Transcatheter Aortic-Valve Implantation for Aortic Stenosis in Patients Who Cannot Undergo Surgery
List of authors.
The investigators, institutions, and research organizations participating in the Placement of Aortic Transcatheter Valves (PARTNER) trial are listed in the Supplementary Appendix, available at NEJM.org.
Abstract
Background
Many patients with severe aortic stenosis and coexisting conditions are not candidates for surgical replacement of the aortic valve. Recently, transcatheter aortic-valve implantation (TAVI) has been suggested as a less invasive treatment for high-risk patients with aortic stenosis.
Methods
We randomly assigned patients with severe aortic stenosis, whom surgeons considered not to be suitable candidates for surgery, to standard therapy (including balloon aortic valvuloplasty) or transfemoral transcatheter implantation of a balloon-expandable bovine pericardial valve. The primary end point was the rate of death from any cause.
Results
A total of 358 patients with aortic stenosis who were not considered to be suitable candidates for surgery underwent randomization at 21 centers (17 in the United States). At 1 year, the rate of death from any cause (Kaplan–Meier analysis) was 30.7% with TAVI, as compared with 50.7% with standard therapy (hazard ratio with TAVI, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P<0.001). The rate of the composite end point of death from any cause or repeat hospitalization was 42.5% with TAVI as compared with 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35 to 0.59; P<0.001). Among survivors at 1 year, the rate of cardiac symptoms (New York Heart Association class III or IV) was lower among patients who had undergone TAVI than among those who had received standard therapy (25.2% vs. 58.0%, P<0.001). At 30 days, TAVI, as compared with standard therapy, was associated with a higher incidence of major strokes (5.0% vs. 1.1%, P=0.06) and major vascular complications (16.2% vs. 1.1%, P<0.001). In the year after TAVI, there was no deterioration in the functioning of the bioprosthetic valve, as assessed by evidence of stenosis or regurgitation on an echocardiogram.
Conclusions
In patients with severe aortic stenosis who were not suitable candidates for surgery, TAVI, as compared with standard therapy, significantly reduced the rates of death from any cause, the composite end point of death from any cause or repeat hospitalization, and cardiac symptoms, despite the higher incidence of major strokes and major vascular events. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)
Methods
Patient Selection
We enrolled in the PARTNER trial patients with severe aortic stenosis and cardiac symptoms for whom conventional surgery to replace the aortic valve was associated with high risk. Severe aortic stenosis was defined as an aortic-valve area of less than 0.8 cm2, a mean aortic-valve gradient of 40 mm Hg or more, or a peak aortic-jet velocity of 4.0 m per second or more. All the patients had New York Heart Association (NYHA) class II, III, or IV symptoms. Patients were divided into two cohorts: those who were considered to be candidates for surgery despite the fact that they were at high surgical risk, as defined by a Society of Thoracic Surgeons (STS) risk score of 10% or higher35 (on a scale of 0% to 100%, with higher scores indicating greater surgical risk) or by the presence of coexisting conditions that would be associated with a predicted risk of death by 30 days after surgery of 15% or higher, and those who were not considered to be suitable candidates for surgery because they had coexisting conditions that would be associated with a predicted probability of 50% or more of either death by 30 days after surgery or a serious irreversible condition. At least two surgeon investigators had to agree that the patient was not a suitable candidate for surgery. In this article, we report the results for the patients with aortic stenosis who were not considered to be suitable candidates for surgery. The randomized trial involving patients at high surgical risk who were nevertheless considered to be candidates for surgery (also NCT00530894) is ongoing.
Pertinent exclusion criteria were a bicuspid or noncalcified aortic valve, acute myocardial infarction, substantial coronary artery disease requiring revascularization, a left ventricular ejection fraction of less than 20%, a diameter of the aortic annulus of less than 18 mm or more than 25 mm, severe (>3+) mitral or aortic regurgitation, a transient ischemic attack or stroke within the previous 6 months, and severe renal insufficiency. The complete list of inclusion and exclusion criteria is provided in Table 1 in the Supplementary Appendix, available with the full text of this article at NEJM.org.
After investigators screened the patients for eligibility, Web-based conference calls were conducted by the executive committee to further review and approve the selection of all patients before randomization. Of the 3105 patients with aortic stenosis who were screened by the investigators and the executive committee, approximately 12% ultimately underwent randomization as part of the PARTNER trial and were assigned to the cohort of patients who were not considered to be suitable candidates for surgery.
Study Device and Procedure
The Edwards SAPIEN heart-valve system (Edwards Lifesciences) consists of a trileaflet bovine pericardial valve and a balloon-expandable, stainless-steel support frame. The heart valve is shown in Figure 1 in the Supplementary Appendix. The TAVI procedure was performed in a sterile environment (catheterization laboratory or operating room), with the patient under general anesthesia; the procedure was performed with the use of transesophageal echocardiography. A standard balloon aortic valvuloplasty was performed, followed by transfemoral insertion of either a 22- or 24-French sheath, depending on the selected size of the valve (23 mm or 26 mm). The bioprosthetic heart valve, crimped onto a balloon catheter, was advanced across the native aortic valve. During rapid right ventricular pacing, balloon inflation of the crimped heart valve and support frame simultaneously deployed the bioprosthetic valve and expanded the frame, which was secured to the underlying aortic-valve annulus and leaflets (see videos 1 and 2, available at NEJM.org). Adjunctive pharmacologic therapy included heparin during the procedure and dual antiplatelet therapy (aspirin and clopidogrel) for 6 months after the procedure.
Study Design and Oversight
The PARTNER study incorporated two parallel prospective, multicenter, randomized, active-treatment–controlled clinical trials. The overall study design is shown in Figure 2 in the Supplementary Appendix. Patients were randomly assigned with the use of a computer-generated scheme, blocked separately at each participating site and for each of the trial cohorts. The PARTNER study was approved by the institutional review board at each participating site, and all patients provided written informed consent.
The trial was designed by the sponsor (Edwards Lifesciences) and members of the executive committee, which included the two academic coprincipal investigators, three interventional cardiologists, and three cardiac surgeons. The sponsor funded the studies and participated in the selection and management of the sites and the collection and monitoring of the data. The executive committee met in person every 6 to 8 weeks to monitor all aspects of the conduct of the trial. The coprincipal investigators and the executive committee had unrestricted access to the data after the database was locked, made the decision to submit the manuscript for publication, prepared all drafts of the manuscript, and attest to the integrity of the trial and the completeness and accuracy of the reported data, as well as to the fidelity of the report to the trial protocol. The protocol, including the statistical analysis plan, is available at NEJM.org.
Data Management
All serious adverse events were adjudicated by an independent clinical events committee. A data and safety monitoring board met frequently and had access to all study data and treatment assignments when requested; the board recommended after each meeting that the study be continued without modification. All data were sent for analysis to independent consulting biostatisticians. Independent core laboratories analyzed all echocardiograms and electrocardiograms. The members of the committees, the institutions, and the research organizations participating in the PARTNER trial are listed in Table 2 in the Supplementary Appendix.
Study End Points
The primary end point was the rate of death from any cause over the duration of the trial. All patients were followed for at least 1 year, and crossover from the standard-therapy group to the TAVI group was not permitted. The coprimary end point was the rate of a hierarchical composite of the time to death from any cause or the time to the first occurrence of repeat hospitalization (after the index procedure) due to valve-related or procedure-related clinical deterioration. This composite end point was also reported with the use of more conventional Kaplan–Meier nonhierarchical analytical methods. Prespecified secondary end points included the rate of death from cardiovascular causes, NYHA functional class, the rate of repeat hospitalization due to valve-related or procedure-related clinical deterioration, the distance covered during a 6-minute walk test,36 valve performance (assessed by echocardiography), and the rates of myocardial infarction, stroke, acute kidney injury, vascular complications, and bleeding. A major stroke was defined as a focal or global neurologic deficit associated with a score of 2 or higher on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms and 6 indicating death. Specific definitions of other important end points are provided in Table 3 in the Supplementary Appendix. All patients were followed during the index hospitalization; at 30 days, 6 months, and 1 year; and yearly thereafter.
Statistical Analysis
We estimated that with a sample of 350 patients, the study would have at least 85% power to show the superiority of TAVI over standard treatment with respect to the primary end point, assuming that 1-year mortality would be 37.5% in the standard-treatment group and 25% in the TAVI group. In calculating the size of the sample, we also assumed that deaths would follow a constant hazard distribution, that follow-up would continue for 12 months after the last patient was enrolled, and that the rate of loss to follow-up would be 10%.
The analysis of the coprimary end point — the hierarchical composite of death or repeat hospitalization — was performed with the use of a nonparametric method described by Finkelstein and Schoenfeld.37 With this method, multiple pairwise comparisons are performed for all patient pairs, first with respect to the time to death and then with respect to the time to repeat hospitalization, if necessary. On the basis of a simulation with the use of SAS software, we estimated that with a total sample of 350 patients, the power for this coprimary end point would be more than 95%. The Hochberg procedure was used to make multiple corrections of the primary and coprimary end points.
Categorical variables were compared with the use of Fisher's exact test. A generalized linear model was used to calculate risk ratios in the subgroup analysis and to test for interactions. Continuous variables, which are presented as means (±SD), were compared with the use of Student's t-test. All the analyses were performed with data from the intention-to-treat population, which included all patients who underwent randomization, regardless of the treatment actually received. Survival curves for time-to-event variables were constructed on the basis of all available follow-up data with the use of Kaplan–Meier estimates and were compared with the use of the log-rank test. A two-sided alpha level of 0.05 was used for all superiority testing. All statistical analyses were performed with the use of SAS software, version 9.2.
Results
Patients and Enrollment
Between May 11, 2007, and March 16, 2009, a total of 358 patients with severe aortic stenosis who were not suitable candidates for surgery were enrolled at 21 sites (17 in the United States) and were randomly assigned to TAVI (179 patients) or standard therapy (179 patients). All the patients were followed for at least 1 year (median follow-up period, 1.6 years; maximum, 2.8 years). The numbers of patients who underwent randomization and follow-up are shown in Figure 3 in the Supplementary Appendix.
Table 1.
Table 1. Baseline Characteristics of the Patients and Echocardiographic Findings.The baseline characteristics of the patients in the two groups were generally well balanced (Table 1). The overall patient population was at high risk (STS score, 11.6±6.0%). However, there were many patients with low STS scores but with coexisting conditions that contributed to the surgeons' determination that the patient was not a suitable candidate for surgery, including an extensively calcified (porcelain) aorta (15.1%), chest-wall deformity or deleterious effects of chest-wall irradiation (13.1%), oxygen-dependent respiratory insufficiency (23.5%), and frailty, as determined by the surgeons according to prespecified criteria (23.1%).
Procedural Outcomes
Of the 179 patients assigned to TAVI, 6 (3.4%) did not receive a transcatheter heart valve (2 patients died before the scheduled implantation, transfemoral access was unsuccessful in 2 patients, and the intraprocedural annulus measurement was too large in 2 patients). After randomization, the median time to TAVI was 6 days (interquartile range, 3 to 11). During the TAVI procedure or in the first 24 hours after the procedure, 2 patients (1.1%) died, 3 (1.7%) had major strokes, 1 (0.6%) had a valve embolization, and 2 (1.1%) underwent multiple (≥2) valve implantations; no patient underwent urgent cardiac surgery to manage complications. In the first 30 days after the procedure, 11 of the 173 patients who underwent TAVI (6.4%) died.
Of the 179 patients assigned to standard therapy, balloon aortic valvuloplasty was performed in 114 patients (63.7%) during the 30 days after randomization and in an additional 36 patients (20.1%) more than 30 days after randomization. Despite the fact that all the patients in this cohort of the PARTNER study were determined not to be suitable candidates for surgery, 12 of the patients who were assigned to standard therapy (6.7%) underwent aortic-valve replacement, 5 (2.8%) underwent placement of a conduit from the left ventricular apex to the descending aorta plus aortic-valve replacement, and 4 (2.2%) underwent TAVI at a nonparticipating site outside the United States. The 1-year rates of death among patients in the standard-therapy group who underwent aortic-valve replacement, conduit plus aortic-valve replacement, or TAVI at a nonparticipating site outside the United States were 33%, 80%, and 0%, respectively.
Rates of Death, Repeat Hospitalization, and Stroke
Table 2.
Table 2. Clinical Outcomes at 30 Days and 1 Year.Figure 1. 
Figure 1. Time-to-Event Curves for the Primary End Point and Other Selected End Points.Event rates were calculated with the use of Kaplan–Meier methods and compared with the use of the log-rank test. Deaths from unknown causes were assumed to be deaths from cardiovascular causes.
At 30 days after randomization, the rate of death from any cause was 5.0% in the TAVI group as compared with 2.8% in the standard-therapy group (P=0.41) (Table 2). At the 1-year follow-up, the rate of death from any cause (the primary end point), as calculated with the use of a Kaplan–Meier analysis, was 30.7% in the TAVI group, as compared with 50.7% in the standard-therapy group (hazard ratio, 0.55; 95% confidence interval [CI], 0.40 to 0.74; P<0.001) (Figure 1A). The rate of death from cardiovascular causes at 1 year (Kaplan–Meier analysis) was also lower in the TAVI group than in the standard-therapy group (20.5% vs. 44.6%; hazard ratio, 0.39; 95% CI, 0.27 to 0.56; P<0.001) (Figure 1B). The specific cardiovascular and noncardiovascular causes of death are shown in Table 4 in the Supplementary Appendix.
The superiority of TAVI with respect to the coprimary end point (the rate of the hierarchical composite of death from any cause or repeat hospitalization) was confirmed by the Finkelstein–Schoenfeld analysis (P<0.001). In addition, the rate of the nonhierarchical composite of death from any cause or repeat hospitalization at the 1-year follow-up (Kaplan–Meier analysis) was 42.5% with TAVI as compared with 71.6% with standard therapy (hazard ratio, 0.46; 95% CI, 0.35 to 0.59; P<0.001) (Figure 1C).
Major strokes were observed more frequently in the TAVI group than in the standard-therapy group at 30 days (5.0% vs. 1.1%, P=0.06) and at 1 year (7.8% vs. 3.9%, P=0.18). However, the rate of the composite of major stroke or death from any cause (Kaplan–Meier analysis) was still significantly lower in the TAVI group than in the standard-therapy group (33.0% vs. 51.3% at 1 year; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P<0.001) (Figure 1D). A more detailed analysis of the neurologic events is shown in Table 5 in the Supplementary Appendix.
Figure 2.
Figure 2. Subgroup Analyses of the Primary End Point of Death from Any Cause.Relative risks and 95% confidence intervals are shown for the primary end point of death from any cause at 1 year among patients randomly assigned to transcatheter aortic-valve implantation (TAVI) or standard therapy. The P value for interaction represents the likelihood of an interaction between the variable and the relative treatment effect. The body-mass index is the weight in kilograms divided by the square of the height in meters. The Society of Thoracic Surgeons (STS) score measures patient risk at the time of cardiovascular surgery on a scale that ranges from 0% to 100%, with higher scores indicating greater risk. Moderate or severe mitral regurgitation was defined as regurgitation of grade 3+ or higher. CABG denotes coronary-artery bypass grafting, COPD chronic obstructive pulmonary disease, LV left ventricular, NNT number needed to treat, and PCI percutaneous coronary intervention.
Subgroup analyses with interaction testing were performed to determine whether the reduction in the primary end point (the rate of death from any cause) after TAVI was consistent across 10 important subgroups (Figure 2). No significant interactions were observed.
Other Clinical Outcomes
Figure 3.
Figure 3. Symptom Status over Time.Symptom status according to New York Heart Association (NYHA) class is shown at baseline and at 30 days, 6 months, and 1 year among patients randomly assigned to transcatheter aortic-valve implantation (TAVI) or standard therapy (Standard).
The frequencies of other important clinical events at 30 days and at 1 year are shown in Table 2. Major vascular complications and major bleeding events were more frequent in the TAVI group than in the standard-therapy group. At 30 days, 6 months, and 1 year, symptoms were significantly reduced in the TAVI group (P<0.001 for all three comparisons) (Figure 3). At 1 year, 74.8% of the surviving patients who had undergone TAVI, as compared with 42.0% of the surviving patients who had received standard therapy, were asymptomatic or had mild symptoms (NYHA class I or II) (P<0.001). The 6-minute walk test could be performed in only a subgroup of patients, owing to the presence of coexisting conditions in many of the patients. At 1 year, a paired analysis of the distance covered during a 6-minute walk test showed that there was significant improvement after TAVI (P=0.002) and no change after standard therapy (P=0.67).
Echocardiographic Findings
Echocardiographic findings are shown in Table 6 in the Supplementary Appendix. Among patients who underwent TAVI, the mean aortic-valve area increased from 0.6±0.2 cm2 at baseline to 1.5±0.5 cm2 at 30 days (P<0.001), and the mean aortic-valve gradient decreased from 44.5±15.7 mm Hg to 11.1±6.9 mm Hg (P<0.001). At the 1-year follow-up assessment, the improvement in aortic-valve area and mean gradient was maintained.
Moderate or severe paravalvular aortic regurgitation was present in 11.8% of the patients in the TAVI group at 30 days and in 10.5% at 1 year. There were no substantial changes (i.e., changes of more than one grade) in paravalvular aortic regurgitation in the TAVI group during the 1-year follow-up period. The incidence of moderate or severe transvalvular aortic regurgitation was 1.3% at 30 days and 4.2% at 1 year among patients in the TAVI group, as compared with 16.9% and 15.2%, respectively, among patients in the standard-therapy group. Three patients in the TAVI group (1.7%) had to undergo an additional procedure (repeat TAVI) to treat clinically significant aortic regurgitation (paravalvular in two patients and transvalvular in one).
Discussion
The main results from the PARTNER trial in the cohort of patients with aortic stenosis who were not suitable candidates for surgery can be summarized as follows. First, standard medical therapy (including balloon aortic valvuloplasty, which was performed in 83.8% of the patients in the standard-therapy group) did not alter the natural history of severe aortic stenosis; at the end of 1 year, the rate of death from any cause was 50.7%, and the rate of death from cardiovascular causes was 44.6%. Second, transfemoral TAVI was superior to standard therapy, markedly reducing the rate of death from any cause (the primary end point), the rate of death from cardiovascular causes, and the rate of repeat hospitalization. In the first year, only five patients needed to be treated with TAVI to prevent one death, and only three patients needed to be treated to prevent either a death or repeat hospitalization. Third, the rate of death at 30 days among patients who underwent TAVI (5.0% in the intention-to-treat population, and 6.4% among patients who underwent TAVI) did not differ significantly from that among patients who received standard therapy in this cohort of patients who were not suitable candidates for surgery, despite the use of early-generation systems for TAVI and minimal operator experience with the TAVI procedure before the trial was initiated. Fourth, TAVI was also associated with a significant reduction in symptoms, as assessed with the use of the NYHA classification system and the results of a 6-minute walk test. Fifth, there were more neurologic events (including all strokes and major strokes), major vascular complications, and major bleeding events in the TAVI group than in the standard-therapy group. Sixth, echocardiographic findings after TAVI indicated that the hemodynamic performance of the bioprosthetic valve was excellent and that there was no evidence of deterioration in the first year. TAVI was accompanied by the frequent occurrence of paravalvular regurgitation, which was usually mild, remained stable during the 1-year follow-up period, and rarely required further treatment for worsening symptoms.
The early clinical outcomes (at ≤30 days) after transfemoral TAVI were similar to those seen in other recent studies of the same balloon-expandable bovine pericardial heart valve.28,29,31,32 Undoubtedly, the large femoral access sheaths that are required to insert this TAVI system contributed to the frequent occurrence of vascular complications and bleeding events. Ongoing studies are assessing the use of a lower-profile valve and support frame, which may reduce vascular complications, allow patients who have smaller iliofemoral arteries than did patients in this study to undergo this procedure, and facilitate percutaneous access and closure.
Strokes remain a troublesome adverse effect following TAVI; strokes occur more frequently among patients who undergo TAVI than among patients who receive standard therapy. Recently, diffusion-weighted magnetic resonance imaging studies have shown that there are new perfusion deficits in many patients after TAVI, presumably due to atherothrombotic emboli.38,39 The combination of smaller, less traumatic TAVI systems than the ones currently in use and novel cerebral protection devices is being evaluated in an effort to reduce the frequency of embolic neurologic events associated with TAVI. Additional randomized clinical trials are needed to compare the frequency of procedural strokes after TAVI with the frequency after surgical aortic-valve replacement.
Our study has several limitations. The protocol-mandated selection criteria excluded important patient subgroups, such as patients requiring treatment of coronary stenoses and patients with severe peripheral vascular disease. An assessment of the durability and the long-term clinical safety and effectiveness of the bioprosthetic valves will require more prolonged follow-up of patients who participated in the PARTNER trial and in other clinical trials of TAVI. Because TAVI was a relatively new procedure in the United States at the time the PARTNER trial was conducted, there was still a learning curve for most of the surgeons and interventional cardiologists who performed TAVI in the United States, and this relative inexperience was compounded by the use of an earlier-generation delivery system that was more likely to cause complications.
On the basis of a rate of death from any cause at 1 year that was 20 percentage points lower with TAVI than with standard therapy, balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery (like the patients enrolled in this study). These results cannot be extrapolated to other patients with aortic stenosis. Additional randomized trials are needed to compare TAVI with aortic-valve replacement among high-risk patients with aortic stenosis for whom surgery is a viable option and among low-risk patients with aortic stenosis.
Supplementary Material
References (39)
1. Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38:61-67
2. Cheitlin MD, Gertz EW, Brundage BH, Carlson CJ, Quash JA, Bode RS Jr. Rate of progression of severity of valvular aortic stenosis in the adult. Am Heart J 1979;98:689-700
3. Otto CM, Pearlman AS, Gardner CL. Hemodynamic progression of aortic stenosis in adults assessed by Doppler echocardiography. J Am Coll Cardiol 1989;13:545-550
4. Davies SW, Gershlick AH, Balcon R. Progression of valvular aortic stenosis: a long-term retrospective study. Eur Heart J 1991;12:10-14
5. Peter M, Hoffmann A, Parker C, Luscher T, Burckhardt D. Progression of aortic stenosis: role of age and concomitant coronary artery disease. Chest 1993;103:1715-1719
6. Turina J, Hess O, Sepulcri F, Krayenbuehl HP. Spontaneous course of aortic valve disease. Eur Heart J 1987;8:471-483
7. Kelly TA, Rothbart RM, Cooper CM, Kaiser DL, Smucker ML, Gibson RS. Comparison of outcome of asymptomatic to symptomatic patients older than 20 years of age with valvular aortic stenosis. Am J Cardiol 1988;61:123-130
8. Bonow RO, Carabello BA, Chatterjee K, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1988 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008;118:e523-e661
9. Schwarz F, Baumann P, Manthey J, et al. The effect of aortic valve replacement on survival. Circulation 1982;66:1105-1110
10. Murphy ES, Lawson RM, Starr A, Rahimtoola SH. Severe aortic stenosis in patients 60 years of age or older: left ventricular function and 10-year survival after valve replacement. Circulation 1981;64:II-184
11. Lund O. Preoperative risk evaluation and stratification of long-term survival after valve replacement for aortic stenosis: reasons for earlier operative intervention. Circulation 1990;82:124-139
12. O'Brien SM, Shahian DM, Filardo G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 2 -- isolated valve surgery. Ann Thorac Surg 2009;88:Suppl:S23-S42
13. O'Brien SM, Shahian DM, Filardo G, et al. The Society of Thoracic Surgeons 2008 cardiac surgery risk models: part 3 -- valve plus coronary artery bypass grafting surgery. Ann Thorac Surg 2009;88:Suppl:S43-S62
14. Bouma BJ, van den Brink RBA, van der Meulen JHP, et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-148
15. Iung B, Cachier A, Baron G, et al. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J 2005;26:2714-2720
16. Varadarajan P, Kapoor N, Bansal RC, Pai RG. Clinical profile and natural history of 453 nonsurgically managed patients with severe aortic stenosis. Ann Thorac Surg 2006;82:2111-2115
17. Bach DS, Siao D, Girard SE, Duvernoy C, McCallister BD Jr, Gualano SK. Evaluation of patients with severe symptomatic aortic stenosis who do not undergo aortic valve replacement. Circ Cardiovasc Qual Outcomes 2009;2:533-539
18. Dewey TM, Brown D, Ryan WH, Herbert MA, Prince SL, Mack MJ. Reliability of risk algorithms in predicting early and late operative outcomes in high-risk patients undergoing aortic valve replacement. J Thorac Cardiovasc Surg 2008;135:180-187
19. Di Eusanio M, Fortuna D, De Palma R, et al. Aortic valve replacement: results and predictors of mortality from a contemporary series of 2256 patients. J Thorac Cardiovasc Surg 2010 July 2 (Epub ahead of print).
20. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis: first human case description. Circulation 2002;106:3006-3008
21. Cribier A, Eltchaninoff H, Tron C, et al. Early experience with percutaneous transcatheter implantation of heart valve prosthesis for the treatment of end-stage inoperable patients with calcific aortic stenosis. J Am Coll Cardiol 2004;43:698-703
22. Cribier A, Eltchaninoff H, Tron C, et al. Treatment of calcific aortic stenosis with the percutaneous heart valve: mid-term follow-up from the initial feasibility studies: the French experience. J Am Coll Cardiol 2006;47:1214-1223
23. Webb JG, Chandavimol M, Thompson CR, et al. Percutaneous aortic valve implantation retrograde from the femoral artery. Circulation 2006;113:842-850
24. Grube E, Laborde JC, Gerckens U, et al. Percutaneous implantation of the CoreValve self-expanding valve prosthesis in high-risk patients with aortic valve disease. Circulation 2006;114:1616-1624
25. Walther T, Simon P, Dewey T, et al. Transapical minimally invasive aortic valve implantation: multicenter experience. Circulation 2007;116:Suppl:I-240
26. Svensson LG, Dewey T, Kapadia S, et al. United States feasibility study of transcatheter insertion of a stented aortic valve by the left ventricular apex. Ann Thorac Surg 2008;86:46-55
27. Grube E, Buellesfeld L, Mueller R, et al. Progress and current status of percutaneous aortic valve replacement: results of three device generations of the CoreValve revalving system. Circ Cardiovasc Interv 2008;1:167-175
28. Himbert D, Descoutures F, Al-Attar N, et al. Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis. J Am Coll Cardiol 2009;54:303-311
29. Webb JG, Altwegg L, Boone RH, et al. Transcatheter aortic valve implantation: impact on clinical and valve-related outcomes. Circulation 2009;119:3009-3016
30. Piazza N, Grube E, Gerckens U, et al. Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) CoreValve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval. EuroIntervention 2008;4:242-249
31. Rodes-Cabau J, Webb JG, Cheung A, et al. Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk. J Am Coll Cardiol 2010;55:1080-1090
32. Thomas M, Schymik G, Walther T, et al. Thirty-day results of the SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry. Circulation 2010;122:62-69
33. Cutlip DE, Windecker S, Mehran R, et al. Clinical end points in coronary stent trials: a case for standardized definitions. Circulation 2007;115:2344-2351
34. Akins CW, Miller DC, Turina MI, et al. Guidelines for reporting mortality and morbidity after cardiac valve interventions. J Thorac Cardiovasc Surg 2008;135:732-738
35. Shroyer AL, Coombs LP, Peterson ED, et al. The Society of Thoracic Surgeons: 30-day operative mortality and morbidity risk models. Ann Thorac Surg 2003;75:1856-1864
36. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-117
37. Finkelstein DM, Schoenfeld DA. Combining mortality and longitudinal measures in clinical trials. Stat Med 1999;18:1341-1354
38. Kahlert P, Knipp SC, Schlamann M, et al. Silent and apparent cerebral ischemia after percutaneous transfemoral aortic valve implantation: a diffusion-weighted magnetic resonance imaging study. Circulation 2010;121:870-878
39. Ghanem A, Muller A, Nahle CP, et al. Risk and fate of cerebral embolism after transfemoral aortic valve implantation: a prospective pilot study with diffusion-weighted magnetic resonance imaging. J Am Coll Cardiol 2010;55:1427-1432
Citing Articles (4657)
Only the 1000 most recent citing articles are listed here.
Letters
Figures/Media
- Table 1. Baseline Characteristics of the Patients and Echocardiographic Findings.
Table 1. Baseline Characteristics of the Patients and Echocardiographic Findings. - Table 2. Clinical Outcomes at 30 Days and 1 Year.
Table 2. Clinical Outcomes at 30 Days and 1 Year. - Figure 1. Time-to-Event Curves for the Primary End Point and Other Selected End Points.
Figure 1. Time-to-Event Curves for the Primary End Point and Other Selected End Points. Event rates were calculated with the use of Kaplan–Meier methods and compared with the use of the log-rank test. Deaths from unknown causes were assumed to be deaths from cardiovascular causes.
- Figure 2. Subgroup Analyses of the Primary End Point of Death from Any Cause.
Figure 2. Subgroup Analyses of the Primary End Point of Death from Any Cause. Relative risks and 95% confidence intervals are shown for the primary end point of death from any cause at 1 year among patients randomly assigned to transcatheter aortic-valve implantation (TAVI) or standard therapy. The P value for interaction represents the likelihood of an interaction between the variable and the relative treatment effect. The body-mass index is the weight in kilograms divided by the square of the height in meters. The Society of Thoracic Surgeons (STS) score measures patient risk at the time of cardiovascular surgery on a scale that ranges from 0% to 100%, with higher scores indicating greater risk. Moderate or severe mitral regurgitation was defined as regurgitation of grade 3+ or higher. CABG denotes coronary-artery bypass grafting, COPD chronic obstructive pulmonary disease, LV left ventricular, NNT number needed to treat, and PCI percutaneous coronary intervention.
- Figure 3. Symptom Status over Time.
Figure 3. Symptom Status over Time. Symptom status according to New York Heart Association (NYHA) class is shown at baseline and at 30 days, 6 months, and 1 year among patients randomly assigned to transcatheter aortic-valve implantation (TAVI) or standard therapy (Standard).
