By Michael Crawford, MD
Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco
Dr. Crawford reports no financial relationships relevant to this field of study.
SYNOPSIS: A post-regulatory approval, observational study of patients with symptomatic functional mitral regurgitation stratified by baseline left ventricular ejection fraction (LVEF) showed that these patients received substantial benefit at low rates of hospital mortality and other adverse events, regardless of baseline LVEF.
SOURCE: Schäfer U, Maisano F, Butter C, et al. Impact of preprocedural left ventricular ejection fraction on 1-year outcomes after MitraClip implantation (from the ACCESS-EU Phase I, a prospective, multicenter, nonrandomized postapproval study of the MitraClip therapy in Europe). Am J Cardiol 2016;118:873-880.
The MitraClip has been used in Europe primarily for functional mitral regurgitation (MR), especially when the risk of surgery is high, such as in patients presenting with low left ventricular ejection fraction (LVEF). This report evaluated 12-month outcomes of the prospective, multicenter, non-randomized, post-approval study of the MitraClip in Europe (ACCESS-EU) in relation to preprocedural LVEF. Patients were enrolled between 2008 and 2011, and were eligible for the study if they demonstrated moderate to severe or severe MR by echocardiography. Among 567 patients enrolled at 14 sites, 393 (69%) had functional MR and 269 completed the 12-month follow-up visit. The patients were stratified into four LVEF groups: 10-20%, > 20-30%, > 30-40%, and > 40%. Differences in baseline characteristics were observed between the EF groups as would be expected. Most of the functional MR patients were symptomatic and had severe MR. Also, almost half of the functional MR patients had either a pacemaker (13%), cardiac resynchronization device (13%), or a defibrillator (20%). During the index procedure, 58% of the functional MR group received one clip, 39% two clips, and 3% received three or more. There were no intraprocedural deaths, strokes, or respiratory failure episodes. There were 11 deaths (2.8%) within 30 days and 67 (17%) at 12 months. Twelve-month survival in the four LVEF groups was 71%, 79%, 87%, and 86% (10-20%, > 20-30%, > 30-40%, > 40%, respectively). Reduction of MR severity to the mild-to-moderate range occurred in 92% of the functional MR patients. At 12 months, all LVEF groups exhibited similar improvements in New York Heart Association (NYHA) class, six-minute walk test, and the Minnesota Living With Heart Failure Questionnaire. The authors concluded that functional MR patients obtained substantial benefit from the MitraClip with low rates of hospital mortality and other adverse events, even in patients with severely reduced LVEF.
In the United States, the MitraClip is FDA approved for symptomatic patients with degenerative mitral leaflet disease, moderate-to-severe or severe MR, and prohibitively high surgical risk. Mitral valve repair or replacement is the preferred treatment for severe symptomatic MR due to leaflet degeneration. Functional MR is caused by disruption of the mitral apparatus without leaflet disease, which is most commonly caused by LV dilation and reduced systolic performance. Such patients often are at high risk for surgery because of their reduced LVEF and other comorbidities. In fact, isolated MV surgery for functional MR has a Class IIb (B) recommendation in the American College of Cardiology/American Heart Association guidelines. Thus, most functional MR patients are treated medically unless coronary bypass surgery is indicated.
Largely because it is such a low-risk procedure, as soon as it was released in Europe, the MitraClip was used mainly in functional MR patients. It was principally aimed at reducing symptoms, since longevity gains were likely to be modest, if any. The current European guidelines give the MitraClip a IIb (C) indication for functional MR. Thus, this prospective, observational study is of interest and will augment the evidence base for this procedure in functional MR. There were no procedural deaths, and the procedure plus hospitalization death rate was quite low, averaging 2%, with a range of 1-4%. As expected, the lowest LVEF group experienced the highest mortality (4%) and the > 40% group the lowest (1%). One-year survival was better than expected for the highest two LVEF groups (87% and 86%), but in the lower LVEF group, survival was similar to what has been reported in medical therapy studies (71-79%). The main benefits of the procedure were the reduction in symptoms. Whereas almost all patients were NYHA class III or IV prior to MitraClip, fewer than half were at one-year follow-up (20-33%). Also, the six-minute walk distance and the Minnesota heart failure score all improved at 12 months’ follow-up. Whether any of these results would be statistically significant in a randomized, controlled trial remains to be seen, but the symptom relief, in particular, is impressive in this observational study. There are weaknesses to this study, beyond its being observational. There was no echocardiographic core laboratory, and there were no strict entry criteria. Also, there were insufficient echo data to evaluate reverse LV remodeling. Fortunately, a more robust trial powered to analyze survival in functional MR patients treated medically vs. the MitraClip is in progress (COAPT). Perhaps once this trial is finished, the device will be considered for functional MR patients by the FDA.