Author + information
- Received April 19, 2017
- Revision received June 20, 2017
- Accepted July 19, 2017
- Published online October 16, 2017.
- Paul Sorajja, MDa,∗ (, )
- Susheel Kodali, MDb,
- Michael J. Reardon, MDc,
- Wilson Y. Szeto, MDd,
- Stanley J. Chetcuti, MDe,
- James Hermiller Jr., MDf,
- Sharla Chenoweth, MSg,
- David H. Adams, MDh and
- Jeffrey J. Popma, MDi
- aValve Science Center, Minneapolis Heart Institute Foundation, Minneapolis, Minnesota
- bColumbia University Medical Center, New York, New York
- cHouston Methodist DeBakey Heart and Vascular Center, Houston, Texas
- dUniversity of Pennsylvania, Philadelphia, Pennsylvania
- eUniversity of Michigan, Ann Arbor, Michigan
- fSt. Vincent’s Heart Center of Indiana, Indianapolis, Indiana
- gMedtronic, Minneapolis, Minnesota
- hMount Sinai Medical Center, New York, New York
- iBeth Israel Deaconess Medical Center, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Paul Sorajja, Valve Science Center, Minneapolis Heart Institute Foundation, Abbott Northwestern Hospital, 920 East 28th Street, Minneapolis, Minnesota 55407.
Objectives The authors sought to compare the outcomes of commercial transcatheter aortic valve replacement (TAVR) with the repositionable Evolut R platform to those observed with the CoreValve device in the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry.
Background TAVR continues to evolve, with rapid adoption of iterative changes for commercial practice. Insight into the outcomes of this adoption is needed.
Methods Patients in the TVT Registry who had TAVR using a 23-, 26-, or 29-mm self-expanding prosthesis were enrolled. Site-reported events for procedural, in-hospital, and 30-day outcomes were examined.
Results Between January 2014 and April 2016, 9,616 patients underwent TAVR with a self-expanding prosthesis with data entered in the TVT Registry. Compared with patients treated with CoreValve TAVR, those who received Evolut R TAVR had a lower STS-PROM score (8.0 ± 5.4% vs. 8.7 ± 5.3%; p < 0.001), more iliofemoral access (91.6% vs. 89.2%; p < 0.001), and more frequently had conscious sedation (27.4% vs. 12.7%; p < 0.001). With Evolut R TAVR, there was less need for a second prosthesis (2.2% vs. 4.5%; p < 0.001), less device migration (0.2% vs. 0.6%; p = 0.01), a lower incidence of moderate/severe paravalvular regurgitation (post-procedure, 4.4% vs. 6.2%; p < 0.001), and shorter median hospital stay (4.0 vs. 5.0 days; p < 0.001). Patients treated with Evolut R TAVR had greater device success (96.3% vs. 94.9%; p = 0.001). At 30 days, Evolut R patients had both lower mortality (3.7% vs. 5.3%; p < 0.001) and less need for a pacemaker (18.3% vs. 20.1%; p = 0.03).
Conclusions Commercial adoption of the Evolut R platform is associated with significant improvements in acute outcomes for patients undergoing TAVR for aortic stenosis.
Transcatheter aortic valve replacement (TAVR) is a life-saving therapy for patients with symptomatic, severe aortic stenosis (1,2). As a revolutionary therapy, the procedure continues to evolve with the ultimate goal being optimization of clinical outcomes and safety. Self-expanding prostheses for TAVR were first used for commercial practice in the United States with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) in 2014, followed by introduction of the repositionable Evolut R platform in 2015 (3–7). Insight into the clinical impact of these iterative changes is needed to further understand their role in the treatment of patients with aortic stenosis.
Accordingly, we undertook the present investigation to examine the clinical outcomes for the repositionable Evolut R platform in comparison to those observed with the CoreValve prosthesis in the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapy (TVT) Registry. The STS/ACC TVT Registry is a national repository for data on clinical outcomes that enables procedural surveillance of commercially approved devices in the United States, in addition to fulfilling national coverage determination requirements (8). In this investigation, we examined the U.S. commercial experience for TAVR with Evolut R, and compared the procedural, in-hospital, and 30-day outcomes to the CoreValve platform to determine clinical improvements that may occur with device iterations.
The STS/ACC TVT Registry
The patient population for this study was derived from the STS/ACC TVT Registry, which is a national registry designed to serve as a platform for device and procedural surveillance, quality assurance and improvement initiatives, and the conduct of studies that facilitate innovation and expansion of device labeling through evidence development (8–10). Participation in the STS/ACC TVT Registry satisfies Centers for Medicare & Medicaid Services national coverage determinations, in which national registry participation is a requirement for reimbursement for commercial therapies and those devices that are under clinical investigation. Centers that participate in the TVT registry collect data on demographics, morbidities, functional status, quality of life, hemodynamic status, procedural details, as well as procedural, 30-day, and 1-year clinical outcomes. The activities of the STS/ACC TVT Registry have been approved by a central institutional review board, and the Duke University School of Medicine institutional review board granted a waiver of informed consent and authorization for this study.
All patients who underwent TAVR in the STS/ACC TVT Registry who met the following criteria were included in the present analysis: 1) native aortic valve disease; 2) use of a Medtronic self-expanding prosthesis (CoreValve or Evolut R), in the sizes of 23, 26, or 29 mm; and 3) a commercial indication for TAVR. Patients who had been treated with a 31-mm CoreValve device were excluded, because no comparator for that prosthesis size was commercially available for the Evolut R platform during the analysis enrollment period. Patients who had TAVR as part of research studies also were excluded.
Site-reported procedural, in-hospital, and 30-day outcomes were analyzed. Device success, as site-reported in the STS/ACC TVT Registry, is defined as successful deployment of a single TAVR prosthesis in the proper anatomic location and retrieval of the delivery system, with intended performance of the prosthetic heart valve (aortic valve area >1.2 cm2 and mean aortic valve gradient <20 mm Hg or peak velocity <3 m/s, without moderate or severe prosthetic regurgitation) (11). Group comparisons were performed for patients treated with the CoreValve platform and those who received TAVR with the Evolut R platform. Unadjusted comparisons were performed using the chi-square test for categorical data, the Student t test for continuous data, paired t test for change from baseline, and log-rank test for Kaplan-Meier analysis. For the endpoints of device success, using logistic regression, mortality, using Cox proportional hazards model, and length of stay, using analysis of variance multivariate adjustments (modeling) were performed with the following variables: age, male sex, body mass index, Society of Thoracic Surgeons-Predicted Risk of Mortality (STS-PROM) score, diabetes mellitus, creatinine >2 mg/dl, chronic dialysis, hypertension, peripheral vascular disease, prior stroke, prior myocardial infarction, prior cardiac surgery, coronary artery disease, severe chronic lung disease, albumin <3.3 g/dl, mean aortic valve gradient, aortic valve area, use of iliofemoral access, use of conscious or moderate sedation, valve size implanted (23, 26, or 29 mm), and use of the Evolut R platform. Continuous variables are reported as either mean ± SD or median (interquartile range), where appropriate. For all analyses, p values <0.05 were considered statistically significant.
Between January 2014 and April 2016, there were 9,616 patients in the STS/ACC TVT Registry who underwent commercial TAVR in native aortic valves with a 23-, 26-, or 29-mm Medtronic self-expanding prosthesis (CoreValve or Evolut R) in the United States (Table 1, Figure 1). Patients were elderly (mean age 81.4 ± 8.1 years; 36.1% men), and significant morbidities were common (STS-PROM 8.4 ± 5.4%) in the analysis population. In comparison to those treated with the CoreValve platform, patients who underwent TAVR with the Evolut R platform more frequently were male, more commonly had severe renal insufficiency or dialysis, and had lower incidences of prior cardiac surgery, severe chronic lung disease, and porcelain aorta. Group comparisons for age, body surface area, and aortic valve hemodynamics were statistically significant because of the large size of the analysis population, although the absolute differences for these variables were relatively small. Overall, the STS-PROM was lower for Evolut R patients (8.0 ± 5.4% vs. 8.7 ± 5.3%; p < 0.001) in comparison to those treated with the CoreValve platform.
Procedural and in-hospital outcomes
Overall, TAVR was performed electively in 91.3% of cases, with 29 mm as the most common prosthesis size (Table 2). Patients treated with the Evolut R platform more commonly underwent TAVR with iliofemoral access (91.6% vs. 89.2%; p < 0.001) and with conscious sedation for anesthesia (27.4% vs. 12.7%; p < 0.001). Following TAVR, patients who received Evolut R had slightly higher residual aortic valve gradients (8.6 ± 5.5 mm Hg vs. 7.9 ± 4.6 mm Hg; p < 0.001), but aortic valve areas were comparable (1.88 ± 0.59 cm2 vs. 1.90 ± 0.64 cm2; p = 0.19) (Figure 2). The hemodynamic comparisons differed across the different prosthetic sizes (23 mm, 13.7 ± 7.9 mm Hg vs. 12.1 ± 6.4 mm Hg; p = 0.05; 26 mm, 8.3 ± 5.7 mm Hg vs. 7.6 ± 4.3 mm Hg; p = 0.001; 29 mm, 8.5 ± 5.0 mm Hg vs. 7.7 ± 4.3 mm Hg; p < 0.001; all Evolut R vs. CoreValve, respectively).
For Evolut R patients, there was a lower rate of permanent pacemaker implantation (16.6% vs. 19.2%; p = 0.002), as well as lower need for a second prosthesis, less device migration, and lower rates of periprocedural atrial fibrillation and myocardial infarction. Severe paravalvular regurgitation in both groups was very low (0.2% Evolut R and 0.3% CoreValve), with moderate or severe paravalvular regurgitation being significantly lower for Evolut R patients (4.4% vs. 6.2%; p < 0.001). In-hospital mortality was lower (2.7% vs. 3.7%; p = 0.01), and there was a higher rate of acute device success for Evolut R patients (96.3% vs. 94.9%; p = 0.001). Patients treated with Evolut R also had shorter length of stay and a higher incidence of discharge directly to home (Figure 3).
At 30-day follow-up, overall mortality in the study population, inclusive of procedural and in-hospital death, was 4.7% (Table 3). Patients who had TAVR with Evolut R had lower all-cause mortality (3.7% vs. 5.3%; p < 0.001). The rate of new permanent pacemaker or implantable cardioverter-defibrillator remained lower for Evolut R (18.3% vs. 20.1%; p = 0.03). In the entire cohort, the stroke rate was 3.1%, and the rates were comparable between the 2 groups. The rates of major vascular complications, device thrombosis, device fracture, and valve-related readmission, were low and also comparable. Quality of life, as measured by Kansas City Cardiomyopathy Questionnaire overall summary scores, improved significantly from baseline for both groups (Figure 4).
By covariate adjustment analysis, the use of Evolut R remained significantly associated with lower 30-day mortality (unadjusted HR: 0.69 [95% confidence interval (CI): 0.56 to 0.85], p < 0.001; adjusted HR: 0.73 [95% CI: 0.58 to 0.92]; p = 0.009), shorter length of stay (both unadjusted and adjusted p < 0.0001), and greater device success (unadjusted odds ratio [OR]: 0.71 [95% CI: 0.58 to 0.88]; p = 0.001; adjusted OR, 0.79 [95% CI: 0.63 to 1.00]; p = 0.05).
For patients with aortic stenosis, TAVR is an established therapy that improves quality-of-life and survival, with outcomes that are either comparable or superior to that of surgery (1–7). Hence, TAVR is used routinely for patients at intermediate or high surgical risk, and randomized trials in comparison to surgery for those at low risk are well underway. Although there is known efficacy and benefit for patients with severe aortic stenosis who currently undergo TAVR, adverse clinical events may still occur without procedural success. These events may portend high morbidity and poor survival, particularly in those at high or extreme surgical risk, who are especially vulnerable to complications (12,13). Continual iteration of device technology and procedural techniques, therefore, remains essential for maximizing beneficial outcomes in patients with aortic stenosis who undergo TAVR.
The principal finding of this investigation is that the commercial adoption of the self-expanding Evolut R platform resulted in greater device success and lower procedural mortality. In comparison to those who received TAVR with a CoreValve prosthesis, patients who were treated with the Evolut R platform also had lower pacemaker dependence, less paravalvular regurgitation, and shorter hospital length-of-stay. Quality-of-life was significantly improved with both Evolut R and CoreValve therapies. These findings have important implications for the field of TAVR and its role in the treatment of patients with severe, native aortic stenosis.
On the basis of demonstrated efficacy and safety in randomized clinical trials, the self-expanding, Medtronic CoreValve prosthesis was introduced into commercial practice in the United States in 2014 (3–6). In 2015, the Evolut R, as a TAVR platform with several novel iterations, was approved for commercial use and rapidly adopted in the United States. In comparison to the CoreValve platform, principal features of Evolut R consist of a smaller delivery profile, improvements in frame design to provide increased oversizing, more consistent radial force across the annular range, and an extended skirt for enhanced sealing, as well as the ability to recapture and reposition the prosthesis. Although there are few data on the Evolut R platform in comparison to the CoreValve platform, studies of patients who had the Evolut R device as part of pre-approval clinical trials reported improved outcomes with lower rates of moderate or severe paravalvular regurgitation (5.3% to 8.5%), permanent pacemaker implantation (14.7% to 22.1%), and 30-day mortality (2.3% to 3.2%) (14–16). Thus far, whether or not these improved clinical outcomes have also occurred with widespread adoption of Evolut R in commercial practice in the United States remains unknown.
In this analysis, which represents the largest clinical experience for Evolut R in patients with aortic stenosis (N = 3,810), we observed improved device success and lower procedural mortality, in comparison to outcomes observed for patients commercially treated with the CoreValve platform in the U.S. Patients treated with Evolut R had greater use of iliofemoral access and lower rates of paravalvular regurgitation, device migration, and need for a second prosthesis. Post-procedural gradients were slightly higher with Evolut R (8.6 ± 5.5 mm Hg vs. 7.9 ± 4.6 mm Hg; p < 0.001), but still were low and well within acceptable hemodynamic bounds for device success, including comparable post-procedural aortic valve area. In addition, the incidence of moderate or severe paravalvular regurgitation was significantly improved with Evolut R (4.4% vs. 6.2%; p < 0.001), including a rate of severe paravalvular regurgitation of only 0.2% in these patients. It is important to note that these outcomes were observed in commercial practice in the United States, where the technology was rapidly adopted in a broad number of hospitals (i.e., 3,810 cases over 9 months in 298 hospitals) (Figure 1). These findings underscore the importance of continued device iteration for further optimizing patient outcomes, even when prior technology has been found to be effective, safe, and already used in routine use.
The procedure for TAVR and the population of patients treated both have evolved significantly since its first introduction over 15 years ago, and this evolution was evident in this analysis of patients undergoing contemporary therapy. The present investigation is a report from a single-arm registry, with comparisons performed against historical patients and outcomes. Such analysis design is susceptible to the potential for selection bias, and there were differences in the comparator groups. With the notable exception of renal failure (creatinine >2 mg/dl, 8.9% vs. 7.1%, Evolut R vs. CoreValve, respectively; p = 0.002), patients who received TAVR with Evolut R had less morbidity and lower STS-PROM. Evolut R patients also more frequently underwent TAVR with conscious sedation, whose use has been associated with fewer procedural complications and reduced hospital length-of-stay (17). Moreover, the field of TAVR was relatively earlier in development for patients undergoing therapy with CoreValve in comparison to Evolut R. This analysis did not permit an examination of the relation of outcomes to differences in operator experience and how this experience could have influenced adoption of iterative techniques and technology.
Similar decreases in the risk profile of patients with commercial adoption of TAVR have been reported previously (18). Importantly, the present investigation includes only commercial patients when TAVR, by product indication, was limited largely to patients at high or extreme surgical risk. To account for baseline differences in the 2 populations, multivariate adjustments models were performed and demonstrated persistent association of the use of Evolut R with lower 30-day mortality (unadjusted HR: 0.69 [95% CI: 0.56 to 0.85]; p < 0.001; adjusted HR: 0.73 [95% CI: 0.58 to 0.92]; p = 0.009), shorter length of stay (both unadjusted and adjusted p < 0.001), and greater device success (unadjusted OR: 0.71 [95% CI: 0.58 to 0.88]; p = 0.001; adjusted OR: 0.79 [95% CI: 0.63 to 1.00]; p = 0.05). It is important to note that the large number of patients examined in this analysis greatly increases the power to detect small differences between groups, even though such differences, arguably, may not be clinically relevant. Taken together, our findings do support the notion that device iterations are significantly associated with improved clinical outcomes.
Vascular injury is a potentially devastating complication in patients who undergo TAVR. In the present investigation, the incidences of vascular complications (4.9% vs. 4.8%, Evolut R vs. CoreValve, respectively; p = 0.69) or any bleeding event (6.6% vs. 7.3%, Evolut R vs. CoreValve, respectively; p = 0.21) were comparable for Evolut R device-treated patients and those treated with the CoreValve platform. Although a lower delivery profile would intuitively be expected to be associated with a lower risk of vascular complications, the absence of such differences may arise for multiple reasons. Ratio of sheath size to minimal lumen diameter (MLD) is an important predictor of vascular complications (19). The use of Evolut R, with its lower profile delivery system, permits the selection of patients with lower MLD (5.0 mm for 23-, 26-, and 29-mm prostheses) in comparison to the recommendations for the CoreValve platform (6 mm). Operators using Evolut R, therefore, could have selected patients with relatively lower MLD for iliofemoral TAVR, when these patients would not have been candidates for devices with larger delivery profiles. Data on MLD in the peripheral arteries used for TAVR are not available in this registry. Nonetheless, it is notable that there was a greater use of iliofemoral access in the Evolut R patients (91.6% vs. 89.2%; p < 0.001), and less use of surgical cut-down (19.6% vs. 24.0%; p < 0.001). For patients who undergo TAVR with Evolut R, the relation between patient selection, peripheral access, and vascular injury requires further study.
The study design of this registry has inherent limitations. Although participation in the STS/ACC TVT Registry helps to fulfill national coverage determination criteria for Centers for Medicare & Medicaid Services reimbursement, data entry is voluntary. Data quality is maximized with assistance from the ACC National Cardiovascular Data Registry (NCDR) data warehouse and Duke Clinical Research Institute Data Analysis Center, who both implement data quality checks, including checks on data range and consistency. Site training also is conducted by the NCDR through frequent informational webinars. Of note, echocardiographic data are site-reported, and not adjudicated by a core laboratory. Although recapturing and repositioning is a key feature of the Evolut R platform, data on the occurrence of these events and their relation to clinical outcomes are not available in the STS/ACC TVT Registry. In prior studies, use of recapture has been reported to be approximately 22% (14,15). In the present investigation, the lower incidences of need for second prosthesis and device migration with Evolut R support the potential benefit of the technological iteration. Nonetheless, the reasons for device migration, need for second prosthesis, as well as rates of pre- or post-dilatation were not available in the TVT registry. Finally, comparable data on use of 31-mm CoreValve prosthesis and the 34-mm Evolut R device were not available, because the latter prosthesis was not commercially available during this analysis period, and the former was excluded because there was not a comparative valve for Evolut R.
For patients who undergo TAVR with self-expanding prostheses, the use of Evolut R is associated with significant improvements in procedural success and lower mortality. These findings demonstrate the importance of device iterations for the benefit of these patients, and these beneficial outcomes should be considered when evaluating patients for TAVR.
WHAT IS KNOWN? Transcatheter aortic valve replacement with Medtronic self-expanding prostheses is a life-saving therapy, and the technology continues to evolve.
WHAT IS NEW? The commercial adoption of the Evolut R platform for TAVR is associated with greater device success and lower 30-day mortality.
WHAT IS NEXT? Further analysis on the long-term implications of these improvements in acute procedural success is needed.
Jessica Dries-Devlin, PhD, CMPP, of Medtronic, created tables and figures, and ensured technical accuracy of the manuscript.
STS/ACC TVT Registry is an initiative of The Society of Thoracic Surgeons and the American College of Cardiology. This research was supported by the American College of Cardiology's National Cardiovascular Data Registry (NCDR). The views expressed in this manuscript represent those of the author(s), and do not necessarily represent the official views of the NCDR or its associated professional societies identified at CVQuality.ACC.org/NCDR. Dr. Sorajja has received consulting fees from Abbott Vascular, Medtronic, and Lake Region; speaking fees from Boston Scientific; and has served on advisory boards for Abbott Vascular and Boston Scientific. Dr. Kodali has received research support from Medtronic, Edwards Lifesciences, Boston Scientific, and Abbott Vascular; is a consultant for Claret Medical and Medtronic; has served on the steering committees of the PARTNER III trial for Edwards Lifesciences and the REPRISE IV trial for Boston Scientific; has served on scientific advisory boards for Boston Scientific, Claret Medical, Thubrikar Aortic Valve, Inc., and Dura Biotech; and has equity in Thubrikar Aortic Valve, Inc. and Dura Biotech. Dr. Reardon has received fees from Medtronic for providing educational services; and has served on an advisory board for Medtronic. Dr. Szeto is an investigator for Medtronic and Edwards Lifesciences; and a member of the Medtronic surgical advisory board. Dr. Chetcuti has received research grants from Abbott Vascular, Medtronic, Edwards Lifesciences, and Gore; has been a consultant/proctor for Medtronic; and has received personal fees from Medtronic. Dr. Hermiller has received fees for educational services from Medtronic; and has been a consultant for Edwards Lifesciences and Medtronic. Ms. Chenoweth is an employee and shareholder of Medtronic. Dr Adams has received grant support from Medtronic and royalty agreements through Mount Sinai School of Medicine with Medtronic and Edwards Lifesciences. Dr. Popma has received grant support to his institution from Medtronic, Abbott Vascular, and Boston Scientific; has served on a medical advisory board for Boston Scientific; and has received personal fees from Direct Flow and Boston Scientific.
- Abbreviations and Acronyms
- American College of Cardiology
- minimal lumen diameter
- National Cardiovascular Data Registry
- odds ratio
- Society of Thoracic Surgeons
- Society of Thoracic Surgeons-Predicted Risk of Mortality
- transcatheter aortic valve replacement
- transcatheter valve therapy
- Received April 19, 2017.
- Revision received June 20, 2017.
- Accepted July 19, 2017.
- 2017 American College of Cardiology Foundation
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