Mitral regurgitation (MR) is most often caused by degenerative disease of the leaflets or develops functionally as a consequence of left ventricular disease (see Figure 1). Patients with severe MR have dyspnea on exertion, fatigue, and, when associated with left ventricular dysfunction or pulmonary hypertension, reduced survival.1 Therefore, surgery to repair or replace the mitral valve is considered to be a class I indication in symptomatic and asymptomatic patients with left ventricular dysfunction. Surgery is also considered reasonable (class IIA) in patients with preserved left ventricular function if the likelihood of a successful repair is high.2
However, surgery has a number of limitations. Serious complications occur in up to 20% of patients, and may include peri-operative myocardial infarction (MI), stroke, septicemia, renal failure, respiratory failure, re-operation, and death. Up to 20% of older patients may have additional complications after discharge, prompting re-admission within 30 days.3 Finally, although many surgical series report a high rate of freedom from re-operation after mitral repair, results including overall survival and the rate of recurrent MR are not as good. For instance, in a recent report of 649 consecutive isolated mitral valve repairs for degenerative MR, the freedom from re-operation at 15 years was 92%.4 However, by 15 years 33% of patients had died and recurrent severe MR was present in 30%.4
The rationale for the development of percutaneous techniques to treat MR stems from a desire to reduce the morbidity and mortality of surgical repair or replacement, and to improve results. The various techniques under development include devices inserted into the coronary sinus in order to remodel the adjacent posterior mitral annulus (‘indirect annuloplasty’), more direct annuloplasty and ventricular remodeling devices, leaflet repair, and percutaneous mitral valve replacement.5 The remainder of this article will focus on leaflet repair using the MitraClip® device (Evalve Inc., Menlo Park).
Percutaneous edge-to-edge repair with the MitraClip device6 is based on a similar surgical approach using suture described by Alfieri.7 In the percutaneous procedure, a 24 French guide catheter (22F in the distal portion) is inserted into the left atrium from the right femoral vein with standard trans-septal techniques. The clip delivery system with the MitraClip attached at its distal end is passed through the guide catheter into the left atrium and steered through the mitral valve using knobs on the proximal handle.
The clip itself is a polyester-covered device that can be opened and closed repeatedly to grasp the leaflets to create a double-orifice mitral valve by co-apting the central leaflet scallops. The tissue can be released and the clip repositioned as necessary to achieve adequate MR reduction, and a second clip can be placed if necessary.
The procedure is performed under general anesthesia, primarily using realtime transesophageal echocardiography in a unique collaboration between the echocardiographer, anesthesiologist, and interventionalist.8 Patient selection using echocardiography is key to the success of the procedure. A minimum of three of the six American Society of Echocardiography (ASE) criteria for moderate to severe (3+) or severe (4+) MR as assessed by a core laboratory are required for study inclusion.9 In addition, specific leaflet dimensions and the origin of the regurgitant jet origin are assessed. An example of a patient treated with this technique is shown in Figure 2.
Approximately 400 patients have now been enrolled in North American trials with the MitraClip system. The Endovascular Valve Edge-to-Edge Repair Study (EVEREST) I enrolled 55 patients in a phase I safety and feasibility trial.6,10 The ongoing EVEREST II trial is a pivotal randomized, prospective trial in 279 patients comparing the MitraClip device with standard surgical repair or replacement. Patients with either degenerative or functional MR are randomized 2:1 to the MitraClip or surgery, with a primary effectiveness end-point of freedom from surgery for valve dysfunction, death, or 3–4+ MR at one year. The EVEREST II trial, which is currently over 70% enrolled, will provide important information on efficacy compared with surgery, and will help cardiologists decide how to apply this new technique in practice. An additional 78 patients were enrolled in a non-randomized registry for patients with a high risk for surgical mortality.
The results obtained in 104 patients, including 55 patients in the EVEREST I feasibility trial and 49 non-randomized ‘roll-in’ patients in the EVEREST II trial, have been reported.6,10,11 These patients represent the first patients treated who have 30-day core laboratory follow-up. The mean age of patients was 71 years, and 61% were 65 years of age or older. Degenerative disease was present in most patients, but 22% had a functional etiology. A single clip was placed in most patients, 11% did not have a clip placed, and two clips were used in 29% of patients.
Complications related to the procedure were quite low, especially when one considers that this cohort included the earliest procedures at each institution. There were no deaths, and 97% of patients were discharged without the need for home healthcare. The rate of 30-day major adverse events, not including blood transfusion, was 3%. Although there were no cases of clip embolization, partial clip detachment occurred in nine patients (9%), but all cases occurred within the first 30 days and were managed successfully with elective surgery. Acute procedural success, defined as a successful clip implantation with core echocardiographic laboratory assessment of MR <2+ at discharge, was achieved in 85% of this initial cohort of patients. Follow-up of these patients demonstrated a durable result in the majority of patients to three years (see Figure 3). In addition, significant reverse left ventricular remodeling confirmed that a benefit of MR reduction was achieved.12
Use of the MitraClip system to repair mitral regurgitation on a beating heart without surgery is feasible, safe, and effective. Keys to the success of this procedure include careful patient selection and a collaborative interdisciplinary team approach with echocardiographer, anesthesiologist, and interventionalist. Future refinements in both the technology and imaging are likely to improve efficacy and further simplify the procedure. Realtime 3D transesophageal imaging has recently become available.13 With this technique, improved visualization of the MitraClip delivery system can be achieved, providing the interventionalist with an ‘en-face’ or ‘surgeon’s view’ of the mitral apparatus and allowing the operator to better co-ordinate steering of the device in 3D space (see Figure 4).