By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: MitraClip is the only approved percutaneous mitral device, which is currently indicated in the United States for repair of moderate-to-severe degenerative mitral regurgitation in patients at high surgical risk. Although MitraClip patients had higher rates of re-operation in the first year, adverse event rates in the 1- to 5-year range were reassuringly low and were comparable with surgery.
SOURCE: Feldman T, et al. Randomized comparison of percutaneous repair and surgery for mitral regurgitation: 5-year results of EVEREST II. J Am Coll Cardiol 2015;66:2844-2854.
Percutaneous repair of mitral regurgitation (MR) remains a challenging endeavor, for which there is currently a single approved device: the MitraClip system. MitraClip was approved in the United States in October 2013, in large part based on the randomized EVEREST II trial. This study, although flawed, was a well-executed trial for which follow-up data collection has been exceptional. EVEREST II randomized 279 patients with moderate to severe (3+ or 4+) MR and high surgical risk in a 2:1 fashion to either percutaneous (n = 184) or surgical (n = 95) treatment. The original analysis included imaging and clinical outcomes at 12 months and demonstrated several key points. The MitraClip procedure itself is safe, and as expected had fewer procedural complications than open surgery. It is less effective than surgical repair, however, with a greater proportion of patients during that first year registering 3+ or 4+ MR and a higher percentage requiring re-operation. Both surgical and percutaneously treated patients showed improvements in symptoms and in parameters of left ventricular remodeling.
MitraClip is fundamentally different from surgical repair. For example, the percutaneous procedure does not include the stabilizing annuloplasty ring, which is central to surgical repair. This, along with greater residual MR observed in the early time points among MitraClip patients, led to obvious concerns regarding the durability of both symptomatic and functional benefits.
At the 5-year time point, 24 patients in each arm had been excluded from the analysis (the majority due to withdrawn consent), leaving 154 patients in the percutaneous arm and 56 in the surgical arm, respectively. The primary outcome was freedom from a composite of death, repeat mitral surgery, or 3+ or 4+ MR. At 5 years, this occurred in 44.2% of MitraClip patients vs 64.3% of surgical patients (P = 0.01). Mortality was not different between groups. The composite outcome was driven by higher rates of moderate-to-severe MR (12.3% vs 1.8%; P = 0.02) and mitral surgery (27.9% vs 8.9%; P = 0.03) in the percutaneous group. Looking at the data over time, however, we see that the majority (78%) of mitral surgeries occurred during the first 6 months. Between 6 months and 5 years, however, there was no difference between the percutaneous and surgical groups in the incidence of surgery for mitral dysfunction.
At the previously reported 12-month time point, a larger percentage of the device-treated patients had 3+ or 4+ MR — none of the surgical patients vs 17.9% of the percutaneous repair patients. This difference persisted at 5 years. However, fears that larger numbers of MitraClip patients would subsequently develop moderate-to-severe MR proved to be unfounded (2.5% vs 18.8%; P = 0.01). Despite the lack of annuloplasty, measurements of septal-lateral annular dimension (both systolic and diastolic) remained stable from 1-5years in patients who received MitraClip.
The authors reported that the primary finding of this follow-up study was the positive durability of MR reduction with MitraClip, with rates of worsening MR and surgery for mitral dysfunction in the 1- to 5-year range being low and comparable to the surgical group.
Lest we get too caught up in the positive findings, we should first remember that both at the 1- and 5-year time points, surgery was more effective than MitraClip in terms of freedom from MR and repeat mitral surgery. MitraClip is not a replacement for surgery, but rather is a viable option for selected patients who are thought to be at prohibitive surgical risk. Relative efficacy, however, tracked with the etiology of mitral dysfunction. Surgery was clearly superior in degenerative MR, while efficacy of the device was comparable to surgery in functional MR patients. The device is approved only for degenerative MR in the United States, while functional MR is the indication for more than half of such procedures in Europe. This simply highlights the uncertainty surrounding the benefit of any interventional therapy for functional MR patients, who overall have worse outcomes and survival rates. The ongoing COAPT trial seeks to define a potential role for MitraClip in this difficult patient subset.
MitraClip device technique has only improved since its commercial launch, due in large part to superior imaging technology (such as the general availability of 3D TEE) and more-focused patient selection. In the trial, a little more than 38% of patients were treated with two or more clips, and 11% had no clips deployed. In modern clinical practice, multiple clips are more commonly deployed to achieve better MR reduction, and failure of the procedure to deploy any clips is clearly lower than that observed in EVEREST.
From a safety perspective, single leaflet device detachment was reported in nine patients within the first year and in a single patient at 14 months. No further episodes were detected, and no cases of device embolization or late mitral stenosis were found. In the 1- to 5-year time period, the benefits of MitraClip therapy were maintained in terms of MR reduction, favorable left ventricular remodeling, and symptom improvement. For those patients who are appropriate for MitraClip, these data are very reassuring and support continued use.