Author + information
- Received December 7, 2015
- Accepted December 15, 2015
- Published online March 15, 2016.
- Paul Sorajja, MDa,∗ (, )
- Michael Mack, MDb,
- Sreekanth Vemulapalli, MDc,
- David R. Holmes Jr., MDd,
- Amanda Stebbins, MSc,
- Saibal Kar, MDe,
- D. Scott Lim, MDf,
- Vinod Thourani, MDg,
- Patrick McCarthy, MDh,
- Samir Kapadia, MDi,
- Paul Grayburn, MDj,
- Wesley A. Pedersen, MDa and
- Gorav Ailawadi, MDf
- aMinneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, Minnesota
- bBaylor Heart Hospital, Plano, Texas
- cDuke University, Durham, North Carolina
- dMayo Clinic, Rochester, Minnesota
- eCedars-Sinai Medical Center, Los Angeles, California
- fUniversity of Virginia, Charlottesville, Virginia
- gEmory University, Atlanta, Georgia
- hNorthwestern University, Chicago, Illinois
- iCleveland Clinic, Cleveland, Ohio
- jBaylor University Medical Center, Dallas, Texas
- ↵∗Reprint requests and correspondence:
Dr. Paul Sorajja, Center for Valve and Structural Heart Disease, Minneapolis Heart Institute at Abbott Northwestern Hospital, 920 East 28th Street, Minneapolis, Minnesota 55401.
Background Transcatheter mitral valve (MV) repair with the MitraClip received approval in 2013 for the treatment of prohibitive-risk patients with primary mitral regurgitation (MR).
Objectives The aim of this study was to report the initial U.S. commercial experience with transcatheter MV repair.
Methods Data from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with this percutaneous mitral valve repair device were analyzed.
Results Of 564 patients (56% men, median age 83 years), severe symptoms were present in 473 (86.0%). The median Society of Thoracic Surgeons Predicted Risk of Mortality scores for MV repair and replacement were 7.9% (interquartile range: 4.7% to 12.2%) and 10.0% (interquartile range: 6.3% to 14.5%), respectively. Frailty was noted in 323 patients (57.3%). Transcatheter MV repair was performed for degenerative disease, present in 90.8% of patients. Overall, MR was reduced to grade ≤2 in 93.0%. In-hospital mortality was 2.3%; 30-day mortality was 5.8%. Other 30-day events were stroke (1.8%), bleeding (2.6%), and device-related complications (1.4%). The median length of stay was 3 days (interquartile range: 1 to 6 days), with 84.0% patients discharged home. Overall, procedure success occurred in 90.6%. Variables associated with reduction in MR were end-diastolic dimension, MR severity, clip location, and case volume.
Conclusions In this study of the initial commercial U.S. experience, it was found that procedural success was achieved in approximately 91% of patients, and the majority of patients were discharged home with moderate or less MR. These data support the effectiveness of this therapy in appropriately selected high-risk patients in a commercial setting. Further study is required to determine the long-term impact of transcatheter MV repair in this patient population.
Degenerative or myxomatous mitral regurgitation (MR) affects approximately 600,000 people in the United States (1). When accompanied by symptoms or left ventricular remodeling, degenerative MR carries a heightened risk for heart failure and poor long-term survival (2–6). Surgical treatment, particularly open repair, is the standard of care for degenerative MR and is recommended by national practice guidelines for all patients with either symptoms or left ventricular dysfunction (7).
There are patients who cannot undergo open surgery, because of significant comorbidities (8,9). As a potentially less invasive therapy, percutaneous transcatheter mitral valve (MV) repair using the MitraClip system (Abbott Vascular, Menlo Park, California) was approved on October 24, 2013, by the U.S. Food and Drug Administration for commercial use (10–12). Candidate patients are those with symptomatic, significant regurgitation (≥3+ severity) due to primary mitral disease, when the operative risk as assessed by a heart team is believed to be prohibitive. Since commercial approval, transcatheter MV repair using this device has become available at approximately 100 sites in the United States. Notably, these centers may or may not have been involved in the EVEREST (Endovascular Valve Edge-to-Edge Repair Study) trials or REALISM (Real World Expanded Multicenter Study of the MitraClip System) continued-access registry and thus employ operators who were trained after commercial launch. Commercial operators also have greater discretion in patient selection and technical approaches for implantation than was granted in pre-approval studies (13).
An explanation of the effectiveness and real-world safety of this therapy is needed to help determine its role in the management of patients with MR. As a condition of Medicare coverage, patients who receive treatment are enrolled in the national Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry. Using data from patients enrolled in the TVT Registry, we undertook the present investigation to examine the in-hospital and 30-day effectiveness and safety outcomes and variables associated with procedure success in patients who have received commercially approved percutaneous mitral valve repair therapy in the United States.
The TVT Registry
The STS/ACC TVT Registry is a joint initiative of the STS and the ACC, with representatives from these societies on the steering and stakeholder advisory committees (14–16). The goals of the registry are to serve as a platform for: 1) device and procedural surveillance; 2) quality assurance and improvement initiatives; and 3) efficient conduct of studies that will speed U.S. access to new devices and support the expansion of device labeling through evidence development. Initially launched in 2011, patient enrollment in the registry satisfies the Centers for Medicare and Medicaid Services (CMS) national coverage determinations in which national registry participation is a requirement for commercially approved valve therapies and those devices under clinical investigation.
Centers that participate in the TVT Registry collect data on demographics, morbidities, functional status, quality of life, hemodynamic status, procedural details, and outcomes (post-operative, 30-day, and 1-year) (17). The ACC National Cardiovascular Data Registry data warehouse and the Duke Clinical Research Institute Data Analysis Center both implement data quality checks, including feedback reports and checks on data range and consistency. Site training also is conducted by the National Cardiovascular Data Registry through frequent informational webinars. Sites are contacted to encourage complete reporting in cases of missing data.
The CMS national coverage determination for transcatheter MV repair mandated participation in a national registry for implanting centers. All patients who underwent commercial therapy with the MitraClip system after initial Food and Drug Administration approval (November 2013 to August 2014) and enrolled in the registry were included in the present investigation. Patients who underwent implantation as part of research studies were excluded. A central Institutional Review Board has approved registry activities. The Duke University School of Medicine Institutional Review Board granted a waiver of informed consent and authorization for the present study.
Data element definitions
The clinical indication for transcatheter MV repair is established for patients with symptomatic primary MR (grade ≥3) who are at prohibitive surgical risk, as determined by a heart team that includes a cardiac surgeon and a cardiologist experienced in MV disease. Although the terms primary and secondary are commonly used in descriptions of the etiology of MR, the TVT Registry uses 1 or more of the following descriptors, without a need to indicate the predominant lesion type: degenerative mitral regurgitation, functional mitral regurgitation, post-inflammatory, endocarditis, and other/indeterminate. In this analysis, prohibitive surgical risk was defined as an STS Predicted Risk of Operative Mortality (STS-PROM) score of either ≥6% for isolated MV repair or ≥8% for isolated MV replacement, or the presence of clinical features not captured in the risk calculator algorithm that are believed to portend such heightened risk (e.g., porcelain aorta, radiation injury, severe liver disease, dementia, frailty) (18). Standard definitions were used for collection of data elements in the registry that were harmonized with the STS national database, wherever possible. MR was classified as mild (grade 1), moderate (grade 2), moderately severe (grade 3), or severe (grade 4). Valve Academic Research Consortium (VARC) and VARC-2 definitions for myocardial infarction, stroke, transient ischemic attack, major bleeding, and major vascular complications were used (19–21). All site-reported stroke, transient ischemic attack, and valve events were adjudicated using a combination of site-reported clinical information and chart reviews.
The techniques for transcatheter MV repair using the only commercially approved percutaneous mitral valve repair system have been described in detail (10,11). In brief, the procedure is performed using a 24-F guiding catheter that is placed into the left atrium with a transseptal approach from the femoral vein. Through the guiding catheter, a steerable sleeve is used to advance a 4-mm cobalt chromium, polyester-covered clip with movable arms into the left ventricle, followed by retraction of the device and grasping of the MV leaflets. The goal of the procedure is to permanently oppose the anterior and posterior leaflets of the MV with the device in the area of regurgitation, leading to the creation of a double-inlet orifice and thus mimicking the surgical Alfieri “edge-to-edge” stitch (13). The procedure is performed with imaging primarily from transesophageal echocardiography. Prior to release of the device, the operator confirms that there has been complete insertion of both leaflets in the clip arms and a significant reduction in MR and that there is no concern for mitral stenosis. Additional clips can be placed to achieve further reduction in MR if needed.
Site-reported events for both in-hospital outcomes and within 30 days of the procedure were examined. The primary outcome of interest was procedural success, defined as a composite of post-implantation MR of grade ≤2, without conversion to open cardiac surgery, and without in-hospital mortality (22). In-hospital procedural complications were defined as cardiac perforation (with or without tamponade), major bleeding (VARC-2 criteria), stroke or transient ischemic attack, myocardial infarction, injury to the mitral leaflets or subvalvular apparatus, transseptal complications, or death. Post-implantation MR was defined using site-reported echocardiography prior to hospital discharge. Device-specific adverse events were defined as occurrence of single leaflet device attachment, complete detachment of leaflet clip, device thrombosis, device, or delivery system component embolization.
The primary outcome of interest was a composite endpoint of reduction of MR to moderate or less (grade ≤2), without conversion to cardiac surgery, and without in-hospital mortality. Covariates of interest were age, sex, prior stroke, diabetes mellitus, current dialysis, oxygen-dependent lung disease, prior myocardial infarction, left ventricular ejection fraction, left ventricular internal systolic dimension, left ventricular internal diastolic dimension, left ventricular end-systolic volume, left ventricular end-diastolic volume, degree of MR, mitral annular calcification, effective orifice area, MV area, mitral mean gradient, MV pathology (degenerative or functional), severe tricuspid regurgitation, frailty, pre-commercial experience, and institutional case volume during the study period. Institutions who had participated in the EVEREST and REALISM research studies prior to commercial approval were classified as having pre-commercial experience. Procedural variables that were examined were implantation site of the clip (A2-P2 vs. other) and number of clips deployed. For variables with missing values, multiple imputation with Markov-chain Monte Carlo and regression methods was used. Logistic regression was used, with final estimates and associated standard errors reflecting the combined analysis with PROC MIANALYZE. Before performing the regression analysis, restricted cubic splines were applied for continuous independent variables to assess if the predictor variable and the dependent variable were linearly related. Spline transformations allowed flexible modeling of the shape of the association. Appropriate transformations such as quadratic terms, log transformations, and linear splines were tested. To select the final set of independent variables, stepwise, backward and forward selection with entry and a retention criterion of p < 0.05 were used. Generalized linear models were generated for the forest plots. Discrete factors are presented as frequencies and percentages. Continuous variables are reported as median (interquartile range [IQR]). SAS version 9.1 (SAS Institute Inc., Cary, North Carolina) was used for all calculations, and analyses were performed at the TVT Registry Analysis Center at the Duke Clinical Research Institute.
Baseline characteristics for the study population are listed in Table 1. During the study period (November 2013 to August 2014), 564 patients (median age 83 years, 56% men) had data entered into the STS/ACC TVT Registry and were enrolled in the present investigation. Severe symptoms of heart failure were highly prevalent. New York Heart Association functional class was III or IV in 86.0%; 292 patients (60.5%) had been hospitalized for heart failure in the year prior to transcatheter MV repair. Morbidities, such as coronary artery disease, diabetes mellitus, atrial arrhythmias, chronic renal insufficiency, and oxygen-dependent lung disease, were common. One-third of the population had histories of prior cardiac surgery, including 32 patients (6.1%) who had undergone multiple cardiac operations. The median STS-PROM scores for MV repair and MV replacement were 7.9% (IQR: 4.7% to 12.2%) and 10.0% (IQR: 6.3% to 14.5%), respectively. Frailty was an indication for the procedure in 323 patients (57.3%), while other prohibitive surgical risk features were also frequently present (Table 1).
Degenerative MR was described in 90.8% of patients, with the posterior leaflet being the most common site of involvement (Table 2). Functional MR was described in 14.4%, including 29 patients in whom degenerative disease also was reported (5.1% of all patients) and 52 other patients with functional MR alone (9.2% of all patients). Overall, the procedure was performed for grade 3 or 4 MR in 530 patients (94.0%). The median left ventricular ejection fraction was 56% (IQR: 45% to 63%); 57.5% of the cohort had ejection fractions of less than 60%. Significant left ventricular dilation (end-systolic dimension ≥40 mm) was present in 37.8% of patients. Of note, baseline mean mitral gradient was reported to be ≥5 mm Hg in 45 patients (8.0%), and MV area was reported to be <4 cm2 in 111 patients (19.7%).
The study patients were treated at 61 hospitals in the United States (Figure 1). Forty-two of these institutions had experience with the therapy prior to commercial approval. The median number of cases per hospital for the entire cohort during the study period was 6 (IQR: 4 to 10 cases; range: 1 to 58 cases).
Procedural and in-hospital outcomes
Device implantation occurred in 96.8% of patients (Table 3). The location of device implantation most commonly was in the A2-P2 segments (78.4%); 37.3% of patients required more than 1 device. Transcatheter MV repair was successful in acutely reducing MR to moderate or less (grade ≤2) in 93.0% (Figure 2). Mild or less residual MR (grade ≤1) occurred in 63.7%. Reduction of MR by ≥2 grades occurred in 453 patients (80.3%). Three patients (0.5%) required conversion to open cardiac surgery.
Thirteen (2.3%) in-hospital deaths were observed; 4 of the in-hospital deaths were cardiac related. Procedural complications occurred in a total of 45 patients (8.0%). The incidence of in-hospital stroke was 1.2%, while major bleeding (VARC-2 criteria) occurred in 3.9% (Table 3). Device-related adverse events occurred in 1.4%, including 6 patients who had single leaflet device attachment (1.1%) and 2 others with device embolization (0.4%). Of note, there were no reported instances of mitral leaflet or subvalvular injury. Overall, procedural success, defined as a reduction to moderate or less MR in the absence of cardiac surgery or in-hospital mortality, occurred in 90.6% of patients.
The median length of hospital stay was 3 days (IQR: 1 to 6 days). Overall, 462 patients (84.0%) were discharged directly home after hospitalization for the procedure; 55 other patients (10.0%) were discharged to extended care.
The 30-day mortality rate was 5.8% (26 deaths); 15 of the deaths were from cardiac causes (Table 4). Stroke at 30 days occurred in a total of 8 patients (1.8%). The 30-day incidence of life-threatening or disabling bleeding (VARC-2 criteria) was 2.6%. Thirteen patients (3.1%) were rehospitalized for heart failure. There were no instances of myocardial infarction during the 30-day study period. Overall, 86% were discharged from the hospital with MR grade ≤2 without cardiac surgery and had 30-day survival.
Clinical variables and procedural outcomes
Variables with univariate associations for post-implantation MR grade ≤2 (and without conversion to cardiac surgery) were left ventricular end-diastolic dimension (odds ratio [OR] per 1-mm increase: 0.69; 95% confidence interval [CI]: 0.51 to 0.95; p = 0.02), A2-P2 location of clip implantation (OR vs. other location: 2.29; 95% CI: 1.20 to 4.36; p = 0.02), baseline MR grade (OR per increasing grade: 0.66; 95% CI: 0.47 to 0.93; p = 0.02), baseline mitral mean gradient (OR per 1 mm Hg: 0.96; 95% CI: 0.92 to 0.99; p = 0.04), and institutional case volume (OR per 2 cases: 1.05; 95% CI: 0.99 to 1.11; p = 0.08) (Figure 3). MV area, valve pathology type (i.e., functional vs. degenerative), and number of clips deployed were not significantly different between patients with and those without residual MR grade ≤2. For the primary composite outcome (i.e., residual MR grade ≤2, no conversion to cardiac surgery, no in-hospital mortality), clip implantation at A2-P2 remained significant in multivariate models (OR: 2.36; 95% CI: 1.26 to 4.46; p = 0.008).
The incidences of single leaflet device attachment and major bleeding were higher for patients with residual MR grade 3 or 4 in comparison with those with post-implantation MR grade ≤2; radiation exposure, post-implantation mitral gradient, and hospital length-of-stay also were all greater (Table 5). Both in-hospital and 30-day mortality was higher for patients with post-implantation MR grade ≥3 than for patients with MR grade ≤2, but these differences did not reach statistical significance.
Overall, 391 patients (69.3%) underwent the procedure at sites with pre-commercial experience. These patients, in comparison with patients treated at sites without pre-commercial experience (n = 179), had a lower prevalence of oxygen dependence (12.3% vs. 20.7%) and frailty (38.2% vs. 65.7%, p < 0.0001) and more commonly had degenerative MR (87.5% vs. 80.9%, p = 0.04); these patients also had lower left ventricular end-diastolic diameter (median 5.1 vs. 5.4 cm, p = 0.01) and less mitral stenosis (2.8% vs. 10.1%, p = 0.0003). Fluoroscopy time (median 27.8 vs. 37.7 min, p < 0.0001) and radiation exposure (median cumulative air kerma 500.0 vs. 831.5 mGy, p = 0.002) were lower for pre-commercial sites, but there was no difference in the rates of procedural complications or device-related adverse events. Reduction to MR grade ≤2 was similar at sites with and without pre-commercial experience (93.8% vs. 91.1%, p = 0.26), though reduction to MR grade ≤1 was more common at pre-commercial sites (66.5% vs. 57.4%, p = 0.04).
The present investigation is the first report on commercial transcatheter MV repair in the United States. The principal findings are as follows: 1) the initial commercial experience of transcatheter MV repair with the percutaneous mitral valve repair device has consisted predominantly of patients with symptomatic, degenerative MR and prohibitive surgical risk; 2) procedural success for commercial transcatheter MV repair is favorable, with approximately 91% of patients having residual MR grade ≤2 and surviving hospitalization; and 3) clinical characteristics, procedural variables, and case experience are associated with MR reduction (Central Illustration). Overall, these results demonstrate the effectiveness and safety of transcatheter MV repair with this device in the treatment of prohibitive risk patients with symptomatic MR.
Patients who underwent commercial transcatheter MV repair in the United States were older (median age 83 years), with a high prevalence of significant morbidities, severe symptoms, recent heart failure hospitalization, and left ventricular dysfunction. Indeed, median STS-PROM scores were high: 7.9% for MV repair and 10.0% for mitral replacement. The majority of patients also had risk factors that were not captured in the STS risk algorithm (e.g., frailty in 57%). In this cohort with prohibitive surgical risk, transcatheter MV repair was successful in reducing MR to grade ≤2 in 93% of patients, with an in-hospital mortality rate of 2.3%. Overall, 91% of the patients underwent transcatheter MV repair and were discharged alive with grade ≤2 MR; 86% had grade ≤2 MR and survived to 30 days. Procedural complications occurred in 8.0%, consisting mainly of major bleeding (3.9%), while device-related events (1.4%) were low. The length of hospital stay was notably short (median 3 days), with 84% of patients discharged directly home.
A key finding of the present study is that the outcomes for commercial transcatheter MV repair with the only commercially approved percutaneous mitral valve repair device are favorable in comparison with the results demonstrated in pre-approval research studies, as well as those reported in other national and multinational registries. In the EVEREST II trial, which compared transcatheter MV repair with surgery, reduction of MR to grade ≤2 was achieved with transcatheter MV repair at a rate of 77% (12). Over a 4-year follow-up period, approximately 25% of the EVEREST II patients who had been randomized to transcatheter MV repair underwent open surgical repair. A reduction of MR to grade ≤2 occurred in 86% of patients with prohibitive surgical risk who had been enrolled in the EVEREST studies and the REALISM continued-access registry (10,23). For patient enrollment in these research studies, there were requirements for certain anatomic criteria and, in the EVEREST II randomized trial, surgical candidacy. Given that this initial commercial experience included new operators and that greater operator discretion in the treatment of pathology was available, the comparable success rates for alleviating MR observed in this study are therefore reassuring. Nonetheless, it should be noted that MR reduction was adjudicated in core laboratories in the pivotal trial, but not in the present investigation. Thus, these variations are subject to different methods for assessing and reporting MR.
Since 2008, the MitraClip has been available for clinical use in Europe, where, unlike in the United States, the predominant pathology treated with transcatheter MV repair is functional MR (>70%) and patients are relatively younger (Table 6). Despite differences in the patient populations, the commercial U.S. outcomes are comparable with those reported in Europe, where rates of procedural success typically have exceeded 90%, with a low incidence of in-hospital mortality (0% to 4%) (22,24–34). Notably, the degree of MR reduction observed in the initial U.S. commercial experience (93.0% with grade ≤2) approaches the rate recently reported for European operators who have been involved with the therapy for several years (i.e., 95.4% in the Transcatheter Valve Treatment Sentinel Registry) (22). In the United States, commercial transcatheter MV repair was rolled out systematically, beginning with sites that had participated in research studies of the therapy and with the support of experienced company clinical specialists in all cases. CMS, through the national coverage determination, also specified site requirements in terms of clinical experience with mitral disease to perform the procedure. Certainly, caution should be exercised when comparing outcomes across these unique registries. Although transcatheter MV repair with the MitraClip is indicated for patients with degenerative MR in the United States, a high degree of success also was observed in selected patients with functional MR, which was described either with or without degenerative MR in 14.4% of the cohort in the present study. Patients with ischemic heart disease were common in this study (∼30%). Use of transcatheter MV repair for functional MR is an off-label indication in the United States and is the subject of the ongoing COAPT (Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy for Extremely High-Surgical Risk Patients) trial.
Performance of transcatheter MV repair requires a number of unique skills. These abilities include accurate and safe transseptal puncture, catheter manipulation in the left atrium, complex echocardiography, management of large-bore vascular access (i.e., 24-F), as well as technical knowledge of the dedicated delivery system and device. Although specialized training programs have become established, operators who perform transcatheter MV repair largely acquire these skills outside of dedicated training fellowships. In this study, there was a relation of case volume to outcome for transcatheter MV repair with this device, similar to what has been observed for other transcatheter therapies and minimally invasive surgery (34–36). The median number of cases per institution was 6 over a 10-month period, with a range of 1 to 58 cases. Greater case volume was related to success in reducing MR. Prior to commercial approval, the U.S. experience with the only FDA-approved percutaneous mitral valve repair device consisted of 1,336 patients who had been treated at 42 institutions as part of research trials. Although these results suggest the importance of ongoing experience with the therapy, they should be interpreted with caution given the low volume per site and high concentrations of patients at a few centers.
Variables related to procedure success included echocardiographic characteristics, such as left ventricular chamber size and clip placement location on the MV. Those with failure to reduce MR had more fluoroscopy time, a higher incidence of single leaflet detachment, and a trend toward longer length of hospital stay. Patients without successful reduction in MR also had higher in-hospital and 30-day mortality, though these differences did not reach statistical significance. Procedural complications included death, and a hierarchical analysis of these components and their association with mortality was not possible. Notably, for patients without procedural complications, the in-hospital and 30-day rates of death were 0.0% and 2.6%, respectively. Although MV area and severe tricuspid regurgitation were not associated with outcomes in this study, caution should be exercised for transcatheter MV repair in these subsets, as limited data exist for these patients (37). Prior studies have demonstrated procedural success with and without recommended anatomic criteria for this therapy (29). The CMS coverage determination highlighted the need for teams experienced in mitral disease to be performing this therapy. The relation of clinical characteristics, procedural variables, and case volume to therapeutic success in our study underscore the importance of appropriate case selection and experience.
High-risk patients have been the focus of transcatheter MV repair, as efficacy has been found to be lower than that of surgery for patients who are suitable for either procedure. In several analyses, including the present investigation, mortality rates have been lower with transcatheter MV repair than expected for surgery. For example, 30-day mortality in the present study was 5.8%, compared with the predicted outcomes of 7.9% for mitral repair and 10.0% for mitral replacement. In EVEREST HRS, observed and predicted 30-day mortality rates were 4.8% and 11.3%, respectively (23). Certainly, risk calculators have imprecision due to statistical limitations and evolving care and may not accurately estimate surgical outcomes, especially at the high end of the spectrum of risk and when they cannot capture all relevant clinical features. In the present study, the median STS-PROM scores for the cohort exceeded what is generally considered to be prohibitive surgical risk (≥6% for mitral repair and ≥8% for mitral replacement) with other extenuating circumstances frequently present. These findings suggest that that the majority of patients undergoing commercial transcatheter MV repair in the United States are not surgical candidates.
Importantly, the results of the present study cannot be extended to patients at less or low surgical risk. Transcatheter MV repair with the MitraClip is approved for use in patients with prohibitive risk, which indicates that the likely benefit of surgery is outweighed by the risk for significant morbidity and mortality. It is well recognized that surgery is more effective than transcatheter MV repair in alleviating MR, and studies have demonstrated prognostic implications of MR even if not severe (3). In the present investigation, significant reduction was considered to be present when post-implantation MR was grade ≤2, a definition common among studies of transcatheter MV repair. Post-implantation MR that was mild or less was achieved in 64%. Prior studies have suggested comparable outcomes for grade ≤2 versus grade ≤1 residual MR in prohibitive-risk patients treated with transcatheter MV repair, and similar survival between transcatheter MV repair and surgery in lower risk patients despite different degrees of MR reduction (10,12). However, these latter studies were limited in size and follow-up duration. Further long-term evaluations are required to address the significance of residual MR in the present population and others treated with transcatheter MV repair. The TVT Registry, as a scientific tool, will enable the collection of these data for analysis and outcome reporting and will lead to further insight into the impact of this important therapy.
Although participation in the TVT Registry is required as part of the CMS national coverage determination, data entry remains voluntary and thus subject to bias reporting. It is important to note that echocardiographic variables are site reported and not assessed in a core laboratory. These variables include the severity of MR, whose assessment was left to physicians’ discretion at each implanting site. Details on the echocardiographic methods, including their timing and loading conditions, were not available. Although post-market approval registries provide valuable information on use in the commercial setting, data adjudication was limited and is a major limitation of the study. For missing data, bias toward the null is likely, but underreporting of poor outcomes certainly may occur. Of note, procedural success with post-implant MR grade ≤2 was similar for patients who with and without complete 30-day follow-up (p = 0.89). Data on functional status or quality of life, which are highly relevant in patients with heart failure, were incomplete and not analyzed in the present study, though 94% of patients were discharged home or to extended care.
In this report of the initial U.S. commercial experience with transcatheter MV repair, we observed that the procedure is being performed predominantly in a population of patients at prohibitive surgical risk, with symptomatic severe MR due to degenerative disease. Procedural success, clinical outcomes, and the rate of adverse events were comparable with pre-approval research studies and other commercial registries. These data highlight the utility of the TVT Registry for post-market surveillance and support the continued role of transcatheter MV repair by heart teams in the treatment of prohibitive-risk patients with symptomatic MR. Ongoing evaluation should be performed to assess long-term functional and cardiovascular outcomes.
COMPETENCY IN MEDICAL KNOWLEDGE: In the initial commercial experience of transcatheter MV repair with the MitraClip in the United States, predominantly involving patients with symptomatic, degenerative MR at prohibitive surgical risk, procedural success was achieved in approximately 91%, and the majority of patients were discharged home with no more than moderate MR.
TRANSLATIONAL OUTLOOK: Further studies are needed to assess the long-term results of this therapy in a larger number of patients.
Dr. Sorajja has served on the speakers bureau and as a consultant for Abbott Vascular; and has served as a consultant for Medtronic and Lake Regions Medical. Dr. Mack served as the co-principal investigator for COAPT (Abbott Vascular) and PARTNER 3 (Edwards Lifesciences). Dr. Vemulapalli has received research grants from Abbott Vascular, Boston Scientific, and the American College of Cardiology. Dr. Kar has served as a consultant and speaker for Abbott Vascular, AGA Medical, Boston Scientific, Coherex Medical, Medtronic, and St. Jude Medical. Dr. Lim has served as a consultant to Abbott Vascular. Dr. Thourani has served on the advisory board for Abbott Vascular. Dr. McCarthy has served as a consultant for Edwards Lifesciences and Abbott Vascular. Dr. Grayburn has received a research grant from and served as a consultant to Abbott Vascular; has received research grants from Medtronic, Boston Scientific, and Tendyne; and has served as a consultant for Bracco, Edwards Lifesciences, and Valtech Cardio. Dr. Pedersen has served on the speakers bureau for Edwards Lifesciences and Abbott Vascular; has served as a consultant for and receives a royalty return from Lake Regions Medical; is co-founder of and has equity interest in Intervalve; and has stock in Medtronic. Dr. Ailawadi has served as a consultant and speaker for Abbott Vascular; and has served as a consultant for Atricure, Edwards Lifesciences, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Presented at the 64th Scientific Sessions of the American College of Cardiology, March 8, 2015. Robert O. Bonow, MD, served as the Guest Editor for this paper.
- Abbreviations and Acronyms
- American College of Cardiology
- confidence interval
- Centers for Medicare and Medicaid Services
- heart failure
- internal mammary artery
- interquartile range
- mitral regurgitation
- mitral valve
- odds ratio
- Society of Thoracic Surgeons
- Society of Thoracic Surgeons Predicted Risk of Operative Mortality
- Transcatheter Valve Therapy
- Valve Academic Research Consortium
- Received December 7, 2015.
- Accepted December 15, 2015.
- 2016 American College of Cardiology Foundation
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