Author + information
- Randolph P. Martin, MD∗ ()
- ↵∗Reprint requests and correspondence:
Dr. Randolph P. Martin, Valvular & Structural Heart Disease Center of Excellence, Marcus Heart Valve Center, 95 Collier Road, N.W., Suite 5015, Atlanta, Georgia 30309.
- commercial percutaneous mitral valve repair
- degenerative (primary) mitral regurgitation
- mitral regurgitation
- transcatheter mitral valve repair
Mitral regurgitation (MR) is believed to be the most common left-sided valvular heart lesion in the United States. The incidence of MR is expected to increase in the future due to the aging of our population as well as the continued influence of inflammatory comorbid conditions. Left untreated, severe MR is associated with very poor outcomes due to the development of left ventricular failure, pulmonary hypertension, and atrial fibrillation. The current American College of Cardiology/American Heart Association Guidelines for Treatment of Valvular Heart Disease (1) emphasize 2 distinct MR types: primary (degenerative) and secondary (functional). These guidelines emphasize that not only do they differ dramatically as to their etiologies, but, importantly, as to their treatments. For primary or degenerative mitral regurgitation (DMR), the best definitive therapy is surgical mitral valve repair (MVR). When performed by an experienced mitral valve surgeon in an experienced surgery center, MVR is curative, maintaining or restoring left ventricular function and providing improvement in both longevity and quality of life.
Despite an emphasis on guideline-driven practices, there are patients who are neither diagnosed nor referred for considerations for surgical repair therapy until they have developed complications from their DMR that may severely limit ever achieving a positive outcome with either surgical repair or even replacement. Additionally, there are many patients who often present with significant comorbidities (densely calcified ascending aortas, frailty, severe liver disease or cirrhosis, severe pulmonary hypertension, immobility, or dementia) that make them extremely at high risk for surgery.
Percutaneous transcatheter MVR (MitraClip System, Abbott Vascular, Menlo Park, California) has been used in >25,000 cases worldwide for the treatment of DMR and functional MR. On the basis of the results of using the device to treat DMR patients enrolled in EVEREST I (Endovascular Valve Edge-to-Edge Repair Study), EVEREST II RCT (EVEREST II Randomized Clinical Trial), EVEREST II High Risk Registry, and REALISM (Real World Expanded Multi-center Study of MitraClip System), the U.S. Food and Drug Administration, in October of 2013, approved the MitraClip system for commercial use in patients who had symptomatic and significant DMR (≥3+ severity) when the operative risk, as assessed by a heart team, was believed to be prohibitive. This approval has led to >100 U.S. sites becoming trained in the placement of the percutaneous transcatheter MVR after the commercial launch. Those patients who received MVR on a post-commercial release basis had to be enrolled in the National Society of Thoracic Surgeons/American College of Cardiology Catheter Valve Therapy Registry.
Data from this registry of patients who received U.S. Food and Drug Administration–approved MVR for prohibitive risk DMR formed the basis of the current study by Sorajja et al. (2) in this issue of the Journal. This paper represents the first published results of U.S. commercial transcatheter MVR, providing a detailed understanding of the short-term effectiveness and real-world safety of this therapy. As recognized experts, the findings of Sorajja et al. (2) are of marked importance.
Although there are multiple limitations of their findings (primarily due to the way in which data are entered in the Transcatheter Valve Therapy Registry), the results are extremely informative and interesting, especially when compared with a previous study by Lim et al. (3), who reported on a prohibitive risk DMR cohort culled from the EVEREST II study. The Lim et al. (3) study assessed 127 high-risk DMR patients considered to be at prohibitive risk for surgical intervention who underwent the procedure and were evaluated for their short-term outcomes as well as 1-year follow-up, with emphasis on assessment of the quality of life and functional status. Due to the nature of the current study by Sorajja et al. (2), the 1-year follow-up data were not available, a finding that is a shortcoming of the current paper. Evaluating both studies, there are important comparative findings. These DMR patients who are undergoing a MVR are an elderly population (median age in the Sorajja et al. study was 83 years, whereas it was 82.4 years in the Lim et al.  study) and are severely symptomatic (≥86% with New York Heart Association functional class III or IV in both studies). In fact, 60% of the patients in the Sorajja et al. (2) study had been hospitalized for congestive heart failure in the year before the procedure was performed. Patients in both studies were clearly at high surgical risk, with a median Society of Thoracic Surgeons risk score of 7.9% for repair and 10% for mitral valve replacement in the Sorajja et al. study, whereas Lim et al. showed a prohibitive risk Society of Thoracic Surgeons risk score of 13.2%. Importantly, in the Sorajja et al. (2) study, procedural success occurred in 90.6% of the cases, with MR being reduced to grade 2 or lower in 93%, with an in-hospital mortality rate of 2.3% and a 30-day mortality rate of 5.8%, findings similar to those of the Lim et al. study. Sorajja et al. (2) showed that nearly 84% of this elderly, very sick patient population who underwent a successful MVR were discharged home—a remarkable finding.
What about post-commercial release experience compared with pre-commercial release experience? Nearly 70% of patients in the current study had MVR procedures at sites with pre-commercial release experience. Surprisingly, the authors reported that there was no difference in procedural complications or device-related adverse events with or without pre-commercial release experience. This may be a reflection of site-specific training and education by proctors and clinical specialists. Additionally, the vendor offers tutorial courses for new commercial implanters, and this combination of education and consultation from more experienced colleagues may be one of the reasons why post-commercial approval of MVR in high-risk patients continues to show an important safety profile. Importantly, however, higher grade reduction of MR, say to grade ≤1+, was more common at sites that had pre-commercial release experience, as was a reduction in fluoroscopy time and radiation exposure. In addition, those sites that had greater case volume had greater success in reducing the degree of MR on pre-discharge echocardiograms, highlighting that experience does matter.
There are significant limitations of this study, due mostly to study design.
1. Commercial operators had the discretion to determine, on the basis of baseline echocardiograms, whether the patient’s MR was primarily degenerative or functional. Many echocardiography experts recognize that echocardiograms can be interpreted as showing “mitral valve prolapse” (i.e., DMR, when the anterior leaflet of the mitral valve overrides a retracted or restricted posterior leaflet). Hence, there is a concern as to whether patients selected might have been weighted more toward the inclusion of patients who would “fit” into a degenerative classification. This concern is further raised by the high percentage of patients who had ischemic heart disease (nearly 33%) (Table 1 in Sorajja et al. ), which is not entirely unexpected in an elderly cohort of patients. In assessing the Sorajja et al. Table 1 (2), however, 33% of patients had had a previous coronary artery bypass graft, 29.7% had had a prior percutaneous coronary intervention, and nearly 25% had had previous myocardial infarctions. Although it is possible that these patients had mixed MR (i.e., both functional and primary), one wonders whether some patients included in this study actually had functional MR—despite the fact that the authors point out that 85.5% of the patients in their study were classified by the entering commercial sites as having DMR.
2. A major concern is that there appeared to be no standard quantitative MR grading on either the pre- or post-implantation echocardiograms and no pre- or post-procedural core lab–adjudicated data on the presence and degree of reduction of MR by MVR. In this regard, the current paper differs significantly from the study by Lim et al. (3) in which core lab quantification of pre-procedural MR severity and post-procedural severity was performed. A recognized limitation of echocardiography is that MR grading of severity is often done subjectively. As noted in the data element definitions of the current paper, there appeared to be very subjective grading of MR pre-clip insertion. There is very limited information on not only how the post-clip insertion MR was graded, but also when it was obtained. It appears that the post-procedural grading was primarily done before hospital discharge, with very little information on how intraprocedural grading was performed.
3. There are no 30-day or 1-year follow-up data provided on the durability of the degree of MR reduction by successful MVR. Also, there is no information about the functional status or the quality of life of these patients who underwent commercial implantation. The current paper is critically important in that it substantiates that the findings by Lim et al. (3) are maintained in a commercially implanted world.
What Have We Learned?
In this group of patients with severe DMR who are symptomatic and at prohibitive risk for surgical intervention, MR reduction to ≤2+ can be obtained in >90% of the cases performed commercially with very low hospital mortality and 30-day mortality. Equally remarkable is the fact that 84% of these patients, who are quite ill and of a median age of 83, can be discharged home after a median hospital stay of only 3 days. As we learned from transcatheter aortic valve replacement, education of new implanters by more experienced colleagues is critical to successful outcomes of the procedure in patients who are symptomatically ill with severe MR. Abbott has made a major push to improve the technical skills and clinical judgment needed to make commercial insertion a safe and appropriate therapy for those who are at prohibitive risk for surgical intervention with DMR. This has been done by not only proctoring physicians being on site, as well as clinical specialists, but the vendor also has launched tutorial courses at those experienced centers. Equally important is that this establishes lines of communication where consultations about challenging cases can easily occur.
The likelihood of post-commercial implantation MR being <2+ is dependent both on institutional and operator case volume, as well as selecting the right cases. Although in the current study, the average case volume was quite low, the data do show that the greater the case volume is, the greater the success in reducing the degree of MR. This may be due in part not only to improving technical skills, but, importantly, selecting patients who will most likely have a good outcome (classic A2-P2 prolapse, improves the results post-clip implantation).
Patients with residual MR grades of 3+ or higher had a higher incidence of single-leaflet device attachment, bleeding, and trends toward longer hospital stay, as well as more fluoroscopy time. This certainly raises the question of patient characteristics. Did these patients have larger left ventricular size or more severe and more complex mitral valve pathology? Questions about the experience of the operators also are raised. Experience gained by performing the procedure or consulting with those heart teams and sites more experienced will lead to greater procedural competence because there will be a better understanding of patients in whom MVR might not result in an ideal outcome or in whom MVR might be difficult to reliably place (for example, in patients with extensive mitral annular calcification or radiation exposure).
What Do We Really Need To Know?
As enthusiasm for the transcatheter approach to MR grows, it is very important for sites performing commercial MVR to help educate us on the following:
1. When not to perform the MitraClip procedure. Thus, are there patients who either have very difficult and complex mitral valve anatomy (dense mitral annular or leaflet calcification, subvalvular chordal retraction or calcification, radiation-induced changes to their mitral valve anatomy) or who have significant comorbidities, such as dementia, marked immobility, or even severe right ventricular dysfunction with secondary severe tricuspid regurgitation in whom the results of the MVR procedure may be less than ideal or really have no major impact on the quality of life or even longevity of the patient? In other words, are there patients who should not be considered for an MVR procedure? For example, those with severe dementia or marked immobility/frailty? And should patients with complex mitral valve anatomy be referred to “Reference Centers” or at least to those centers that have more experience?
2. What are the predictors of limited procedural success? Are there certain characteristics of the patients in their echocardiographic findings that suggest that the ability to reduce MR by 2 grades or more is highly unlikely? Leaving patients with ≥3+ MR after a clip procedure forebodes a very poor 1-year outcome. The data of Lim et al. (3) clearly show that those patients discharged with ≥3+ MR have 1-year mortality approaching 50%. The lesson to be learned is what are the predictors of those patients who might have very minimal, if any, reduction in MR from the clip procedure?
3. Patients with severe tricuspid regurgitation who are being considered for commercial use of the mitral clip for DMR need special attention. A recent publication by Ohno et al. (4) found that moderate to severe tricuspid regurgitation at the time of the mitral clip procedure predicted those with a 1-year marked increased risk of recurrent hospitalization or even death. Although there is early excitement about potential transcatheter approaches to treating patients with functional severe tricuspid regurgitation, patients who present for consideration for commercial implantation for severe DMR who also have severe tricuspid regurgitation and/or significant right ventricular dysfunction need to be counseled, as do their caregivers, about realistic outcomes to be expected. Clearly, those with moderate or severe tricuspid regurgitation as well as severe DMR seen on pre-procedural echocardiograms highlight a very high-risk group in whom the outcomes, despite successful insertion, may be very guarded.
In summary, the authors are to be complimented for giving us the initial look at the experience gained after commercial approval of MVR. The findings are very encouraging and mirror data obtained from other centers throughout the world. As we have learned from primary or DMR repair surgery, procedural success will be based on patient selection and the experience of the team taking care of the patient. This brings me to the important final message. The Centers for Medicare and Medicaid Services coverage emphasizes that for MVR procedures, a heart team truly experienced in mitral valve disease needs to be evaluating the patients and performing these procedures. This is critical to not only the successful outcome of this procedure, but also the well-being of the patients. It is my contention that the heart team taking care of and/or performing MVR procedures should not only involve skilled imagers and interventional cardiologists, but also surgeons experienced in mitral valve surgery. By bringing the expertise of this team to each case, the field will advance and, most importantly, our patients will be properly and better served.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Martin is on the speakers bureau of Medtronic, Edwards Lifesciences, and Abbott Vascular.
Robert O. Bonow, MD, served as Guest Editor for this paper.
- American College of Cardiology Foundation
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- Sorajja P.,
- Mack M.,
- Vemulapalli S.,
- et al.
- Lim D.S.,
- Reynolds M.R.,
- Feldman T.,
- et al.
- Ohno Y.,
- Attizzani G.F.,
- Capodanno D.,
- et al.