MitraClip is a device developed by Evalve and acquired by Abbott Vascular (Fig. 17.1a, b), which reproduces the edge-to-edge surgical technique introduced into clinical practice by Alfieri [11, 13, 20–22]. The surgical technique consists in suturing the free margins of both mitral leaflets at the origin of regurgitation, under direct vision with extracorporeal circulation and cardioplegic arrest. In the case of percutaneous treatment, the leaflets are joined by applying a clip under echocardiograpy guidance on the beating heart (Fig. 17.2).

Compared to the surgical edge-to-edge procedure, the percutaneous MitraClip implant offers the advantage of a reduced trauma. Of note, it also allows real time assessment of the hemodynamic effects of the clip implant by online echocardiography. In case the result is suboptimal, the clip can be repositioned or additional clips can be implanted.

The edge-to-edge surgical experience has proven to be effective and versatile. Versatility is a characteristic retained also by the percutaneous device. In fact, MitraClip implant can be performed either in degenerative or functional MR.

The percutaneous technique was introduced in 2003 [23] and, up to now, more than 8,000 patients have been treated with this device all over the world. The majority of cases has been performed in Europe. Moreover, MitraClip therapy has been evaluated in several trials and registries.

The EVEREST study (Endovascular Valve Edge-to-edge REpair of mitral regurgitation STudy) comprises a series of trials [14, 16, 17, 24–35], including the first randomized controlled trial in which the percutaneous approach was compared to surgical treatment in selected patients with MR (mainly with degenerative etiology). Patients included were selected with inclusion and exclusion criteria (Table 17.2), but, most important they had particular anatomical characteristics evaluated by echocardiography (Figs. 17.3 and 17.4). The study results showed that after 1 year surgery is superior to percutaneous treatment in terms of efficacy (measured as freedom from recurrence of MR and survival), whereas the percutaneous strategy was associated with reduced blood transfusions rates [25]. In a post-hoc analysis, the MitraClip therapy has proven to be non inferior to surgery in terms of effectiveness in three subgroups of patients: patients older than 70 years, those with left ventricular dysfunction and those with functional MR.

Despite important limitations, the EVEREST randomized controlled trial is an important milestone in the field of percutaneous treatment of MR. First of all, this is the first study that has adjudicated both surgical and percutaneous outcomes from an independent core-lab. Secondly, since the EVEREST is the first core-lab study on MitraClip therapy, 3-year durability data are available (Fig. 17.5). They demonstrated that the degree of MR reduction obtained 1 year after the procedure remains stable over time (Feldman, ACC 2012, Chicago, personal communication). At landmark analysis, it became evident that the eventual failure of the procedure occurs mainly in the first 6 months after implantation. After this time, patients who require surgical revision after MitraClip are rare and their number is not significantly different from that observed in the cohort randomized to surgical treatment. These data are crucial as they suggest two conclusions. First, failure of the percutaneous treatment occurs in the first few months after implantation and is potentially preventable with better patient selection and improved implantation technique. Second, in patients with acceptable 1-year result, the hemodynamic benefit of the procedure appears to be stable over time. The durability of the MitraClip was questioned because of previous experiences with the surgical edge-to-edge approach. Indeed, absence of an annuloplasty system has been associated with a lower durability of the repair. Despite convincing surgical data about better results of concomitant edge-to-edge and annuloplasty, EVEREST data suggest that the absence of annuloplasty is not associated with reduced durability.

However, the EVEREST study has limitations that should be taken into account. Indeed, treated patients were quite healthy, with a low mean age, good EF and affected mainly by degenerative MR. These patients do not represent the population of patients currently undergoing MitraClip in the real world. Indeed, most of them are elderly, with comorbidities and decreased left ventricular function. Moreover, in the majority of cases, the MitraClip is used in functional rather than in degenerative mitral valve disease. Furthermore, the study started when the technical experience was in a very early stage and the results were strongly influenced by the learning curve Another limitation of the EVEREST randomized trial is that the surgical outcomes were worse than expected (with in-hospital mortality approaching 6 %, a value that compares unfavourably with the hospital mortality of 1.2 % for this type of intervention reported in the STS database) and there was a high rate of replacement over repair. This may be due to several factors, including surgical experience of the participating centers and clinical characteristics of the patients enrolled in the study. Due to these limitations, additional controlled randomized trials focusing on the current indications for MitraClip therapy are needed.

To fill the gap between the evidence from the randomized trial and that emerging from current practice, unbiased analysis of real-world post-market registries could provide preliminary information.

The high risk registry (HRR) enrolled patients who had clinical or anatomical exclusion criteria for the MitraClip arm of the EVEREST randomized trial. The outcomes were compared with a control group represented by patients who were not treated because of anatomical contraindications to the implant. Compared to the control group, the 30-day mortality of patients treated with MitraClip was similar, while the survival at 1 year of follow-up was higher (although without statistically significant difference, Fig. 17.6) [35].

The HRR is the first study that demonstrated a prognostic benefit in high-risk patients treated with the MitraClip. Moreover,, it is noteworthy that it showed a benefit in terms of health economics: the group of patients treated with the MitraClip showed a decreased number of hospitalizations (reduced by a factor of 55 % as compared to the year before implantation) with a documented benefit observed in both the degenerative and functional MR groups (Fig. 17.7). Unfortunately, in this registry the comparator group was inadequate due to the fact that more than 50 % of comparative patients presented problems of screening. In addition, risk assessment was augmented by less rigourous “up assignment” [36].

The ACCESS-EU registry is a prospective, observational, multicenter post-market trial. The registry collected data from 567 patients treated in 14 high-volume centers in Europe. The study had two phases: phase I completed the enrollment on April 2011 and phase II was initiated in September 2011 and finished in 2012. The main difference between the two phases is that in phase II ultrasound data were evaluated by a single core lab, while in phase I outcomes were adjudicated by individual centers.

The ACCESS registry offers a snapshot of the characteristics of patients who currently undergo the procedure in the real word: mainly elderly patients with comorbidities, high surgical risk and a high prevalence of functional mitral regurgitation (Table. 17.3). The mean age of patients was 74 ± 10 years, with a prevalence of male gender (64 %). The patients had several comorbidities, with an average surgical risk of 23 ± 18 % estimated by the logistic EuroSCORE. The etiology of MR was functional in 77 % of patients, equally distributed between idiopathic and post-ischemic forms. The majority of patients were severely symptomatic (NYHA class III-IV in 85 % of cases) and an ejection fraction less than 40 % was present in 53 % of them. Procedural success rate was 99.6 %, with only two patients out of 566 in whom it was not possible to implant a clip. In 60 % of cases, a single clip was deployed (340 patients), in 37 % two clips (208 patients) and in 3 % (16 patients) three or four clips. The mean procedural time was 117 ± 69 min. The mean length of stay in ICU was 2.5 ± 6.5 days and the overall mean hospitalization was 7.7 ± 8.2 days. Mortality at 30 days was 3.4 %. This mortality rate is notable low, especially if we consider that the majority of patients were at high surgical risk and affected by MR secondary to chronic heart failure. There were the following in-hospital adverse events: stroke (4 patients, 0.7 %), acute myocardial infarction (4 patients, 0.7 %), renal failure (24 patients, 4.2 %), respiratory insufficiency (4 patients, 0.7 %), cardiac arrest requiring resuscitation (10 patients, 1.8 %), cardiac tamponade (6 patients, 1.1 %) and bleeding (21 patients, 3.7 %). In 80 % of the cases, patients were discharged home, with no need of rehabilitative or home care.