Early Insight into Mitralign Direct Annuloplasty for Treatment of Functional Mitral Regurgitation

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Abstract

The Mitralign system (Mitralign, Inc., Tewksbury, Massachusetts, US) is a set of devices approaching the posterior mitral annulus through the left ventricle (LV). Two pairs of surgical pledgets are delivered at the P1 and P3 site of the annulus. The paired pledgets are pulled together to decrease the annulus circumference, and the achieved plication is locked in place. In swine hearts the permanent implants, pledgets and locks, lack any adverse pathology such as necrosis, thrombosis, haemorrhage, mineralisation or exuberant inflammation, and the overall tissue response at 30-day follow-up is considered benign. The clinical experience is limited to a few patients enrolled in a first-in-man study. In a perfect candidate with relatively preserved LV function, moderately enlarged ventricle and limited leaflet tethering, Mitralign annuloplasty may reduce mitral regurgitation significantly from grade 4+ to grade 1+. More research and clinical trials are needed to understand this novel technique for percutaneous mitral valve repair.

Support: The publication of this article was funded by Mitralign, Inc.

Disclosure
Lazar Mandinov is an employee of Mitralign, Inc. The remaining authors have no conflicts of interest to declare.
Correspondence
Lazar Mandinov is an employee of Mitralign, Inc. The remaining authors have no conflicts of interest to declare.
Received date
04 July 2011
Accepted date
21 July 2011
Citation
ICR - Volume 6 Issue 2;2011:6(2):170-172
Correspondence
Lazar Mandinov is an employee of Mitralign, Inc. The remaining authors have no conflicts of interest to declare.
DOI
http://dx.doi.org/10.15420/icr.2011.6.2.170

Functional mitral regurgitation (FMR) is a common complication after myocardial infarction and results from significant left ventricle (LV) remodelling with annulus dilatation and papillary muscle displacement causing tethering and incomplete coaptation of the leaflets.1,2 Surgical management of FMR has consisted of mitral valve repair with suture, band or ring annuloplasty, or mitral valve replacement. Based on a recent meta-analysis of the current relevant literature, mitral valve repair for FMR is associated with 2.5 times better short-term and 35 % better long-term survival compared with mitral valve replacement,3 and is considered the treatment of choice for symptomatic patients with moderate or severe FMR. Percutaneous interventions for FMR derived from surgical mitral valve repair techniques have been intensely developed as less invasive procedures over the last five years4,5 and, if successful, could become a viable treatment option for a number of patients with FMR.

The Mitralign Percutaneous Procedure

Mitralign, Inc. (Tewksbury, Massachusetts, US) has developed a proprietary mitral valve repair system for direct annuloplasty which mimics surgical suture annuloplasty and aims to plicate the dilated posterior mitral valve annulus in patients with FMR. A deflectable 12.5 Fr guide catheter provides retrograde femoral access to the LV and directs all subsequent catheters towards the posterior mitral annulus (see Figure 1). An 8 Fr steerable wire-delivery catheter is advanced through, and extended beyond, the tip of the guide catheter to reach a target point at the P1 or P3 scallop location of the mitral annulus (see Figure 1). Once a target point is selected, and touched by the tip of the steerable catheter, a 0.020 inch, 330 cm long radio-frequency (RF) wire is placed in a position ready to penetrate the annulus. The wire is connected to an RF generator (Valleylab Force FX-C® Generator: Boulder, Colorado) and is advanced through the annulus into the left atrium by applying RF energy for one to two seconds (see Figure 1). Then the wire is pushed deeply in the left atrium and pulmonary vein to decrease the risk of losing position during the subsequent exchange of the wire-delivery catheter with the Bident translational catheter. The Bident catheter is a double-leg, fork-shaped catheter, tracked over one crossing wire to provide positioning of a second wire. Once the Bident catheter is advanced to the mitral annulus, the two legs open up spacing the wires 1.4 or 1.7 cm apart (see Figure 1). Then a second wire is delivered and penetrates the annulus with RF as described above (see Figure 1).

While maintaining the two wires’ positioning, the Bident catheter is withdrawn and a 7 Fr catheter pre-loaded with a pledget is advanced over each of the wires, one at a time. The pledget-delivery catheter is integrated with a handle, which stores the suture and aids the delivery and cinching of the pledget across the annulus. The catheter is pushed forwards over the crossing wire through the annulus to deploy half of the pledget on the atrial side and the other half on the ventricular side of the annulus (see Figure 1). The pledget and the attached suture serve as a buttressed anchor for plication of the annulus (see Figure 1). To plicate the annulus, a pair of pledgets has to be delivered and cinched together. The plication catheter is a 10 Fr long catheter pre-loaded with a stainless steel locking implant and is tracked to the annulus over the two sutures. The plication catheter, in conjunction with an external handle, provides a means for plication of the mitral annulus by pulling the two pledgets together (see Figure 1). Once plication is achieved, the plication catheter deploys the lock onto the sutures, thereby securing the plication. The suture cutter performs the final suture cut following deployment of the lock. Once the procedure is completed at one location (P1 or P3), a second pair of pledgets is delivered at the other scallop location (P3 or P1), and the plication is locked in place (see Figure 1).

The Safety of the Permanent Implants

The permanent implants of the Mitralign system are limited to four surgical pledgets and two stainless steel locks. The overall healing response to the locks and pledgets, including endothelialisation, was studied in swine valve models. Three pairs of pledgets were placed across the annulus, plicated and locked. The animals were followed up for 30 days. Macroscopically, the pledgets and locks had no adverse effect with respect to the overall healing response, with no differences in tissue response regardless of the pledget implantation configuration (i.e. single versus non-overlapped versus overlapped pairs). The pledget surfaces on both sites, ventricular and atrial, were well endothelialised and embedded within the mitral valve annulus tissue (see Figure 2). All pledgets were associated with some degree of protrusion into the atrial surface of the mitral valve annulus; however, overall the magnitude was similar regardless of location along the annulus (i.e. P1, P2 or P3) or pledget implantation configuration (i.e. single, overlapped or non-overlapped) (see Figure 2).

Histologically, the pledgets appeared as two opposing bundles of polyfilaments (i.e. pledget sutures), one above and one below the annulus of the mitral valve, lacking any adverse pathology such as necrosis, thrombosis, haemorrhage, mineralisation or exuberant inflammation (see Figure 2). The stainless steel lock on the ventricular side of the annulus is well endothelialised (see Figure 2). The overall tissue response was considered benign and a first-in-man study has been initiated.

The Best Candidate

In carefully selected patients, restrictive annuloplasty is a safe surgical procedure which can eliminate mitral regurgitation (MR), set off reverse LV remodelling, reduce symptoms and improve quality of life whereas, in suboptimal candidates, it is associated with higher mortality and a significant risk of residual or recurrent MR.6,7 Therefore, patient selection for annuloplasty plays a critically important role in the success and long-term durability of this surgical procedure. With the current limited experience with percutaneous direct annuloplasty, patient selection for the Mitralign procedure is merely based on surgical knowledge. In this respect there are multiple echocardiographic variables related to the mitral valve and LV that can be used in the screening process to predict worse outcomes and exclude suboptimal candidates. Patients with multiple jets on Doppler echocardiography are more likely to develop residual MR after surgical annuloplasty and the procedure should be avoided.8 More importantly, patients with advanced LV remodelling triggering severe leaflet tethering with a tenting distance above the range of 1.0–1.5 cm encountered a high rate of recurrent or even residual MR. Similarly, an angle between the posterior leaflet and annular plane greater than 45° is also a marker of severe leaflet tethering and can predict unsatisfactory results after surgery.9 This is particularly important for patients with only mild annulus dilatation in whom the primary cause of FMR is papillary muscle displacement. Since the leaflet tethering caused by papillary muscle displacement is correlated with LV size, in general, the larger the heart, the greater the risk of longer tenting distance and therefore suboptimal outcomes after surgery. On the other hand, reverse LV remodelling, typically seen after successful MR eradication, is associated with less dilated ventricles and preserved contractile reserve.10 Thus the most favourable outcomes after direct annuloplasty may be expected in patients with less leaflet tethering and moderately enlarged LV with end-systolic and end-diastolic diameters below 5.1 cm and 6.5 cm, respectively.11

Finally, a perfect candidate should be in an earlier stage of the disease with short duration of symptoms and no pulmonary hypertension. Indeed, Mitralign annuloplasty carried out in a perfect candidate with New York Heart Association (NYHA) class II, ejection fraction 41%, tenting distance 7.4 mm, end-systolic and end-diastolic diameters of 5.1 and 6.0 cm, respectively, and no pulmonary hypertension, reduced MR from grade 4+ to grade 1+ and demonstrated sustained results at six-month follow-up (see Figure 3).

Future Potential

An important lesson learned from the surgery is that the effectiveness of restrictive annuloplasty can be enhanced by using complementary surgical procedures. Double-orifice mitral valve technique in addition to annuloplasty has been shown to reduce the rate of recurrent MR and improved long-term outcomes as compared with annuloplasty alone. The combination of these two surgical techniques is certainly considered beneficial in FMR patients, particularly those with severe tenting. Percutaneous mitral valve repair with a clip (MitraClip®: Abbott, Abbott Park, Illinois, US) that grasps and approximates the edges of the leaflets mimics the surgical double-orifice mitral valve technique. Although less effective than conventional surgery, mitral valve repair with MitraClip demonstrated superior safety.12 Basically, this procedure cannot be carried out in patients with a coaptation length <2 mm; however, if direct annuloplasty is performed first to improve the coaptation of the leaflets, then more patients would be considered for mitral clipping. Most certainly, Mitralign annuloplasty has the potential to improve coaptation between the two leaflets, even in patients with no coaptation at all (see Figure 4). Provided that the investigational Mitralign direct annuloplasty becomes an approved treatment for FMR, the next step towards efficacy optimisation and target population expansion might be its combination with another complementary percutaneous mitral valve repair technique such as clipping with the MitraClip. This potential opens the door to exciting research in the years to come.

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