Self-expanding intra-annular versus commercially available transcatheter heart valves in high and extreme risk patients with severe aortic stenosis (PORTICO IDE): a randomised, controlled, non-inferiority trial.

BACKGROUND: Randomised trial data assessing the safety and efficacy of the self-expanding intra-annular Portico transcatheter aortic valve system (Abbott Structural Heart, St Paul, MN, USA) compared with any commercially available valves are needed to compare performance among designs. METHODS: In this prospective, multicentre, non-inferiority, randomised controlled trial (the Portico Re-sheathable Transcatheter Aortic Valve System US Investigational Device Exemption trial [PORTICO IDE]), high and extreme risk patients with severe symptomatic aortic stenosis were recruited from 52 medical centres experienced in performing transcatheter aortic valve replacement in the USA and Australia. Patients were eligible if they were aged 21 years or older, in New York Heart Association functional class II or higher, and had severe native aortic stenosis. Eligible patients were randomly assigned (1:1) using permuted block randomisation (block sizes of 2 and 4) and stratified by clinical investigational site, surgical risk cohort, and vascular access method, to transcatheter aortic valve replacement with the first generation Portico valve and delivery system or a commercially available valve (either an intra-annular balloon-expandable Edwards-SAPIEN, SAPIEN XT, or SAPIEN 3 valve [Edwards LifeSciences, Irvine, CA, USA]; or a supra-annular self-expanding CoreValve, Evolut-R, or Evolut-PRO valve [Medtronic, Minneapolis, MN, USA]). Investigational site staff, implanting physician, and study participant were unmasked to treatment assignment. Core laboratories and clinical event assessors were masked to treatment allocation. The primary safety endpoint was a composite of all-cause mortality, disabling stroke, life-threatening bleeding requiring transfusion, acute kidney injury requiring dialysis, or major vascular complication at 30 days. The primary efficacy endpoint was all-cause mortality or disabling stroke at 1 year. Clinical outcomes and valve performance were assessed up to 2 years after the procedure. Primary analyses were by intention to treat and the Kaplan-Meier method to estimate event rates. The non-inferiority margin was 8·5% for primary safety and 8·0% for primary efficacy endpoints. This study is registered with ClinicalTrials.gov, NCT02000115, and is ongoing. FINDINGS: Between May 30 and Sept 12, 2014, and between Aug 21, 2015, and Oct 10, 2017, with recruitment paused for 11 months by the funder, we recruited 1034 patients, of whom 750 were eligible and randomly assigned to the Portico valve group (n=381) or commercially available valve group (n=369). Mean age was 83 years (SD 7) and 395 (52·7%) patients were female. For the primary safety endpoint at 30 days, the event rate was higher in the Portico valve group than in the commercial valve group (52 [13·8%] vs 35 [9·6%]; absolute difference 4·2, 95% CI -0·4 to 8·8 [upper confidence bound {UCB} 8·1%]; pnon-inferiority=0·034, psuperiority=0·071). At 1 year, the rates of the primary efficacy endpoint were similar between the groups (55 [14·8%] in the Portico group vs 48 [13·4%] in the commercial valve group; difference 1·5%, 95% CI -3·6 to 6·5 [UCB 5·7%]; pnon-inferiority=0·0058, psuperiority=0·50). At 2 years, rates of death (80 [22·3%] vs 70 [20·2%]; p=0·40) or disabling stroke (10 [3·1%] vs 16 [5·0%]; p=0·23) were similar between groups. INTERPRETATION: The Portico valve was associated with similar rates of death or disabling stroke at 2 years compared with commercial valves, but was associated with higher rates of the primary composite safety endpoint including death at 30 days. The first-generation Portico valve and delivery system did not offer advantages over other commercially available valves. FUNDING: Abbott.

Transcatheter or Surgical Aortic-Valve Replacement in Intermediate-Risk Patients.

BACKGROUND: Previous trials have shown that among high-risk patients with aortic stenosis, survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. We evaluated the two procedures in a randomized trial involving intermediate-risk patients. METHODS: We randomly assigned 2032 intermediate-risk patients with severe aortic stenosis, at 57 centers, to undergo either TAVR or surgical replacement. The primary end point was death from any cause or disabling stroke at 2 years. The primary hypothesis was that TAVR would not be inferior to surgical replacement. Before randomization, patients were entered into one of two cohorts on the basis of clinical and imaging findings; 76.3% of the patients were included in the transfemoral-access cohort and 23.7% in the transthoracic-access cohort. RESULTS: The rate of death from any cause or disabling stroke was similar in the TAVR group and the surgery group (P=0.001 for noninferiority). At 2 years, the Kaplan-Meier event rates were 19.3% in the TAVR group and 21.1% in the surgery group (hazard ratio in the TAVR group, 0.89; 95% confidence interval [CI], 0.73 to 1.09; P=0.25). In the transfemoral-access cohort, TAVR resulted in a lower rate of death or disabling stroke than surgery (hazard ratio, 0.79; 95% CI, 0.62 to 1.00; P=0.05), whereas in the transthoracic-access cohort, outcomes were similar in the two groups. TAVR resulted in larger aortic-valve areas than did surgery and also resulted in lower rates of acute kidney injury, severe bleeding, and new-onset atrial fibrillation; surgery resulted in fewer major vascular complications and less paravalvular aortic regurgitation. CONCLUSIONS: In intermediate-risk patients, TAVR was similar to surgical aortic-valve replacement with respect to the primary end point of death or disabling stroke. (Funded by Edwards Lifesciences; PARTNER 2 ClinicalTrials.gov number, NCT01314313.).

Comparison of coronary revascularization appropriateness for non-acute coronary syndrome cases under the 2017 update vs the 2012 appropriate use criteria.

OBJECTIVES: To compare coronary revascularization appropriateness for non-acute coronary syndrome cases under the 2017 update vs the 2012 appropriate use criteria (AUC). BACKGROUND: In 2017, the 2012 AUC for coronary revascularization were updated. We examined how applying these new 2017 updates to our previous inappropriate cases would change their appropriateness. METHODS: We identified 50 cases of patients who underwent coronary revascularization for stable ischemic heart disease who were deemed inappropriate under the 2012 AUC. Two separate physicians reviewed the cases and applied a new AUC based on the 2017 AUC. Next, if there was a change, the reason was identified. RESULTS: Average age was 64, majority being male (29; 58%). Forty-two (84%) were asymptomatic upon presentation. Most cases (27, 54%) dealt with percutaneous coronary intervention (PCI) of the right coronary artery. After applying the 2017 AUC, 34 of the 50 inappropriate failures (68%) would be changed from "inappropriate" to "may be appropriate care." Of the 34 cases, 25 (73.5%) were changed due to the new AUC no longer expecting the patient to be on ≥2 anti-angina medications prior to PCI. Of the 34 cases, eight (23.5%) were changed due to the new AUC expanding the use of non-invasive modalities. CONCLUSIONS: Applying the 2017 AUC led to a statistically higher number of cases being deemed "may be appropriate." The most common cause for the change included the change in requirement for anti-angina regimen and the expanded role of non-invasive modalities.

Role of contractile reserve as a predictor of mortality in low-flow, low-gradient severe aortic stenosis following transcatheter aortic valve replacement.

OBJECTIVES: The aim of this study was to determine the prognostic value of contractile reserve (CR) at baseline in patients with low-flow, low-gradient severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Patients with severe AS, left ventricular dysfunction, and low transaortic gradient are at high risk for mortality during surgical aortic valve replacement (SAVR). Furthermore, patients without CR have been shown to have perioperative mortality comparable to that of patients treated medically for severe AS. METHODS: We retrospectively analyzed patients who underwent TAVR with a diagnosis of low-gradient severe AS (mean transvalvular aortic gradient < 40 mmHg, LVEF < 50%, and AVA ≤ 1.0 cm2 or AVAi ≤ 0.6 cm2 ) and who had a pre-TAVR dobutamine stress echocardiogram (DSE). Patients were stratified by the presence or absence of CR, defined as an increase in stroke volume ≥ 20% during DSE. RESULTS: From 2008 to 2016, 61 patients with low-gradient severe AS underwent TAVR and had pre-TAVR DSE. CR was present in 31 patients (51%) and absent in 30 (49%). There was no significant difference between the two groups in baseline demographics, medical history, access site, or types of valves. All-cause mortality was similar in both groups at 30 days (13% with CR vs 10% without CR, P = 1.00) and 1 year (29% with CR vs 33% without CR, HR 1.20, 95% CI 0.49-2.96, P = 0.69). CONCLUSION: In patients with low-flow, low-gradient severe AS undergoing TAVR, the presence or absence of CR does not predict all-cause mortality at 30 days or 1 year.

Possible Subclinical Leaflet Thrombosis in Bioprosthetic Aortic Valves.

BACKGROUND: A finding of reduced aortic-valve leaflet motion was noted on computed tomography (CT) in a patient who had a stroke after transcatheter aortic-valve replacement (TAVR) during an ongoing clinical trial. This finding raised a concern about possible subclinical leaflet thrombosis and prompted further investigation. METHODS: We analyzed data obtained from 55 patients in a clinical trial of TAVR and from two single-center registries that included 132 patients who were undergoing either TAVR or surgical aortic-valve bioprosthesis implantation. We obtained four-dimensional, volume-rendered CT scans along with data on anticoagulation and clinical outcomes (including strokes and transient ischemic attacks [TIAs]). RESULTS: Reduced leaflet motion was noted on CT in 22 of 55 patients (40%) in the clinical trial and in 17 of 132 patients (13%) in the two registries. Reduced leaflet motion was detected among patients with multiple bioprosthesis types, including transcatheter and surgical bioprostheses. Therapeutic anticoagulation with warfarin, as compared with dual antiplatelet therapy, was associated with a decreased incidence of reduced leaflet motion (0% and 55%, respectively, P=0.01 in the clinical trial; and 0% and 29%, respectively, P=0.04 in the pooled registries). In patients who were reevaluated with follow-up CT, restoration of leaflet motion was noted in all 11 patients who were receiving anticoagulation and in 1 of 10 patients who were not receiving anticoagulation (P<0.001). There was no significant difference in the incidence of stroke or TIA between patients with reduced leaflet motion and those with normal leaflet motion in the clinical trial (2 of 22 patients and 0 of 33 patients, respectively; P=0.16), although in the pooled registries, a significant difference was detected (3 of 17 patients and 1 of 115 patients, respectively; P=0.007). CONCLUSIONS: Reduced aortic-valve leaflet motion was shown in patients with bioprosthetic aortic valves. The condition resolved with therapeutic anticoagulation. The effect of this finding on clinical outcomes including stroke needs further investigation. (Funded by St. Jude Medical and Cedars-Sinai Heart Institute; Portico-IDE ClinicalTrials.gov number, NCT02000115; SAVORY registry, NCT02426307; and RESOLVE registry, NCT02318342.).

Utility of an additive frailty tests index score for mortality risk assessment following transcatheter aortic valve replacement.

BACKGROUND: The impact of frailty assessment on outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear. Our aim was to evaluate the individual effect of each frailty test and the utility of an additive frailty index score on short- and long-term survival following TAVR. METHODS: Retrospective analysis of consecutive TAVR patients for whom a complete set of frailty tests was obtained: algorithm defined grip strength and 5-m walking tests, body mass index <20 kg/m2, Katz activities of daily living ≤4/6, serum albumin <3.5 g/dL. Frailty status was defined as having 3 or more positive frailty tests. Included were 498 patients with a mean age of 82±8 years. RESULTS: Frailty status, observed in 266 (53%) patients, was associated with both 30-day and 1-year mortality (6% vs. 2%, P=.016; 20% vs. 9%, P<.001; within the respective frailty groups). As compared to 0-2 frailty criteria, a higher frailty index score was associated with increased risk of death at 1 year (OR 2.23; 95% CI 1.14-4.34; P=.019 and OR 3.30; 95% CI 1.36-8.00; P=.008 for 3 and 4-5 frailty criteria met, respectively). In Cox regression analysis, frailty status was correlated with 1-year mortality (HR=2.2; 95%CI 1.25-3.96; P=.007), and a higher frailty index was associated with increased mortality risk (HR=2.0; 95% CI 1.08-3.7; P=.027; and HR=3.07; 95% CI 1.4-6.7; P=.005; for any 3, and 4-5 frailty criteria, respectively). CONCLUSIONS: Frailty status and a higher frailty index score were associated with increased 1-year mortality risk following TAVR.

Temporal trends in patient referral for Transcatheter aortic valve replacement and reasons for exclusion at a high-volume Center in the United States.

BACKGROUND: Clinical indications for transcatheter aortic valve replacement (TAVR) and elements of the implantation procedure, including delivery system miniaturization and novel access options, have evolved over time. The reasons patients are excluded from TAVR also have changed. The impact of these changes on patient referral for and exclusion from TAVR is unknown. METHODS: We retrospectively analyzed patients referred to our center for TAVR from January 2010 to August 2016 to evaluate reasons for patient exclusion. Patients were divided into three groups based on initial screening date for trends in demographics and exclusion: Group 1, 2010-2012; Group 2, 2012-2014; Group 3, 2014 to August 1, 2016. Annual trends for patient exclusion from TAVR were assessed. RESULTS: One thousand nine hundred fifty-three patients were referred and underwent screening for TAVR. The rates at which patients were referred for TAVR were 23.8, 25.9, and 24.5 per month in groups 1, 2, and 3, respectively. Rate of patient exclusion from TAVR decreased from 68% in Group 1 to 38% in Group 3 (P < .001). The largest percentage of patients (29.4%) were initially excluded from TAVR for cardiac reasons, but this trend has decreased over time. Twenty-five percent are excluded for lack of procedural indication. Exclusion from TAVR for vascular access reasons decreased from 7.9% in 2010 to 1.0% in 2016 (P = .017). CONCLUSIONS: Referral numbers have been robust since TAVR became available. The percentage of patients excluded from TAVR has decreased over time. Patients are most commonly excluded from TAVR for concomitant coronary artery disease (CAD), asymptomatic severe AS, moderate AS, or non-cardiac critical illness. Patients with CAD and those with asymptomatic severe AS or moderate AS should be a focus for continued research in TAVR.

Impact of right ventricular function on outcome of severe aortic stenosis patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Right ventricular (RV) dysfunction was shown to be associated with adverse outcomes in a variety of cardiac patients and is considered a risk factor for adverse outcome according to the updated Valve Academic Research Consortium criteria. OBJECTIVE: Our goal was to assess the impact of RV function at baseline on 1-year mortality among patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). METHODS: All patients with severe AS treated with TAVR from May 2007 to March 2015 at our center were included in the present study, and baseline and procedural characteristics were recorded for each patient. The patients were categorized according to RV function at baseline as assessed by current guidelines, and a comparison of mortality rates up to 1 year was performed. RESULTS: Among 650 patients, 606 had adequate echocardiogram quality and 146 (24%) had RV dysfunction. There were significant differences between the 2 groups, as patients with RV dysfunction were younger (81±9 vs 84±7 years, P=.01) and were more likely to be male (65% vs 42%, P<.001). In addition, patients with RV dysfunction had higher rates of prior myocardial infarction (26% vs 16%, P=.02) and atrial fibrillation (51% vs 39%, P=.02). Echocardiographic parameters demonstrated higher rates of left ventricular ejection fraction <40% (40% vs 18%, P<.001), tricuspid regurgitation above moderate (16% vs 9%, P=.04), and higher pulmonary artery systolic pressure (50±17 vs 44±16 mm Hg, P<.001) among patients with severe AS and RV dysfunction compared with patients with normal RV function. Despite the unfavorable cardiac function, patients with severe AS undergoing TAVR have similar functional class (P=.22) and mortality rates at 1year (27% vs 23%, log-rank P=.45). CONCLUSIONS: Patients with severe AS and RV dysfunction have similar 1-year mortality and functional class after TAVR to patients with normal RV function. The presence of RV dysfunction does not correlate with outcome in patients with severe AS.

Does direct stenting with drug-eluting stents improve outcome? A meta-analysis of 10,900 patients.

OBJECTIVES: The aim of this study is to summarize the outcomes of patients undergoing direct stenting (DS) with drug-eluting stents (DES) compared to those who underwent balloon predilatation. BACKGROUND: DS has been associated with improved outcomes in the bare-metal stent era. Although DS with DES implantation has been increasingly adopted in clinical practice, its safety and effectiveness remain controversial. METHODS: The search criteria identified 546 studies in the Medline/PubMed, Cochrane, and EMBASE databases from 2001 to July 2014. From these, seven studies totaling 10,900 patients were selected. Summarized estimates [odds ratio (OR) and 95% confidence intervals] were obtained using a random-effects model. The primary outcomes were a composite of major adverse cardiac events (MACE), including all-cause death, myocardial infarction (MI), and repeat revascularization. The secondary outcomes included a composite of death and MI and the rates of target lesion revascularization (TLR). RESULTS: Overall, 4101 (38%) and 6799 (62%) patients underwent DS with DES and balloon pre-dilatation, respectively. DS with DES reduced the likelihood of MACE (OR: 0.81 [0.71-0.93]). Additionally, DS with DES was associated with reduced rates of death/MI (OR: 0.76 [0.62-0.92]), and TLR (OR: 0.66 [0.44-0.98]). CONCLUSIONS: DS with DES is safe and may be associated with better outcomes in selected patients. © 2016 Wiley Periodicals, Inc.

Outcome of implantation of a second self-expanding valve for the treatment of residual significant aortic regurgitation.

BACKGROUND: Residual aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is associated with adverse outcome. We sought to evaluate the efficacy and safety of second CoreValve (CV) implantation to treat residual AR following the initial CV deployment. METHODS AND RESULTS: TAVR patients treated with a second CV due to moderate and above residual AR were compared to single device implantation. Valvular function parameters were compared at baseline, post procedure, and 30 days. Among 172 CV TAVR patients, 11 required a second device (6%) due to significant residual AR. The main differences between the groups were higher rates of low ejection fraction in patients with 2 CV implanted and higher annular diameter (27 [29-25] vs. 25 [26-24] mm, P = 0.03), requiring a larger device. Although two patients in the two CV group had high initial implantation, low implantation was similar between the groups. A second CV achieved adequate reduction in residual AR in six patients (55%), while an additional four patients had moderate residual AR. Only one remained with moderate to severe AR after 30 days follow-up. There were no cases of peri-procedural stroke or mortality. CONCLUSIONS: Second implantation of self-expanding valve can successfully reduce residual significant AR following initial CV implantation and should be considered as therapeutic option for this population. © 2017 Wiley Periodicals, Inc.

Comparison of transradial and transfemoral access in patients undergoing percutaneous coronary intervention for complex coronary lesions.

OBJECTIVE: Comparison of transradial versus transfemoral access for complex percutaneous coronary intervention (PCI) with regard to both complications and long-term outcomes. BACKGROUND: Radial access has been shown to confer superior results in patients undergoing PCI, especially in patients with acute coronary syndromes. However, radial access has limitations of sheath and device size, which may increase procedure time and result in inferior outcomes. METHODS: Patients undergoing PCI for complex lesions, defined as type C according the ACC/AHA classification system, were included in this study. Propensity matching was performed to adjust for differences in baseline characteristics. Transradial patients were then compared to transfemoral patients in regard to procedural, in-hospital, and 6-month outcomes. RESULTS: Among 2142 patients with 2591 lesions treated, 1876 had femoral access and 267 had radial access. Radial access patients were more likely to be male (75% vs. 66%, P = 0.003) and less likely to present with acute myocardial infarction (27% vs. 42%, P < 0.001). Procedural characteristics demonstrated lower use of heparin in the femoral group (17% vs. 73%, P < 0.001) with similarly low use of glycoprotein inhibitors (5.6% vs. 3.4%, P = 0.14). Patients in the femoral group had higher rates of transfusions (3.7% vs. 0%, P = 0.004) and vascular complications (1.7% vs. 0%, P = 0.03). Following propensity matching, there was no difference in mid-term outcomes between radial and femoral groups. CONCLUSIONS: In patients with complex coronary lesions undergoing PCI, the radial approach demonstrates similar mid-term outcomes as the femoral approach with a potentially lower rate of complications. © 2016 Wiley Periodicals, Inc.

Contemporary transcatheter aortic valve replacement with third-generation balloon-expandable versus self-expanding devices.

OBJECTIVES: To evaluate balloon-expandable and self-expanding third-generation transcatheter aortic valve replacement (TAVR) devices according to patient selection criteria and outcomes. BACKGROUND: Two competing third-generation TAVR technologies are currently commercially available in the US. There are no published head-to-head comparisons of the relative performance of these two devices. METHODS: 257 consecutive patients undergoing TAVR with a third-generation balloon-expandable (Edwards Sapien 3) or self-expanding device (Medtronic CoreValve Evolut R) at a single US medical center were included. Choice of TAVR device was at the discretion of the multidisciplinary Heart Team. Baseline clinical characteristics, echocardiographic and CT imaging, procedural and 30-day outcomes were prospectively collected. RESULTS: 74 patients received a self-expanding valve (SEV) and 183 received a balloon-expandable valve (BEV). Patients selected for SEV were more frequently women, with lower body surface area and smaller calcified iliofemoral arteries. Three SEV patients required implantation of a second valve to successfully treat paravalvular leak. Only one BEV patient had moderate paravalvular regurgitation. There was no difference in the rate of stroke, major vascular complication or bleeding. Permanent pacemaker implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30-day mortality was comparable (1.4% vs 1.6%, P = 1.00). CONCLUSIONS: Short-term outcomes were equivalent between the two technologies. Clinically significant paravalvular regurgitation was rare. SEV were more frequently selected in women and patients with challenging transfemoral access, but were associated with higher permanent pacemaker implantation rate and longer hospital length of stay.

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.

5-year outcomes of transcatheter aortic valve replacement or surgical aortic valve replacement for high surgical risk patients with aortic stenosis (PARTNER 1): a randomised controlled trial.

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.

Cerebrovascular accidents after percutaneous coronary interventions from 2002 to 2014: Incidence, outcomes, and associated variables.

BACKGROUND: Cerebrovascular accident (CVA) and transient ischemic attack (TIA) related to percutaneous coronary intervention (PCI) are relatively rare complications, but they are associated with high morbidity and mortality. Given the evolution of both CVA risk and PCI techniques over time, this study was conducted to evaluate trends in CVA and TIA associated with PCI and to identify variables associated with neurologic events. METHODS: Consecutive patients undergoing PCI at the Washington Hospital Center between January 2002 and June 2015 were included. Prespecified data were prospectively collected, including baseline and procedural characteristics, in-hospital outcomes, and 1-year mortality. The subjects who had a CVA or TIA during or immediately after PCI were compared with those without procedure-associated CVA or TIA. RESULTS: Overall, 25,626 patients were included in the study. The mean age was 65.0 ± 12.4 years, 16,949 (65.2%) were male, and 7,436 (28.6%) were African American. From 2002 to 2015, 110 neurologic events post-PCI were diagnosed (0.43%); this included 86 CVAs (0.34%) and 24 TIAs (0.09%). The annual rate of postprocedural neurologic events was 0.42% ± 0.12%. There were significant changes in baseline risk factors over time, with increasing age, incidence of insulin-dependent diabetes, and chronic kidney disease. Patients with neurologic events were more often African American (43.6% vs 28.6%, P < .001) with prior history of CVA (24.5% vs 7.8%, P < .001), chronic renal insufficiency (26.6% vs 15.2%, P < .001), and insulin-dependent diabetes (19.1% vs 12.4%, P = .03). Acute myocardial infarction (56% vs 30.4%, P < .001) and cardiogenic shock (20.2% vs 3%, P < .001) were also more common among patients with neurologic events post-PCI. After multivariable adjustment, use of an intraaortic balloon pump was strongly associated with neurologic events (odds ratio [OR] 4.9, 95% CI 2.7-8.8, P < .001), as was prior CVA (OR 2.4, 95% CI 1.4-4.4, P = .002) and African American race (OR 2.4, 95% CI 1.5-3.9, P < .001); there was a borderline association with the use of a thrombus extraction device (OR 1.7, 95% CI 0.9-3.2, P = .09). In-hospital mortality (20.0% vs 1.5%, P < .001) and 1-year mortality (45.0% vs 7.3%, P < .001) were also much higher in patients with neurologic events. CONCLUSION: Neurologic events post-PCI are associated with markedly worse in-hospital outcomes. The incidence of CVA and TIA post-PCI, however, remained stable over the last 12 years despite an increase in risk factors for CVA.

Clinical profiles and correlates of mortality in nonagenarians with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is the current standard for nonoperable and high-risk surgical patients with aortic stenosis, including those of advanced age. However, the clinical profiles, procedural characteristics, and outcomes of nonagenarians undergoing TAVR have not been thoroughly reported. METHODS: A total of 654 patients (n = 107 >90 years old and n = 547 <90 years) with severe aortic stenosis undergoing TAVR were included in this analysis. Baseline characteristics, procedural variables, and in-hospital outcomes and complications at 30 days and 12 months were analyzed. RESULTS: Overall, of the patients included, 46% were high risk and 53% inoperable. Although nonagenarians had a higher Society of Thoracic Surgeons score of 9.2 ± 4 (12.1 ± 4 vs 8.6 ± 4, P < .001), other factors were considerably lower in this group: diabetes (22% vs 36%, P = .008), hyperlipidemia (65% vs 83%, P < .001), prior coronary artery bypass (13% vs 39%, P < .001), and mean body mass index (24.5 ± 5 vs 28.1 ± 7 kg/m(2), P < .001). The correlates for 1-year mortality in nonagenarians were as follows: ≥moderate aortic insufficiency post-TAVR (hazard ratio [HR] 5.07, 95% CI 1.17-22, P = .03), pacemaker implantation after TAVR (HR 6.87, 95% CI 2.32-20.3, P = .001), and peripheral vascular disease (HR 2.35, 95% CI 1.03-5.38, P = .042). Mortality at 30 days (12.1% vs 7.1%, P = .07) and at 1 year (25% vs 21%, P = .35) was similar between groups. CONCLUSION: Nonagenarians undergoing TAVR had a healthier clinical profile compared with younger patients. Age alone should not be a discriminatory factor when screening elderly patients with aortic stenosis because even the nonagenarians are doing well when compared with the younger elderly population. Transcatheter aortic valve replacement remains a viable option for the treatment of severe symptomatic aortic stenosis for the elderly regardless of their age.

Impact of baseline mitral regurgitation on short- and long-term outcomes following transcatheter aortic valve replacement.

BACKGROUND: The prevalence of concomitant significant mitral regurgitation (MR) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) ranges from 2% to 33%. The impact of significant MR on post-TAVR outcomes remains controversial. METHODS: The data from a cohort of patients with symptomatic severe AS undergoing TAVR at out institution were retrospectively analyzed. The last transthoracic echocardiogram (TTE) before the index TAVR procedure was selected as the baseline assessment of the degree of MR. The total study cohort (N = 589) was divided into 2 groups: significant ≥moderate MR (n = 68) versus nonsignificant

Does the disparity in baseline characteristics of patients undergoing transcatheter aortic valve replacement with 23 mm vs. 26 mm valves impact clinical outcome?

OBJECTIVES: We sought to identify if baseline characteristic differences in patients who receive a 23 mm vs. 26 mm valve impact clinical outcomes. BACKGROUND: Transcatheter aortic valve replacement (TAVR) is currently an approved therapy for patients with severe aortic stenosis who are considered inoperable or are at high risk. METHODS: We retrospectively examined baseline characteristics and outcomes of patients receiving a 23 mm (n = 132) vs. 26 mm valve (n = 81) via the transfemoral approach. RESULTS: Gender (P < 0.01), previous coronary artery bypass surgery (P < 0.01), history of atrial fibrillation (P = 0.04), and mean Society of Thoracic Surgeons (STS) score (P < 0.01) were significantly different between groups. There were no significant differences in the rates of minor/major vascular complications (2.2 vs. 3.7%, P = 0.68 and 13.0 vs. 12.3%, P = 0.89, respectively). Bleeding complications were also comparable (major bleed 2.3 vs. 1%, P >0.99, minor bleed 19.0 vs. 22.0%, P = 0.67 and life threatening bleed 7.0 vs. 5.0%, P = 0.77). In-hospital death (6.0 vs. 5.0%, P >0.99), 30-day all-cause death (7.6 vs. 6.2%, P = 0.69), and all-cause death at 1 year (17.4 vs. 25.9%, P = 0.13) were also similar between groups. Gender, valve size, previous coronary bypass surgery and atrial fibrillation were not independently associated with mortality; however, on multivariate analysis STS score was (HR 1.11; 95% CI 1.02-1.19; P = 0.01). CONCLUSION: Patients undergoing TAVR with 23 and 26 mm valves have similar clinical outcomes despite significant differences in baseline characteristics. © 2015 Wiley Periodicals, Inc.

The influence of advancing age on implantation of drug-eluting stents.

BACKGROUND: The influence of age upon the use of drug-eluting stents (DES) in patients aged ≥ 65 years is uncertain. The aim of this study is to investigate the impact of age increase in patients aged ≥ 65 years in the use of DES in patients undergoing percutaneous coronary intervention (PCI). METHOD: The study cohort comprised 8,598 patients ≥ 65 years of age who underwent stent implantation from April 2003 to March 2014. We defined the first DES era as the period April 2003 to July 2008 and the second DES era as the period July 2008 to March 2014. Multivariable logistic regression was performed for both eras to assess the impact of age increase and analyze independent factors associated with DES implantation. RESULTS: In the first DES era cohort, the two groups of patients differed in their risk factor profile with lower rates of male sex, diabetes, smokers, and hypercholesterolemia in those aged ≥ 75 years. There were more Caucasian and less African-Americans in this age group. Furthermore, patients aged ≥ 75 years had lower left ventricular ejection fraction (LVEF) and baseline haematocrit concentration were more likely to present with an acute myocardial infarction (MI) than stable or unstable angina and had higher rates of a previous history for congestive heart failure (CHF), chronic renal insufficiency (CRI), and peripheral vascular disease (PVD). These differences were broadly similar for patients in the second DES era except for similarities in LVEF, presentation with unstable angina, and PVD, as well as a lower rate for previous PCI. DES use was reduced with increasing age in both the first (OR=0.78; 95% CI=0.69-0.89) and second DES era (OR=0.53; 95% CI=0.47-0.58). In both eras, DES use was less likely in current smokers, patients presenting with acute MI and cardiogenic shock, and those with a previous history of CHF. CONCLUSION: In patients aged ≥ 65 years, the use of DES decreased with increasing age. This observation was apparent in both the first and second DES era. © 2015 Wiley Periodicals, Inc.