In this observational and multicenter study, data were obtained from the Spanish MitraClip registry. This registry is endorsed by the Cardiac Catheterization and Interventional Cardiology (SHCI) Section of the Spanish Society of Cardiology and has prospectively included consecutive patients treated with MitraClip since June 1, 2012. The inclusion of patients treated with the MitraClip in the Spanish registry is open to all members of the SHCI who perform the technique. This study analyzed the data of the patients included until July 1, 2018, from 16 Spanish hospitals. The indication for TMVR with MitraClip was established as the best therapeutic option after evaluation of each patient by the multidisciplinary team (Heart Team) of each center.

For the purpose of the study, 3 groups were defined according to MR cause3,4: primary MR or DMR, which entails a direct and structural involvement of some of the components of the mitral apparatus; secondary MR or FMR, which shows structurally normal leaflets and chordae but an imbalance between the closing and tethering forces in the valve, secondary to alterations in left ventricular geometry; and finally, mixed MR (MMR), whose etiological mechanism is mainly functional, but there is leaflet degeneration that could have implications for percutaneous repair.

A specialized centralized database was designed for the prospective and consecutive inclusion of all of the patients’ demographic, echocardiographic, procedural, and follow-up variables.

All included patients signed an informed consent form.

The MitraClip device is a percutaneous treatment system for MR that is based on the surgical technique proposed by Alfieri.6,7 The system consists of a cobalt-chromium clip with 2 arms and 2 grippers that are used to trap both mitral leaflets to create a double orifice valve. The device is transseptally introduced and, under echocardiographic and fluoroscopic visualization, its delivery system is advanced until it is placed at the site of maximum regurgitation. The use of real-time 3-dimensional transesophageal echocardiography is essential to guide the procedure and also makes it possible to attempt the treatment of morphologically complex valves. Once transesophageal echocardiography has confirmed that both leaflets have been introduced into the arms of the system, the device can be closed and the result of the MR reduction can be checked by transesophageal echocardiography. If the result is acceptable, the clip can be released; if not, it can be reopened and relocated for another attempt. The implantation is performed in the catheterization laboratory under general anesthesia to obtain an adequate image of the mitral valve and properly capture the leaflets in the device.6,7

Procedural success was defined as the correct implantation of at least 1 clip and MR reduction to a grade less than or equal to moderate (2+). Procedural time was defined as the duration from anesthetic induction to the end of the procedure. Device implantation time was calculated from the insertion of the release system until its removal. Procedure-related bleeding and its severity were defined according to the criteria of the Bleeding Academic Research Consortium (BARC).15 Functional class was defined according to the classification of the New York Heart Association (NYHA).

Percutaneous mitral repair was defined as urgent when it was performed during patient admission for acute HF and clinical instability, either due to recurrent acute lung edema episodes requiring intravenous medication or due to the development of cardiogenic shock.

MR severity, both at diagnosis and in the evaluation after the procedure and during follow-up, was determined according to the recommendations of the European Society of Cardiology.4,16

The primary study endpoint was a composite of all-cause mortality and readmission for HF during the first year of follow-up.

The secondary objectives were post-TMVR analysis of functional class and MR severity according to its cause.

In the descriptive analysis, absolute (No.) and relative (%) frequencies were calculated for qualitative variables. For quantitative variables, the normality of the variables was assessed with the Kolmogorov-Smirnov goodness-of-fit test; variables are expressed as mean ± standard deviation if normally distributed and as median [interquartile range] if not. To address the study endpoints, analyses were performed to compare the 3 MR types (DMR, FMR, and MMR). The differences among these groups in the qualitative variables were calculated as a percentage difference with the Pearson chi-square test; if 20% or more of cells had expected frequencies < 5, likelihood ratio correction was performed. Comparisons among the 3 groups for continuous quantitative variables were analyzed by one-way ANOVA, with post hoc analysis of multiple Bonferroni comparisons or with the Kruskal-Wallis test according to the distribution of the variable.

The nonparametric Kaplan-Meier survival estimator was used to determine the time to all-cause mortality during 12 months of follow-up, as well as readmissions for HF and the composite of mortality and readmissions. In conjunction with the log-rank test, the median survival and the survival curves were used to compare the event-free survival rates among the groups according to MR cause.

Finally, independent predictors of the primary study endpoint were analyzed by Cox proportional hazards regression; hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for all patients, with adjustment for age, sex, type of MR, and the variables with P <.1 in the univariate analysis, using a stepwise forward model. A 95% level of significance was applied in the statistical tests (P <.05).

For data analysis, the SPSS version 23.0 statistical package was used (IBM Corp.; Armonk, New York, United States).

In total, 558 patients were included: 364 had FMR (65.2%), 111 had DMR (19.9%), and 83 had MMR (14.9%). Baseline characteristics are shown in table 1. The mean age was 72.8±11.1 years and men comprised 70.3%. Compared with patients with FMR, patients with DMR were older, were more likely to have had prior cardiac surgery, and had higher surgical risk. Among patients with FMR and MMR, there were higher proportions of men, previous ischemic heart disease, percutaneous revascularization, and previous surgery and worse ejection fraction.

Procedural characteristics are shown in table 2. The procedure was successful in 93% of patients, without significant differences according to MR cause. There were also no significant differences in procedure duration, although the procedures were longer in the FMR group, or in the number of clips implanted. In 5% of the patients, the indication for TMVR was urgent, without significant differences according to type of MR.

Procedural and in-hospital complications are shown in table 3. Procedure-related pericardial effusion was observed in 13 patients, 4 with DMR, 8 with FMR, and 1 with MMR. Of these, 4 patients required pericardiocentesis (2 with DMR and 2 with FMR). Only 1 patient in the FMR group required surgical treatment for pericardial effusion. There was clinically significant bleeding (BARC 3a or 3b) in 3.1% (9 patients). In-hospital mortality was 2.5% (14 patients) and was significantly higher in the FMR and MMR groups than in the DMR group (3% and 3.6% vs 0%; P=.041).

There were 14 in-hospital deaths: 11 patients had FMR and 3 had MMR. The causes of the in-hospital mortality in the FMR group were as follows: 7 due to refractory HF, 2 due to sepsis (1 of urinary origin and another of respiratory origin), 1 stroke, and 1 multiorgan failure. In the MMR group, the causes were refractory HF in 2 and respiratory failure in 1. There were no in-hospital deaths in the DMR group.

At 12 months of follow-up, the total number of events of the primary study endpoint was 95 (18.9%) in the entire series: 11 in the DMR group (11.3%), 71 in the FMR group (21.3%), and 13 in the MMR group (18.1%), with no significant differences among the 3 groups (P=.101). All-cause mortality in the entire series at 12 months of follow-up was 14% (78 patients), distributed according to MR type as follows: 13 patients in the DMR group (11.7%), 57 in the FMR group (15.7%), and 8 in the MMR group (9.6%), with no significant differences among the 3 groups (P=.728). The percentage of readmissions for HF in the entire series at 12 months was 18% (101 patients): 13 in the DMR group (11.7%), 77 in the FMR group (21.2%), and 11 in the MMR group (13.3%); the rate was significantly higher in the FMR group (P=.047). Figure 1 shows the 12-month survival curves for the composite endpoint (figure 1A), all-cause mortality (figure 1B), and readmissions for HF (figure 1C), according to MR cause.

Figure 1.

Twelve-month survival curves for the composite event (A), all-cause mortality (B), and readmission for heart failure (C) according to mitral regurgitation cause.

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Univariate and multivariate analyses of the composite endpoint at 12 months are shown in table 4 and table 5, respectively. The variables associated with the primary endpoint were functional class (P=.029), previous surgical revascularization (P=.031), the EuroSCORE II (P=.003), diabetes mellitus (P=.037), and left ventricular ejection fraction (P=.015). Follow-up was complete for 79.93% of the sample.

Regarding the changes in the NYHA functional class (figure 2), there was a clear improvement at 3 months. This was maintained at 1 year, with 75.1% of the patients in NYHA I or II. This improvement was evident for all etiological groups of MR. The changes over time in the MR grade are shown in figure 3. There was a significant reduction in MR grade at 3 months, which was maintained at 12 months. At the end of follow-up, 73.2% of the patients had ≤ grade II MR. This improvement was found in all etiological groups of MR.

Figure 2.

Changes over time in NYHA functional class during follow-up in the entire series and according to mitral regurgitation cause. NYHA, New York Heart Association.

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Figure 3.

Changes over time in MR grade during follow-up in the entire series and according to MR cause. MR, mitral regurgitation.

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This work has some limitations. The number of patients comprising this series is small and the follow-up is not particularly long. Because this is an observational study, there is no evidence that it has sufficient power to detect significant differences in the primary endpoint; in addition, the different distributions of some variables among the 3 groups could introduce biases during follow-up. The classification of some patients as having MMR is controversial and this approach could represent the loss of a percentage, albeit small, of patients from the other 2 subgroups. Finally, another limitation may be the absence of a centralized imaging laboratory.