In this cohort of patients with severe MR who were unsuitable for surgery, we found that more than one mitral clip was needed in 69 patients (54%) and that vena contracta width was an independent predictor of the need for multiple clips (Fig. 4). A vena contracta width cutoff of 7.5 mm was highly specific (95%) but not sensitive (18%). However, the presence of mitral annular calcification correlated inversely with the use of multiple clips (see Fig. 5). Importantly, we found that the use of multiple clips was safe and not associated with a higher incidence of periprocedural complications. Comparing the one- and multiple-clip groups, there was no significant difference in terms of any of the composite endpoints (mortality, procedural complication, residual regurgitation, and reintervention).
Our study included mainly patients with secondary MR (82%). The minority of patients with primary MR were equally distributed between group I (17%) and group II (19%). Prior studies have reported on the use of MitraClip® in degenerative MR. However, two recent multicenter trials examined the use of MitraClip® in secondary MR and obtained contradictory results [1, 2].
In our study, the incidence of the need for more than one clip (54%) was consistent with what had previously been reported by Alergia et al. [4]. However, Giordano et al. observed a lower incidence of multiple clipping. Of note, in that small study, more of the patients were classified as Carpentier Class II (23.3%) [6]. In our larger study, only 7% of the patients were Carpentier Class II. Due to the more localized pathology in Carpentier Class II MR, such cases can often be targeted with one clip.
Our study corroborates the primary finding of Alegria-Bareiro et. al., specifically, that the width of the vena contracta predicts the necessity of using multiple clips [4].. The current guidelines differentiate between the quantification of primary and secondary MR [7]. Even the American and European guidelines are not consistent regarding when to diagnose severe, secondary MR [7, 8]. Most of our patients had secondary MR with an ERO between 0.2 and 0.4 cm2. The previously proposed 7.5-mm cutoff width [4] had an excellent specificity of 95% and a low sensitivity of 19%. Therefore, we recommend using the zipping technique in patients with secondary MR and vena contracta > 7.5 mm. We believe that a vena contracta width ≥ 7.5 mm is the best applicable cutoff in secondary MR because of the high specificity. Other researchers found no clear-cut features that could predict the need for multiple clips.
The new guidelines address the role of left atrial dilatation as a possible mechanism of secondary MR [7, 8]. In our study, the mean left atrial diameter and mean mitral annular diameter was significantly larger in those patients who required more than one clip. Conversely, neither the left ventricular diameter nor left ventricular function differed significantly between groups. Other parameters, such as left ventricular volume, coaptation depth, and sphericity index, were not available for the retrospective study. However, these parameters could be relevant here. Severe mitral annular calcification, which is mostly associated with extensive valve pathology and restricted mobility of the leaflets, correlates inversely with the use of more than one clip.
Fourteen patients (11%) died during the follow-up period of 3 months. These deaths were primarily due to terminal heart failure, as most of our patients had severely depressed left ventricular function at baseline. In previous studies, 6-month mortality ranged from 10 to 13%, and the 1-year mortality rate was between 6 and 24% [1,2,3, 9]. The EVEREST II Trial [5], which reported the lowest mortality rate (6%), included younger patients with a better functional class (mean age 67 years in EVEREST II vs. 77 years in our study, and NYHA III in 50% in EVEREST II vs. 91% in our study). Other studies, which included sicker patients with more secondary MR, have mortality rates in keeping with our study [1, 2].
Although mitral clipping significantly reduced MR to ≤ grade 2 in 80% of the study patients, it improved heart failure symptoms significantly in only 51%. This discrepancy can easily be explained by the fact that secondary MR is not so much a valvular disease; instead, it is the result of left ventricular abnormalities (e.g., dilated or ischemic cardiomyopathies) and associated issues with mitral annular dilatation and/or papillary muscle displacement. Thus, secondary to remodeling and dilatation of the left ventricle, the mitral valve does not coapt properly. In patients with secondary MR, even after the MR is reduced, the impaired left ventricular function remains. So it is unsurprising that heart failure symptoms do not improve to the same degree as the MR itself. Furthermore, we included high-risk patients with multiple comorbidities (coronary artery disease 34%, renal impairment 29%, and chronic lung disease 26%). Given that we assessed the symptomatic improvement only with NYHA class, a modest improvement in dyspnea could be missed in these patients.
The rate of MR reduction in our study is less than reported previously in the COAPT trial [2], but, as alluded to above, we performed these mitral clipping procedures as last-line therapy after failure of optimal medical and device therapies. In the COAPT trial, MR improved in 46% of patients in the control group, which might be explained by further optimization of medical therapy after randomization. Moreover, 11.7% of the intervention group in the COAPT trial received resynchronization therapy or mechanical support after clipping.