Propensity-matched comparisons of clinical outcomes after transapical or transfemoral transcatheter aortic valve replacement: a placement of aortic transcatheter valves (PARTNER)-I trial substudy.

BACKGROUND: The higher risk of adverse outcomes after transapical (TA) versus transfemoral (TF) transcatheter aortic valve replacement (TAVR) could be attributable to TA-TAVR being an open surgical procedure or to clinical differences between TA- and TF-TAVR patients. We compared outcomes after neutralizing patient differences using propensity score matching. METHODS AND RESULTS: From April 2007 to February 2012, 1100 Placement of Aortic Transcatheter Valves (PARTNER)-I patients underwent TA-TAVR and 1521 underwent TF-TAVR with Edwards SAPIEN balloon-expandable bioprostheses. Propensity matching based on 111 preprocedural variables, exclusive of femoral access morphology, identified 501 well-matched patient pairs (46% of possible matches), 95% of whom had peripheral arterial disease. Matched TA-TAVR patients experienced more adverse procedural events, longer length of stay (5 versus 8 days; P<0.0001), and slower recovery (New York Heart Association class I, 31% versus 38% at 30 days, equalizing by 6 months at 51% versus 47%); stroke risk was similar (3.4% versus 3.3% at 30 days and 6.0% versus 6.7% at 3 years); mortality was elevated for the first 6 postprocedural months (19% versus 12%; P=0.01); but aortic regurgitation was less (34% versus 52% mild and 8.9% versus 12% moderate to severe at discharge, P=0.001; 36% versus 50% mild and 10% versus 15% moderate to severe at 6 months, P<0.0001). CONCLUSIONS: The likelihood of adverse periprocedural events and prolonged recovery is greater after TA-TAVR than TF-TAVR in vasculopathic patients after accounting for differences in cardiovascular risk factors, although stroke risk is equivalent and aortic regurgitation is less. As smaller delivery systems permit TF-TAVR in many of these patients, we recommend a TF-first access strategy for TAVR when anatomically feasible. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

5-year outcomes of transcatheter aortic valve replacement compared with standard treatment for patients with inoperable aortic stenosis (PARTNER 1): a randomised controlled trial.

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 cm(2) 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.

Long-term outcomes of inoperable patients with aortic stenosis randomly assigned to transcatheter aortic valve replacement or standard therapy.

BACKGROUND: The long-term outcomes of transcatheter aortic valve replacement (TAVR) in inoperable patients with severe aortic stenosis remain unknown. METHODS AND RESULTS: In the Placement of Aortic Transcatheter Valves (PARTNER) study, 358 patients were randomly assigned to TAVR or standard therapy. We report the 3-year outcomes on these patients, and the pooled outcomes for all randomly assigned inoperable patients (n=449) in PARTNER, as well, including the randomized portion of the continued access study (n=91). The 3-year mortality rate in the TAVR and standard therapy groups was 54.1% and 80.9%, respectively (P<0.001; hazard ratio, 0.53; 95% confidence interval, 0.41-0.68; P<0.001). In survivors, there was significant improvement in New York Heart Association functional class sustained at 3 years. The cumulative incidence of strokes at 3-year follow-up was 15.7% in TAVR patients versus 5.5% in patients undergoing standard therapy (hazard ratio, 2.81; 95% confidence interval, 1.26-6.26; P=0.012); however, the composite of death or strokes was significantly lower after TAVR versus standard therapy (57.4% versus 80.9%, P<0.001; hazard ratio, 0.60; 95% confidence interval, 0.46-0.77; P<0.001). Echocardiography showed a sustained increase in aortic valve area and decrease in transvalvular gradient after TAVR. Analysis of the 449 pooled randomly assigned patients (TAVR, n=220; standard therapy, n=229) demonstrated significant improvement in all-cause mortality and functional status during early and 3-year follow-up. The results of the pooled cohort were similar to the results obtained from the pivotal PARTNER trial. CONCLUSIONS: TAVR resulted in better survival and functional status in inoperable patients with severe aortic stenosis with durable hemodynamic benefit on long-term follow-up. However, high residual mortality, even in successfully treated TAVR patients, highlights the need for more strategic patient selection. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.

Transcatheter aortic-valve replacement for inoperable severe aortic stenosis.

BACKGROUND: Transcatheter aortic-valve replacement (TAVR) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The outcomes beyond 1 year in such patients are not known. METHODS: We randomly assigned patients to transfemoral TAVR or to standard therapy (which often included balloon aortic valvuloplasty). Data on 2-year outcomes were analyzed. RESULTS: A total of 358 patients underwent randomization at 21 centers. The rates of death at 2 years were 43.3% in the TAVR group and 68.0% in the standard-therapy group (P<0.001), and the corresponding rates of cardiac death were 31.0% and 62.4% (P<0.001). The survival advantage associated with TAVR that was seen at 1 year remained significant among patients who survived beyond the first year (hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.92; P=0.02 with the use of the log-rank test). The rate of stroke was higher after TAVR than with standard therapy (13.8% vs. 5.5%, P=0.01), owing, in the first 30 days, to the occurrence of more ischemic events in the TAVR group (6.7% vs. 1.7%, P=0.02) and, beyond 30 days, to the occurrence of more hemorrhagic strokes in the TAVR group (2.2% vs. 0.6%, P=0.16). At 2 years, the rate of rehospitalization was 35.0% in the TAVR group and 72.5% in the standard-therapy group (P<0.001). TAVR, as compared with standard therapy, was also associated with improved functional status (P<0.001). The data suggest that the mortality benefit after TAVR may be limited to patients who do not have extensive coexisting conditions. Echocardiographic analysis showed a sustained increase in aortic-valve area and a decrease in aortic-valve gradient, with no worsening of paravalvular aortic regurgitation. CONCLUSIONS: Among appropriately selected patients with severe aortic stenosis who were not suitable candidates for surgery, TAVR reduced the rates of death and hospitalization, with a decrease in symptoms and an improvement in valve hemodynamics that were sustained at 2 years of follow-up. The presence of extensive coexisting conditions may attenuate the survival benefit of TAVR. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Two-year outcomes after transcatheter or surgical aortic-valve replacement.

BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. METHODS: At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. RESULTS: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). CONCLUSIONS: A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.).

Transcatheter versus surgical aortic-valve replacement in high-risk patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery.

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 (Kaplan­Meier 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.).

Comprehensive analysis of mortality among patients undergoing TAVR: results of the PARTNER trial.

BACKGROUND: Patients with severe aortic stenosis (AS) who were deemed too high risk or inoperable for conventional aortic valve replacement (AVR) in the PARTNER (Placement of Aortic Transcatheter Valves) trial were randomized to transcatheter aortic valve replacement (TAVR) versus AVR (PARTNER-A arm) or standard therapy (PARTNER-B arm). OBJECTIVES: This study compared when and how deaths occurred after TAVR versus surgical AVR or standard therapy. METHODS: The PARTNER-A arm included 244 transfemoral (TF) and 104 transapical (TA) TAVR patients, and 351 AVR patients; the PARTNER-B arm included 179 TF-TAVR patients and 179 standard therapy patients. Deaths were categorized as cardiovascular, noncardiovascular, or uncategorizable, and were characterized by multiphase hazard modelling. RESULTS: In the PARTNER-A arm, the risk of death peaked after randomization in the TA-TAVR and AVR groups, falling to low levels commensurate with the U.S. population within 3 months. Early risk was less in TF-TAVR patients, resulting in initial superior survival; between 12 and 18 months, risk increased, such that within 2 years, TF-TAVR and AVR patients had similar survival rates. Cardiovascular, noncardiovascular, and uncategorizable deaths for TF-TAVR were 37%, 43%, and 20%, respectively, versus 22%, 41%, and 37%, respectively, for TA-TAVR and 33%, 43%, and 24%, respectively, for AVR. In the PARTNER-B arm, risk with standard therapy was 60% per year; TF-TAVR reduced risk to 20% per year, resulting in 0.5 years of life added within 2.5 years. CONCLUSIONS: In inoperable AS patients, TAVR substantially reduced the risk of cardiovascular death. In high-risk patients, TA-TAVR and AVR were associated with elevated peri-procedural risk more than with TF-TAVR, although cardiovascular death was higher after TF-TAVR. Therefore, TF-TAVR should be considered the standard of care for severely symptomatic inoperable patients or those at high risk of noncardiovascular mortality after conventional surgery. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).

Comparison of transcatheter and surgical aortic valve replacement in severe aortic stenosis: a longitudinal study of echocardiography parameters in cohort A of the PARTNER trial (placement of aortic transcatheter valves).

OBJECTIVES: This study sought to compare echocardiographic findings in patients with critical aortic stenosis following surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR). BACKGROUND: The PARTNER (Placement of Aortic Transcatheter Valves) trial randomized patients 1:1 to SAVR or TAVR. METHODS: Echocardiograms were obtained at baseline, discharge, 30 days, 6 months, 1 year, and 2 years after the procedure and analyzed in a core laboratory. For the analysis of post-implantation variables, the first interpretable study (≤6 months) was used. RESULTS: Both groups showed a decrease in aortic valve gradients and increase in effective orifice area (EOA) (p < 0.0001), which remained stable over 2 years. Compared with SAVR, TAVR resulted in larger indexed EOA (p = 0.038), less prosthesis-patient mismatch (p = 0.019), and more total and paravalvular aortic regurgitation (p < 0.0001). Baseline echocardiographic univariate predictors of death were lower peak transaortic gradient in TAVR patients, and low left ventricular diastolic volume, low stroke volume, and greater severity of mitral regurgitation in SAVR patients. Post-implantation echocardiographic univariate predictors of death were: larger left ventricular diastolic volume, left ventricular systolic volume and EOA, decreased ejection fraction, and greater aortic regurgitation in TAVR patients; and smaller left ventricular systolic and diastolic volumes, low stroke volume, smaller EOA, and prosthesis-patient mismatch in SAVR patients. CONCLUSIONS: Patients randomized to either SAVR or TAVR experience enduring, significant reductions in transaortic gradients and increase in EOA. Compared with SAVR, TAVR patients had higher indexed EOA, lower prosthesis-patient mismatch, and more aortic regurgitation. Univariate predictors of death for the TAVR and SAVR groups differed and might allow future refinement in patient selection. (THE PARTNER TRIAL: Placement of AoRTic TraNscathetER Valve Trial; NCT00530894).