Author + information
- Received August 27, 2015
- Revision received October 7, 2015
- Accepted October 13, 2015
- Published online December 29, 2015.
- David R. Holmes Jr., MD∗∗ (, )
- Rick A. Nishimura, MD∗,
- Frederick L. Grover, MD†,
- Ralph G. Brindis, MD, MPH‡,
- John D. Carroll, MD†,
- Fred H. Edwards, MD§,
- Eric D. Peterson, MD, MPH‖,
- John S. Rumsfeld, MD, PhD¶,
- David M. Shahian, MD#,
- Vinod H. Thourani, MD∗∗,
- E. Murat Tuzcu, MD††,
- Sreekanth Vemulapalli, MD‖,
- Kathleen Hewitt, RN, MSN‡‡,
- Joan Michaels, RN, MSNm‡‡,
- Susan Fitzgerald, RN, MS‡‡,
- Michael J. Mack, MD§§,
- STS/ACC TVT Registry
- ∗Mayo Clinic, Rochester, Minnesota
- †University of Colorado, Denver, Colorado
- ‡University of California, San Francisco, California
- §University of Florida, Jacksonville, Florida
- ‖Duke University Medical Center, Durham, North Carolina
- ¶Denver VA Medical Center, Denver, Colorado
- #Massachusetts General Hospital, Boston, Massachusetts
- ∗∗Emory University, Atlanta, Georgia
- ††Cleveland Clinic, Cleveland, Ohio
- ‡‡American College of Cardiology, Washington, DC
- §§Baylor Scott and White Health, Plano, Texas
- ↵∗Reprint requests and correspondence:
Dr. David R. Holmes, Jr., Mayo Clinic, 200 First Street Southwest, Rochester, Minnesota 55905.
Background The Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry has been a joint initiative of the STS and the ACC in concert with multiple stakeholders. The TVT Registry has important information regarding patient selection, delivery of care, science, education, and research in the field of structural valvular heart disease.
Objectives This report provides an overview on current U.S. TVT practice and trends. The emphasis is on demographics, in-hospital procedural characteristics, and outcomes of patients having transcatheter aortic valve replacement (TAVR) performed at 348 U.S. centers.
Methods The TVT Registry captured 26,414 TAVR procedures as of December 31, 2014. Temporal trends between 2012 and 2013 versus 2014 were compared.
Results Comparison of the 2 time periods reveals that TAVR patients remain elderly (mean age 82 years), with multiple comorbidities, reflected by a high mean STS predicted risk of mortality (STS PROM) for surgical valve replacement (8.34%), were highly symptomatic (New York Heart Association functional class III/IV in 82.5%), frail (slow 5-m walk test in 81.6%), and have poor self-reported health status (median baseline Kansas City Cardiomyopathy Questionnaire score of 39.1). Procedure performance is changing, with an increased use of moderate sedation (from 1.6% to 5.1%) and increase in femoral access using percutaneous techniques (66.8% in 2014). Vascular complication rates are decreasing (from 5.6% to 4.2%), whereas site-reported stroke rates remain stable at 2.2%.
Conclusions The TVT Registry provides important information on characteristics and outcomes of TAVR in contemporary U.S. clinical practice. It can be used to identify trends in practice and opportunities for quality improvement.
- aortic stenosis
- aortic valve replacement
- transcatheter aortic valve replacement
- valvular heart disease
The Society of Thoracic Surgeons (STS) and the American College of Cardiology (ACC) developed the STS/ACC Transcatheter Valve Therapy (TVT) Registry in concert with multiple stakeholders, including regulatory agencies and industry (1–4). Originally designed to satisfy the Center for Medicare & Medicaid Services (CMS) National Coverage Determination (NCD) requirements for coverage with evidence development, TVT captures data on patient characteristics, procedural variables, and outcomes, including quality of life. Among other requirements, key provisions are that the heart team and hospital are participating in a prospective, national, audited registry that: 1) consecutively enrolls patients; 2) accepts all manufactured devices; and 3) follows the patient for at least 1 year. Implementation of the registry satisfies these requirements. The completeness of the datasets is designed to document specific answers to clinical and device questions required by the coverage with evidence developments, and the data are sufficiently detailed to allow robust retrospective analyses of deidentified data for quality assessment and performance improvement purposes, including: 1) generation of important descriptive information regarding evolving trends in overall patient selection, device use, and outcomes; 2) the development of validated risk prediction models; 3) the ability to provide individual patient risk prediction; and 4) benchmarking of site and provider-level outcomes on the basis of patient risk. These functions serve as the basis for informing patient and provider decisions regarding the appropriateness of available therapeutic strategies using outcome-driven data. Additional benefits include the ability to prospectively pose specific clinical research questions that can be used to query selective deidentified datasets within the registry. Monitoring of temporal trends in existing retrospective deidentified data from this (and other similar well-designed and conducted) registries, regarding real-world patient selection, procedural outcomes, and adverse events, may also prove to have important pre- and post-market regulatory implications relative to device label expansion and surveillance.
This report provides an update on the information obtained from this joint initiative, provides a baseline benchmark report for the performance of transcatheter aortic valve replacement (TAVR) in the United States, and informs development of global registries (5,6). It also facilitates identification of specific items of interest, which can then be selected for more focused statistical assessment to better understand inference and/or causal relationships (7–9).
Since inception of the TVT Registry in December 2011 and implementation of the CMS NCD, TAVR technology has been dispersed, with 348 centers performing TAVR in 48 of 50 states (Figure 1) in 2014. It has been the platform for 4 Food and Drug Administration (FDA) post-approval studies for SAPIEN (Edwards Lifesciences, Irvine, California), CoreValve (Medtronic, Inc., Minneapolis, Minnesota), and MitraClip devices (Abbott Vascular, Temecula, California).
In the process of implementation, a data dictionary was developed using standardized definitions (10,11) and was subsequently refined to include 308 elements, including baseline patient characteristics, outcomes, procedural performance, and device selection.
The registry captures patient-reported health status (Kansas City Cardiomyopathy Questionnaire [KCCQ]) not previously collected by a national registry (12,13), which includes social and quality-of-life indicators. It also assesses disability, neurocognitive function, and effect on social/recreational activities in patients who experience a stroke. In addition, discharge location documents the need for extended or nursing home care. Finally, a Unique Device Identifier field has been added to allow tracking of specific unique devices, pending implementation of a Unique Device Identifier strategy by the FDA.
Although the initial TVT Registry was limited to the SAPIEN device and its initial specific indication for approval (i.e., transfemoral access for high-risk or inoperable native aortic stenosis), new modules have been added to allow for alternative access, new iterations of FDA-approved TAVR valves from various manufacturers, and the application of TAVR for treatment of degenerated surgical biological valves. Finally, the TVT Registry has been expanded to include elements specific for MitraClip and other transcatheter mitral devices.
Baseline patient characteristics and in-hospital outcomes were summarized by percentages and compared across subgroups using chi-square, Wilcoxon, or Kruskal-Wallis 2-sided tests, as appropriate. For all analyses, p values <0.05 were considered statistically significant, and all analyses were performed at the Duke Clinical Research Institute using SAS software (version 9.3, SAS Institute, Cary, North Carolina).
This initial report profiles in-hospital characteristics and outcomes of TAVR. Initial detailed outcomes of MitraClip will be reported separately. Subsequent updates will also include longer-term outcomes on both TAVR and any approved transcatheter mitral valve therapies.
Sites and procedures
At 348 centers, as of December 2014, there were 26,414 TAVR patient records (Figure 1, Central Illustration). Data are currently captured for all commercial TAVR devices including SAPIEN, SAPIEN XT, and CoreValve. Approximately 10,000 additional TAVR procedures are not currently captured in the TVT Registry because they were performed as part of investigational device exemption trials; regulatory concerns currently preclude inclusion of investigational devices in TVT Registry reports.
For this first update, data are divided into 2 major groups: 1) patients with TAVR procedures between January 1, 2012, and December 31, 2013; and 2) patients with TAVR procedures between January 1, 2014, and December 31, 2014.
Overall, 50.5% of patients with TAVR procedures from 2012 to 2014 were male, with a mean age of 82 years; 91% were ≥70 years of age, whereas 68% were ≥80 years of age (Table 1, Figure 2). Less than 5% of all patients were black. Multiple comorbidities were common, including prior revascularization (either percutaneous coronary intervention or coronary artery bypass graft), prior stroke, diabetes, and peripheral arterial disease. Other high-risk characteristics include moderate or severe chronic lung disease (Online Figure 1) and prior myocardial infarction (Table 1). Approximately 83% of patients were in New York Heart Association functional class III/IV (Online Figure 2). Concordant with this, approximately 82% had evidence of frailty, with a slow 5-m walk test (Table 1). The KCCQ provided a further estimate of abnormal self-reported health status. Although only obtained in approximately 76% of patients, the mean KCCQ score was 41, with a statistically significant, but clinically insignificant increase over time (p for trend <0.0001). This indicates poor health status, including reduced function and quality of life (Figure 3). Finally, a history of or current atrial fibrillation was identified in approximately 41% of patients.
The changes in baseline characteristics over the 2 timeframes were clinically minor, although statistically significant due to the size of the registry. Overall, the mean STS risk score (14) was 8.34%, with a decrease in the median STS risk score from 2012 to 2014 (Figure 4A) (p for trend <0.0001). This is probably related in part to the expansion of TAVR to high-risk patients, from its initial restriction to inoperable or prohibitive-risk patients. The absolute breakdown of STS risk scores can be seen in Figure 4B, showing some decline in the highest-risk patients (STS risk score ≥15).
Hemodynamic assessment data is shown in Table 2. By protocol, all patients had to have severe native aortic stenosis determined by the heart team to be eligible for treatment. The etiology of the aortic stenosis was degenerative due to tricuspid disease in most patients (91.7%). In the remainder, the etiology either was bicuspid or could not be confidently distinguished, usually because of excessive calcification and leaflet fusion. The majority of patients had no, trace/trivial, or only mild aortic regurgitation; only 20% had moderate or severe regurgitation. Assessment of pre-procedural aortic annulus size varied among sites; transesophageal echocardiography use for this specific purpose has decreased, whereas the use of computed tomography angiography has increased (p for trend <0.0001) (Online Figure 3).
More than 90% of patients had severe native aortic stenosis as the primary indication. A small number of patients (2.2%) were treated with the off-label indication of valve-in-valve for degenerated biologic prostheses. As per the CMS NCD, 2 surgeons were required to evaluate each patient for suitability for TAVR. This process was documented in 94.8% of patients. The initial categories (Figure 5) included extreme and high risk but continue to evolve as the procedure is performed in intermediate- and even lower-risk patients.
Diagnostic angiography identified that 37% of patients had no significant coronary lesions or had patent grafts to vascular beds that had been previously found to have significant stenoses. The distribution of significant coronary artery disease in the remaining patients ranged between the 2 groups, but most commonly involved 1 or 3 major epicardial vessels. Severe left ventricular dysfunction (ejection fraction <30%) was documented in approximately 7.4% of patients by assessment of left ventricular function, assessed by either catheterization or echocardiography.
Greater than 90% of cases were performed electively (Table 3); the remainder were usually classified as urgent. During the 2 time periods analyzed, the procedure itself was typically performed in a hybrid operating room suite (Online Figure 4); only 10% to 13% were performed in a catheterization laboratory. This may change as the technology improves with decreasing catheter sizes and may shift the procedure in the future to more frequent performance in a catheterization laboratory.
The specific mode of anesthesia (Online Figure 5) was typically general, with moderate sedation used in <5%, although with a clinically and statistically meaningful increase in use over time (p for trend <0.0001). This has changed with smaller TAVR catheters, so that the use of moderate sedation has become increasingly frequent in selected centers (15). This trend can be expected to increase because it can result in a shorter length of hospital stay and should result in improved patient preference and tolerance of the procedure. Performance of cardiopulmonary bypass was infrequent (<5%) and usually performed emergently as the result of a complication.
Access site has changed substantially (Central Illustration) (p for trend <0.0001), which is the result of several factors, including the initial FDA indications for use (i.e., transfemoral vs. alternative access), the presence or absence of peripheral arterial disease (which may preclude a femoral approach), or the specific devices available. It is anticipated that this will continue to change. Another important benchmark is the sheath access method (Online Figure 6), with variability characterized by increasing use of a percutaneous approach.
Approximately 95% of TAVR valves had a mean pressure gradient <20 mm Hg post-implantation (Table 4). The degree of site-reported post-TAVR aortic regurgitation was typically none or trace/trivial, with a statistical but not clinically substantial change over time (p for trend <0.0001) (Figure 6). However, these results were not assessed by a core laboratory and may represent difficulty in accurate site-reported assessment and/or under-reporting. This has implications for longer follow-up, as increasing degrees of residual aortic regurgitation are associated with worse long-term outcome. Post-TAVR aortic regurgitation was often assessed by echocardiography, although angiography was used in some institutions. The degree of regurgitation may change over time with changing new technology, as well as more optimal prosthetic valve sizing on the basis of computed tomography measurements.
The success rate with device implantation in the correct anatomic position has been excellent, and most recently was 97.4% (Table 4). Using Valve Academic Research Consortium (VARC)-1 criteria, device success was 92.7%, reflecting that the device was in the correct anatomic position, as well as satisfactory intended performance of the valve (10,11,16).
In the most recent experience, about one-third of all patients had a hospital complication. However, procedure-related cardiac complications were uncommon at <2% (Table 5). The most common intraprocedural cardiac complication was the need for a new pacemaker (Figure 7), which occurred in approximately 10% of patients overall, but has increased over time (p for trend <0.0001). This is most likely the result of expanding the types of prostheses implanted to include CoreValve, which has been associated with a higher incidence of conduction system abnormalities (17–20). New onset of atrial fibrillation was seen in approximately 7%. Life-threatening intraprocedural complications, such as annular dissection, aortic rupture, or perforation with tamponade, were uncommon. Device migration or embolization was rare.
Noncardiac complications predominated (Figures 8 and 9). Vascular complications were the most common, were typically related to access-site or arterial bleeding, and resulted in the frequent need for blood transfusions (Online Figure 7). There was a decrease in VARC bleeding (p for trend <0.0001) and vascular complications (p for trend <0.0001) over time. These may continue to decrease as the technology matures, with smaller access sheaths and catheters and improved approaches using vascular access closure devices. That will be an important metric to follow because vascular complications have been associated with increased morbidity/mortality. A new requirement for dialysis was infrequent (1.8%), as was the development of acute kidney injury (2.5%).
Neurological events in association with TAVR have received considerable attention. The TVT Registry has a unique protocol in place that provides centralized clinical adjudication for site-reported neurological events according to VARC definitions. The frequency of clinically adjudicated stroke was low, at approximately 2%.
Discharge status and length of stay can be seen in Online Figures 8 and 9. The mean post-procedure length of stay continues to shorten (Online Figure 9) (p for trend <0.0001), with the most recent 2014 data documenting a mean length of stay of 6.2 days. As previously stated, the use of more moderate sedation, more transfemoral access, vascular closure devices for true percutaneous entry, and potentially, the shift to a catheterization laboratory environment with recovery in a cardiac care unit (rather than a surgical intensive care unit) can be expected to further decrease length of stay, making the procedure more cost-efficient. An important finding is that two-thirds of patients were able to be dismissed home, and another one-fourth were dismissed to a temporary extended-care facility, despite these patients having a mean age of 82 years and with approximately 80% having New York Heart Association functional class III/IV symptoms pre-TAVR.
Overall unadjusted in-hospital mortality (Figure 10) throughout this time period was <5%. The primary cause of mortality was cardiac, and was not substantially different over the period of observation (Table 6).
These benchmark data from the TVT Registry have multiple important messages:
1. TAVR candidates have advanced age and multiple comorbidities, which either make them at high risk for surgical aortic valve replacement or render them inoperable.
2. The patients are highly symptomatic, with symptoms that are often refractory.
3. There has been little clinically significant change in patient demographics since the inception of the TVT Registry. However, it does draw attention to the change in initial indications for TAVR, which included patients at very high risk for surgery or inoperable. This is highlighted by the mean STS PROM (Predicted Risk of Mortality) score of 8.16% in 2014 and 8.34% for all 3 years, which are quite different than the recommendation in the guidelines (21). It is possible that some unusual characteristics that would lead experts to consider a patient surgically inoperable are not included in the current STS PROM risk model. With the CMS mandate, 2 experienced cardiovascular surgeons reviewed the patients independently and rendered the opinion that they were either high-risk or inoperable.
4. The procedure continues to evolve, with clinically and statistically significant changes in procedural access, procedural performance, and need for anesthesia.
5. Mortality, myocardial infarction, kidney injury, and neurological complications are low, and patients appear to be clinically stable despite statistically significant changes.
6. The most common complications are vascular and bleeding requiring transfusion. As technology continues to provide smaller access equipment, these complications should improve.
Uses of the registry now and in the future
These results of the earliest TAVR experience in the United States captured by the TVT Registry have provided important scientific information on early outcomes of TAVR compared with other selected clinical experiences and pivotal randomized trials. The TVT Registry data have been used to broaden the indications for use by the FDA (22) and have provided important information on patient subsets that are at particularly high risk of adverse events, namely, those with significant chronic obstructive pulmonary disease, chronic renal disease, and high STS score (9). Furthermore, linkage of patients enrolled in the TVT Registry with CMS administrative claims data has produced critically-needed insights into longer-term patient follow-up, including rehospitalization and mortality rates in the first year following TAVR (9). Future reports will be able to quantify outcomes over subsequent years, as well as trends in short- and long-term outcomes related to new technologies, changing patient selection criteria, and evolving clinical management strategies, and may facilitate comparative assessment of different devices.
Several important uses of TVT Registry data have occurred or are being planned that will further expand the importance of these updated reports:
1. Development of a TAVR-specific risk prediction algorithm focusing on in-hospital mortality. Future risk prediction algorithms will look at longer-term mortality, stroke, and other nonfatal outcomes.
2. These data will also be used to evaluate the relationship between volume and outcome for TAVR, which has important implications for continued utilization of the approach.
3. TVT Registry data is currently serving as a primary input for FDA-mandated device surveillance. This is under consideration as part of a broader FDA initiative for Medical Device Reporting requirements. At the present time, the TVT Registry functions as a platform for FDA-approved post-market surveillance studies for new iterations of current and future devices.
4. Quality improvement initiatives have assumed a central role in medical care. Hospital-specific data is sent to each participating institution (Online Figures 10A and 10B) through an online reporting “dashboard” that allows each institution to benchmark its own practice and outcomes to national and other comparable group averages and is helpful in identifying areas for improvement and optimization.
5. Delivery of care societal issues can also be addressed. A particularly noteworthy finding from the TVT Registry is that black patients make up only 5% of the U.S. TAVR population. Whether this represents differential disease prevalence or access issues remains to be studied.
Registries have both advantages and disadvantages. Although they are not randomized trials, randomized controlled trials can be nested within national registries. In contrast to randomized controlled trials, registries typically include a broader group of patients who are often more heterogeneous than those enrolled in pivotal trials. Compliance to specific regimens and recommended treatment standards for both patients and health care teams is difficult to quantify. The issue of confounding but unmeasured variables in patient selection, as well as procedural performance, is extremely important. Statistical assessment is always an “on-treatment analysis.” In the TVT Registry, these issues exist along with the absence of core laboratories for image analysis (specifically, the issue of paravalvular leaks), site-reported events, and only partially audited data. Moreover, outcomes are currently unadjusted; thus, comparison of trends over time may be biased by changing patient characteristics and risk profiles.
Finally, these data are limited to commercial TAVR patients. Although discussions have taken place, because of regulatory issues, the inclusion of noncommercial (i.e., cases receiving investigational devices) is not possible until after trials have completed enrollment and have been reported. At that time, patients could be combined retrospectively. These limitations are balanced by the TVT Registry’s use of standard definitions, enrollment of virtually all patients undergoing commercial TAVR procedures in the entire United States, and linkage to CMS administrator claims data for longer-term outcomes.
The TVT Registry was developed and implemented by the ACC and STS during the dispersion of the transformational technology of TAVR. It provides a broad overview of the evolving technology of TAVR and can be used as a benchmark for U.S. TAVR clinical practice patterns and patient outcomes. The TVT Registry is central to a novel approach for post-market surveillance and is the foundation for continuing efforts to provide timely and actionable learning on the basis of scientific evidence throughout the full product life cycle of new emerging technology.
COMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: Technological advances in device configuration, smaller catheter sizes, and patient-specific access site selection can lower the risk of extracardiac complications in patients undergoing TAVR. Even so, patients undergoing TAVR typically have multiple comorbidities, including advanced age, and the risk of periprocedural stroke remains an important concern.
TRANSLATIONAL OUTLOOK: Long-term surveillance registries of consecutive patients undergoing TAVR can inform the design of prospective trials to help ensure that innovations in technology and procedural management yield improved clinical outcomes.
For a complete list of STS/ACC TVT Registry participating hospitals as well as supplemental figures, please see the online version of this article.
A link to the current list of STS/ACC TVT Registry participating hospitals is available in the Online Appendix. Dr. Grover has served as a consultant to Somalution; and is the vice chair of the STS/ACC/TVT Registry Steering Committee. Dr. Brindis is a senior medical officer for the National Cardiovascular Data Registry. Dr. Carroll has served as an investigator in research trials sponsored by Edwards Lifesciences, Abbott Vascular, and Direct Flow. Dr. Peterson has received grants from Janssen and Eli Lily; has received personal fees from Janssen, Eli Lilly, Boehringer Ingelheim, Bayer, and AstraZeneca; and has been a consultant for Merck and Sanofi. Dr. Rumsfeld is chief science officer for the National Cardiovascular Data Registry. Dr. Thourani is an advisor for Edwards Lifesciences; and conducts research for Edwards Lifesciences and Medtronic. Dr. Vemulapalli has received research grant support from Boston Scientific; has received funding for travels from Abbott Vascular; and received payment for travel from Philips Medical Systems. Dr. Mack is a member of the Executive Committee of the PARTNER Trial, sponsored by Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Raj Makkar, MD, served as Guest Editor for this paper.
This article is copublished in the Journal of the American College of Cardiology and The Annals of Thoracic Surgery.
- Abbreviations and Acronyms
- American College of Cardiology
- Kansas City Cardiomyopathy Questionnaire
- Society of Thoracic Surgeons
- STS PROM
- Society of Thoracic Surgeons Predicted Risk of Mortality
- transcatheter aortic valve replacement
- transcatheter valve therapy
- Valve Academic Research Consortium
- Received August 27, 2015.
- Revision received October 7, 2015.
- Accepted October 13, 2015.
- 2015 American College of Cardiology Foundation and The Society of Thoracic Surgeons
- Carroll J.D.,
- Edwards F.H.,
- Marinac-Dabic D.,
- et al.
- Rumsfeld J.S.,
- Holmes D.R. Jr..,
- Stough W.G.,
- et al.
- Carroll J.D.,
- Shuren J.,
- Jensen T.S.,
- et al.
- ↵Center for Devices and Radiological Health, U.S. Food and Drug Administration. Strengthening our national system for medical device postmarket surveillance: update and next steps. 2013. Available at: http://www.fda.gov/downloads/MedicalDevices/Safety/CDRHPostmarketSurveillance/UCM348845.pdf. Accessed October 15, 2015.
- Leon M.B.,
- Piazza N.,
- Nikolsky E.,
- et al.
- Kappetein A.P.,
- Head S.J.,
- Généreux P.,
- et al.
- Green C.P.,
- Porter C.B.,
- Bresnahan D.R.,
- et al.
- Arnold S.V.,
- Spertus J.A.,
- Lei Y.,
- et al.
- Bleiziffer S.,
- Ruge H.,
- Hörer J.,
- et al.
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- ↵Husten L. Using registry data, FDA expands indication for Edwards’ Sapien Transcatheter Heart Valves. Forbes. September 23, 2013. Available at: http://www.forbes.com/sites/larryhusten/2013/09/23/using-registry-data-fda-expands-indication-for-edwards-sapien-transcatheter-heart-valves/. Accessed October 15, 2015.