Five-Year Outcomes after PCI or CABG for Left Main Coronary Disease.

BACKGROUND: Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established. METHODS: We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction. RESULTS: At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], -0.9 to 6.5; P = 0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, -1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, -1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, -1.9 percentage points; 95% CI, -3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, -0.8 percentage points; 95% CI, -2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0). CONCLUSIONS: In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.).

Everolimus-Eluting Stents or Bypass Surgery for Left Main Coronary Artery Disease.

BACKGROUND: Patients with obstructive left main coronary artery disease are usually treated with coronary-artery bypass grafting (CABG). Randomized trials have suggested that drug-eluting stents may be an acceptable alternative to CABG in selected patients with left main coronary disease. METHODS: We randomly assigned 1905 eligible patients with left main coronary artery disease of low or intermediate anatomical complexity to undergo either percutaneous coronary intervention (PCI) with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). Anatomic complexity was assessed at the sites and defined by a Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score of 32 or lower (the SYNTAX score reflects a comprehensive angiographic assessment of the coronary vasculature, with 0 as the lowest score and higher scores [no upper limit] indicating more complex coronary anatomy). The primary end point was the rate of a composite of death from any cause, stroke, or myocardial infarction at 3 years, and the trial was powered for noninferiority testing of the primary end point (noninferiority margin, 4.2 percentage points). Major secondary end points included the rate of a composite of death from any cause, stroke, or myocardial infarction at 30 days and the rate of a composite of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years. Event rates were based on Kaplan-Meier estimates in time-to-first-event analyses. RESULTS: At 3 years, a primary end-point event had occurred in 15.4% of the patients in the PCI group and in 14.7% of the patients in the CABG group (difference, 0.7 percentage points; upper 97.5% confidence limit, 4.0 percentage points; P=0.02 for noninferiority; hazard ratio, 1.00; 95% confidence interval, 0.79 to 1.26; P=0.98 for superiority). The secondary end-point event of death, stroke, or myocardial infarction at 30 days occurred in 4.9% of the patients in the PCI group and in 7.9% in the CABG group (P<0.001 for noninferiority, P=0.008 for superiority). The secondary end-point event of death, stroke, myocardial infarction, or ischemia-driven revascularization at 3 years occurred in 23.1% of the patients in the PCI group and in 19.1% in the CABG group (P=0.01 for noninferiority, P=0.10 for superiority). CONCLUSIONS: In patients with left main coronary artery disease and low or intermediate SYNTAX scores by site assessment, PCI with everolimus-eluting stents was noninferior to CABG with respect to the rate of the composite end point of death, stroke, or myocardial infarction at 3 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776 .).

Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial.

BACKGROUND: No medium-term data are available on the random comparison between everolimus-eluting bioresorbable vascular scaffolds and everolimus-eluting metallic stents. The study aims to demonstrate two mechanistic properties of the bioresorbable scaffold: increase in luminal dimensions as a result of recovered vasomotion of the scaffolded vessel. METHODS: The ABSORB II trial is a prospective, randomised, active-controlled, single-blind, parallel two-group, multicentre clinical trial. We enrolled eligible patients aged 18-85 years with evidence of myocardial ischaemia and one or two de-novo native lesions in different epicardial vessels. We randomly assigned patients (2:1) to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetes status and number of planned target lesions. At 3 year follow-up, the primary endpoint was superiority of the Absorb bioresorbable scaffold versus the Xience metallic stent in angiographic vasomotor reactivity after administration of intracoronary nitrate. The co-primary endpoint is the non-inferiority of angiographic late luminal loss. For the endpoint of vasomotion, the comparison was tested using a two-sided t test. For the endpoint of late luminal loss, non-inferiority was tested using a one-sided asymptotic test, against a non-inferiority margin of 0·14 mm. The trial is registered at ClinicalTrials.gov, number NCT01425281. FINDINGS: Between Nov 28, 2011, and June 4, 2013, we enrolled 501 patients and randomly assigned them to the Absorb group (335 patients, 364 lesions) or the Xience group (166 patients, 182 lesions). The vasomotor reactivity at 3 years was not statistically different (Absorb group 0·047 mm [SD 0·109] vs Xience group 0·056 mm [0·117]; psuperiority=0·49), whereas the late luminal loss was larger in the Absorb group than in the Xience group (0·37 mm [0·45] vs 0·25 mm [0·25]; pnon-inferiority=0·78). This difference in luminal dimension was confirmed by intravascular ultrasound assessment of the minimum lumen area (4·32 mm2 [SD 1·48] vs 5·38 mm2 [1·51]; p<0·0001). The secondary endpoints of patient-oriented composite endpoint, Seattle Angina Questionnaire score, and exercise testing were not statistically different in both groups. However, a device-oriented composite endpoint was significantly different between the Absorb group and the Xience group (10% vs 5%, hazard ratio 2·17 [95% CI 1·01-4·70]; log-rank test p=0·0425), mainly driven by target vessel myocardial infarction (6% vs 1%; p=0·0108), including peri-procedural myocardial infarction (4% vs 1%; p=0·16). INTERPRETATION: The trial did not meet its co-primary endpoints of superior vasomotor reactivity and non-inferior late luminal loss for the Absorb bioresorbable scaffold with respect to the metallic stent, which was found to have significantly lower late luminal loss than the Absorb scaffold. A higher rate of device-oriented composite endpoint due to target vessel myocardial infarction, including peri-procedural myocardial infarction, was observed in the Absorb group. The patient-oriented composite endpoint, anginal status, and exercise testing, were not statistically different between both devices at 3 years. Future studies should investigate the clinical impact of accurate intravascular imaging in sizing the device and in optimising the scaffold implantation. The benefit and need for prolonged dual antiplatelet therapy after bioresorbable scaffold implantation could also become a topic for future clinical research. FUNDING: Abbott Vascular.

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].)

Impact of chronic obstructive pulmonary disease on prognosis after percutaneous coronary intervention and bypass surgery for left main coronary artery disease: an analysis from the EXCEL trial.

OBJECTIVES: Percutaneous coronary intervention (PCI) is often favoured over coronary artery bypass grafting (CABG) surgery for revascularization in patients with chronic obstructive pulmonary disease (COPD). We studied whether COPD affected clinical outcomes according to revascularization in the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial, in which PCI with everolimus-eluting stents was non-inferior to CABG for the treatment of patients with left main coronary artery disease and low or intermediate SYNTAX scores. METHODS: Patients with a history of COPD were propensity score matched to those without COPD. Outcomes at 30 days and 3 years in both groups were compared in patients randomized to PCI versus CABG. RESULTS: COPD status was available for 1901 of 1905 randomized patients (99.8%), 148 of whom had COPD (7.8%). Propensity score matching yielded 135 patients with COPD and 675 patients without COPD. Patients with COPD had higher 3-year rates of the primary composite end point of death, myocardial infarction or stroke (31.7% vs 14.5%, P < 0.0001), death (17.1% vs 7.5%, P = 0.0005) and myocardial infarction (18.3% vs 7.3%, P < 0.0001), but not stroke (3.3% vs 2.9%, P = 0.84). There were no statistically significant interactions in the relative risks of PCI versus CABG for the primary composite end point in patients with and without COPD at 30 days [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.12-1.21 vs HR 0.55, 95% CI 0.29-1.06; Pinteraction = 0.61] or at 3 years (HR 0.85, 95% CI 0.46-1.56 vs HR 1.28, 95% CI 0.84-1.94; Pinteraction = 0.27). CONCLUSIONS: In the EXCEL trial, COPD was independently associated with poor prognosis after left main coronary artery disease revascularization. The relative risks of PCI versus CABG at 30 days and 3 years were consistent in patients with and without COPD. CLINICAL TRIAL REGISTRATION NUMBER: http://www.clinicaltrials.gov; NCT01205776.

Bypass Surgery or Stenting for Left Main Coronary Artery Disease in Patients With Diabetes.

BACKGROUND: The randomized EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial reported a similar rate of the 3-year composite primary endpoint of death, myocardial infarction (MI), or stroke in patients with left main coronary artery disease (LMCAD) and site-assessed low or intermediate SYNTAX scores treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Whether these results are consistent in high-risk patients with diabetes, who have fared relatively better with CABG in most prior trials, is unknown. OBJECTIVES: In this pre-specified subgroup analysis from the EXCEL trial, the authors sought to examine the effect of diabetes in patients with LMCAD treated with PCI versus CABG. METHODS: Patients (N = 1,905) with LMCAD and site-assessed low or intermediate CAD complexity (SYNTAX scores ≤32) were randomized 1:1 to PCI with everolimus-eluting stents versus CABG, stratified by the presence of diabetes. The primary endpoint was the rate of a composite of all-cause death, stroke, or MI at 3 years. Outcomes were examined in patients with (n = 554) and without (n = 1,350) diabetes. RESULTS: The 3-year composite primary endpoint was significantly higher in diabetic compared with nondiabetic patients (20.0% vs. 12.9%; p < 0.001). The rate of the 3-year primary endpoint was similar after treatment with PCI and CABG in diabetic patients (20.7% vs. 19.3%, respectively; hazard ratio: 1.03; 95% confidence interval: 0.71 to 1.50; p = 0.87) and nondiabetic patients (12.9% vs. 12.9%, respectively; hazard ratio: 0.98; 95% confidence interval: 0.73 to 1.32; p = 0.89). All-cause death at 3 years occurred in 13.6% of PCI and 9.0% of CABG patients (p = 0.046), although no significant interaction was present between diabetes status and treatment for all-cause death (p = 0.22) or other endpoints, including the 3-year primary endpoint (p = 0.82) or the major secondary endpoints of death, MI, or stroke at 30 days (p = 0.61) or death, MI, stroke, or ischemia-driven revascularization at 3 years (p = 0.65). CONCLUSIONS: In the EXCEL trial, the relative 30-day and 3-year outcomes of PCI with everolimus-eluting stents versus CABG were consistent in diabetic and nondiabetic patients with LMCAD and site-assessed low or intermediate SYNTAX scores.(Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776).

Diagnostic Accuracy of Coronary CT Angiography for the Evaluation of Bioresorbable Vascular Scaffolds.

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of coronary computed tomography angiography (CTA) for bioresorbable vascular scaffold (BVS) evaluation. BACKGROUND: Coronary CTA has emerged as a noninvasive method to evaluate patients with suspected or established coronary artery disease. The diagnostic accuracy of coronary CTA to evaluate angiographic outcomes after BVS implantation has not been well established. METHODS: In the ABSORB II (A Bioresorbable Everolimus-Eluting Scaffold Versus a Metallic Everolimus-Eluting Stent II) study, patients were randomized either to receive treatment with the BVS or everolimus-eluting metallic stent. At the 3-year follow-up, 238 patients (258 lesions) treated with BVS underwent coronary angiography with intravascular ultrasound (IVUS) evaluation and coronary CTA. The diagnostic accuracy of coronary CTA was assessed by the area under the receiver-operating characteristic curve with coronary angiography and IVUS as references. RESULTS: The mean difference in coronary CTA-derived minimal luminal diameter was -0.14 mm (limits of agreement -0.88 to 0.60) with quantitative coronary angiography as reference, whereas the mean difference in minimal lumen area was 0.73 mm2 (limits of agreement -1.85 to 3.30) with IVUS as reference. The per-scaffold diagnostic accuracy of coronary CTA for detecting stenosis based on coronary angiography diameter stenosis of ≥50% revealed an area under the receiver-operating characteristic curve of 0.88 (95% confidence interval [CI]: 0.82 to 0.92) with a sensitivity of 80% (95% CI: 28% to 99%) and a specificity of 100% (95% CI: 98% to 100%), whereas diagnostic accuracy based on IVUS minimal lumen area ≤2.5 mm2 showed an area under the receiver-operating characteristic curve of 0.83 (95% CI: 0.77 to 0.88) with a sensitivity of 71% (95% CI: 44% to 90%) and a specificity of 82% (95% CI: 75% to 87%). The diagnostic accuracy of coronary CTA was similar to coronary angiography in its ability to identify patients with a significant lesion based on the IVUS criteria (p = 0.75). CONCLUSIONS: Coronary CTA has good diagnostic accuracy to detect in-scaffold luminal obstruction and to assess luminal dimensions after BVS implantation. Coronary angiography and coronary CTA yielded similar diagnostic accuracy to identify the presence and severity of obstructive disease. Coronary CTA might become the method of choice for the evaluation of patients treated with BVS.

Outcomes Among Patients Undergoing Distal Left Main Percutaneous Coronary Intervention.

BACKGROUND: Distal left main (LM) coronary artery bifurcation disease increases percutaneous coronary intervention (PCI) procedural complexity and is associated with worse outcomes than isolated ostial/shaft disease. The optimal treatment strategy for distal LM disease is undetermined. We sought to determine whether outcomes after PCI of LM distal bifurcation lesions are influenced by treatment with a provisional 1-stent versus planned 2-stent technique, and if so, whether such differences are conditioned by the complexity of the LM bifurcation lesion. METHODS AND RESULTS: The clinical and angiographic characteristics, procedural methods and outcomes, and clinical events through 3-year follow-up were compared in patients undergoing distal LM PCI with a 1-stent provisional versus planned 2-stent technique in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). Among 529 patients undergoing planned distal LM PCI, 344 (65.0%) and 185 (35.0%) were treated with intended 1-stent provisional and planned 2-stent techniques, respectively. The primary composite end point rate of death, myocardial infarction, or stroke at 3 years was significantly lower in patients treated with the provisional 1-stent versus planned 2-stent method (14.1% versus 20.7%; adjusted hazard ratio, 0.55; 95% CI, 0.35-0.88; P=0.01), driven by differences in cardiovascular death (3.3% versus 8.3%, P=0.01) and myocardial infarction (7.7% versus 12.8%, P=0.06). The 3-year rate of ischemia-driven revascularization of the LM complex was also lower in the provisional group (7.2% versus 16.3%, P=0.001). In 342 patients with distal LM bifurcation disease that did not involve both major side branch vessels, the 3-year primary end point was lower with a provisional 1-stent versus planned 2-stent technique (13.8% versus 23.3%, P=0.04), whereas no significant difference was present in 182 patients with distal LM bifurcation disease that did involve both side branch vessels (14.3% versus 19.2%, P=0.36). CONCLUSIONS: Among patients with distal LM bifurcation disease in the EXCEL trial randomized to PCI, 3-year adverse outcomes were worse with planned 2-stent treatment compared with a provisional 1-stent approach, a difference that was confined to patients without major involvement of both LM side branch vessels. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01205776.

Outcomes After Left Main Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting According to Lesion Site: Results From the EXCEL Trial.

OBJECTIVES: The authors sought to determine the extent to which the site of the left main coronary artery (LM) lesion (distal bifurcation versus ostial/shaft) influences the outcomes of revascularization with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG). BACKGROUND: Among 1,905 patients with LM disease and site-assessed SYNTAX scores of <32 randomized in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, revascularization with PCI and CABG resulted in similar rates of the composite primary endpoint of death, myocardial infarction (MI), or stroke at 3 years. METHODS: Outcomes from the randomized EXCEL trial were analyzed according to the presence of angiographic core laboratory-determined diameter stenosis ≥50% involving the distal LM bifurcation (n = 1,559; 84.2%) versus disease isolated to the LM ostium or shaft (n = 293; 15.8%). RESULTS: At 3 years, there were no significant differences between PCI and CABG for the primary composite endpoint of death, MI, or stroke for treatment of both distal LM bifurcation disease (15.6% vs. 14.9%, odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.81 to 1.42; p = 0.61) and isolated LM ostial/shaft disease (12.4% vs. 13.5%, OR: 0.90, 95% CI: 0.45 to 1.81; p = 0.77) (pinteraction = 0.65). However, at 3 years, ischemia-driven revascularization occurred more frequently after PCI than CABG in patients with LM distal bifurcation disease (13.0% vs. 7.2%, OR: 2.00, 95% CI: 1.41 to 2.85; p = 0.0001), but were not significantly different in patients with disease only at the LM ostium or shaft (9.7% vs. 8.4%, OR: 1.18, 95% CI: 0.52 to 2.69; p = 0.68) (pinteraction = 0.25). CONCLUSIONS: In the EXCEL trial, PCI and CABG resulted in comparable rates of death, MI, or stroke at 3 years for treatment of LM disease, including those with distal LM bifurcation disease. Repeat revascularization rates during follow-up after PCI compared with CABG were greater for lesions in the distal LM bifurcation but were similar for disease isolated to the LM ostium or shaft.

Serial Assessment of Strut Coverage of Biodegradable Polymer Drug-Eluting Stent at 1, 2, and 3 Months After Stent Implantation by Optical Frequency Domain Imaging: The DISCOVERY 1TO3 Study (Evaluation With OFDI of Strut Coverage of Terumo New Drug Eluting Stent With Biodegradable Polymer at 1, 2, and 3 Months).

BACKGROUND: To assess the vessel-healing pattern of Ultimaster drug-eluting stent using optical frequency domain imaging. Our hypothesis is that biodegradable polymer-based drug-eluting technology allows complete very early strut coverage. METHODS AND RESULTS: The DISCOVERY 1TO3 study (Evaluation With OFDI of Strut Coverage of Terumo New Drug Eluting Stent With Biodegradable Polymer at 1, 2, and 3 Months) is a prospective, single-arm, multicenter study. A total of 60 patients with multivessel disease requiring staged procedure at 1 month were treated with Ultimaster. Optical frequency domain imaging was acquired at baseline, 1, 2, and 3 months. The primary end point is optical frequency domain imaging-assessed strut coverage at 3 months. Mean age of patients was 67.2±9.9 years, and 73.3% were male, and 36.7% presented with acute coronary syndrome. A total of 132 lesions were treated, with average 1.4 lesions per patient treated at baseline and 1.1 lesions treated at 1 month. Strut coverage at 3 months of single implanted stents (n=71, primary end point) was 95.2±5.2% and of combined single and overlapped stents was 95.4±4.9%. Strut coverage of combined single and overlapped stents at 1 (n=49) and 2 months (n=38) was 85.1±12.7% and 87.9±10.8%, respectively. The median neointimal hyperplasia thickness was 0.04, 0.05, and 0.06 mm, whereas mean neointimal hyperplasia obstruction was 4.5±2.4%, 5.2±3.4%, and 6.6±3.3% at 1, 2, and 3 months, respectively. CONCLUSIONS: Nearly complete strut coverage was observed in this complex population very early after implantation of Ultimaster drug-eluting stent. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01844843.

Implantation and 30-Day Follow-Up on All 4 Valve Sizes Within the Portico Transcatheter Aortic Bioprosthetic Family.

OBJECTIVES: The aim of this study was to evaluate the short-term safety and performance of the full range of valve sizes offered within the Portico transcatheter aortic valve replacement system. BACKGROUND: The Portico transcatheter aortic heart valve is a fully resheathable, repositionable, and self-expanding bioprosthesis designed to achieve optimal valve position and hemodynamic performance and limit conduction disturbances. METHODS: Patients (n = 222) with symptomatic (New York Heart Association functional class ≥II) severe aortic stenosis considered by a multidisciplinary heart team to be at high surgical risk were recruited between December 2011 and September 2015 in this prospective, nonrandomized, multicenter study. Patients were implanted with the full range of Portico heart valves (23, 25, 27, and 29 mm) using the transfemoral approach. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints included valve performance, improvement in functional class, and procedural outcomes as defined by Valve Academic Research Consortium criteria. RESULTS: A total of 220 patients (mean age 83.0 ± 4.6 years, 74.3% women, mean Society of Thoracic Surgeons score 5.8%) had valves implanted. All resheathing and repositioning attempts (n = 72) were successful. At 30 days, all-cause mortality was 3.6%. Procedural outcomes included disabling (major) stroke (3.2%), major vascular complications (7.2%), and permanent pacemaker implantation (13.5%). Compared with baseline, 75.8% of patients improved by ≥1 New York Heart Association functional class at 30 days. The rate of moderate paravalvular leak was 5.7%, with no severe paravalvular leak reported. No differences in paravalvular leak incidence and severity were observed among valve sizes (p = 0.24). CONCLUSIONS: Across all valve sizes, use of the repositionable Portico transcatheter aortic valve replacement system resulted in safe and effective treatment of aortic stenosis in high-risk patients.

Everolimus eluting stent vs first generation drug-eluting stent in primary angioplasty: A pooled patient-level meta-analysis of randomized trials.

BACKGROUND: Several concerns have emerged about the higher risk of very late stent thrombosis (ST) with first generation drug-eluting stent (DES) especially among STEMI patients. Newer generation DES has demonstrated to reduce ST at mid-term follow-up. Therefore, the aim of the present study is to perform an individual patient's data meta-analysis of trials comparing 1st generation DES vs. 2nd generation DES (everolimus-eluting stent, EES) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. METHODS: We performed a formal search of electronic databases (MEDLINE and CENTRAL) and scientific session presentations from January 2010 to June 2016. We included all completed randomized trials comparing 1st vs. EES for patient presenting with STEMI. RESULTS: Individual patients data were obtained from 3 trials, including a total of 1581 patients (686 or 43.4% randomized to 1st generation DES and 895 or 56.4% randomized to EES). At long-term follow-up (1584±588days), EES did not significantly reduce mortality (7.8.% vs 11.7%, HR [95%CI]=0.77 [0.52, 1.13], p=0.18, pheterogeneity=0.93), cardiac mortality (6.2% vs 7.6%, HR [95%CI]=0.90 [0.56, 1.44], p=0.65, pheterogeneity=0.85), and reinfarction (8.1% versus 11.2%, respectively; HR [95%CI]=0.74 [0.51, 1.07], p=0.11, pheterogeneity=0.52). However, EES significantly reduced the occurrence of ST (3.4% versus 6.1% respectively, HR [95%CI]=0.56 [0.32, 0.97], p=0.04, pheterogeneity=0.42) and target vessel revascularization (TVR) (14.2% versus 20.1%; HR [95%CI]=0.63 [0.42, 0.96], p=0.03, pheterogeneity=0.55). Landmark analysis showed more consistent benefits in ST with EES within 1year, whereas benefits in TVR were mostly observed later than 1year. CONCLUSIONS: The present pooled patient-level meta-analysis demonstrates that among STEMI patients undergoing primary PCI, EES as compared to 1st generation DES is associated with a significant reduction in ST and TVR at long-term follow-up.

Comparison of Outcome After Percutaneous Mitral Valve Repair With the MitraClip in Patients With Versus Without Atrial Fibrillation.

Percutaneous mitral valve repair with the MitraClip is an established treatment for patients with mitral regurgitation (MR) who are inoperable or at high risk for surgery. Atrial Fibrillation (AF) frequently coincides with MR, but only scarce data of the influence of AF on outcome after MitraClip is available. The aim of the current study was to compare the clinical outcome after MitraClip treatment in patients with versus without atrial fibrillation. Between January 2009 and January 2016, all consecutive patients treated with a MitraClip in 5 Dutch centers were included. Outcome measures were survival, symptoms, MR grade, and stroke incidence. In total, 618 patients were treated with a MitraClip. Patients with AF were older, had higher N-terminal B-type natriuretic peptide levels, more tricuspid regurgitation, less often coronary artery disease and a better left ventricular function. Survival of patients treated with the MitraClip was similar for patients with AF (82%) and without AF (non-AF; 85%) after 1 year (p = 0.30), but significantly different after 5-year follow-up (AF 34%; non-AF 47%; p = 0.006). After 1 month, 64% of the patients with AF were in New York Heart Association class I or II, in contrast to 77% of the patients without AF (p = 0.001). The stroke incidence appeared not to be significantly different (AF 1.8%; non-AF 1.0%; p = 0.40). In conclusion, patients with AF had similar 1-year survival, MR reduction, and stroke incidence compared with non-AF patients. However, MitraClip patients with AF had reduced long-term survival and remained more symptomatic compared with those without AF.

Matched Comparison of Self-Expanding Transcatheter Heart Valves for the Treatment of Failed Aortic Surgical Bioprosthesis: Insights From the Valve-in-Valve International Data Registry (VIVID).

BACKGROUND: Transcatheter valve-in-valve implantation is an established therapy for high-risk patients with failed surgical aortic bioprosthesis. There are limited data comparing outcomes of valve-in-valve implantation using different transcatheter heart valves (THV). METHODS AND RESULTS: Patients included in the Valve-in-Valve International Data registry (VIVID) and treated with self-expanding THV devices were analyzed using centralized core laboratory blinded to clinical events. St. Jude Medical Portico versus Medtronic CoreValve were compared in a 1:2 fashion after propensity score matching. A total of 162 patients, Portico- (n=54) and CoreValve- (n=108) based valve-in-valve procedures comprised the study population with no significant difference in baseline characteristics (age, 79±8.2 years; 60% women; mean STS [Society of Thoracic Surgery] score 8.1±5.5%). Postimplantation, CoreValve was associated with a larger effective orifice area (1.67 versus 1.31 cm2; P=0.001), lower mean gradient (14±7.5 versus 17±7.5 mm Hg; P=0.02), and lower core laboratory-adjudicated moderate-to-severe aortic insufficiency (4.2% versus 13.7%; P=0.04), compared with Portico. Procedural complications including THV malpositioning, second THV requirement, or coronary obstruction were not significantly different between the 2 groups. Survival and stroke rates at 30 days were similar, but overall mortality at 1 year was higher among patients treated with Portico compared with CoreValve (22.6% versus 9.1%; P=0.03). CONCLUSIONS: In this first matched comparison of THVs for valve-in-valve implantations, Portico and CoreValve demonstrated differences in postprocedural hemodynamics and long-term clinical outcomes. Although this could be related to THV design characteristics, the impact of other procedural factors cannot be excluded and require further evaluation.

Randomised comparison of a bioresorbable everolimus-eluting scaffold with a metallic everolimus-eluting stent for ischaemic heart disease caused by de novo native coronary artery lesions: the 2-year clinical outcomes of the ABSORB II trial.

AIMS: The one-year randomised data of the ABSORB II trial showed that the everolimus-eluting bioresorbable scaffold and the everolimus-eluting metallic stent were comparable for the composite secondary clinical outcomes of patient-oriented composite endpoint (PoCE) and device-oriented composite endpoint (DoCE)/target lesion failure (TLF), MACE and TVF. This report describes the two-year clinical outcomes of the ABSORB II trial. METHODS AND RESULTS: Patients were randomly assigned in a 2:1 ratio to receive treatment with an everolimus-eluting bioresorbable scaffold (Absorb; Abbott Vascular, Santa Clara, CA, USA) or treatment with an everolimus-eluting metallic stent (XIENCE; Abbott Vascular). The trial enrolled 501 patients. Clinical follow-up at two years was available in 320 patients in the Absorb BVS arm and 160 patients in the XIENCE arm. At two years, the PoCE for the Absorb and XIENCE arms was 11.6% and 12.8% (p=0.70) and the DoCE/TLF was 7.0% and 3.0% (p=0.07), respectively. The hierarchical ID-MACE rate was 7.6% vs. 4.3% (p=0.16) and the rate of TVF was 8.5% vs. 6.7% (p=0.48). The definite/probable thrombosis rate was 1.5% in the Absorb arm vs. 0% in the XIENCE arm (p=0.17). Thirty-six percent and 34% of patients remained on DAPT at two years, respectively. Ninety-two percent of patients in both arms remained on aspirin. CONCLUSIONS: Two-year clinical results demonstrate sustained low rates of PoCE, MACE, DoCE and TVF with the Absorb BVS as compared to the XIENCE stent.

Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria.

BACKGROUND: Microalbuminuria is associated with increased risk of cardiovascular events. We assessed whether therapeutic intervention aimed at lowering urinary albumin excretion would reduce cardiovascular events in microalbuminuric subjects (15 to 300 mg/24 hours). METHODS AND RESULTS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) cohort (n=8592), 1439 subjects fulfilled the inclusion criteria of the PREVEND Intervention Trial (PREVEND IT). Of these subjects, 864 were randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo. The mean follow-up was 46 months, and the primary end point was cardiovascular mortality and hospitalization for cardiovascular morbidity. Mean age was 51+/-12 years; 65% of subjects were male, and 3.4% had a previous cardiovascular event. Mean cholesterol level was 5.8+/-1.0 mmol/L, mean systolic/diastolic blood pressure was 130+/-18/76+/-10 mm Hg, and median urinary albumin excretion was 22.8 (15.8 to 41.3) mg/24 hours. The primary end point occurred in 45 subjects (5.2%). Fosinopril reduced urinary albumin excretion by 26% (P<0.001). Subjects treated with fosinopril showed a 40% lower incidence of the primary end point (hazard ratio 0.60 [95% CI 0.33 to 1.10], P=0.098, log-rank). Pravastatin did not reduce urinary albumin excretion, and subjects treated with pravastatin showed a 13% lower incidence of the primary end point than subjects in the placebo group (0.87 [0.49 to 1.57], P=0.649, log-rank). CONCLUSIONS: In microalbuminuric subjects, treatment with fosinopril had a significant effect on urinary albumin excretion. In addition, fosinopril treatment was associated with a trend in reducing cardiovascular events. Treatment with pravastatin did not result in a significant reduction in urinary albumin excretion or cardiovascular events.

Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial.

BACKGROUND: Despite the use of aspirin, reocclusion of the infarct-related artery occurs in approximately 30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. METHODS AND RESULTS: At coronary angiography <48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (< or =TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P<0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P<0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively (P<0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% (P=NS). CONCLUSIONS: As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.

Microalbuminuria modifies the mortality risk associated with electrocardiographic ST-T segment changes.

OBJECTIVES: We sought to investigate whether microalbuminuria, a proposed marker of generalized vascular damage, enhances the prognostic value of ST-T segment changes for all-cause and cardiovascular mortality in the general population. BACKGROUND: ST-T segment changes on the rest electrocardiogram (ECG) predict mortality in the general population. However, the excess risk seems to be low, particularly in nonhospitalized populations with a low cardiovascular risk profile. METHODS: In a population of 7,330 male and female subjects, a total of 89 deaths (1.2%) occurred during a median three-year follow-up. In 69 of these, the cause of death was obtained from the Central Bureau of Statistics: 25 subjects died of cardiovascular causes (36%). Using computerized Minnesota coding, ST-T segment changes were coded as 4.1-4 and 5.1-4. Microalbuminuria was defined as a urinary albumin excretion of 30 to 300 mg per 24 h. RESULTS: The combination of ST-T segment changes and microalbuminuria showed a higher hazard ratio (HR) for all-cause mortality (HR 8.6 [95% confidence interval [CI] 4.8 to 15.2, p < 0.0001), as compared with ST-T segment changes in the absence of microalbuminuria (HR 1.3 [95% CI 0.7 to 2.5]), which was independent of other cardiovascular risk factors (HR 3.3 [95% CI 1.5 to 7.1], p = 0.002). The combination showed a higher HR when only cardiovascular deaths were taken into account, as compared with all-cause mortality (HR 24.5 [95% CI 7.9 to 76.0], p < 0.0001), which also counted for ST-T segment changes alone (HR 4.4 [95% CI 1.4 to 14.5], p = 0.02). After controlling for other risk factors, the HRs were 10.4 (95% CI 2.5 to 43.6, p = 0.001) for the combination and 2.7 (95% CI 0.6 to 12.3) for ST-T segment changes alone. CONCLUSIONS: This study suggests that, in subjects with ST-T segment changes on their rest ECG, microalbuminuria could identify those at increased risk of all-cause and cardiovascular mortality.

Determination of vessel size: a putative framework to assess clinical outcome.

BACKGROUND: Unknown is the predictive value of the coronary artery diameter without the administration of vasomotor stimuli. A small reference diameter of the target vessel has been demonstrated to be an adverse prognostic factor in patients undergoing revascularisation. The present study investigated the prognostic value of the proximal non-stenotic left anterior descending coronary artery (LAD) diameter in patients referred for a first diagnostic angiogram without a previous revascularisation. METHODS: A total of 277 patients (mean age 57 year, 61% male) were eligible for analysis. The proximal non-stenotic diameter of the LAD was measured by quantitative coronary angiography without prior nitrate infusion. We defined a small LAD as a diameter < or =2.5 mm. Cardiovascular events were defined as cardiac death, myocardial infarction, and hospitalizations for unstable angina. RESULTS: During a median follow-up of 47 months, 24 major cardiac events occurred. The cumulative survival for patients with a small LAD was significantly lower, than for patients with a large LAD (hazard ratio 2.51; 95% confidence interval 1.11-5.66, p=0.03). In the multivariate analysis, a LAD diameter < or =2.5 mm remained a significant predictor of cardiovascular events after adjustment for age, gender, and the presence of significant coronary artery disease (hazard ratio 2.32; 95% confidence interval 1.01-5.34, p=0.048). CONCLUSION: In patients referred for a first diagnostic angiogram without a previous revascularisation, the diameter of the proximal non-stenotic LAD is an independent predictor of cardiovascular events.

Differential localisation of the renin-angiotensin system in de-novo lesions and in-stent restenotic lesions in in-vivo human coronary arteries.

OBJECTIVE: Different components of the renin-angiotensin system (RAS) have been demonstrated in atherosclerotic plaques. However, the involvement of the RAS in in-stent restenosis is not clear. We studied the differential immunolocalisation of angiotensin converting enzyme (ACE) and the angiotensin II type 1 (AT1) receptor in de-novo stenotic lesions and in-stent restenotic lesions in human coronary arteries. METHODS: Using a pullback atherectomy catheter, biopsies from de-novo coronary lesions (n=19) and in-stent restenotic lesions (n=19) were obtained. The biopsies were immunostained for vascular smooth muscle cells (VSMCs), macrophages, ACE and the AT1 receptor. RESULTS: In biopsies from de-novo stenotic lesions ACE-positive macrophages were more numerous than in in-stent restenotic lesions (P=0.002). Moreover, in the latter lesions, ACE-positive macrophages decreased when the time interval of stent implantation was longer. On the other hand, in-stent restenotic lesions contained predominantly young VSMCs, which abundantly expressed AT1 receptors. CONCLUSIONS: Lesional ACE expression is not a prominent feature of in-stent restenotic lesions. In contrast, AT1 receptors are abundantly expressed on young VSMCs. In de-novo lesions ACE and AT1 receptors were found on macrophages and VSMCs, which were present in all specimens.