Objective. To evaluate candidacy for surgical mitral valve (MV) repair of recurrent mitral regurgitation (MR) after failed MitraClip. Background. Percutaneous mitral repair with MitraClip is safe and effective in patients with degenerative and functional MR with high surgical risk. However, some patients require subsequent mitral surgery for recurrence of significant MR. Methods. This single-center, observational study includes consecutive patients who underwent mitral surgery after failed MitraClip. Results. Twenty-five patients (age, 69 ± 15 years; 52% women) with severe symptomatic MR after failed MitraClip implantation underwent mitral surgery after a median interval of 5.1 months (interquartile range, 2.5-14 months). Ten patients underwent MV repair (8 with robotic minithoracotomy) and 15 underwent MV replacement (most with sternotomy). Two patients in whom MV repair was intended underwent MV replacement because MitraClip-related leaflet damage prohibited repair. Examples of relative contraindication for MV repair that led to pursuing MV replacement were advanced patient age in 4 patients (mean age, 85 ± 7.6 years), endocarditis in 1 patient, and severely calcified or rheumatic leaflets in 5 patients. Perioperative complications were rare and intermediate-term mortality was similar between groups (3 patients in the MV repair group [30%] vs 4 patients in the MV replacement group [27%]; P=.90). Conclusion. When performed by an experienced mitral surgeon and within 1 year of failed MitraClip implantation, surgical MV repair is feasible in most patients who were surgical repair candidates before the clip. Having the option for surgical MV repair after failed MitraClip is important to preserve optimal long-term outcomes for patients who undergo transcatheter mitral repair with MitraClip, especially as ongoing trials are shifting to study lower-risk patients who are also candidates for surgical repair.
J INVASIVE CARDIOL 2021;33(4):E236-E243.
Key words: MitraClip, mitral regurgitation, mitral surgery, transcatheter valve repair
Percutaneous edge-to-edge mitral valve (MV) repair with the MitraClip system (Abbott Vascular) has been shown to be safe and effective in the treatment of symptomatic patients with both degenerative mitral regurgitation (DMR)1 and functional mitral regurgitation (FMR) with high surgical risk.2,3 In patients with DMR, surgical MV repair is associated with better short- and long-term outcomes compared with MV replacement;4 thus, recent trends in surgical techniques show persistent increase in the rate of MV repair.5 Since receiving CE mark in 2008, over 100,000 MitraClip procedures have been performed worldwide. Following its United States Food and Drug Administration approval in 2013, an annual procedural growth of 84% has been reported, exceeding that of any other transcatheter mitral technology.5 Ongoing improvements in MitraClip design and new device iterations may further broaden its applications and improve its efficacy.6 Thus, ongoing trials are evaluating the effectiveness and outcomes of MitraClip compared with surgical MV repair in patients at moderate surgical risk.7 Compared with MV surgery, MitraClip is less invasive, typically does not require intensive care unit stay, and is even performed as a same-day procedure at some centers. Nevertheless, surgical MV repair is still considered the gold standard in terms of repair success and durability, as a portion of MitraClip recipients will develop significant recurrent MR even if the reduction of MR was initially satisfactory.8,9 Given the increasing number of MitraClip procedures performed, MV surgery for recurrent MR after a MitraClip is likely to occur more often in the future — especially in patients with DMR. Once deployed, the MitraClip device has been shown to endothelialize over time, but it also induces inflammation and fibrosis of the clipped mitral leaflets.10 Significant damage (ie, leaflet perforation or chordal rupture) as well as single-leaflet device attachment have been described as causes for subsequent MV surgery.11-15 Several small studies have suggested that surgical MV repair after MitraClip is challenging, if not impossible, rendering MV replacement — which has worse short- and long-term outcomes compared with MV repair — the only surgical option. Herein, we report our experience of MV surgery after failed MitraClip implantation in a high-volume MitraClip and MV surgery center.
Patients and follow-up. We queried our cardiothoracic surgical database for patients who underwent MV surgery (repair or replacement) and had a previous MitraClip procedure between October 2005 and October 2019. Two patients who underwent orthotopic heart transplantation and 2 patients who underwent MV surgery at an outside institution were excluded (Figure 1). Demographic, clinical, and laboratory data of included patients were obtained from our cardiothoracic surgical database and from electronic health records. All patients had transthoracic echocardiograms before and after MitraClip, as well as at their MV surgery. Most patients also had preprocedural transesophageal echocardiograms (TEEs) at both MitraClip and surgical procedures. Intraprocedural TEE was available for all patients during MitraClip and MV surgery. Complications of the MitraClip procedure or MV surgery were collected from operative reports and clinical documentation in the medical records. Alive status was established from routine yearly follow-up, which is done for all of our surgical patients.
The Cedars-Sinai institutional review board approved this study and waived the requirement for individual written consent.
Mitral surgery approach and data. As reference, the annual volume of MitraClip procedures and MV surgeries at Cedars-Sinai Medical Center (based on the last 3 years before 2019) is approximately 200 cases and 150 cases, respectively. A total of 1204 MitraClip procedures occurred within the study inclusion period.
All patients met with a cardiothoracic surgeon as part of our heart valve team before MitraClip procedure. After failure of the MitraClip was determined clinically and echocardiographically, a repeat surgical consultation was performed. In all cases, the primary surgical strategy (ie, MV repair vs replacement and the surgical approach) was made a priori as documented in the consultation note.
A median sternotomy or a right lateral (mini) thoracotomy were the preferred approaches for MV replacement and MV repair, respectively. Most MV repairs were performed robotically through a 3-4 cm right inframammary incision in the fourth or fifth intercostal space. The robotic-assisted repairs were initially performed with the first-generation and more recently the second-generation da Vinci Robotic Surgical HD system (Intuitive Surgical). MV replacement was performed with hypothermic circulatory arrest through a median sternotomy.16,17
Removal of the MitraClip was performed by removing endothelium covering the clip and unlocking the clip followed by dissecting it off the leaflets; if this technique was impossible, the clipped leaflet segment was resected. Unlocking the clip was attempted first, but successful clip removal was influenced by the maturity of the tissue bridge and the fibrous encapsulation.10,18 If the grippers were not endothelialized, a pair of forceps were used to lift the grippers, allowing the leaflets to slide out. Alternatively, a 2-0 suture was fed through the lock harness and Frazier suction tube and pulled. The arms were then opened, and the grippers were lifted off the leaflets.14,19 If these maneuvers failed, the clip was dissected off the leaflets by debulking the fibrous coverage, and then shaving or peeling the clip off the leaflet.
MV repair was performed in accordance with contemporary practice. This included triangular or quadrangular leaflet resections, chordal transposition or replacement, commissural and cleft suture closure, decalcification, and insertion of a flexible annular band.16,17 Intraoperative TEE was used to confirm success of MV surgery.
MV replacement with a bioprosthetic valve and additional valve or coronary surgery were performed in accordance with contemporary practices and established guidelines.17
Data analysis. Patient characteristics (demographic, clinical, laboratory, and echocardiographic) were summarized as mean ± standard deviation and number (percentage) for the overall cohort and compared between patients undergoing MV repair vs MV replacement using Student’s t-test and Chi-square statistics, as appropriate.
A total of 25 patients who underwent MV surgery after failed MitraClip (out of 1204 MitraClip procedures performed within the same time frame) were included in the study, after exclusion of 2 patients who went on to heart transplant and 2 patients who underwent MV surgery at an outside hospital. Of these 25 patients, 10 underwent MV repair and 15 underwent MV replacement. The patient selection flow chart, the selected surgery, and the reasons for the latter are presented in Figure 1. The median time interval between MitraClip placement and MV surgery was 5.1 months (interquartile range [IQR], 2.5-14 months) and was numerically longer in patients who underwent MV repair vs patients undergoing MV replacement (P=.10) (Table 1). The etiology of MR was DMR in 9 patients (90%) undergoing MV repair, while it was a near-equal mix of DMR in 8 patients (53%) and FMR in 7 patients (47%) undergoing MV replacement. As patients with FMR were more likely to undergo MV replacement, the left ventricular ejection fraction was lower and brain natriuretic peptide levels were numerically higher in this group. Otherwise, patient characteristics were similar between the 2 surgical groups, including the number of MitraClips placed.
The decision to perform MV replacement rather than MV repair was in most cases based on non-suitability for repair due to underlying valve pathology unrelated to the MitraClip in 6 cases (40%), patient age in 4 cases (27%; mean age, 81 years), or other procedure-related limitations (ie, surgery not performed by a mitral surgeon and high-risk MV replacement without aortic cross-clamp) in 3 cases (20%). In only 2 cases (13%), MV replacement was performed because of significant valve damage caused by MitraClip placement (1 case of a torn leaflet and 1 case with inability of the surgeon to detach the clip or resect the clipped portion from the mitral leaflets). These results suggest that the underlying MV pathology is a much more important determinant of MV repairability after MitraClip failure than the damage sustained from the clip itself.
Despite the overall high-risk features of the study population, surgical outcomes were excellent, and complications were low irrespective of the surgical procedure (Table 1). However, the mean length of stay tended to be shorter in patients undergoing MV repair vs MV replacement. During a median follow-up of 24 months (IQR, 8.4-38.4 months), mortality was equal between the MV repair group (30%) vs the MV replacement group (27%; P=.90).
The major findings of our high-volume center study are the following: (1) in most cases, previous MitraClip implantation did not prevent subsequent successful surgical MV repair if performed by an experienced mitral surgeon within approximately 1 year; (2) MitraClip-induced leaflet damage led to MV replacement in only a minority of cases (13%) in which an a priori plan to repair the valve was made; (3) as expected, repair rate was much higher when the etiology was DMR, compared with FMR; (4) although our study sample included patients who were at high surgical risk, short-term outcomes were excellent both in patients who underwent MV repair and MV replacement; and (5) intermediate-term mortality rates were similar to prior studies of high-risk patients undergoing MV surgery; thus, MitraClip did not seem to worsen patients’ survival trajectories.
Our results are particularly relevant because ongoing trials are evaluating MitraClip in patients with severe DMR and moderate surgical risk.7 If percutaneous MV procedures are to follow the same trend as transcatheter aortic valve replacement and extend into lower-risk populations, it is likely that a certain proportion of patients will require a subsequent MV surgery for recurrent MR following an unsuccessful or non-durable MitraClip procedure. Knowledge that surgical MV repair is still feasible and durable post MitraClip is specifically important in patients with DMR, as MV repair is associated with more favorable outcomes compared with surgical MV replacement in this patient group. It is important to note that most MV surgeries occurred within 1 year of MitraClip placement, which may have caused limited fibrosis of the leaflets. Therefore, it may be crucial to identify suboptimal reduction of MR by MitraClip early and plan subsequent MV surgery sooner rather than later.
Repairability of the MV post MitraClip procedure. Edge-to-edge repair with placement of ≥1 MitraClips creates mechanical fusion of the anterior and posterior mitral leaflets, resembling surgical edge-to-edge repair with an Alfieri stitch.20 The deployed clips eventually endothelialize, and therefore anticoagulation is not necessary. However, other post-MitraClip histological changes of the mitral leaflets have been described, and primarily include inflammation and fibrosis, which can result in leaflet thickening and scarring.10 The exact time course of these changes is unknown and whether they become more severe over time is unclear. It is important to note, however, that most surgical MV repairs in our study occurred within 1 year of MitraClip placement. More advanced fibrotic changes of the mitral leaflets likely make subsequent surgical MV repair more challenging. Unintended leaflet damage during MitraClip placement (including leaflet rupture or tear of the chordae tendinae) can further complicate future surgical repair, but is relatively rare in experienced hands.11-15
Several case series have been published on surgical management and outcomes after failed MitraClip. In these case series, the rate of MV repair ranged from 0%-83%.12-14,19,21,22 While our overall repair rate (40%) was within range of these studies, this number does not appropriately represent the intended repair rate, which was 90% in our study. Logically, if a surgeon does not intend to repair the MV, then it will be replaced. Thus, the key question is what percentage of failed MitraClip valves can be repaired as intended and do not require MV replacement. While in our experience, most clipped valves (90%) indeed could be repaired if so intended, the rate of intended repair vs failed repair in the previously reported case series is unknown. Here, we describe our general approach, which is similar to other published techniques.23 Removing the endothelium to expose the locking mechanism to open the MitraClip arms is most atraumatic. If this maneuver fails, then the clipped portion of the mitral leaflet should be removed while trying to conserve as much mitral leaflet tissue as possible. This is not very challenging in myxomatous valves with excess valve tissue. MitraClip removal with concomitant annuloplasty and leaflet repair can also be done robotically by experienced surgeons, thus preserving minimally invasive options for patients. Acquisition of these techniques by mitral surgeons will be important for the future of mitral therapies.
In some patients, steering the MitraClip into the correct position and subsequently deploying the device can cause chordal rupture and leaflet perforation. While these complications are relatively rare in experienced centers, and at times can be fixed with additional clip placement,24 they do pose a challenge to evolving new treatment models in which the MitraClip could play an important role as the primary or initial attempt to reduce MR. Clearly, if MitraClip is an alternative primary treatment strategy in a patient who otherwise would be a surgical candidate, a collaborative approach between surgeons and interventional cardiologists in a heart team must evaluate the following issues: (1) What is the likelihood of success with either MitraClip and surgical repair considering anatomy and location of primary valve pathology, eg, posterior vs anterior leaflet pathology? (2) How extensive would clipping and thus potential valve damage be? For example, what is the flail gap and the width of the regurgitant jet and valvular pathology? (3) What is the likelihood of durable reduction of MR with either approach? (4) What is the patient’s preference after an informed discussion of benefits, risks, and estimated success rate of either procedure? Clearly, to better inform this discussion, additional data of the MitraClip procedure compared with surgical MV repair in patients who are not high or prohibitive surgical risk are needed and studies are underway.7 From a patient preference and cost perspective, MitraClip has clear advantages.
Mortality of MV surgery after MitraClip. Mortality estimates after MV surgery for failed MitraClip are heavily confounded by the patient characteristics, which deemed them to be at high or prohibitive surgical risk and thus led to MitraClip eligibility in the first place. There was no in-hospital or 30-day mortality after MV surgery in our study (compared with a 30-day mortality rate of 5% in another study),25 while intermediate-term follow-up mortality was similar compared with other studies (~30% vs 24%-39%).8,13,21 It is important to better understand the mortality impact of MitraClip placement on subsequent MV surgery. Taken from our experience, it did not seem to significantly change survival (ie, our mortality rates were similar to those expected after MV surgery in high-risk patients with a mean age of 84 years).26-28 However, this needs to be verified in larger studies. It would be expected that mid- to long-term mortality rates of bail-out MV surgery after failed MitraClip would be significantly lower in patients without high surgical risk features before MitraClip placement. In addition, MitraClip has been shown to stabilize patients in cardiogenic shock and improve mortality in heart failure,2,29 and thus may be a temporary measure to give high-risk patients the option of durable MV surgery at a later time.
Study limitations. Our study is limited by its observational design and relatively low statistical power to detect differences between surgical groups. In addition, our results may not be generalizable, especially to medical centers with lower volumes (which influence success of both MitraClip and MV repair.30 Furthermore, most MV repairs occurred within 1 year of MitraClip placement, so we cannot comment on repairability of a clipped valve beyond that time. This underscores the importance of identifying and treating a failed MitraClip in a timely fashion.
When performed by an experienced mitral surgeon, surgical MV repair after failed MitraClip is feasible in most patients who were potential candidates for surgical repair based on their MV anatomy, at least when performed within 1 year of clipping. Preserving an option for subsequent MV repair for a failed or non-durable MitraClip will be a key issue in the future, as the use of MitraClip is being extended to lower-risk populations, especially for patients with DMR, who benefit from surgical MV repair compared with MV replacement. Additional large studies are needed in order to better understand the prognosis and durability of MV repair in this population. Establishing guidelines and training programs on MV repair after MitraClip may be a worthwhile effort.
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From the 1Smidt Heart Institute, Department of Cardiology, Cedars-Sinai Medical Center, Los Angeles, California; 2Department of Cardiology, Tel Aviv Sourasky Medical Center affiliated to the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3University of Southern California, College of Letters, Arts and Sciences; and 4Smidt Heart Institute, Department of Cardiothoracic Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
The authors report that patient consent was provided for publication of the images used herein.
Manuscript accepted August 3, 2020.
Address for correspondence: Florian Rader, MD, MSc, Smidt Heart Institute, Cedars-Sinai Medical Center, 127 San Vincente Blvd, AHSP A3408, Los Angeles, CA 90048. Email: Florian.Rader@cshs.org