Mitral valve repair (MVR) remains the standard of care for patients with severe valve incompetence. MVR is usually accomplished by either an open surgical (sternotomy) approach or by minimally invasive (right lateral minithoracotomy) access techniques. Recently there has been an intense interest in developing percutaneous catheter-based techniques, especially for high-risk patients.^1-4

Although the success of transcatheter aortic valve replacement (TAVR) has been rapid, progress toward percutaneous correction of mitral regurgitation (MR) has been much more modest.⁵ The success of catheter-based treatment of aortic stenosis can be attributed to a number of factors: the singular pathophysiology of the diseased valve, the aortic valve’s anatomical location that allows for precise valve stent implantations at the annular level, and the successful development of delivery systems using conventional imaging techniques. The field of percutaneous MVR, however, has not progressed so rapidly for a host of reasons including the complex pathophysiology of MR with a diversity of etiologies, as well as challenges in imaging and delivery and secure anchoring of the valve without impingement on surrounding cardiac structures. These obstacles have led to slower than anticipated clinical adoption of catheter-based approaches for the treatment of MR. To understand the potential for successful therapy, it is first instructive to examine the pathophysiology of the various mechanisms of the disease.

The mitral valve (MV) is a complex structure composed of two leaflets, a fibrous annulus with varying degrees of continuity and integrity, and a subvalvular apparatus consisting of chordae tendineae and papillary muscles attached to the wall of the left ventricle (LV). The etiology of MR can be categorized into two ways: primary also called degenerative or organic, and secondary or functional MR.

In primary MR (Carpentier Type II), the intrinsic disease is a result of leaflet degeneration, ranging from fibroelastic deficiency to an excess of connective tissue called Barlow’s disease, in patients with MV prolapse. Although MR of intrinsic disease occurs initially as isolated leaflet disease, secondary annular dilatation occurs in the majority of patients by the time that they present for treatment.

The largest proportion of patients who present with MR, however, are those with secondary MR (Carpentier Type IIIB), in which the valve is anatomically normal but has been stretched by tethering and ventricular dilatation.⁶ Secondary MR is not a primary valvular pathology but is a result of a cascade of events initiated by this ventricular dilation. Ventricular dilation leads to apical and lateral distraction of the papillary muscles, which results in tethering of the mitral leaflets. This tethering causes central regurgitation secondary to failure of coaptation of the anatomically normal leaflets during systole.⁷ The causes and prognosis of secondary MR are inherently different from intrinsic disease. Although annular dilatation also occurs in this disease, it is a secondary phenomenon. The principle utilized during surgical repair of secondary MR is based upon overcorrection of the annular dilatation component by performing an undersized annuloplasty to restore leaflet coaptation. To date, it is still unknown whether correcting secondary MR has any impact on the underlying pathology or affects long-term survival.^8-11

There is a wide spectrum of devices and approaches to manage MR from a percutaneous or transcatheter approach (Table 41-1).¹² Most catheter-based repair techniques are based on techniques that have been proven to be effective in open surgical MVR. Examples include the edge-to-edge technique, placement of artificial chords, and annular remodeling. However, the challenges in adapting these techniques to catheter-based treatment are significant and center mainly on device delivery and imaging. In contrast to open surgical therapy which employs a combination of techniques, transcatheter approaches have not yet successfully combined these different techniques, and, thus, complex pathologies are hard to correct.

Although many different strategies and devices have been developed, only three have received European (CE Mark) approval to date. These are the MitraClip (Abbott Vascular, Irvine, CA), NeoChord DS 1000 (NeoChord, Inc., Louis Park, MN), and Carillon Mitral Contour System (Cardiac Dimensions, Inc., Kirkland, WA). MitraClip has also received US Food and Drug Administration (FDA) approval for commercial sale in the United States, but only for patients with primary MR who are at high risk for surgical repair. Other devices are in various stages of development.

Some devices such as the MitraClip have been employed to treat both primary and secondary MR. Most, however, have been designed to treat only one etiology or the other, with the majority devoted to secondary MR because of the larger clinical need and the existence of excellent surgical repair techniques for primary disease. We will first review the procedures and devices for the management of primary mitral disease.

Primary Mitral Regurgitation

PERCUTANEOUS EDGE-TO-EDGE REPAIR

The MitraClip system is the only device with extensive clinical application, now with over 19,000 implantations worldwide. The MitraClip mimics the surgical edge-to-edge repair technique of Alfieri (Fig. 41-1).¹³ The device received CE approval in 2008, and FDA approval in 2013. However, the FDA approved the MitraClip only for primary MR in high surgical risk patients and not for patients with secondary MR.

The MitraClip system is designed to allow off-pump endovascular reconstruction of the regurgitant MV. It includes a clip device (MitraClip) and a steerable guiding catheter that enables placement of the clip on the free edges of the MV leaflets. The clip ensures permanent leaflet approximation and creates a double orifice MV (Fig. 41-2). The procedure is performed percutaneously via the femoral vein with transseptal puncture in a cardiac catheterization laboratory or in a hybrid suite with echocardiographic guidance under general anesthesia. The addition of three-dimensional and X-plane echocardiography has significantly facilitated the procedure, as the improved visualization allows for more accurate MitraClip positioning (Fig. 41-3).

Without any strict recommendations from the manufacturer on type or duration of postoperative antiplatelet therapy, several anticoagulation regimens have been proposed. In the Everest I and II trials, aspirin 325 mg daily for 6 months to 1 year was implemented with 75 mg of clopidogrel daily for 1 month.^14-16 In Europe 100 mg of aspirin daily for 3 months and 75 mg of clopidogrel daily without a loading dose for 4 weeks are more commonly used.^14,17

The primary benefit associated with the use of the MitraClip is reduction of MR with elimination of the needs for open chest surgery, cardiopulmonary bypass, and cardiac arrest. The potential risks include those associated with cardiac catheterization and transseptal puncture. The major concern regarding this technique is uncertainty regarding the efficacy of a procedure that results in a less complete correction of MR than is usually accomplished surgically. This concern is based on the knowledge that surgical edge-to-edge repair without annuloplasty is associated with a higher rate of recurrent severe regurgitation if the residual MR is greater than 1+ postoperatively.¹⁸ Whether partial reduction of MR is sufficient to translate into ventricular reverse remodeling and, more importantly, any clinical benefit remains to be determined.^9,11 Additional concerns have been raised regarding the potential impairment of the ability to perform a subsequent surgical valve repair should this become necessary.^19-21

There is a recent trend to implant multiple clips during a single procedure to achieve better coaptation and, thus, improved outcomes.²² Of note, there have been very few reports of mitral stenosis necessitating intervention following MitraClip repair.^23,24 Even after multiple clip implantations in the same patient, mitral stenosis has rarely occurred.

MitraClip has undergone significant clinical testing. In the initial clinical feasibility trial (Everest I: Endovascular Valve Edge-to-Edge REpair STudy), 55 patients were enrolled, and both the safety and efficacy of the device were demonstrated. The pivotal Everest II trial was a multicenter randomized controlled trial to evaluate the benefits and risks of MVR using the MitraClip device compared with open MV surgery in 279 relatively low-risk patients with moderate or severe MR. It was conducted as a per-protocol analysis on a noninferiority hypothesis. Although transfusion was the major component of the composite safety endpoint in the surgical arm, the device met the safety noninferiority hypothesis criteria even if transfusion was eliminated. The primary effectiveness endpoint was determined as freedom from the combined outcome of death, MV surgery or reoperation, and MR greater than 2+ at 12 months. The trial also met the clinical success noninferiority hypothesis, which set a prespecified margin of 31%, at 12 months. The clinical success rate in the device group was 72.4% compared with 87.8% in the control group, an absolute observed difference margin of 15.4%. However, most likely due to the early learning curve with this device, acute procedural success (MR ≤ 2+ at discharge) was achieved in only 77% of patients, and 21% required subsequent open MV surgery. Ultimately, the Everest II trial showed that the MitraClip is safer, particularly by reducing the frequency of postoperative transfusions, but not as effective in reducing MR as compared to conventional MV surgery.²⁵

The EVEREST II High-Risk Registry and REALISM Continued Access Study High-Risk Arm investigated the outcome of MitraClip therapy in 351 high-risk patient with 3 to 4+ MR. MR was reduced to ≤2+ in 86% of patients at discharge.²⁶ Despite a mean STS-predicted operative mortality risk of 11.3 ± 7.7% for mitral replacement, the Kaplan-Meier freedom from death was 77.2% at 12 months. Freedom from MV surgery was 97.8% over this interval, even though 16.4% of patients had MR > 2+ at 12 months. This result may have been inflated, however, by the high operative risk in these patients.

Since MitraClip was approved in Europe, several registries have demonstrated high rates of procedural success and favorable short-term outcomes. The Transcatheter Mitral Valve Interventions (TRAMI) Registry with 1064 patients (71% with secondary MR) showed that the procedure can be performed at a high success rate (95% device success) with no procedural deaths in a high-risk patient cohort (median STS mortality score 10; 69% of the patients with LVEF <50%).²⁷ In the ACCESS-EU registry, the MitraClip was implanted in 567 patients at 14 sites.²⁸ The mean logistic EuroSCORE was 23%, and 77% of patients had secondary MR. Multiple clips were used in 40% of patients. MR was reduced to ≤2+ in 91% of patients without any procedural deaths. NYHA class and 6-minute walk distance had both improved at 1-year follow-up. The European Sentinal Pilot Registry, with a similar rate of secondary MR patients (71% of 628), confirms these results while maintaining high procedural success (95.4%) and low mortality rates (in-hospital mortality 2.9%). Although the rehospitalization for heart failure was more common in the secondary MR group (25.8 vs 12.0%, p = .009), recurrence of severe MR was present only in 6% of patients at 1 year following the procedure.²⁹

The current guidelines are largely influenced by the encouraging results of these clinical trials. The 2012 ESC/EACTS Valve and HF guidelines provide a class IIb (LOE C) recommendation to consider MitraClip use in symptomatic patients with both severe primary and secondary MR.³⁰ The patients need to be judged inoperable or at high surgical risk by a “heart team” and should have a life expectancy greater than 1 year. Patients with secondary MR additionally need to be under optimal medical therapy and cardiac resynchronization therapy, if indicated.

Despite the fact that MitraClip has CE mark approval in secondary MR and has achieved good results in the large European registries for this disease category, the FDA has approved MitraClip only for the treatment of patients with primary MR in high surgical risk patients. Thus, in the 2014 ACCF/AHA Valve guidelines, MitraClip is recommended with class IIb (LOE b) guidance for severe primary MR in symptomatic patients at prohibitive risk for MV surgery.³¹