The use of transcatheter aortic-valve replacement has been shown to reduce mortality among high-risk patients with aortic stenosis who are not candidates for surgical replacement. However, the two ...procedures have not been compared in a randomized trial involving high-risk patients who are still candidates for surgical replacement.
At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either transcatheter aortic-valve replacement with a balloon-expandable bovine pericardial valve (either a transfemoral or a transapical approach) or surgical replacement. The primary end point was death from any cause at 1 year. The primary hypothesis was that transcatheter replacement is not inferior to surgical replacement.
The rates of death from any cause were 3.4% in the transcatheter group and 6.5% in the surgical group at 30 days (P=0.07) and 24.2% and 26.8%, respectively, at 1 year (P=0.44), a reduction of 2.6 percentage points in the transcatheter group (upper limit of the 95% confidence interval, 3.0 percentage points; predefined margin, 7.5 percentage points; P=0.001 for noninferiority). The rates of major stroke were 3.8% in the transcatheter group and 2.1% in the surgical group at 30 days (P=0.20) and 5.1% and 2.4%, respectively, at 1 year (P=0.07). At 30 days, major vascular complications were significantly more frequent with transcatheter replacement (11.0% vs. 3.2%, P<0.001); adverse events that were more frequent after surgical replacement included major bleeding (9.3% vs. 19.5%, P<0.001) and new-onset atrial fibrillation (8.6% vs. 16.0%, P=0.006). More patients undergoing transcatheter replacement had an improvement in symptoms at 30 days, but by 1 year, there was not a significant between-group difference.
In high-risk patients with severe aortic stenosis, transcatheter and surgical procedures for aortic-valve replacement were associated with similar rates of survival at 1 year, although there were important differences in periprocedural risks. (Funded by Edwards Lifesciences; Clinical Trials.gov number, NCT00530894.).
Background All neurologic events in the PARTNER randomized trial comparing transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (AVR) were analyzed. Methods High-risk ...patients with aortic stenosis were stratified into transfemoral (TF, n = 461) or transapical (TA, n = 196) strata based on their arterial anatomy and randomized: 657 received treatment assigned (“as treated”), 313 underwent AVR, and 344 TAVR. Neurologic events were prospectively adjudicated by an independent Clinical Events Committee. Multivariable, multiphase hazard analysis elucidated factors associated with increased likelihood of neurologic events. Results Forty-nine neurologic events (15 transient ischemic attacks, 34 strokes) occurred in 47 patients (TAVR, n = 31; AVR, n = 16). An early peaking high hazard phase occurred within the first week, which declined to a constant late hazard phase out to 2 years. The risk in the early phase was higher after TAVR than AVR, and in the TAVR arm in patients with a smaller aortic valve area index. In the late risk phase, the likelihood of neurologic event was linked to patient-related factors in both arms (“non-TF candidate,” history of recent stroke or transient ischemic attack, and advanced functional disability), but not by treatment (TAVR vs AVR) or any intraprocedural variables. The likelihood of sustaining a neurologic event was lowest in the AVR subgroup in the TF stratum during all available follow-up. Conclusions After either treatment, there were 2 distinct hazard phases for neurologic events that were driven by different risk factors. Neurologic complications occurred more frequently after TAVR than AVR early, but thereafter the risk was influenced by patient- and disease-related factors.
Summary Background The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that mortality at 1 year, 2 years, and 3 years is much the same with transcatheter aortic valve replacement ...(TAVR) or surgical aortic valve replacement (SAVR) for high-risk patients with aortic stenosis. We report here the 5-year outcomes. Methods We did this randomised controlled trial at 25 hospitals, in Canada (two), Germany (one), and the USA (23). We used a computer-generated randomisation sequence to randomly assign high-risk patients with severe aortic stenosis to either SAVR or TAVR with a balloon-expandable bovine pericardial tissue valve by either a transfemoral or transapical approach. Patients and their treating physicians were not masked to treatment allocation. The primary outcome of the trial was all-cause mortality in the intention-to-treat population at 1 year, we present here predefined outcomes at 5 years. The study is registered with ClinicalTrials.gov , number NCT00530894. Findings We screened 3105 patients, of whom 699 were enrolled (348 assigned to TAVR, 351 assigned to SAVR). Overall mean Society of Thoracic Surgeons Predicted Risk of Mortality score was 11·7%. At 5 years, risk of death was 67·8% in the TAVR group compared with 62·4% in the SAVR group (hazard ratio 1·04, 95% CI 0·86–1·24; p=0·76). We recorded no structural valve deterioration requiring surgical valve replacement in either group. Moderate or severe aortic regurgitation occurred in 40 (14%) of 280 patients in the TAVR group and two (1%) of 228 in the SAVR group (p<0·0001), and was associated with increased 5-year risk of mortality in the TAVR group (72·4% for moderate or severe aortic regurgitation vs 56·6% for those with mild aortic regurgitation or less; p=0·003). Interpretation Our findings show that TAVR as an alternative to surgery for patients with high surgical risk results in similar clinical outcomes. Funding Edwards Lifesciences.
Summary Background Based on the early results of the Placement of Aortic Transcatheter Valves (PARTNER) trial, transcatheter aortic valve replacement (TAVR) is an accepted treatment for patients with ...severe aortic stenosis who are not suitable for surgery. However, little information is available about the late clinical outcomes in such patients. Methods We did this randomised controlled trial at 21 experienced valve centres in Canada, Germany, and the USA. We enrolled patients with severe symptomatic inoperable aortic stenosis and randomly assigned (1:1) them to transfemoral TAVR or to standard treatment, which often included balloon aortic valvuloplasty. Patients and their treating physicians were not masked to treatment allocation. The randomisation was done centrally, and sites learned of the assignment only after a patient had been screened, consented, and entered into the database. The primary outcome of the trial was all-cause mortality at 1 year in the intention-to-treat population, here we present the prespecified findings after 5 years. This study is registered with ClinicalTrials.gov , number NCT00530894. Findings We screened 3015 patients, of whom 358 were enrolled (mean age 83 years, Society of Thoracic Surgeons Predicted Risk of Mortality 11·7%, 54% female). 179 were assigned to TAVR treatment and 179 were assigned to standard treatment. 20 patients crossed over from the standard treatment group and ten withdrew from study, leaving only six patients at 5 years, of whom five had aortic valve replacement treatment outside of the study. The risk of all-cause mortality at 5 years was 71·8% in the TAVR group versus 93·6% in the standard treatment group (hazard ratio 0·50, 95% CI 0·39–0·65; p<0·0001). At 5 years, 42 (86%) of 49 survivors in the TAVR group had New York Heart Association class 1 or 2 symptoms compared with three (60%) of five in the standard treatment group. Echocardiography after TAVR showed durable haemodynamic benefit (aortic valve area 1·52 cm2 at 5 years, mean gradient 10·6 mm Hg at 5 years), with no evidence of structural valve deterioration. Interpretation TAVR is more beneficial than standard treatment for treatment of inoperable aortic stenosis. TAVR should be strongly considered for patients who are not surgical candidates for aortic valve replacement to improve their survival and functional status. Appropriate selection of patients will help to maximise the benefit of TAVR and reduce mortality from severe comorbidities. Funding Edwards Lifesciences.
Objectives The purpose of this study was to characterize operative outcomes for ascending aorta and arch replacement on a national scale and to develop risk models for mortality and major morbidity. ...Background Contemporary outcomes for ascending aorta and arch replacement in North America are unknown. Methods We queried the Society of Thoracic Surgeons Database for patients undergoing ascending aorta (with or without root) with or without arch replacement from 2004 to 2009. The database captured 45,894 cases, including 12,702 root, 22,048 supracoronary ascending alone, 6,786 ascending plus arch, and 4,358 root plus arch. Baseline characteristics and clinical outcomes were analyzed. A parsimonious multivariable logistic regression model was constructed to predict risks of mortality and major morbidity. Results Operative mortality was 3.4% for elective cases and 15.4% for nonelective cases. A risk model for operative mortality (c-index 0.81) revealed a risk-adjusted odds ratio for death after emergent versus elective operation of 5.9 (95% confidence interval: 5.3 to 6.6). Among elective patients, end-stage renal disease and reoperative status were the strongest predictors of mortality (adjusted odds ratios: 4.0 95% confidence interval: 2.6 to 6.4 and 2.3 (95% confidence interval: 1.9 to 2.7, respectively; p < 0.0001). Conclusions Current outcomes for ascending aorta and arch replacement in North America are excellent for elective repair; however, results deteriorate for nonelective status, suggesting that increased screening and/or lowering thresholds for elective intervention could potentially improve outcomes. The predictive models presented may serve clinicians in counseling patients.
In patients with aortic stenosis (AS), risk stratification for aortic valve replacement (AVR) relies mainly on valve-related factors, symptoms and co-morbidities. We sought to evaluate the prognostic ...impact of a newly-defined staging classification characterizing the extent of extravalvular (extra-aortic valve) cardiac damage among patients with severe AS undergoing AVR.
Patients with severe AS from the PARTNER 2 trials were pooled and classified according to the presence or absence of cardiac damage as detected by echocardiography prior to AVR: no extravalvular cardiac damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage (Stage 4). One-year outcomes were compared using Kaplan-Meier techniques and multivariable Cox proportional hazards models were used to identify 1-year predictors of mortality. In 1661 patients with sufficient echocardiographic data to allow staging, 47 (2.8%) patients were classified as Stage 0, 212 (12.8%) as Stage 1, 844 (50.8%) as Stage 2, 413 (24.9%) as Stage 3, and 145 (8.7%) as Stage 4. One-year mortality was 4.4% in Stage 0, 9.2% in Stage 1, 14.4% in Stage 2, 21.3% in Stage 3, and 24.5% in Stage 4 (Ptrend < 0.0001). The extent of cardiac damage was independently associated with increased mortality after AVR (HR 1.46 per each increment in stage, 95% confidence interval 1.27-1.67, P < 0.0001).
This newly described staging classification objectively characterizes the extent of cardiac damage associated with AS and has important prognostic implications for clinical outcomes after AVR.
Objectives The logistic European System for Cardiac Operative Risk Evaluation (LES) score and the Society of Thoracic Surgeons (STS) score are validated to predict 30-day outcomes following surgical ...aortic valve replacement (SAVR) with or without coronary artery bypass grafting. Their performance when applied to patients undergoing transcatheter aortic valve replacement (TAVR) is controversial. Methods We compared predicted and observed 30-day/in-hospital and 1-year mortality of patients undergoing TAVR in the first Placement of Aortic Transcatheter Valves trial and continued access registry (N = 2466). The performance of the LES and STS scores (prospectively calculated) was evaluated using standard assessments of discrimination and calibration. Performance of STS and LES scores among 307 patients undergoing SAVR from the high-risk cohort of the randomized trial were also examined. Results In patients undergoing TAVR, the observed 30-day/in-hospital mortality was 6.5%, whereas the predicted 30-day mortality was higher by both STS score (11.4% ± 3.9%) and LES score (26.6% ± 16.2%). The discrimination for both scores was poor for 30-day/in-hospital and 1-year mortality. Calibration was better for STS score than for LES at 1 year but poor for both at 30 days among TAVR cohort. These results were consistent among the subgroups of patients undergoing transfemoral and transapical access; however, the STS score had better performance among the high-risk patients who underwent SAVR at 30 days but not 1 year. Conclusions The STS and LES surgical risk scores overestimated 30-day/in-hospital mortality and were poor discriminators of post-TAVR mortality, but the calibration of the STS score was better in these high-risk patients. These data highlight the need for TAVR-specific risk models to optimize patient selection.
It is unknown whether transcatheter valves will have similar durability as surgical bioprosthetic valves. Definitions of structural valve deterioration (SVD), based on valve related reintervention or ...death, underestimate the incidence of SVD.
This study sought to determine and compare the 5-year incidence of SVD, using new standardized definitions based on echocardiographic follow-up of valve function, in intermediate-risk patients with severe aortic stenosis given transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) in the PARTNER (Placement of Aortic Transcatheter Valves) 2A trial and registry.
In the PARTNER 2A trial, patients were randomly assigned to receive either TAVR with the SAPIEN XT or SAVR, whereas in the SAPIEN 3 registry, patients were assigned to TAVR with the SAPIEN 3. The primary endpoint was the incidence of SVD, that is, the composite of SVD-related hemodynamic valve deterioration during echocardiographic follow-up and/or SVD-related bioprosthetic valve failure (BVF) at 5 years.
Compared with SAVR, the SAPIEN-XT TAVR cohort had a significantly higher 5-year exposure adjusted incidence rates (per 100 patient-years) of SVD (1.61 ± 0.24% vs. 0.63 ± 0.16%), SVD-related BVF (0.58 ± 0.14% vs. 0.12 ± 0.07%), and all-cause (structural or nonstructural) BVF (0.81 ± 0.16% vs. 0.27 ± 0.10%) (p ≤ 0.01 for all). The 5-year rates of SVD (0.68 ± 0.18% vs. 0.60 ± 0.17%; p = 0.71), SVD-related BVF (0.29 ± 0.12% vs. 0.14 ± 0.08%; p = 0.25), and all-cause BVF (0.60 ± 0.15% vs. 0.32 ± 0.11%; p = 0.32) in SAPIEN 3 TAVR were not significantly different to a propensity score matched SAVR cohort. The 5-year rates of SVD and SVD-related BVF were significantly lower in SAPIEN 3 versus SAPIEN XT TAVR matched cohorts.
Compared with SAVR, the second-generation SAPIEN XT balloon-expandable valve has a higher 5-year rate of SVD, whereas the third-generation SAPIEN 3 has a rate of SVD that was not different from SAVR. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves - PII A PARTNERII A; NCT01314313; The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves II - PARTNER II - PARTNERII - S3 Intermediate PARTNERII S3i; NCT03222128)
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Abstract Objectives The purpose of this study was to determine the safety and effectiveness of the SAPIEN XT versus SAPIEN systems (Edwards Lifesciences, Irvine, California) in patients with ...symptomatic, severe aortic stenosis (AS) who were not candidates for surgery. Background Transcatheter aortic valve replacement (TAVR) has become the standard of care for inoperable patients with severe, symptomatic AS. In the PARTNER (Placement of Aortic Transcatheter Valves) IB trial, a reduction in all-cause mortality was observed in patients undergoing TAVR with the balloon-expandable SAPIEN transcatheter heart valve compared with standard therapy, but the SAPIEN valve was associated with adverse periprocedural complications, including vascular complications, major bleeding, and paravalvular regurgitation. The newer, low-profile SAPIEN XT system was developed to reduce these adverse events. Methods A total of 560 patients were enrolled at 28 sites in the United States from April 2011 to February 2012. Patients were randomized to receive the SAPIEN or SAPIEN XT systems. The primary endpoint was a nonhierarchical composite of all-cause mortality, major stroke, and rehospitalization at 1 year in the intention-to-treat population, assessed by noninferiority testing. Pre-specified secondary endpoints included cardiovascular death, New York Heart Association functional class, myocardial infarction, stroke, acute kidney injury, vascular complications, bleeding, 6-min walk distance, and valve performance (by echocardiography). Results Both overall and major vascular complications were higher at 30 days in patients undergoing TAVR with SAPIEN compared with SAPIEN XT (overall: 22.1% vs. 15.5%; p = 0.04; major: 15.2% vs. 9.5%; p = 0.04). Bleeding requiring blood transfusions was also more frequent with SAPIEN compared with SAPIEN XT (10.6% vs. 5.3%; p = 0.02). At 1-year follow-up, the nonhierarchical composite of all-cause mortality, major stroke, or rehospitalization was similar (37.7% SAPIEN vs. 37.2% SAPIEN XT; noninferiority p value <0.002); no differences in the other major pre-specified endpoints were found. Conclusions In inoperable patients with severe, symptomatic AS, the lower-profile SAPIEN XT is noninferior to SAPIEN with fewer vascular complications and a lesser need for blood transfusion. (The PARTNER II Trial: Placement of AoRTic TraNscathetER Valves; NCT01314313 )
Summary Background Transcatheter aortic valve replacement (TAVR) with the SAPIEN 3 valve demonstrates good 30 day clinical outcomes in patients with severe aortic stenosis who are at intermediate ...risk of surgical mortality. Here we report longer-term data in intermediate-risk patients given SAPIEN 3 TAVR and compare outcomes to those of intermediate-risk patients given surgical aortic valve replacement. Methods In the SAPIEN 3 observational study, 1077 intermediate-risk patients at 51 sites in the USA and Canada were assigned to receive TAVR with the SAPIEN 3 valve 952 88% via transfemoral access) between Feb 17, 2014, and Sept 3, 2014. In this population we assessed all-cause mortality and incidence of strokes, re-intervention, and aortic valve regurgitation at 1 year after implantation. Then we compared 1 year outcomes in this population with those for intermediate-risk patients treated with surgical valve replacement in the PARTNER 2A trial between Dec 23, 2011, and Nov 6, 2013, using a prespecified propensity score analysis to account for between-trial differences in baseline characteristics. The clinical events committee and echocardiographic core laboratory methods were the same for both studies. The primary endpoint was the composite of death from any cause, all strokes, and incidence of moderate or severe aortic regurgitation. We did non-inferiority (margin 7·5%) and superiority analyses in propensity score quintiles to calculate pooled weighted proportion differences for outcomes. Findings At 1 year follow-up of the SAPIEN 3 observational study, 79 of 1077 patients who initiated the TAVR procedure had died (all-cause mortality 7·4%; 6·5% in the transfemoral access subgroup), and disabling strokes had occurred in 24 (2%), aortic valve re-intervention in six (1%), and moderate or severe paravalvular regurgitation in 13 (2%). In the propensity-score analysis we included 963 patients treated with SAPIEN 3 TAVR and 747 with surgical valve replacement. For the primary composite endpoint of mortality, strokes, and moderate or severe aortic regurgitation, TAVR was both non-inferior (pooled weighted proportion difference of −9·2%; 90% CI −12·4 to −6; p<0·0001) and superior (−9·2%, 95% CI −13·0 to −5·4; p<0·0001) to surgical valve replacement. Interpretation TAVR with SAPIEN 3 in intermediate-risk patients with severe aortic stenosis is associated with low mortality, strokes, and regurgitation at 1 year. The propensity score analysis indicates a significant superiority for our composite outcome with TAVR compared with surgery, suggesting that TAVR might be the preferred treatment alternative in intermediate-risk patients. Funding None.
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