Author + information
- Received June 17, 2017
- Revision received September 6, 2017
- Accepted September 8, 2017
- Published online October 30, 2017.
- Paul Sorajja, MDa,∗ (, )
- Sreekanth Vemulapalli, MDb,
- Ted Feldman, MDc,
- Michael Mack, MDd,
- David R. Holmes Jr., MDe,
- Amanda Stebbins, MSb,
- Saibal Kar, MDf,
- Vinod Thourani, MDg and
- Gorav Ailawadi, MDh
- aValve Science Center, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota
- bDuke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina
- cEvanston Hospital, Evanston, Illinois
- dHeart Hospital Baylor Plano, Dallas, Texas
- eMayo Clinic, Rochester, Minnesota
- fCedars Sinai Medical Center, Los Angeles, California
- gMedstar Washington Hospital Center, Washington, DC
- hUniversity of Virginia, Charlottesville, Virginia
- ↵∗Address for correspondence:
Dr. Paul Sorajja, Minneapolis Heart Institute Foundation, Valve Science Center, Abbott Northwestern Hospital, 920 East 28th Street, Minneapolis, Minnesota 55401.
Presented at the 66th Scientific Sessions of the American College of Cardiology, Washington, DC, March 18, 2017.
Background Post-market surveillance is needed to evaluate the real-world clinical effectiveness and safety of U.S. Food and Drug Administration–approved devices.
Objectives The authors examined the commercial experience with transcatheter mitral valve repair for the treatment of mitral regurgitation.
Methods Data from the Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy Registry on patients commercially treated with transcatheter mitral valve repair were analyzed. The study population consisted of 2,952 patients treated at 145 hospitals between November 2013 and September 2015. In 1,867 patients, data were linked to patient-specific Centers for Medicare and Medicaid Services administrative claims for analyses.
Results The median age was 82 years (55.8% men), with a median Society of Thoracic Surgery predicted risk of mortality of 6.1% (interquartile range: 3.7% to 9.9%) and 9.2% (interquartile range: 6.0% to 14.1%) for mitral repair and replacement, respectively. Overall, in-hospital mortality was 2.7%. Acute procedure success occurred in 91.8%. Among the patients with Centers for Medicare and Medicaid Services linkage data, the mortality at 30 days and at 1 year was 5.2% and 25.8%, respectively, and repeat hospitalization for heart failure at 1 year occurred in 20.2%. Variables associated with mortality or rehospitalization for heart failure after multivariate adjustment were increasing age, lower baseline left ventricular ejection fraction, worse post-procedural mitral regurgitation, moderate or severe lung disease, dialysis, and severe tricuspid regurgitation.
Conclusions Our findings demonstrate that commercial transcatheter mitral valve repair is being performed in the United States with acute effectiveness and safety. Our findings may help determine which patients have favorable long-term outcomes with this therapy.
Degenerative mitral regurgitation (MR) affects ∼1% to 2% of the general population, and, in certain patient subsets, can lead to debilitating heart failure and poor long-term survival (1–4). Although surgery represents the standard of care for these patients, many do not undergo such therapy because of heightened perioperative risk (5–7). In 2013, transcatheter mitral valve (MV) repair using the MitraClip system (Abbott Vascular, Menlo Park, California) was approved as a commercial therapy for patients with symptomatic, primary, severe (grade ≥3+) MR and prohibitive surgical risk (8,9). Since commercialization, more than 3,000 patients have undergone transcatheter MV repair at >250 centers in the United States. Importantly, prior research studies were not designed prospectively to test efficacy and safety for the indication for which the therapy was approved. Thus, a detailed understanding of the real-world, post-market, long-term outcomes of this practice is needed to help determine the role of this therapy in the management of patients with MR.
Accordingly, we undertook this investigation to examine the in-hospital, 30-day, and 1-year outcomes of transcatheter MV repair in the United States. We examined data from the national Society of Thoracic Surgery/American College of Cardiology Transcatheter Valve Therapy (STS/ACC TVT) Registry. In this investigation, we update previously published data on acute procedural success and also extend the evaluation of these patients to 1-year follow-up (10).
The TVT registry
The STS/ACC TVT Registry was launched in 2011 as a joint initiative of the STS and ACC. The primary goals of the TVT Registry are to facilitate device and procedure surveillance, promote quality assurance and improvement initiatives, and conduct studies that help with access to new therapies and expansion of device labeling through evidence development (11,12). Patient enrollment in the TVT registry satisfies Centers for Medicare and Medicaid Services (CMS) national coverage determinations in which national registry participation is a requirement for both commercial therapies and those that are under clinical investigation. Centers who participate in the TVT Registry use standardized definitions to collect patient-specific data on demographics, morbidities, functional status, quality of life, hemodynamics, procedural details, and outcomes (in-hospital, 30-day, and 1-year) (13). The ACC National Cardiovascular Data Registry warehouse and the Duke Clinical Research Institute Data Analysis Center both implement data quality checks, including feedback reports, and examine data ranges and consistency to optimize completeness and accuracy. For protection of patient participants, the STS and ACC have signed a Federal Wide Assurance with the Department of Health and Human Services, and all research is conducted in compliance with the Common Rule (45 CFR §46). A central institutional review board (Chesapeake Research Review Inc.) approves activities of the TVT registry. The present investigation has been granted a waiver of informed consent.
Transcatheter MV repair with MitraClip was first approved for commercial use in the United States on October 24, 2013. The CMS National Coverage Determination for transcatheter MV repair with this technology requires the presence of symptomatic, severe (grade 3 or 4) primary MR in a patient at prohibitive surgical risk, an evaluation of the patient by a cardiac surgeon, and participation of the clinical center in a national registry. Prohibitive surgical risk is considered to be an STS predicted risk of operative mortality 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 portend such heightened risk (e.g., severe liver disease, radiation injury, dementia, porcelain aorta, frailty) (14).
All patients who underwent commercial therapy with the MitraClip system since initial U.S. Food and Drug Administration approval and who were enrolled in the TVT registry through September 1, 2015, were included in the present investigation. Patients who underwent implantation as part of a research study were excluded. The clinical records of the TVT registry were linked to Medicare administrative claims data using direct patient identifiers (name and social security number) (15).
Transcatheter MV repair
The procedure for transcatheter MV repair has been previously described in detail (16). In brief, using a transseptal approach from the femoral vein, a 24-F guiding catheter is placed into the left atrium. A steerable sleeve is advanced through the guiding catheter and is steered toward the MV under imaging guidance principally performed by transesophageal echocardiography. A 4-mm, cobalt chromium, polyester-covered clip with movable arms is placed into the left ventricle, followed by retraction of the arms 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 clip in the area of MR, and thus mimicking the surgical Alfieri “edge-to-edge” stitch. Before release of the device, the operator confirms complete insertion of both leaflets in the clip arms, a significant reduction in MR, and no evidence of significant for mitral stenosis. If further MR reduction is needed, additional clips can be placed using the same techniques.
Study outcomes and definitions
Procedural and in-hospital outcomes were determined from data in the TVT Registry. Standard definitions, in accordance with the Valve Academic Research Consortium, were used for collection of data elements in the registry that are harmonized with the STS national database, wherever possible (17). MR was reported by site and classified as mild (grade 1), moderate (grade 2), moderately severe (grade 3), or severe (grade 4), with recommendations for use of standard criteria for classification (5). Acute procedure success was defined as acute reduction in MR to grade 2 or less, without conversion to cardiac surgery and without in-hospital mortality. All site-reported strokes, cardiac surgery, and valve events were adjudicated using a combination of site-reported clinical information and chart reviews by a board-certified cardiologist at the Duke Clinical Research Institute. Procedural complications were defined as cardiac perforation (with or without tamponade), major bleeding (Valve Academic Research Consortium-2 criteria), stroke or transient ischemic attack, myocardial infarction, or death. 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.
For clinical events after hospital discharge (i.e., 30-day and 1-year outcomes), data from CMS administrative claims were used (15). Death following hospital discharge was identified using the Medicare Denominator file. Rehospitalization events were determined from CMS administrative claims data using the following International Classification of Diseases, Ninth Revision, Clinical Modification codes: 398.x, 402.x1, 404.x1, 404.x3, and 428.x for rehospitalization for heart failure; 35.02, 35.12, 35.23, 35.24, 35.96, and 35.97 for repeat transcatheter MV repair; and 35.12, 35.23, and 35.24 for cardiac mitral surgery.
Outcomes that occurred during the procedure, hospitalization, within 30 days, and within 1 year after the initial procedure were examined. The primary outcomes of interest for the present investigation were death, rehospitalization for heart failure, and the combined endpoint of death or heart failure rehospitalization within 1 year. Patients were censored at 1 year, at the time of death, or on September 30, 2015, whichever came first. Unadjusted and adjusted proportional hazard models were generated for each fatal endpoint, nonfatal endpoints were assessed with Fine and Gray subdistributions. General estimated equation method with exchangeable working correlation structure was performed to account for within-hospital clustering. Adjusted models included the following covariates: age, male, prior stroke, body mass index, diabetes mellitus, current dialysis, oxygen-dependent lung disease, prior myocardial infarction, ischemic cardiomyopathy, left ventricular ejection fraction, left ventricular internal systolic dimension, left ventricular internal diastolic dimension, degree of MR at baseline, MV pathology (degenerative or functional), severity of tricuspid regurgitation, and post-procedural MR. Patients in which both degenerative and functional MR had been described in the TVT Registry were categorized as functional MR for analytical purposes. Both adjusted and unadjusted hazard ratios (HRs) were estimated with 95% confidence intervals and Wald-type p values are reported. Cumulative incidence figures with Fine and Gray subdistribution p values are reported for the primary endpoints. A 2-sided p < 0.05 was considered statistically significant. Discrete factors are presented as frequencies and percentages. Continuous variables reported as the median with 25th and 75th percentiles and interquartile ranges (IQRs). SAS statistical software, version 9.3 (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.
Between November 2013 and September 2015, 2,952 patients underwent commercial transcatheter MV repair in the United States and had data entered into the STS/ACC TVT Registry (Table 1). The cohort consisted of patients who had been treated at 145 hospitals. Patients were elderly (median age, 82 years [IQR: 74 to 86 years]; 55.8% men), and most had advanced symptoms (New York Heart Association functional class III or IV in 85.0%). Morbidities, such as prior stroke, diabetes mellitus, coronary artery disease, atrial fibrillation, dialysis, oxygen-dependent lung disease, peripheral artery disease, and prior sternotomy were common. Frailty was described in 50.3%, whereas other prohibitive surgical risk features were also frequently present. Overall, the median (IQR) STS-predicted risks of mortality for MV repair and MV replacement were 6.1% (3.7% to 9.9%) and 9.2% (6.0% to 14.1%), respectively.
The predominant pathology treated with transcatheter MV repair was degenerative MR, which was reported in 85.9% (Table 2). Functional MR was described in 17.5%, including 262 patients in whom degenerative disease was concurrently reported (8.9% of total patients) and 254 other patients with functional MR alone (8.6% of total patients). Overall, the procedure was performed for grade 3 or 4 MR in 93.0%. Significant left ventricular dilation (end-systolic dimension ≥40 mm) was present in 32.2%. The median left ventricular ejection fraction was 55% (40% to 60%); the ejection fraction was <50% in 35.4% of the patients. Mitral stenosis was common: the baseline mean mitral gradient was ≥5 mm Hg in 9.2%, and the MV area was <4 cm2 in 20.5%. Severe tricuspid regurgitation was present in 16.0%.
Procedural and in-hospital outcomes
The most frequent site of clip implantation was the A2-P2 segments of the MV (82.8% of cases) (Table 3). Multiple clips were implanted in 34.5%. Single-leaflet device attachment occurred in only 1.5%. For post-procedural MR, the rates of grade ≤1, grade 2, and grade ≥3 were 61.8%, 31.2%, and 7.0%, respectively. There were 4 reported cases of device embolization (0.1%). Major or life-threatening bleeding occurred in 3.9%. The rates of stroke (0.4%) and myocardial infarction (0.1%) were both low. Twenty patients (0.7%) had in-hospital conversion to open cardiac surgery. In the entire cohort, in-hospital mortality was 2.7%. Overall, reduction to moderate or less MR in the absence of cardiac surgery or in-hospital mortality occurred in 91.8% of patients. Mild or less residual MR, in the absence of cardiac surgery or in-hospital mortality, was achieved in 60.9%. The median length of hospital stay was 2 days (1 to 5 days). The vast majority (85.9%) of the treated patients were discharged directly home. Achievement of residual MR grade ≤2 with transcatheter MV repair, in comparison to patients without such MR reduction, was significantly associated with shorter hospital length of stay (2.0 days [1.0 to 5.0 days] vs. 3.0 days [2.0 to 8.0 days]; p < 0.001) and lower in-hospital mortality (2.1% vs. 10.2%; p < 0.001).
Of those who underwent commercial transcatheter MV therapy, 1,867 patients (63.2%) from 139 hospitals had records that could be linked to CMS administrative claims. Compared with patients without CMS data linkage, those with linkage were older (age, 83 years [77 to 87 years] vs. 78 years [66 to 85 years]; p < 0.0001), more commonly white in ethnicity (93.5% vs. for 84.5%; p < 0.0001), and had a lower prevalence of smoking (3.9% vs. 8.8%; p < 0.0001), diabetes mellitus (23.5% vs. 27.7%; p = 0.01), hemodialysis (2.9% vs. 6.3%; p < 0.0001), and prior myocardial infarction (25.4% vs. 30.5%; p = 0.002). Patients with linked CMS claims data also had higher left ventricular ejection fraction (55.0% [43.0% to 60.0%] vs. 53% [35% to 60%]; p < 0.0001), and less frequently had functional MR reported as the pathology treated (15.9% vs. 20.3%; p < 0.0001). Overall, the STS-predicted risk of operative mortality risk scores for mitral repair (6.5 [4.1 to 10.5] vs. 5.3 [2.8 to 8.9]; p < 0.0001) and replacement (9.8 [6.4 to 14.7] vs. 8.1 [4.8 to 13.0]; p < 0.0001), respectively, were higher in comparison to patients without linked CMS claims data.
In the cohort of patients with linked CMS claims data (n = 1,867), the 30-day mortality, including in-hospital events, was 5.2% (Table 4). The 30-day rate of rehospitalization for heart failure was 4.9%. Overall, 95.5% were discharged from hospital with MR grade ≤2 without cardiac surgery and had 30-day survival.
Among the patients with linked CMS claims data, death occurred within 1 year in 25.8% (Table 5). The rate of re-hospitalization for heart failure was 20.2%. For the occurrence of either death or heart failure hospitalization at 1 year, the rate was 37.9%. Repeat transcatheter MV repair occurred in 6.2%. The cumulative rate of stroke was 2.7%. Figure 1 shows the cumulative incidence of death and rehospitalization for heart failure for the patient cohort during the study period (Central Illustration).
Significant differences in the 1-year outcomes were present according to the mitral pathology treated. The cumulative incidences of mortality (24.7%), rehospitalization for heart failure (20.5%), and the combined endpoint for both of these 2 outcomes (35.7%) were lower for patients with degenerative MR, in comparison to those observed with functional MR (31.2%, 32.6%, and 49.0%, respectively) (Figure 2). The subgroup of patients with severe tricuspid regurgitation also had significantly worse outcomes, with 1-year cumulative incidences of 38.5%, 31.5%, and 54.3% for death, heart failure rehospitalization, and the combined endpoint of death and heart failure rehospitalization, respectively, observed in these patients (Figure 3). Mortality and the rate of heart failure rehospitalization at 1 year were higher for patients who had residual MR grade 3 or 4 following transcatheter MV repair, as defined before hospital discharge, in comparison to other patients (Figure 4, Table 5). For post-procedural MR grade ≤1, grade 2, and grade ≥3, the cumulative incidences of death at 1 year were 21.7%, 29.2%, and 48.9%, respectively (p < 0.0001). For combined endpoint of death or heart failure rehospitalization, these respective 1-year incidences were 35.7%, 39.2%, and 54.4% (p < 0.0001).
Figure 5 shows the results of multivariate analyses. Age (HR: 1.13; 95% confidence interval [CI]: 1.04 to 1.24; p = 0.005), left ventricular ejection fraction (HR: 0.93; 95% CI: 0.89 to 0.96; p < 0.0001), severe tricuspid regurgitation (HR: 1.91; 95% CI: 1.42 to 2.55; p < 0.001), dialysis (HR: 2.19; 95% CI: 1.28 to 3.74; p = 0.004), moderate or severe lung disease (HR: 1.36; 95% CI: 1.06 to 1.74; p < 0.02), and residual MR were significantly associated with 1-year mortality. For the combined endpoint of death and rehospitalization for heart failure at 1 year, age (HR per 5 years: 1.08; 95% CI: 1.01 to 1.15; p = 0.02), dialysis (HR: 2.09; 95% CI: 1.37 to 3.28; p = 0.001), left ventricular ejection fraction (HR per 5%: 0.92; 95% CI: 0.88 to 0.95; p < 0.001), moderate or severe lung disease (HR: 1.28; 95% CI: 1.05 to 1.58; p < 0.02), severe tricuspid regurgitation (HR: 1.89; 95% CI: 1.49, 2.39; p < 0.001), and post-procedural residual MR were significant covariates.
The principal findings of the present investigation are: 1) in the United States, transcatheter MV repair is being performed predominantly for patients with severely symptomatic, degenerative MR, and prohibitive surgical risk in accordance with the labeled indications; 2) acute reduction in MR to grade 2 or less is achieved ∼92% of patients with low incidences of adverse events, including an in-hospital mortality of 2.7%; 3) at 1-year follow-up, death occurs in 25.8%, and the rate of rehospitalization for heart failure is 20.2%; and 4) clinical variables of age, left ventricular ejection fraction, dialysis, moderate-severe lung disease, severe tricuspid regurgitation, and post-procedural residual MR are associated with both death and heart failure rehospitalization in follow-up.
The presence of severe MR confers an adverse prognosis with a heightened risk of heart failure and impaired long-term survival (2–4). For those with prohibitive surgical risk, transcatheter MV repair is an important advance because these patients have markedly limited therapeutic options (8). MitraClip is known to be effective for reducing MR, promoting beneficial left ventricular remodeling, and lessening symptoms of heart failure (8,9).
In the present study of patients undergoing commercial treatment transcatheter MV repair (TMVR) in the United States, the vast majority of patients were treated on-label, with a high prevalence of severe symptoms, degenerative MR, and prohibitive surgical risk. There was a reduction in MR to grade 2 or less in 92%, with a low risk of adverse events, including an in-hospital mortality of only 2.7%. The median hospital stay was short (i.e., 2 days), and 86% of patients were discharged directly home. By 30 days, 96% of patients had significant reduction of MR and had survived. These findings, which are consistent with prior reports on the effectiveness and safety of transcatheter MV repair, are important observations as the treatment population expands, new hospital sites for the therapy accrue, and a number of potentially eligible patients remain untreated (6,7,10). Taken together, the findings demonstrate that transcatheter MV repair is being performed effectively and safely in patients in the United States who are at prohibitive surgical risk.
Although transcatheter MV repair is acutely successful in the vast majority of treated patients, survival impairment can still occur from elderly age, the pathological consequences of MR, and underlying cardiac and noncardiac comorbidities. As observed in the present study, these clinical derangements are particularly common in MR patients who are at high surgical risk. To examine the 1-year survival of the study cohort, we performed linkage to CMS administrative claims data for the clinical outcomes of death and heart failure rehospitalization (15). Within 1 year after transcatheter MV repair, 25.8% of the patients died, and rehospitalization for heart failure occurred in 20.2%. For the study population, the cumulative incidence of death or rehospitalization for heart failure within 1 year, notably, was 37.9%.
Other studies of high-risk patient populations also have reported on risks of death and heart failure hospitalization, despite initially successful transcatheter MV therapy (15,18–26). Notably, the incidences of death (25.8%) and heart failure rehospitalization (20.2%) in our study were similar to the rates (23.8% and 18.0%, respectively) observed in an analysis of high-risk patients in the EVEREST (Endovascular Valve Edge-to-Edge Repair Study) II and REALISM (Real World Expanded Multicenter Study of the MitraClip) System Continued Access Study High-Risk arm (20). These observations are particularly relevant because data from the EVEREST/REALISM cohort were used to garner commercial approval in the United States. In comparison to registries of TMVR outside the United States, the mortality rate in the present investigation is generally higher than what has been observed (11% to 23%), whereas the incidence of rehospitalization for heart failure (14% to 26%) is largely comparable. Differences in mortality are difficult to reconcile because of the potential for selection bias in comparisons across different studies, although it is important to note that patients in the present study are considerably older (median age, 82 years) than in other national registries outside the United States (median age, 71 to 75 years).
Similar observations on persistent risk of death have been reported for other forms of transcatheter therapy, when such therapy is used in patients with high or prohibitive surgical risk (e.g., transcatheter aortic valve replacement or transcatheter aortic valve replacement for severe aortic stenosis) (15,27–29). These persistent risks are attributable, at least in part, to untreated comorbidities. As an example, there was a highly significant relation between severe tricuspid regurgitation at baseline and subsequent, poorer outcome after transcatheter MV repair in the present study. Concomitant lung disease and renal failure also were variables importantly associated with 1-year outcomes. The EVEREST/REALISM studies excluded patients with significant tricuspid regurgitation and those with severe lung disease. These observations in the commercial experience emphasize the importance of appropriate patient selection, with the therapeutic goal being the maximization of beneficial, long-term clinical outcomes.
Ventricular function is a well-known predictor of survival in a variety of cardiovascular disease states. In the present study, the presence of higher left ventricular ejection fraction was associated with a lower risk of death (HR: 0.93; 95% CI: 0.89 to 0.96; p < 0.0001), as well as a lower likelihood of death or rehospitalization for heart failure (HR: 0.92; 95% CI: 0.88 to 0.95; p < 0.001) within 1 year of follow-up. For patients with functional MR, in which ventricular dysfunction is the cause of the MR, there also was relatively poorer survival, with a 1-year mortality of 31.2% (vs. 24.7% for degenerative MR); 49.0% of patients with functional MR had either death or subsequent heart failure hospitalization within 1 year after therapy. Of note, functional MR is not an approved indication for this therapy in the United States, and thus data on these patients reflect off-label use.
In current practice outside the United States, functional or secondary MR is the predominant pathology treated with transcatheter MV repair (∼70% of cases) (19,21). It is important to note that the present study is a single-arm registry, in which data on clinical outcomes with other forms of therapy for MR are not available for comparison. Such controls, whether medical or surgical, are necessary to determine the magnitude (or lack thereof) of any clinical benefit of transcatheter MV repair in these patients, particularly in high-risk individuals in which there may be continued adverse events despite initially successful therapy (30–32). In models that accounted for baseline ventricular function in our study, functional MR also was not significantly associated with 1-year outcomes. In this light, the potential clinical impact of transcatheter MV repair is being compared with guideline-directed medical therapy in 2 trials: COAPT Trial (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation; NCT01626079) and MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary MR; NCT01920698). Of note, severe tricuspid regurgitation and severe lung disease are exclusion criteria for these trials, and both of these morbidities were associated with worse survival in our study.
In the present study, there was a significant relation between the degree of residual MR after transcatheter MV repair and survival. In comparison with patients with residual MR grade I/II, those with residual MR grade III/IV had ∼4-fold greater in-hospital mortality (10.2% vs. 2.7%; p = 0.001), and death occurred in 49% of these patients within 1 year (vs. 24% for residual MR grade I/II; p < 0.001). In this registry, data on specific cause of death and circumstantial events are limited, and the relative contributions of multiple potential etiologies for the poor prognosis of these patients cannot be determined with certainty. For patients with persistent severe MR, these potential contributions include higher rates of acute complications (e.g., single-leaflet device attachment) and subsequent procedures (e.g., repeat transcatheter MV repair and subsequent cardiac surgery), both of which carry additional risks. Mortality at 1 year was lowest for patients with mild or no residual MR. Certainly, the dependency on site-reporting of MR grade and potential variation in grading of severity is a limitation of our study. Nonetheless, our findings support the rationale for achieving significant MR reduction, including minimizing need for future surgical therapy, with procedural expertise when possible, even though the desired therapeutic goal may be less certain when treating patients with limited or no other therapeutic options (i.e., prohibitive surgical risk patients). Further study into the causative or associative relation between residual MR and survival in these patients is needed.
The absence of information on clinical justification for hospitalization or repeat surgical procedures is an important limitation of the use of CMS administrative claims data. Without such information, the relation between those subsequent events and various possible causes cannot be accurately determined. For example, MR and its treatment may not be the predominant reasons for such events when there are other coexisting cardiac conditions (e.g., coronary artery disease, atrial fibrillation) that may cause heart failure, or any morbidity that could result in death. Nonetheless, CMS administrative claims data are an accurate reflection of resource utilization, which is of significant importance for examining the role of commercialized therapies in practice. Patients who cannot be linked to CMS claims data are those who have third-party insurance or Medicare advantage. Site participation in the TVT registry fulfills 1 of the requirements the CMS national coverage determination for transcatheter MV repair; however, it is important to note that such participation is voluntary with data reported from sites being susceptible to bias reporting. In particular, MR etiology and severity grading are not adjudicated in an echocardiographic core laboratory. Although there are conventional definitions for degenerative versus functional MR, data on these etiologies are site reported. MR grading after transcatheter MV repair notably can be challenging with limitations from acoustic shadowing from TMVR, multiple potential regurgitant orifices, and the eccentric nature of post-procedural regurgitation in these patients. There were significant differences in patients with and without linked CMS claims data. Within the patients with linked claims data, modeling was performed to help account for characteristics of that study population. Finally, the outcomes in this study are the results of a single-arm registry, without a comparator group available.
TMVR is being performed effectively and safely for severely symptomatic patients with MR and prohibitive surgical risk in the United States. Within 1 year of therapy, mortality occurs in approximately one-fourth of patients, and approximately one-fifth are rehospitalized for heart failure. These adverse events are related to age and associated with decreased left ventricular function, functional MR, severe tricuspid regurgitation, moderate or severe lung disease, and post-procedural residual MR.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: Although TMVR is associated with a high rate of procedural success in the United States, roughly 1 in 5 patients are rehospitalized with heart failure, and 1 in 4 do not survive beyond 1 year.
TRANSLATIONAL OUTLOOK: More research is needed to improve long-term outcomes following TMVR.
This study was supported by an Abbott Vascular Grant. Dr. Sorajja is a consultant with Abbott Vascular, Medtronic, Boston Scientific, and Integer; and has received research grants and speakers fees from Abbott Vascular, Medtronic, Boston Scientific, and Integer. Dr. Vemulapalli is a consultant with Abbott Vascular, Boston Scientific, American College of Cardiology, Society of Thoracic Surgeons, and Patient Centered Outcomes Research Institute. Dr. Feldman is a consultant with Abbott Vascular, Boston Scientific, Edwards Lifesciences, and Gore Medical; and has received honoraria from Abbott Vascular, Boston Scientific, and Edwards Lifesciences. Dr. Mack is a consultant with Abbott Vascular and Edwards Lifesciences. Dr. Holmes is a consultant with Boston Scientific. Dr. Kar is a consultant with Abbott Vascular, Boston Scientific, Edwards Lifesciences, Gore Medical, and Mitralign; and has received research grants from Abbott Vascular, Boston Scientific, and Edwards Lifesciences. Dr. Thourani is a consultant with Abbott Vascular. Dr. Ailawadi is a consultant with Abbott Vascular, Atricure, Edwards Lifesciences, Medtronic, and St. Jude. Ms. Stebbins has reported that she has no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American College of Cardiology
- Center for Medicare and Medicaid Services
- hazard ratio
- interquartile range
- mitral regurgitation
- mitral valve
- Society of Thoracic Surgery
- transcatheter mitral valve repair
- Transcatheter Valve Therapy
- Valve Academic Research Consortium
- Received June 17, 2017.
- Revision received September 6, 2017.
- Accepted September 8, 2017.
- 2017 American College of Cardiology Foundation
- Enriquez-Sarano M.,
- Tajik A.J.,
- Schaff H.V.,
- et al.
- Grigioni F.,
- Tribouilloy C.,
- Avierinos J.F.,
- et al.
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- Goel S.S.,
- Bajaj N.,
- Aggarwal B.,
- et al.
- Lim D.S.,
- Reynolds M.R.,
- Feldman T.,
- et al.
- Feldman T.,
- Kar S.,
- Elmariah S.,
- et al.
- Sorajja P.,
- Mack M.,
- Vemulapalli S.,
- et al.
- Carroll J.D.,
- Edwards F.H.,
- Marinac-Dabic D.,
- et al.
- ↵American College of Cardiology: Society of Thoracic Surgeons. ACC/STS TVT Registry home page. Available at: https://www.ncdr.com/TVT/Home/Default.aspx. Accessed February 11, 2017.
- ↵American College of Cardiology: Society of Thoracic Surgeons. ACC/STS TVT Registry: NCDR participants/site manager contact. Available at: https://www.ncdr.com/TVT/Private/Resources/ParticipantDirectory.aspx. Accessed February 11, 2017.
- ↵Society of Thoracic Surgeons. Online STS risk calculator. Available at: http://riskcalc.sts.org/STSWebRiskCalc273. Accessed February 11, 2017.
- Feldman T.,
- Wasserman H.S.,
- Herrmann H.C.,
- et al.
- Leon M.B.,
- Piazza N.,
- Nikolsky E.,
- et al.
- Attizzani G.F.,
- Ohno Y.,
- Capodanno D.,
- et al.
- Nickenig G.,
- Estevez-Loureiro R.,
- Franzen O.,
- et al.
- Glower D.D.,
- Kar S.,
- Trento A.,
- et al.
- Maisano F.,
- Franzen O.,
- Baldus S.,
- et al.
- Lesevic H.,
- Sonne C.,
- Braun D.,
- et al.
- Pighi M.,
- Estevez-Loureirio R.,
- Maisano F.,
- et al.
- Tigges E.,
- Kalbacher D.,
- Thomas C.,
- et al.
- Webb J.G.,
- Doshi D.,
- Mack M.J.,
- et al.
- Arnold S.V.,
- Afilalo J.,
- Spertus J.A.,
- et al.
- Swaans M.J.,
- Bakker A.L.M.,
- Alipour A.,
- et al.
- Giannini C.,
- Fiorelli F.,
- De Carlo M.,
- et al.