Mark A. de Belder

Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry.

OBJECTIVES The objective was to define the characteristics of a real-world patient population treated with transcatheter aortic valve implantation (TAVI), regardless of technology or access route, and to evaluate their clinical outcome over the mid to long term. BACKGROUND Although a substantial body of data exists in relation to early clinical outcomes after TAVI, there are few data on outcomes beyond 1 year in any notable number of patients. METHODS The U.K. TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry was established to report outcomes of all TAVI procedures performed within the United Kingdom. Data were collected prospectively on 870 patients undergoing 877 TAVI procedures up until December 31, 2009. Mortality tracking was achieved in 100% of patients with mortality status reported as of December 2010. RESULTS Survival at 30 days was 92.9%, and it was 78.6% and 73.7% at 1 year and 2 years, respectively. There was a marked attrition in survival between 30 days and 1 year. In a univariate model, survival was significantly adversely affected by renal dysfunction, the presence of coronary artery disease, and a nontransfemoral approach; whereas left ventricular function (ejection fraction <30%), the presence of moderate/severe aortic regurgitation, and chronic obstructive pulmonary disease remained the only independent predictors of mortality in the multivariate model. CONCLUSIONS Midterm to long-term survival after TAVI was encouraging in this high-risk patient population, although a substantial proportion of patients died within the first year.

Facilitated PCI in Patients with ST-Elevation Myocardial Infarction

BACKGROUND We hypothesized that percutaneous coronary intervention (PCI) preceded by early treatment with abciximab plus half-dose reteplase (combination-facilitated PCI) or with abciximab alone (abciximab-facilitated PCI) would improve outcomes in patients with acute ST-segment elevation myocardial infarction, as compared with abciximab administered immediately before the procedure (primary PCI). METHODS In this international, double-blind, placebo-controlled study, we randomly assigned patients with ST-segment elevation myocardial infarction who presented 6 hours or less after the onset of symptoms to receive combination-facilitated PCI, abciximab-facilitated PCI, or primary PCI. All patients received unfractionated heparin or enoxaparin before PCI and a 12-hour infusion of abciximab after PCI. The primary end point was the composite of death from all causes, ventricular fibrillation occurring more than 48 hours after randomization, cardiogenic shock, and congestive heart failure during the first 90 days after randomization. RESULTS A total of 2452 patients were randomly assigned to a treatment group. Significantly more patients had early ST-segment resolution with combination-facilitated PCI (43.9%) than with abciximab-facilitated PCI (33.1%) or primary PCI (31.0%; P=0.01 and P=0.003, respectively). The primary end point occurred in 9.8%, 10.5%, and 10.7% of the patients in the combination-facilitated PCI group, abciximab-facilitated PCI group, and primary-PCI group, respectively (P=0.55); 90-day mortality rates were 5.2%, 5.5%, and 4.5%, respectively (P=0.49). CONCLUSIONS Neither facilitation of PCI with reteplase plus abciximab nor facilitation with abciximab alone significantly improved the clinical outcomes, as compared with abciximab given at the time of PCI, in patients with ST-segment elevation myocardial infarction. (ClinicalTrials.gov number, NCT00046228 [ClinicalTrials.gov].)

Randomized Comparison of Percutaneous Coronary Intervention With Coronary Artery Bypass Grafting in Diabetic Patients: 1-Year Results of the CARDia (Coronary Artery Revascularization in Diabetes) Trial

OBJECTIVES The purpose of this study was to compare the safety and efficacy of percutaneous coronary intervention (PCI) with stenting against coronary artery bypass grafting (CABG) in patients with diabetes and symptomatic multivessel coronary artery disease. BACKGROUND CABG is the established method of revascularization in patients with diabetes and multivessel coronary disease, but with advances in PCI, there is uncertainty whether CABG remains the preferred method of revascularization. METHODS The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), and stroke, and the main secondary outcome included the addition of repeat revascularization to the primary outcome events. A total of 510 diabetic patients with multivessel or complex single-vessel coronary disease from 24 centers were randomized to PCI plus stenting (and routine abciximab) or CABG. The primary comparison used a noninferiority method with the upper boundary of the 95% confidence interval (CI) not to exceed 1.3 to declare PCI noninferior. Bare-metal stents were used initially, but a switch to Cypher (sirolimus drug-eluting) stents (Cordis, Johnson & Johnson, Bridgewater, New Jersey) was made when these became available. RESULTS At 1 year of follow-up, the composite rate of death, MI, and stroke was 10.5% in the CABG group and 13.0% in the PCI group (hazard ratio [HR]: 1.25, 95% CI: 0.75 to 2.09; p=0.39), all-cause mortality rates were 3.2% and 3.2%, and the rates of death, MI, stroke, or repeat revascularization were 11.3% and 19.3% (HR: 1.77, 95% CI: 1.11 to 2.82; p=0.02), respectively. When the patients who underwent CABG were compared with the subset of patients who received drug-eluting stents (69% of patients), the primary outcome rates were 12.4% and 11.6% (HR: 0.93, 95% CI: 0.51 to 1.71; p=0.82), respectively. CONCLUSIONS The CARDia (Coronary Artery Revascularization in Diabetes) trial is the first randomized trial of coronary revascularization in diabetic patients, but the 1-year results did not show that PCI is noninferior to CABG. However, the CARDia trial did show that multivessel PCI is feasible in patients with diabetes, but longer-term follow-up and data from other trials will be needed to provide a more precise comparison of the efficacy of these 2 revascularization strategies. (The Coronary Artery Revascularisation in Diabetes trial; ISRCTN19872154).

Transcatheter Aortic Valve Implantation in the United Kingdom Temporal Trends, Predictors of Outcome, and 6-Year Follow-Up: A Report From the UK Transcatheter Aortic Valve Implantation (TAVI) Registry, 2007 to 2012

Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 μmol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P <0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome. Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors. # CLINICAL PERSPECTIVE {#article-title-29}Background— We assessed trends in the performance of transcatheter aortic valve implantation in the United Kingdom from the first case in 2007 to the end of 2012. We analyzed changes in case mix, complications, outcomes to 6 years, and predictors of mortality. Methods and Results— Annual cohorts were examined. Mortality outcomes were analyzed in the 92% of patients from England and Wales for whom independent mortality tracking was available. A total of 3980 transcatheter aortic valve implantation procedures were performed. In successive years, there was an increase in frequency of impaired left ventricular function, but there was no change in Logistic EuroSCORE. Overall 30-day mortality was 6.3%; it was highest in the first cohort (2007–2008), after which there were no further significant changes. One-year survival was 81.7%, falling to 37.3% at 6 years. Discharge by day 5 rose from 16.7% in 2007 and 2008 to 28% in 2012. The only multivariate preprocedural predictor of 30-day mortality was Logistic EuroSCORE ≥40. During long-term follow-up, multivariate predictors of mortality were preprocedural atrial fibrillation, chronic obstructive pulmonary disease, creatinine >200 &mgr;mol/L, diabetes mellitus, and coronary artery disease. The strongest independent procedural predictor of long-term mortality was periprocedural stroke (hazard ratio=3.00; P<0.0001). Nonfemoral access and postprocedural aortic regurgitation were also significant predictors of adverse outcome. Conclusions— We analyzed transcatheter aortic valve implantation in an entire country, with follow-up over 6 years. Although clinical profiles of enrolled patients remained unchanged, longer-term outcomes improved, and patients were discharged earlier. Periprocedural stroke, nonfemoral access, and postprocedural aortic regurgitation are predictors of adverse outcome, along with intrinsic patient risk factors.

Influence of Arterial Access Site Selection on Outcomes in Primary Percutaneous Coronary Intervention : Are the Results of Randomized Trials Achievable in Clinical Practice?

OBJECTIVES This study sought to investigate the influence of access site utilization on mortality, major adverse cardiac and cardiovascular events (MACCE), bleeding, and vascular complications in a large number of patients treated by primary percutaneous coronary intervention (PPCI) in the United Kingdom over a 5-year period, through analysis of the British Cardiovascular Intervention Society database. BACKGROUND Despite advances in antithrombotic and antiplatelet therapy, bleeding complications remain an important cause of morbidity and mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing PPCI. A significant proportion of such bleeding complications are related to the access site, and adoption of radial access may reduce these complications. These benefits have not previously been studied in a large unselected national population of PPCI patients. METHODS Mortality (30-day), MACCE (a composite of 30-day mortality and in-hospital myocardial re-infarction, target vessel revascularization, and cerebrovascular events), and bleeding and access site complications were studied based on transfemoral access (TFA) and transradial access (TRA) site utilization in PPCI STEMI patients. The influence of access site selection was studied in 46,128 PPCI patients; TFA was used in 28,091 patients and TRA in 18,037. Data were adjusted for potential confounders using Cox regression that accounted for the propensity to undergo radial or femoral approach. RESULTS TRA was independently associated with a lower 30-day mortality (hazard ratio [HR]: 0.71, 95% confidence interval [CI]: 0.52 to 0.97; p < 0.05), in-hospital MACCE (HR: 0.73, 95% CI: 0.57 to 0.93; p < 0.05), major bleeding (HR: 0.37, 95% CI: 0.18 to 0.74; p < 0.01), and access site complications (HR: 0.38, 95% CI: 0.19 to 0.75; p < 0.01). CONCLUSIONS This analysis of a large number of PPCI procedures demonstrates that utilization of TRA is independently associated with major reductions in mortality, MACCE, major bleeding, and vascular complication rates.

Meta-analysis of randomized trials comparing anti-embolic devices with standard PCI for improving myocardial reperfusion in patients with acute myocardial infarction

Failure to achieve adequate myocardial reperfusion often occurs during PCI in patients with STEMI. This is in part due to atheromatous and thrombotic distal embolization. Several anti‐embolic devices have been developed to protect against distal embolization during percutaneous coronary interventions (PCI) to improve myocardial reperfusion and enhance event free survival. Evidence from current studies has not shown a consistent benefit, but anti‐embolic devices continue to be used.

Access Site Practice And Procedural Outcomes In Relation To Clinical Presentation In 439,947 Patients Undergoing Percutaneous Coronary Intervention In The United Kingdom

OBJECTIVES This study sought to determine the relationships among access site practice, clinical presentation, and procedural outcomes in a large patient population. BACKGROUND Transradial access (TRA) has been associated with improved patient outcomes in selected populations in randomized trials. It is unclear whether these outcomes are achievable in clinical practice. METHODS Using the BCIS (British Cardiovascular Intervention Society) database, we investigated outcomes for percutaneous coronary intervention procedures undertaken between 2007 and 2012 according to access site practice. Patients were categorized as stable, non-ST-segment elevation acute coronary syndrome (NSTEACS) and ST-elevation acute coronary syndrome (STEACS). The impact of access site on 30-day mortality, major adverse cardiac events, bleeding, and arterial access site complications was studied. RESULTS Data from 210,260 TRA and 229,687 transfemoral access procedures were analyzed. Following multivariate analysis, TRA was independently associated with a reduction in bleeding in all presenting syndromes (stable odds ratio [OR]: 0.24, p < 0.001; NSTEACS OR: 0.35, p < 0.001; STEACS OR: 0.47, p < 0.001) as well as access site complications (stable OR: 0.21, p < 0.001; NSTEACS OR: 0.19; STEACS OR: 0.16, p < 0.001). TRA was associated with reduced major adverse cardiac events only in patients with unstable syndromes (stable OR: 1.08, p = 0.25; NSTEACS OR: 0.72, p < 0.001; STEACS OR: 0.70, p < 0.001). TRA was associated with improved outcomes compared with a transfemoral access (TFA) with a vascular closure device in a propensity matched cohort. CONCLUSIONS In this large study, TRA is associated with reduced percutaneous coronary intervention-related complications in all patient groups and may reduce major adverse cardiac events and mortality in ACS patients. TRA is superior to transfemoral access with closure devices. Use of TRA may lead to important patient benefits in routine practice. TRA should be considered the preferred access site for percutaneous coronary intervention.

Baseline Bleeding Risk and Arterial Access Site Practice in Relation to Procedural Outcomes After Percutaneous Coronary Intervention

BACKGROUND Transradial access (TRA) has been associated with reduced access site-related bleeding complications and mortality after percutaneous coronary intervention (PCI). It is unclear, however, whether these observed benefits are influenced by baseline bleeding risk. OBJECTIVES This study investigated the relationship between baseline bleeding risk, TRA utilization, and procedure-related outcomes in patients undergoing PCI enrolled in the British Cardiovascular Intervention Society database. METHODS Baseline bleeding risk was calculated by using modified Mehran bleeding risk scores in 348,689 PCI procedures performed between 2006 and 2011. Four categories for bleeding risk were defined for the modified Mehran risk score (MMRS): low (<10), moderate (10 to 14), high (15 to 19), and very high (≥20). The impact of baseline bleeding risk on 30-day mortality and its relationship with access site were studied. RESULTS TRA was independently associated with a 35% reduction in 30-day mortality risk (odds ratio [OR]: 0.65 [95% confidence interval (CI): 0.59 to 0.72]; p < 0.0001), with the magnitude of mortality reduction related to baseline bleeding risk (MMRS <10, OR: 0.73 [95% CI: 0.62 to 0.86]; MMRS ≥20, OR: 0.53 [95% CI: 0.47 to 0.61]). In patients with an MMRS <10, TRA was used in 71,771 (43.2%) of 166,083 PCI procedures; TRA was used in 8,655 (40.1%) of 21,559 PCI procedures in patients with an MMRS ≥20, illustrating that TRA was used less in those at highest risk from bleeding complications (p < 0.0001). CONCLUSIONS TRA was independently associated with reduced 30-day mortality, and the magnitude of this effect was related to baseline bleeding risk; those at highest risk of bleeding complications gained the greatest benefit from adoption of TRA during PCI.

Major bleeding after percutaneous coronary intervention and risk of subsequent mortality: a systematic review and meta-analysis

Objectives To examine the relationship between periprocedural bleeding complications and major adverse cardiovascular events (MACEs) and mortality outcomes following percutaneous coronary intervention (PCI) and study differences in the prognostic impact of different bleeding definitions. Methods We conducted a systematic review and meta-analysis of PCI studies that evaluated periprocedural bleeding complications and their impact on MACEs and mortality outcomes. A systematic search of MEDLINE and EMBASE was conducted to identify relevant studies. Data from relevant studies were extracted and random effects meta-analysis was used to estimate the risk of adverse outcomes with periprocedural bleeding. Statistical heterogeneity was assessed by considering the I2 statistic. Results 42 relevant studies were identified including 533 333 patients. Meta-analysis demonstrated that periprocedural major bleeding complications was independently associated with increased risk of mortality (OR 3.31 (2.86 to 3.82), I2=80%) and MACEs (OR 3.89 (3.26 to 4.64), I2=42%). A differential impact of major bleeding as defined by different bleeding definitions on mortality outcomes was observed, in which the REPLACE-2 (OR 6.69, 95% CI 2.26 to 19.81), STEEPLE (OR 6.59, 95% CI 3.89 to 11.16) and BARC (OR 5.40, 95% CI 1.74 to 16.74) had the worst prognostic impacts while HORIZONS-AMI (OR 1.51, 95% CI 1.11 to 2.05) had the least impact on mortality outcomes. Conclusions Major bleeding after PCI is independently associated with a threefold increase in mortality and MACEs outcomes. Different contemporary bleeding definitions have differential impacts on mortality outcomes, with 1.5–6.7-fold increases in mortality observed depending on the definition of major bleeding used.

Do Outcomes from Transcatheter Aortic Valve Implantation Vary According to Access Route and Valve Type? The UK TAVI Registry

OBJECTIVES To determine whether outcomes from transcatheter aortic valve implantation (TAVI) vary according to access route and valve type in a real-world population. BACKGROUND Registry and uncontrolled trial data have found that patients undergoing nonfemoral TAVI have higher early and late mortality. It is not clear whether worse outcomes relate directly to access route. There have been no direct comparisons of outcomes according to valve type. METHODS Data were collected prospectively on 1,620 patients undergoing TAVI in the UK and compared in 4 groups: SAPIEN transfemoral (TF); SAPIEN transapical (TA); CoreValve TF, CoreValve subclavian. Univariable and multivariable regression analysis was performed to identify independent predictors of mortality. RESULTS Mortality in patients undergoing SAPIEN TAVI via a TA approach was higher than with TF at 30 days (11.2% vs. 4.4%, P < 0.01), 1 year (28.7% vs. 18.1%, P = 0.01), and 2 years (56.0% vs. 43.5%, P = 0.01). Logistic EuroSCORE was higher in TA patients (22.5 ± 12.9% vs. 17.7 ± 11.1%, P < 0.0001). After multivariable analysis TA access was associated with increased mortality at 30 days (OR 2.56, 95% CI 1.46-4.48, P < 0.01) and 2 years (OR 1.75, 1.08-2.74, P = 0.02). There was no significant difference in mortality at any time-point between patients treated with SAPIEN (n = 812) and CoreValve (n = 808) prostheses. CoreValve-treated patients had a higher rate of permanent pacemaker implantation (23.1% vs. 7.2%, P < 0.0001), and grade ≥2 aortic regurgitation on postprocedure echocardiography (13.0% vs. 7.3%, P < 0.01). CONCLUSIONS Patients undergoing TA TAVI experienced increased early and late mortality compared to a TF approach. Survival was not influenced by valve type.