Faculty Bibliography

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.

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.

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.

BACKGROUND: Hybrid percutaneous coronary intervention offers an alternative method of revascularization for high-risk surgical populations. We report the outcomes of a single-stage hybrid strategy in valvular cardiac surgery and explore its effects on operative risk and bleeding. METHODS: In a hybrid operating room, 26 patients underwent hybrid surgery consisting of femoral arterial access, then coronary stenting followed by valve surgery, with appropriate heparin dosing. Clopidogrel (300 mg) was given on anesthesia induction in nonreoperative cases, or at the time of cross clamping (after stenting) for reoperative cases. RESULTS: Mean follow-up was 680 +/- 277 days. The planned coronary stenting and surgery was successful in all patients. Major cardiovascular and cerebrovascular adverse events occurred in 1 patient, with no inhospital deaths observed. No vascular complication or stent thrombosis was observed with the described antiplatelet regimen. Outcomes were comparable to those of standard bypass valve replacement surgery. CONCLUSIONS: This study demonstrates the feasibility and early safety of a single-stage hybrid strategy with coronary stenting followed by valvular surgery in patients at increased surgical risk. Hybrid procedures may lower operative risk by eliminating or reducing the need for bypass grafting.

B-type natriuretic peptide (BNP) levels have shown a correlation with outcomes in studies of aortic valve surgery. Results from multicenter trials of BNP in transcatheter aortic valve surgery (TAVR) are lacking. The aim of this study was to investigate the prognostic role of serial measurement of BNP in transfemoral TAVR. A total of 1,097 patients who underwent TAVR via transfemoral access were analyzed by tertile of baseline BNP. Of those, 933 with BNP levels at 30 days were divided into 2 groups on the basis of increases (334 patients) or decreases or no change (599 patients) in BNP compared with baseline. Patients in the low-tertile BNP group had a lower rate of death at 1 year than those in the higher tertile group (15.0% vs 23.0%, p<0.01) which was not significant in multivariate analysis. Over 1 year, BNP decreased from 1,258.13±2,988.33 to 594.37±1,087.30 (p<0.01) in the entire group. Patients in the BNP-rise group had higher rates of death at 1 year (20.3% vs 11.4%, p<0.01) and an overall increase in moderate or severe aortic regurgitation over 1 year (p<0.01). Multivariate predictors of 1-year mortality were moderate or severe aortic regurgitation (hazard ratio 2.04, 95% confidence interval 1.36 to 3.05, p<0.01), increase in BNP at 30 days (hazard ratio 1.82, 95% confidence interval 1.26 to 2.62, p<0.01) and Society of Thoracic Surgeons score (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p=0.03). In conclusion, increase in BNP at 30 days from baseline and moderate or severe aortic regurgitation at 30 days in patients who undergo transfemoral TAVR are independently associated with 1-year mortality. Increase in BNP at 30 days should prompt evaluation for causes of elevated wall stress, including aortic regurgitation.

Recent multicenter trials have shown that transcatheter aortic valve replacement is an alternative to surgery in a high risk population of patients with severe, symptomatic aortic stenosis. Echocardiography and multislice computed tomographic imaging are accepted tools in the pre-procedural imaging of the aortic valve complex and vascular access. Transesophageal echocardiography can be valuable for intraprocedural confirmation of the landing zone morphology and measurements, positioning of the valve and post-procedural evaluation of complications. The current paper provides recommendations for pre-procedural and intraprocedural imaging used in assessing patients for transcatheter aortic valve replacement with either balloon-expandable or self-expanding transcatheter heart valves.

AIM/OBJECTIVE:The impact of paravalvular regurgitation (PVR) following transcatheter aortic valve replacement (TAVR) remains uncertain. In this analysis, we sought to evaluate the impact of varying degrees of PVR on both mortality and changes in ventricular geometry and function. METHODS AND RESULTS/RESULTS:Clinical and echocardiographic outcomes of patients who underwent TAVR from the randomized cohorts and continued access registries in the PARTNER trial were analysed after stratifying by severity of post-implant PVR, which was graded as none/trace in 52.9% (n = 1288), mild in 38.0% (n = 925), and moderate/severe in 9.1% (n = 221). There were significant differences in baseline clinical and echocardiographic characteristics. After TAVR, all the patients demonstrated increase in left ventricular (LV) function and reduction in the LV mass index, although the magnitude of mass regression was lower in the moderate/severe PVR group. The 30-day mortality (3.1 vs. 3.4 vs. 4.5%, P = 0.56) and stroke (3.4 vs. 3.7 vs. 2.3%, P = 0.59) were similar in all groups (none/trace, mild, and moderate/severe). At 1 year, there was increased all-cause mortality (15.9 vs. 22.2 vs. 35.1%, P < 0.0001), cardiac mortality (6.1 vs. 7.4% vs. 16.3%, P < 0.0001) and re-hospitalization (14.4 vs. 23.0 vs. 31.3%, P < 0.0001) with worsening PVR. A multivariable analysis indicated that the presence of moderate/severe PVR (HR: 2.18, 95% CI: 1.57-3.02, P < 0.0001) or mild PVR (HR: 1.37, 95% CI: 1.14-1.90, P = 0.012) was associated with higher late mortality. CONCLUSION/CONCLUSIONS:Differences in baseline characteristics in patients with increasing severities of PVR may increase the risk of this complication. Despite these differences, multivariable analysis demonstrated that both mild and moderate/severe PVR predicted higher 1-year mortality.

OBJECTIVES/OBJECTIVE:The purpose of this study was to identify predictors and clinical implications of permanent pacemaker (PPM) implantation after transcatheter aortic valve replacement (TAVR). BACKGROUND:Cardiac conduction disturbances requiring PPM are a frequent complication of TAVR. However, limited data is available regarding this complication after TAVR with a balloon-expandable valve. METHODS:The study included patients without prior pacemaker who underwent TAVR in the PARTNER (Placement of AoRtic TraNscathetER Valves) trial and registry and investigated predictors and clinical effect of new PPM. RESULTS:Of 2,559 TAVR patients, 586 were excluded due to pre-existing PPM. A new PPM was required in 173 of the remaining 1,973 patients (8.8%). By multivariable analysis, predictors of PPM included right bundle branch block (odds ratio [OR]: 7.03, 95% confidence interval [CI]: 4.92 to 10.06, p < 0.001), prosthesis diameter/left ventricular (LV) outflow tract diameter (for each 0.1 increment, OR: 1.29, 95% CI: 1.10 to 1.51, p = 0.002), LV end-diastolic diameter (for each 1 cm, OR: 0.68, 95% CI: 0.53 to 0.87, p = 0.003), and treatment in continued access registry (OR: 1.77, 95% CI: 1.08 to 2.92, p = 0.025). Patients requiring PPM had a longer mean duration of post-procedure hospitalization (7.3 ± 2.7 days vs. 6.2 ± 2.8 days, p = 0.001). At 1 year, new PPM was associated with significantly higher repeat hospitalization (23.9% vs. 18.2%, p = 0.05) and mortality or repeat hospitalization (42.0% vs. 32.6%, p = 0.007). There was no difference between groups in LV ejection fraction at 1 year. CONCLUSIONS:PPM was required in 8.8% of patients without prior PPM who underwent TAVR with a balloon-expandable valve in the PARTNER trial and registry. In addition to pre-existing right bundle branch block, the prosthesis to LV outflow tract diameter ratio and the LV end-diastolic diameter were identified as novel predictors of PPM after TAVR. New PPM was associated with a longer duration of hospitalization and higher rates of repeat hospitalization and mortality or repeat hospitalization at 1 year. (THE PARTNER TRIAL: Placement of AoRtic TraNscathetER Valves Trial; NCT00530894).

BACKGROUND: The introduction of transcatheter aortic valve replacement mandates attention to outcomes after surgical aortic valve replacement (SAVR) in low-risk, intermediate-risk, and very high-risk patients. METHODS: The study population included 141,905 patients who underwent isolated primary SAVR from 2002 to 2010. Patients were risk-stratified by Society of Thoracic Surgeons (STS) predicted risk of mortality (PROM) <4% (group 1, n = 113,377), 4% to 8% (group 2, n = 19,769), and >8% (group 3, n = 8,759). The majority of patients were considered at low risk (80%), and only 6.2% were categorized as being at high risk. Outcomes were analyzed based on two time periods: 2002 to 2006 (n = 63,754) and 2007 to 2010 (n = 78,151). RESULTS: The mean age was 65 years in group 1, 77 in group 2, and 77 in group 3 (p < 0.0001). The median STS PROM for the entire population was 1.84: 1.46% in group 1, 5.24% in group 2, and 11.2% in group 3 (p < 0.0001). Compared with PROM, in-hospital mean mortality was lower than expected in all patients (2.5% vs 2.95%) and when analyzed within risk groups was as follows: group 1 (1.4% vs 1.7%), group 2 (5.1% vs 5.5%), and group 3 (11.8% vs 13.7%) (p < 0.0001). In the most recent surgical era, operative mortality was significantly reduced in group 2 (5.4% vs 6.4%, p = 0.002) and group 3 (11.9% vs 14.4%, p = 0.0004) but not in group 1. CONCLUSIONS: Nearly 80% of patients undergoing SAVR have outcomes that are superior to those by the predicted risk models. In the most recent era, early results have further improved in medium-risk and high-risk patients. This large real-world assessment serves as a benchmark for patients with aortic valve stenosis as therapeutic options are further evaluated.