The aim of this study was to report on the 30-day and 1-year outcomes of percutaneous mitral valve repair with the MitraClip technique in patients with grade ≥3+ mitral regurgitation (MR) at high risk for conventional surgical therapy enrolled in the prospective Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation (GRASP) registry. Acute device success was defined as residual MR ≤2+ after clip implantation. The primary safety end point was the rate of major adverse events at 30 days. The primary efficacy end point was freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR at 30 days and 1 year. A total of 117 patients were treated. Eighty-nine patients (76%) presented with functional MR and 28 patients (24%) with organic MR. Acute device success was observed in all patients. Device implantation time significantly diminished with experience and varied significantly between cases with 1 versus ≥2 clips. No procedural mortality was recorded. Major adverse events occurred in 4 patients at 30 days (4.3%). Deterioration to MR ≥3+ was recorded in 25% of patients with degenerative MR and 7% of those with functional MR at 1 year. No surgery for mitral valve dysfunction occurred within 1 year. Freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR was 96.4% and 75.8% at 30 days and 1 year, respectively. No significant differences were noted in the primary efficacy end point between patients with degenerative MR and those with functional MR. In conclusion, percutaneous mitral valve repair with the MitraClip technique was shown to be safe and reasonably effective in 117 patients from a real-world setting.
Surgical mitral valve repair (or replacement) is the treatment standard for patients with severe (≥3+) mitral regurgitation (MR) on the basis of current guideline criteria. Indeed, overall mortality from mitral valve surgery for some categories of patients can be significant, especially when combined with coronary artery bypass grafting, with operative mortality exceeding 14% in subjects aged >75 years or presenting with multiple co-morbidities. In addition, although surgical repair is the best option for degenerative MR, in which the valve itself is diseased, its results are less optimal in functional MR, which occurs more as a consequence of ventricular dilatation than anatomic problems. The MitraClip (Abbot Vascular, Abbot Park, Illinois) procedure is a percutaneous approach that mimics the surgical edge-to-edge Alfieri technique by promoting mechanical tissue coaptation between the mitral leaflets. Data from the Endovascular Valve Edge-to-Edge Repair Study (EVEREST) studies and the results of registries in Europe and the United States suggest that the MitraClip procedure has a high procedural success rate, a low rate of procedural events, and early improvements in functional New York Heart Association class, MR grade, walking distance, and quality of life. The MitraClip has now >3 years of CE-mark approval and a rapidly expanding clinical experience, with >4,500 MitraClip procedures conducted in Europe. However, current 2012 European Society of Cardiology guidelines make a soft class IIb statement on the use of MitraClip therapy in patients with symptomatic severe primary MR who fulfill the echocardiographic criteria of eligibility, are judged inoperable or at high surgical risk by a “heart team,” and have life expectancy >1 year, reflecting the paucity of published series with follow-up extending beyond 30 days. In this report, we describe the 30-day and 1-year follow-up experience with the MitraClip technique at a single high-volume center.
Methods
Patients with moderate to severe (3+) or severe (4+) MR determined to be at high surgical risk by joint evaluation of a panel of cardiovascular surgeons and cardiologists underwent percutaneous mitral valve repair from August 2008 to October 2012 at Ferrarotto Hospital (Catania, Italy) as part of the ongoing, prospective Getting Reduction of Mitral Insufficiency by Percutaneous Clip Implantation (GRASP) registry. After receiving a complete oral and written explanation of the issues surrounding the procedure, all patients included in the study signed written consent. Qualifying inclusion and exclusion criteria for MitraClip therapy (clinical or echocardiographic), as well as details of the procedure, have been previously reported. MR grade throughout the study period was serially assigned as recommended by the American Society of Echocardiography on the basis of a validated integrative method and the consensus of 2 expert observers. In case of disagreement, the opinion of a third observer was obtained, and the final decision was made by consensus.
Acute device success was defined as residual MR ≤2+ after clip implantation. The primary safety end point was the rate of major adverse events (MAEs) at 30 days, defined as the composite of death, myocardial infarction, reoperation for failed mitral valve surgery, nonelective cardiovascular surgery for adverse events, stroke, renal failure, deep wound infection, mechanical ventilation for >48 hours, gastrointestinal complication requiring surgery, new-onset permanent atrial fibrillation, septicemia, and transfusion of ≥2 U of blood. The primary efficacy end point was freedom from death, surgery for mitral valve dysfunction, or grade ≥3+ MR at 30 days and 1 year after clip implantation.
Continuous variables were analyzed for normal distribution using the Shapiro-Wilk test. Continuous variables following a normal distribution are presented as mean ± SD and were compared using Student’s unpaired t tests. Variables not following a normal distribution are expressed as median (interquartile range [IQR]) and were compared using Mann-Whitney rank-sum tests. One-way analysis of variance or Jonckheere-Terpstra test were used as appropriate for comparisons across multiple groups and to generate p values for trend tests. Categorical variables are presented as counts and percentages. Survival curves were generated using the Kaplan-Meier method, and log-rank tests were used to evaluate differences between groups. Crude event rates were estimated using the Kaplan-Meier method. Patients lost to follow-up were considered at risk until the date of the last contact, at which point they were censored. The incidence of mortality was provided as cumulative incidence and incidence density. Incidence density was defined as the number of patients who died divided by the total number of patient-years and expressed as a number per 100 patient-years of observation. All p values reported are 2 sided, and p values <0.05 were considered significant. All data were processed using the SPSS version 15 (SPSS, Inc., Chicago, Illinois).
Results
One hundred seventeen patients (mean age 72 ± 10 years, 67% men) were treated. Demographic and clinical characteristics are listed in Table 1 . The mean logistic European System for Cardiac Operative Risk Evaluation score was 12 ± 14%. Eighty-nine patients (76%) presented with functional MR and 28 patients (24%) with organic MR. Patients with functional MR presented more commonly with diabetes mellitus, hypertension, history of coronary artery disease, previous percutaneous coronary intervention, and low left ventricular ejection fraction than those with degenerative MR ( Table 1 ). EVEREST leaflet anatomic criteria (i.e., coaptation depth <11 mm, coaptation length >2 mm) were met in 63% of patients.
| Variable | Overall (n = 117) | Degenerative (n = 28) | Functional (n = 89) | p Value |
|---|---|---|---|---|
| Age (yrs) | 72 ± 10 | 73 ± 9 | 72 ± 11 | 0.50 |
| Men | 78 (67%) | 19 (68%) | 59 (66%) | 0.88 |
| NYHA class ≥III | 93 (80%) | 23 (82%) | 70 (79%) | 0.69 |
| NYHA functional status | 2.9 ± 0.6 | 3.0 ± 0.6 | 2.0 ± 0.6 | 0.39 |
| Diabetes mellitus | 40 (34%) | 5 (18%) | 25 (39%) | 0.04 |
| Hypertension | 92 (79%) | 18 (64%) | 74 (83%) | 0.03 |
| Chronic kidney disease ∗ | 44 (38%) | 8 (29%) | 36 (40%) | 0.33 |
| Coronary artery disease † | 57 (49%) | 7 (25%) | 50 (56%) | 0.004 |
| Previous coronary artery bypass graft | 22 (19%) | 2 (7%) | 20 (23%) | 0.07 |
| Previous percutaneous coronary intervention | 38 (33%) | 3 (11%) | 35 (39%) | 0.005 |
| Previous myocardial infarction | 33 (28%) | 1 (4%) | 32 (36%) | 0.001 |
| Previous stroke | 8 (7%) | 2 (7%) | 6 (7%) | 1.00 |
| Chronic obstructive pulmonary disease | 24 (21%) | 3 (11%) | 21 (24%) | 0.26 |
| Atrial fibrillation | 47 (40%) | 11 (39%) | 36 (40%) | 0.91 |
| Left ventricular ejection fraction (%) | 38 ± 13 | 55 ± 7 | 33 ± 10 | <0.001 |
| Logistic EuroSCORE (%) | 12 ± 14 | 11 ± 16 | 13 ± 13 | 0.46 |
∗ Estimated glomerular filtration rate <60 ml/min/1.73 m 2 .
† Stenosis >50% diameter in ≥1 major coronary artery segment.
General anesthesia was used in all patients except 1, who was treated under a deep conscious sedation because of contraindications to anesthetic drugs. Acute device success was observed in all patients ( Figure 1 ). Reduction of MR to 1+ and 2+ was achieved in 61% and 39% of patients with degenerative MR and 64% and 36% of patients with functional MR, respectively (p = 0.75). One clip was implanted in 69 patients (59%), 2 clips in 47 patients (40.2%), and 3 clips in 1 patient (0.8%). At least 2 clips were more commonly needed when the cause of MR was degenerative (64% vs 34%, p = 0.005). Device implantation time, defined as the time from guide insertion until clip delivery system removal, significantly diminished with experience. Overall, the median device implantation time was 64 minutes (IQR 50 to 90, range 21 to 170). The procedures performed in the first third of the study period (n = 39) had a median device implantation time of 71 minutes (IQR 50 to 110), those performed in the second third had a median device implantation time of 65 minutes (IQR 49 to 90), and those performed in the final third had a median device implantation time of 58 minutes (IQR 41 to 71) (p for trend = 0.012). The median device implantation time varied significantly between patients with 1 versus ≥2 clips (55 minutes [IQR 40 to 69] vs 90 minutes [IQR 65 to 115], respectively, p <0.001) and between those with functional and degenerative MR (60 minutes [IQR 44 to 82] vs 90 minutes [IQR 65 to 115], respectively, p <0.001). No procedural mortality was recorded.
MAEs occurred in 4 patients at 30 days (4.3%; Table 2 ). One patient, a 76-year-old man with thrombocytopenia and renal failure on hemodialysis, died 2 weeks after the procedure from gastrointestinal bleeding. No patient underwent emergency cardiac surgery for failed clip implantation. All MAEs were recorded in patients with functional MR.
| Outcome | Overall (n = 117) | Degenerative (n = 28) | Functional (n = 89) |
|---|---|---|---|
| Any MAE | 4 (3.4%) | 0 | 4 (4.5%) |
| Death | 1 (0.9%) | 0 | 1 (1.1%) |
| Myocardial infarction | 0 | 0 | 0 |
| Reoperation for failed surgical repair or replacement | 0 | 0 | 0 |
| Urgent or emergency cardiovascular surgery for adverse event | 0 | 0 | 0 |
| Major stroke | 1 (0.9%) | 0 | 1 (1.1%) |
| Renal failure | 0 | 0 | 0 |
| Deep wound infection | 0 | 0 | 0 |
| Mechanical ventilation for >48 h | 0 | 0 | 0 |
| Gastrointestinal complication requiring surgery | 0 | 0 | 0 |
| New onset of permanent atrial fibrillation | 1 (0.9%) | 0 | 1 (1.1%) |
| Septicemia | 0 | 0 | 0 |
| Transfusion of ≥2 U of blood | 1 (0.9%) | 0 | 1 (1.1%) |
Clinical follow-up was available in all patients at a mean of 410 ± 414 days (median 217, IQR 53 to 728). A total of 19 patients (16.2%) died during the follow-up period, at a median of 353 days (IQR 69 to 669). The incidence density of mortality was 14.4 per 100 patient-years of observation. Death occurred early within 30 days in 1 patient, as previously mentioned, and late within the first year in 10 patients. Another 8 patients died between 1 and 3 years. The cumulative incidence of early mortality at 30 days was 0.9%. Late mortality occurred at a cumulative incidence of 14.0% at 1 year. Cardiovascular causes accounted for 5 of 11 deaths (45%) occurring within 1 year. Other causes of death were noncardiac, including acute pneumonia (2 patients), liver failure (2 patients), acute leukemia (1 patient), and gastrointestinal bleeding (1 patient). No surgery for mitral valve dysfunction was needed within the first year after clip implantation. No cases of clip detachment or embolization were observed. Changes in MR at 30 days and 1 year are reported in Figure 2 . In patients with actuarial follow-up at 30 days, deterioration to MR ≥3+ was recorded in 4% of those with degenerative MR and 8% of those with functional MR. In patients with actuarial follow-up at 1 year, deterioration to MR ≥3+ was recorded in 25% of those with degenerative MR and 7% of those with functional MR. New York Heart Association functional class improved in 77% of patients with paired data at baseline and 30 days and 74% of those with paired data at baseline and 1 year.
