agilis, St. Jude Medical, St. Paul, MN). The delivery system is 7.5F. By transseptal percutaneous approach, the 12F guiding catheter is delivered into the left atrium and steered towards the mitral valve, and the applicator catheter end is advanced into the left ventricle. The MISTRAL ventricular spiral is released, and by echo guidance, the spiral is turned to capture anterior and posterior leaflet chordae. The spiral is turned back and forth, and the regurgitant jet is measured by echo until the desired outcome is achieved. The applicator catheter is then drawn back to the atrium, and the atrial spiral is released. Some implants have been done in an acute porcine model, and one procedure was done, in January 2016, in a patient with tricuspid valve regurgitation, under compassionate use.

Fig. 10.15

The MISTRAL chordal repair uses a transseptally delivered 3D nitinol spiral-shaped wire implant for grasping the chordae tendineae from both mitral valve leaflets in order to bring them closer together. When the spiral is rotated, the chordae become closer, the gap between the leaflets is decreased, and coaptation is significantly improved

Mitralis: Mitralis (Norwell, MA) has described a system for degenerative mitral regurgitation with a leaflet restraint, still in the concept stage (Fig. 10.16). This system uses an annular anchor and extensions anchored in the LV and so is not distinctly either an annuloplasty or a chordal device. An annuloplasty device is placed along the mitral annulus, and an anchor is then embedded into tissue in the left ventricle. A restraining matrix is extended between the annuloplasty member and the LV anchor such that the restraining matrix is draped over a leaflet of the mitral valve. Adjustment of the restraining matrix is performed to correct one or more prolapsing segments of the leaflet.

Fig. 10.16

Mitralis has described a system for degenerative MR, still in the concept stage. This system uses an annular anchor and extensions anchored in the LV, so it is not distinctly either an annuloplasty or a chordal device. An annuloplasty device is placed along the mitral annulus, and an anchor is then embedded into tissue in the left ventricle. A restraining matrix is extended between the annuloplasty member and the LV anchor such that the restraining matrix is draped over a leaflet of the mitral valve. Adjusting the restraining matrix is done to correct one or more prolapsing segments of the leaflet

NeoChord: The transapical off-pump mitral valve intervention with neochord implantation (TOP-MINI) is performed using the NeoChord DS1000 system (NeoChord, Inc., Eden Prairie, MN) under 2D and 3D transesophageal echocardiography guidance for both implantation and tension adjustment of the neochordae [24, 25]. The Transapical Artificial Chordae Tendineae (TACT) trial showed that the procedure is feasible and reproducible, with low rate of complications [26]. A recent registry confirmed the acute safety of the procedure, with improved clinical outcomes compared with previous published reports [27]. Further outcomes have been reported at 3 months [28]. Forty-nine patients with severe symptomatic degenerative MR were treated. Median age was 72 years (IQR 58–78) and median Euroscore-I was 3.26% (IQR 0.88–8.15); 89.8% presented with posterior leaflet prolapse, 8.2% with anterior prolapsed, and 2% with bileaflet prolapse. Acute procedure success, defined as successful placement of at least three neochords with residual MR less than 2+, was achieved in all patients. In-hospital mortality was 2%. At 30 days, major adverse events included one AMI (2%) successfully treated percutaneously and one case of sepsis (2%), with no stroke or bleeding events. At 3 months, overall survival was 98%. MR was absent in 33.4%, grade 1+ in 31.2%, and grade 2+ in 25%; 10.4% developed recurrent severe MR due to anterior native chord rupture. Four of these were successfully reoperated. At 3 months follow-up, freedom from reoperation was 91.7 ± 4%.

Valtech V-Chordal: Degenerative MR frequently (84%) involves ruptured or elongated chordae. Conventional surgical procedures involve creation of neochordae using Gore-tex suture anchored in the papillary muscle and are technically challenging. Estimation of proper length is made on a flaccid heart. Improper chordal length contributes to residual MR. The V Chordal Adjustable Artificial Chordae System (Or Yehuda, Israel) proposes accurate and reliable fixation to the head of the papillary muscle using beating-heart procedures. Fine-tuning of the leaflet coaptation length and depth is possible with millimeter resolution, and off-pump adjustment of chordal length is done under physiological loading conditions. In animal models there is an excellent tissue ingrowth. Surgical feasibility has been shown in six patients in a European study. Four patients completed 1 year of follow-up. The accumulated implant time was about 10 years, with one death, which was not device-related, 3 months post procedure.

A conceptual transfemoral V Chordal procedure has several steps. Reaching the papillary muscle is accomplished by placing a wire through the mitral valve, inserting a chordae-capturing device over it, and advancing the capturing device to the papillary muscle. Anchoring to the papillary muscle is done using the chordae-capturing device for advancement of an anchor to the papillary muscle. The capturing device is removed, leaving the anchor in place. A guide wire exits from the anchor. Grasping of the leaflets is accomplished by advancing a grasping device over the wire that extends from the anchor. The clip is positioned at the location of the prolapse. The clip is attached to the leaflet, connecting the adjustment element to the anchor. Length adjustment is made with an adjustment tool over the wire to minimize MR, with further adjustment as needed before detaching the system and leaving the implant in place. Each of the component steps is based on existing capabilities from other device developments.

Conclusions

There are a remarkable number and spectrum of devices under development for percutaneous mitral repair. The slow development of catheter mitral replacement systems and the growing positive international experience with the EC- and US-approved repair devices suggest there will be a role for percutaneous mitral repair for at least the near future, if not indefinitely.