Coronary Artery Calcium and Incident Cerebrovascular Events in an Asymptomatic Cohort: The MESA Study

ObjectivesThis study assessed the predictive value of coronary artery calcium (CAC) score for cerebrovascular events (CVE) in an asymptomatic multiethnic cohort.BackgroundThe CAC score, a measure of atherosclerotic burden, has been shown to improve prediction of coronary heart disease events. However, the predictive value of CAC for CVE is unclear.MethodsCAC was measured at baseline examination of participants (N = 6,779) of MESA (Multi-Ethnic Study of Atherosclerosis) and then followed for an average of 9.5 ± 2.4 years for the diagnosis of incident CVE, defined as all strokes or transient ischemic attacks.ResultsDuring the follow-up, 234 (3.5%) adjudicated CVE occurred. In Kaplan-Meier analysis, the presence of CAC was associated with a lower CVE event-free survival versus the absence of CAC (log-rank chi-square: 59.8, p < 0.0001). Log-transformed CAC was associated with increased risk for CVE after adjusting for age, sex, race/ethnicity, body mass index, systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, cigarette smoking status, blood pressure medication use, statin use, and interim atrial fibrillation (hazard ratio [HR]: 1.13 [95% confidence interval (CI): 1.07 to 1.20], p < 0.0001). The American College of Cardiology/American Heart Association–recommended CAC cutoff was also an independent predictor of CVE and strokes (HR: 1.70 [95% CI: 1.24 to 2.35], p = 0.001, and HR: 1.59 [95% CI: 1.11 to 2.27], p = 0.01, respectively). CAC was an independent predictor of CVE when analysis was stratified by sex or race/ethnicity and improved discrimination for CVE when added to the full model (c-statistic: 0.744 vs. 0.755). CAC also improved the discriminative ability of the Framingham stroke risk score for CVE.ConclusionsCAC is an independent predictor of CVE and improves the discrimination afforded by current stroke risk factors or the Framingham stroke risk score for incident CVE in an initially asymptomatic multiethnic adult cohort.     

Comparative Effectiveness and Safety of New-Generation Versus Early-Generation Drug-Eluting Stents According to Complexity of Coronary Artery Disease: A Patient-Level Pooled Analysis of 6,081 Patients

ObjectivesThe purpose of this study was to compare the 2-year safety and effectiveness of new- versus early-generation drug-eluting stents (DES) according to the severity of coronary artery disease (CAD) as assessed by the SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score.BackgroundNew-generation DES are considered the standard-of-care in patients with CAD undergoing percutaneous coronary intervention. However, there are few data investigating the effects of new- over early-generation DES according to the anatomic complexity of CAD.MethodsPatient-level data from 4 contemporary, all-comers trials were pooled. The primary device-oriented clinical endpoint was the composite of cardiac death, myocardial infarction, or ischemia-driven target-lesion revascularization (TLR). The principal effectiveness and safety endpoints were TLR and definite stent thrombosis (ST), respectively. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated at 2 years for overall comparisons, as well as stratified for patients with lower (SYNTAX score ≤11) and higher complexity (SYNTAX score >11).ResultsA total of 6,081 patients were included in the study. New-generation DES (n = 4,554) compared with early-generation DES (n = 1,527) reduced the primary endpoint (HR: 0.75 [95% CI: 0.63 to 0.89]; p = 0.001) without interaction (p = 0.219) between patients with lower (HR: 0.86 [95% CI: 0.64 to 1.16]; p = 0.322) versus higher CAD complexity (HR: 0.68 [95% CI: 0.54 to 0.85]; p = 0.001). In patients with SYNTAX score >11, new-generation DES significantly reduced TLR (HR: 0.36 [95% CI: 0.26 to 0.51]; p < 0.001) and definite ST (HR: 0.28 [95% CI: 0.15 to 0.55]; p < 0.001) to a greater extent than in the low-complexity group (TLR p_int = 0.059; ST p_int = 0.013). New-generation DES decreased the risk of cardiac mortality in patients with SYNTAX score >11 (HR: 0.45 [95% CI: 0.27 to 0.76]; p = 0.003) but not in patients with SYNTAX score ≤11 (p_int = 0.042).ConclusionsNew-generation DES improve clinical outcomes compared with early-generation DES, with a greater safety and effectiveness in patients with SYNTAX score >11.     

Radial Versus Femoral Access for Coronary Angiography/Intervention in Women With Acute Coronary Syndromes: Insights From the RIVAL Trial (Radial Vs femorAL access for coronary intervention)

ObjectivesThe purpose of this study was to determine the efficacy and safety of radial versus femoral access in women undergoing coronary angiography/intervention.BackgroundThe risk of bleeding and vascular access site complications are higher in women than in men.MethodsIn a pre-specified RIVAL (RadIal Vs femorAL access for coronary intervention) subgroup analysis, we compared outcomes in women (n = 1,861) and men (n = 5,160) randomized to radial versus femoral access.ResultsOverall, women were at higher risk of major vascular complications compared with men (4.7% vs. 1.7%; p < 0.0001). Major vascular complications were significantly reduced with radial access in women (3.1% vs. 6.1%; hazard ratio [HR]: 0.5; 95% confidence interval [CI]: 0.32 to 0.78; p = 0.002) and in men (0.7% vs. 2.8%; HR: 0.27; 95% CI: 0.17 to 0.45; p < 0.0001; interaction p = 0.092). Crossover rates were higher with radial compared with femoral access in women (11.1% vs. 1.9%; HR: 5.88; p < 0.0001) and men (6.3% vs. 1.9%; HR: 3.32; p < 0.0001; interaction p = 0.054). Percutaneous coronary intervention (PCI) success rates were similar irrespective of access site (women: HR: 1.05; p = 0.471; men: HR: 1.00; p = 0.888; interaction p = 0.674), with no differences in PCI complications. In multivariable analyses, female sex was an independent predictor of major vascular complications (HR: 2.39; 95% CI: 1.76 to 3.25; p < 0.0001). There were consistent findings for women and men, with no difference for the primary composite endpoint of death, myocardial infarction, stroke, and non–coronary artery bypass grafting bleeding (women: 3.9% vs. 5.0%; HR: 0.77; 95% CI: 0.50 to 1.19; men: 3.54% vs. 3.5%; HR: 1.00; 95% CI: 0.75 to −1.34; interaction p = 0.325).ConclusionsWomen undergoing coronary angiography and PCI have a higher risk of vascular access site complications compared with men, and radial access is an effective method to reduce these complications.     

Metabolically healthy obese subjects are at risk of fatty liver but not of pre-clinical atherosclerosis

Backgrounds and aimsWhether obesity increases risk of cardiovascular disease (CVD) and fatty liver because of the co-existence of other risk factors is uncertain. We investigated odds ratios (ORs) for: a) a measure of pre-clinical atherosclerosis and b) fatty liver, in metabolically healthy obese (MHO) subjects, metabolically abnormal obese (MAO) subjects and metabolically abnormal non obese subjects (MANO), using a metabolically healthy non obese (MHNO) group as the reference.Methods and results14,384 South Koreans from an occupational cohort underwent cardiac computed tomography (CT) estimation of CAC score, liver ultrasound determination of fatty liver, and measurement of cardiovascular risk factors. Pre-clinical atherosclerosis was defined by a CAC score >0. We used logistic regression to determine ORs for CAC >0, and fatty liver in MHO, MAO and MANO subjects (reference group MHNO). There was no increase in OR for CAC score >0 (OR = 0.93, [95% CIs 0.67,1.31], p = 0.68), in the MHO group, whereas there was an increase in the ORs for CAC score >0 in the MAO, and MANO groups (OR = 1.64 [95% CI 1.36,1.98], p < 0.001) and (OR = 1.38 [95% CI 1.17,1.64], p < 0.001), respectively. In contrast, for fatty liver, there was an increase in OR in each group (OR = 3.63 [95% CI 3.06, 4.31] p < 0.001); (OR = 5.89 [5.18,6.70] p < 0.001); and (OR = 1.83 [95% CI 1.69,2.08]) in the MHO, MAO group and MANO groups respectively.ConclusionMHO subjects are at risk of fatty liver but attenuated risk of pre-clinical atherosclerosis. Both MAO and MANO subjects are at risk of fatty liver and pre-clinical atherosclerosis.     

Outcomes in Patients With Cardiogenic Shock Following Percutaneous Coronary Intervention in the Contemporary Era: An Analysis From the BCIS Database (British Cardiovascular Intervention Society)

ObjectivesThis study sought to determine mortality rates among cardiogenic shock (CGS) patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome in the contemporary treatment era and to determine predictors of mortality.BackgroundIt is unclear whether recent advances in pharmacological and interventional strategies have resulted in further improvements in short- and long-term mortality and which factors are associated with adverse outcomes in patients presenting with CGS and undergoing PCI in the setting of acute coronary syndrome.MethodsThis study analyzed prospectively collected data for patients undergoing PCI in the setting of CGS as recorded in the BCIS (British Cardiovascular Intervention Society) PCI database.ResultsIn England and Wales, 6,489 patients underwent PCI for acute coronary syndrome in the setting of CGS. The mortality rates at 30 days, 90 days, and 1 year were 37.3%, 40.0%, and 44.3%, respectively. On multiple logistic regression analysis, age (for each 10-year increment of age: odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.51 to 1.68; p < 0.0001), diabetes mellitus (OR: 1.47, 95% CI: 1.28 to 1.70; p < 0.0001), history of renal disease (OR: 2.03, 95% CI: 1.63 to 2.53; p < 0.0001), need for artificial mechanical ventilation (OR: 2.56, 95% CI: 2.23 to 2.94; p < 0.0001), intra-aortic balloon pump use (OR: 1.57, 95% CI: 1.40 to 1.76; p < 0.0001), and need for left main stem PCI (OR: 1.90, 95% CI: 1.62 to 2.23; p < 0.0001) were associated with higher mortality at 1 year.ConclusionsIn this large U.K. cohort of patients undergoing PCI in the context of CGS, mortality remains high in spite of the use of contemporary PCI strategies. The highest mortality occurs early, and this time period may be a particular target of therapeutic intervention.     

Outcomes After Emergency Percutaneous Coronary Intervention in Patients With Unprotected Left Main Stem Occlusion: The BCIS National Audit of Percutaneous Coronary Intervention 6-Year Experience

ObjectivesThis study sought to evaluate in-hospital outcomes and 3-year mortality of patients presenting with unprotected left main stem occlusion (ULMSO) treated with primary percutaneous coronary intervention (PPCI).BackgroundLimited data exists about management and outcome following presentation with ULMSO.MethodsFrom January 1, 2007 to December 21, 2012, 446,257 PCI cases were recorded in the British Cardiovascular Intervention Society database of all PCI cases in England and Wales. Of those, 568 were patients having emergency PCI for ST-segment elevation infarction (0.6% of all PPCI) who presented with ULMSO (TIMI [Thrombolysis In Myocardial Infarction] flow grade 0/1 and stenosis >75%), and they were compared with 1,045 emergency patients treated with nonocclusive LMS disease. Follow-up was obtained through linkage with the Office of National Statistics.ResultsPresentation with ULMSO, compared with nonocclusive LMS disease, was associated with a doubling in the likelihood of periprocedural shock (57.9% vs. 27.9%; p < 0.001) and/or intra-aortic balloon pump support (52.5% vs. 27.2%; p < 0.001). In-hospital (43.3% vs. 20.6%; p < 0.001), 1-year (52.8% vs. 32.4%; p < 0.001), and 3-year mortality (73.9% vs 52.3%, p < 0.001) rates were higher in patients with ULMSO, compared with patients presenting with a patent LMS, and were significantly influenced by the presence of cardiogenic shock. ULMSO and cardiogenic shock were independent predictors of 30-day (hazard ratio [HR]: 1.61 [95% confidence interval (CI): 1.07 to 2.41], p = 0.02, and HR: 5.43 [95% CI: 3.23 to 9.12], p<0.001, respectively) and 3-year all-cause mortality (HR: 1.52 [95% CI: 1.06 to 2.17], p = 0.02, and HR: 2.98 [95% CI: 1.99 to 4.49], p < 0.001, respectively).ConclusionsIn patients undergoing PPCI for ULMSO, acute outcomes are poor and additional therapies are required to improve outcome. However, long-term outcomes for survivors of ULMSO are encouraging.     

Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis

BackgroundLocal hemodynamic factors are important determinants of atherosclerotic plaque development and progression.ObjectivesThe goal of this study was to determine the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis.MethodsSixty-five patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%) were included. Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using 2-plane coronary angiography and intravascular ultrasound, was used to reconstruct the three-dimensional anatomy of the left anterior descending artery. Each reconstructed artery was divided into sequential 3-mm segments and analyzed for local ESS with computational fluid dynamics; that is, lower ESS levels at both a 3-mm regional level (average ESS and low ESS) and at a vessel level (lowest ESS per artery) and for plaque characteristics (plaque area, plaque thickness, and plaque burden).ResultsCoronary segments in arteries with abnormal microvascular function exhibited lower ESS compared with segments in arteries with normal microvascular function (average ESS: 1.67 ± 1.04 Pa vs. 2.03 ± 1.72 Pa [p = 0.050]; lowest ESS: 0.54 ± 0.25 Pa vs. 0.72 ± 0.32 Pa [p = 0.014]). Coronary segments in arteries with abnormal epicardial endothelial function also exhibited significantly lower ESS compared with segments in arteries with normal epicardial function (average ESS: 1.49 ± 0.89 Pa vs. 1.93 ± 1.50 Pa [p < 0.0001]; low ESS: 1.26 ± 0.81 Pa vs. 1.56 ± 1.30 Pa [p = 0.001]; lowest ESS: 0.51 ± 0.27 Pa vs. 0.65 ± 0.29 Pa [p = 0.080]). Patients with abnormal microvascular endothelial function exhibited a progressive decrease in average and low ESS, starting from patients with normal epicardial endothelial function to those with both microvascular and epicardial endothelial dysfunction (p < 0.0001 and p = 0.004, respectively).ConclusionsThese data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans.     

Coronary Artery Calcification and Family History of Myocardial Infarction in the Dallas Heart Study

ObjectivesThis study aimed to investigate the independent and joint associations between family history of myocardial infarction (FH) and coronary artery calcification (CAC) with incident coronary heart disease (CHD).BackgroundFH and CAC are associated with each other and with incident CHD. It is not known whether FH retains its predictive value after CAC results are accounted for.MethodsAmong 2,390 participants without cardiovascular disease enrolled in the Dallas Heart Study, we assessed FH (myocardial infarction in a first-degree relative) and prevalent CAC by electron-beam computed tomography. The primary outcome, a composite of CHD-related death, myocardial infarction, and percutaneous or surgical coronary revascularization, was assessed over a mean follow-up of 8.0 ± 1.2 years. The individual and joint associations with the CHD composite outcome were determined for FH and CAC.ResultsThe mean age of the population was 44 ± 9 years; 32% had FH and 47% had a CAC score of 0. In multivariate models adjusted for traditional risk factors, FH was independently associated with CHD (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). Further adjustment for prevalent CAC did not diminish this association (adjusted hazard ratio: 2.6; 95% confidence interval: 1.6 to 4.2; p < 0.001). FH and CAC were additive: CHD event rates in those with both FH and CAC were 8.8% vs. 3.3% in those with prevalent CAC alone (p < 0.001). CHD rates were 1.9% in those with FH alone compared with 0.4% in those with neither FH nor CAC (p < 0.017). Among subjects without CAC, FH characterized a group with a more unfavorable cardiometabolic profile.ConclusionsFH provided prognostic information that was independent of and additive to CAC. Among those with CAC, FH identified subjects at particularly high short-term risk, and, among those without it, selected a group with an adverse risk-factor profile.     

Intravascular Ultrasound-Derived Minimal Lumen Area Criteria for Functionally Significant Left Main Coronary Artery Stenosis

ObjectivesThis study sought to evaluate the intravascular ultrasound (IVUS) minimal lumen area (MLA) for functionally significant left main coronary artery (LMCA) stenosis using fractional flow reserve (FFR) as the standard.BackgroundThe evaluation of significant LMCA stenosis remains challenging.MethodsWe identified 112 patients with isolated ostial and shaft intermediate LMCA stenosis (angiographic diameter stenosis of 30% to 80%) who underwent IVUS and FFR measurement.ResultsThe FFR was ≤0.80 in 66 LMCA lesions (59%); these exhibited smaller reference vessels, smaller minimal lumen diameter, greater diameter of stenosis, longer lesion length, smaller MLA, larger plaque burden, and more frequent plaque rupture. The independent factors of an FFR of ≤0.80 were plaque rupture (odds ratio [OR]: 4.47; 95% Confidence Interval (CI): 1.35 to 14.8; p = 0.014); body mass index (OR: 1.19; 95% CI: 1.00 to 1.41; p = 0.05), age (OR: 0.95; 95% CI: 0.90 to 1.00; p = 0.031), and IVUS MLA (OR: 0.37; 95% CI: 0.25 to 0.56; p < 0.001). The optimal IVUS MLA cutoff value for an FFR of ≤0.80 was 4.5 mm² (77% sensitivity, 82% specificity, 84% positive predictive value, 75% negative predictive value, area under the curve: 0.83, 95% CI: 0.76 to 0.96; p < 0.001) overall and 4.1 to 4.5 mm² in various subgroups. Adjustment for the body surface area, body mass index, and left ventricular mass did not improve the diagnostic accuracy of the IVUS MLA.ConclusionsIn patients with isolated ostial and shaft intermediate LMCA stenosis, an IVUS-derived MLA of ≤4.5 mm² is a useful index of an FFR of ≤0.80.     

Real-Time Ultrasound Guidance Facilitates Transradial Access: RAUST (Radial Artery Access With Ultrasound Trial)

ObjectivesThis study sought to assess the utility of ultrasound (US) guidance for transradial arterial access.BackgroundUS guidance has been demonstrated to facilitate vascular access, but has not been tested in a multicenter randomized fashion for transradial cardiac catheterization.MethodsWe conducted a prospective multicenter randomized controlled trial of 698 patients undergoing transradial cardiac catheterization. Patients were randomized to needle insertion with either palpation or real-time US guidance (351 palpation, 347 US). Primary endpoints were the number of forward attempts required for access, first-pass success rate, and time to access.ResultsThe number of attempts was reduced with US guidance [mean: 1.65 ± 1.2 vs. 3.05 ± 3.4, p < 0.0001; median: 1 (interquartile range [IQR]: 1 to 2) vs. 2 (1 to 3), p < 0.0001] and the first-pass success rate improved (64.8% vs. 43.9%, p < 0.0001). The time to access was reduced (88 ± 78 s vs. 108 ± 112 s, p = 0.006; median: 64 [IQR: 45 to 94] s vs. 74 [IQR: 49 to 120] s, p = 0.01). Ten patients in the control group required crossover to US guidance after 5 min of failed palpation attempts with 8 of 10 (80%) having successful sheath insertion with US. The number of difficult access procedures was decreased with US guidance (2.4% vs. 18.6% for ≥5 attempts, p < 0.001; 3.7% vs. 6.8% for ≥5min, p = 0.07). No significant differences were observed in the rate of operator-reported spasm, patient pain scores following the procedure, or bleeding complications.ConclusionsUltrasound guidance improves the success and efficiency of radial artery cannulation in patients presenting for transradial catheterization. (Radial Artery Access With Ultrasound Trial [RAUST]; NCT01605292)     

Inverse Relationship Between Membranous Septal Length and the Risk of Atrioventricular Block in Patients Undergoing Transcatheter Aortic Valve Implantation

ObjectivesThis study sought to examine whether imaging of the atrioventricular (AV) membranous septum (MS) by computed tomography (CT) can be used to identify patient-specific anatomic risk of high-degree AV block and permanent pacemaker (PPM) implantation before transcatheter aortic valve implantation (TAVI) with self-expandable valves.BackgroundMS length represents an anatomic surrogate of the distance between the aortic annulus and the bundle of His and may therefore be inversely related to the risk of conduction system abnormalities after TAVI.MethodsSeventy-three consecutive patients with severe aortic stenosis underwent contrast-enhanced CT before TAVI. The aortic annulus, aortic valve, and AV junction were assessed, and MS length was measured in the coronal view.ResultsIn 13 patients (18%), high-degree AV block developed, and 21 patients (29%) received a PPM. Multivariable logistic regression analysis revealed MS length as the most powerful pre-procedural independent predictor of high-degree AV block (odds ratio [OR]: 1.35, 95% confidence interval [CI]: 1.1 to 1.7, p = 0.01) and PPM implantation (OR: 1.43, 95% CI: 1.1 to 1.8, p = 0.002). When taking into account pre- and post-procedural parameters, the difference between MS length and implantation depth emerged as the most powerful independent predictor of high-degree AV block (OR: 1.4, 95% CI: 1.2 to 1.7, p < 0.001), whereas the difference between MS length and implantation depth and calcification in the basal septum were the most powerful independent predictors of PPM implantation (OR: 1.39, 95% CI: 1.2 to 1.7, p < 0.001 and OR: 4.9, 95% CI: 1.2 to 20.5, p = 0.03; respectively).ConclusionsShort MS, insufficient difference between MS length and implantation depth, and the presence of calcification in the basal septum, factors that may all facilitate mechanical compression of the conduction tissue by the implanted valve, predict conduction abnormalities after TAVI with self-expandable valves. CT assessment of membranous septal anatomy provides unique pre-procedural information about the patient-specific propensity for the risk of AV block.     

Long-Term Survival Benefit of Revascularization Compared With Medical Therapy in Patients With Coronary Chronic Total Occlusion and Well-Developed Collateral Circulation

ObjectivesThe purpose of this study was to compare the long-term clinical outcomes of patients with chronic total occlusion (CTO) and well-developed collateral circulation treated with revascularization versus medical therapy.BackgroundLittle is known about the clinical outcomes and optimal treatment strategies of CTO with well-developed collateral circulation.MethodsWe screened 2,024 consecutive patients with at least 1 CTO detected on coronary angiogram. Of these, we analyzed data from 738 patients with Rentrop 3 grade collateral circulation who were treated with medical therapy alone (n = 236), coronary artery bypass grafting (n = 170) or percutaneous coronary intervention (n = 332; 80.1% successful). Patients who underwent revascularization and medical therapy (revascularization group, n = 502) were compared with those who underwent medical therapy alone (medication group, n = 236) in terms of cardiac death and major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction, and repeat revascularization.ResultsDuring a median follow-up duration of 42 months, multivariate analysis revealed a significantly lower incidence of cardiac death (hazard ratio [HR]: 0.29; 95% confidence interval [CI]: 0.15 to 0.58; p < 0.01) and MACE (HR: 0.32; 95% CI: 0.21 to 0.49; p < 0.01) in the revascularization group compared with the medication group. After propensity score matching, the incidence of cardiac death (HR: 0.27; 95% CI: 0.09 to 0.80; p = 0.02) and MACE (HR: 0.44; 95% CI: 0.23 to 0.82; p = 0.01) were still significantly lower in the revascularization group than in the medication group.ConclusionsIn patients with coronary CTO and well-developed collateral circulation, aggressive revascularization may reduce the risk of cardiac mortality and MACE.     

Randomized Comparison of Everolimus-Eluting Stents and Sirolimus-Eluting Stents in Patients With ST Elevation Myocardial Infarction: RACES-MI Trial

ObjectivesThe aim of the current study was to compare everolimus-eluting stents (EES) with sirolimus-eluting stents (SES) in patients undergoing primary angioplasty.BackgroundDrug-eluting stents may offer benefits in terms of repeat revascularization. However, as shown for first-generation drug-eluting stents, they may be counterbalanced by a potential higher risk of stent thrombosis, especially among patients with ST-segment elevation myocardial infarction (STEMI). No data have been reported so far on the long-term benefits and safety of the new generation of drug-eluting stents in STEMI.MethodsConsecutive STEMI patients admitted within 12 h of symptom onset and undergoing primary angioplasty and stent implantation at a tertiary center with 24-h primary percutaneous coronary intervention capability were randomly assigned to SES or EES. The primary endpoint was a major adverse cardiac event at 3-year follow-up. The secondary endpoints were death, reinfarction, definite or probable stent thrombosis, and target vessel revascularization at 3-year follow-up. No patient was lost to follow-up.ResultsFrom April 2007 to May 2009, 500 patients with STEMI were randomized to EES (n = 250) or SES (n = 250). No difference was observed in terms of baseline demographic and clinical characteristics between the groups. No difference was observed between the groups in terms of number of implanted stents per patient or total stent length. However, a larger reference diameter was observed with SES (3.35 ± 0.51 mm vs. 3.25 ± 0.51 mm, p = 0.001), whereas patients randomized to EES more often received glycoprotein IIb/IIIa inhibitors (54.4% vs. 42.4%, p = 0.006). Follow-up data were available in all patients (1,095 ± 159 days). No significant difference was observed between EES and SES in major adverse cardiac events (16% vs. 20.8%, adjusted hazard ratio [HR]: 0.75 [95% confidence interval (CI): 0.5 to 1.13], p = 0.17), cardiac death (4.4% vs. 5.6%, adjusted HR: 0.77 [95% CI: 0.35 to 1.71], p = 0.53), recurrent MI (6.4% vs. 10%, adjusted HR: 0.62 [95% CI: 0.33 to 1.16], p = 0.13), and target vessel revascularization (4.8% vs. 4.8%, adjusted HR: 1.00 [95% CI: 0.45 to 2.32], p = 0.99). However, EES was associated with a significant reduction in stent thrombosis (1.6% vs. 5.2%, adjusted HR: 0.3 [95% CI: 0.1 to 0.92], p = 0.035).ConclusionsThis study shows that among STEMI patients undergoing primary angioplasty, EES has similar efficacy as SES, but is associated with a significant reduction in stent thrombosis. (Randomized Comparison of Everolimus Eluting Stents and Sirolimus Eluting Stent in Patients With ST Elevation Myocardial Infarction [RACES-MI]; NCT01684982)     

Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent Relative to Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex Vivo in a Swine Shunt Model

ObjectivesThis study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model.BackgroundPrevious pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers.MethodsAn ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy.ResultsXience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p < 0.001; Synergy: 8.64, 95% CI: 4.43 to 12.84, p < 0.001; Nobori: 4.22, 95% CI: -0.06 to 8.49, p = 0.055; Orsiro: 2.95, 95% CI: -1.26 to 7.15, p = 0.286). The number of cell nuclei on strut surfaces was also the least in Xience-EES, with a significant difference relative to BioMatrix Flex, Nobori, and Orsiro (mean ratios: BioMatrix Flex: 4.73, 95% CI: 2.46 to 9.08, p < 0.001; Synergy: 1.44, 95% CI: 0.75 to 2.76, p = 0.51; Nobori: 5.97, 95% CI: 3.11 to 11.44, p < 0.001; Orsiro: 5.16, 95% CI: 2.69 to 9.91, p < 0.001).ConclusionsXience-EES’s overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis.     

Predictors of Recurrent Events in Patients With Cryptogenic Stroke and Patent Foramen Ovale Within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) Trial

ObjectivesThis study sought to identify predictors of recurrent ischemic neurologic events within the CLOSURE I (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke and/or Transient Ischemic Attack Due to Presumed Paradoxical Embolism Through a Patent Foramen Ovale) trial.BackgroundThe CLOSURE I trial found that transcatheter patent foramen ovale (PFO) closure using the STARFlex device was not superior to medical therapy in patients with cryptogenic stroke or transient ischemic attack (TIA) and PFO.MethodsThe CLOSURE I trial is a multicenter, randomized trial of transcatheter PFO closure compared with medical therapy in patients who presented with cryptogenic stroke or TIA and had a PFO. We identified clinical predictors of recurrent ischemic stroke or TIA during 2 years of follow-up using Cox proportional hazards regression within the pooled intention-to-treat cohort.ResultsIn 909 patients, the incidence of recurrent events was 5.7% with 25 patients suffering a recurrent stroke and 30 a TIA. Patients who had a recurrent event had higher body mass index (30.2 ± 6.2 vs. 28.3 ± 5.8%; p = 0.03) and more frequently had diabetes (19.2% vs. 7.1%; p = 0.0016), hypertension (46.2% vs. 30.1%; p = 0.015), and ischemic heart disease (3.8% vs. 0.9%; p = 0.05). Diabetes (hazard ratio [HR]: 3.39; 95% confidence interval [CI]: 1.69 to 6.84; p = 0.0007), index TIA (HR vs. stroke: 2.13; 95% CI: 1.20 to 3.80; p = 0.01), and the detection of atrial fibrillation after study enrollment (HR: 4.85; 95% CI: 2.05 to 11.47; p = 0.0003) independently predicted recurrent ischemic neurologic events. Recurrent neurologic events were more frequent in subjects with RoPE (Risk of Paradoxical Embolism) score ≤5 than those with >5 (14.5% vs. 4.2%; p < 0.0001).ConclusionsThese findings suggest an alternative etiology to paradoxical embolism was frequently responsible for recurrent events within the CLOSURE I trial. (Evaluation of the STARFlex Septal Closure System in Patients With a Stroke or TIA Due to the Possible Passage of a Clot of Unknown Origin Through a Patent Foramen Ovale (PFO) [CLOSURE I]; NCT00201461)     

Clinical Outcomes and Revascularization Strategies in Patients With Low-Flow,Low-Gradient Severe Aortic Valve Stenosis According to the Assigned Treatment Modality

ObjectivesThis study compared clinical outcomes and revascularization strategies among patients presenting with low ejection fraction, low-gradient (LEF-LG) severe aortic stenosis (AS) according to the assigned treatment modality.BackgroundThe optimal treatment modality for patients with LEF-LG severe AS and concomitant coronary artery disease (CAD) requiring revascularization is unknown.MethodsOf 1,551 patients, 204 with LEF-LG severe AS (aortic valve area <1.0 cm², ejection fraction <50%, and mean gradient <40 mm Hg) were allocated to medical therapy (MT) (n = 44), surgical aortic valve replacement (SAVR) (n = 52), or transcatheter aortic valve replacement (TAVR) (n = 108). CAD complexity was assessed using the SYNTAX score (SS) in 187 of 204 patients (92%). The primary endpoint was mortality at 1 year.ResultsLEF-LG severe AS patients undergoing SAVR were more likely to undergo complete revascularization (17 of 52, 35%) compared with TAVR (8 of 108, 8%) and MT (0 of 44, 0%) patients (p < 0.001). Compared with MT, both SAVR (adjusted hazard ratio [adj HR]: 0.16; 95% confidence interval [CI]: 0.07 to 0.38; p < 0.001) and TAVR (adj HR: 0.30; 95% CI: 0.18 to 0.52; p < 0.001) improved survival at 1 year. In TAVR and SAVR patients, CAD severity was associated with higher rates of cardiovascular death (no CAD: 12.2% vs. low SS [0 to 22], 15.3% vs. high SS [>22], 31.5%; p = 0.037) at 1 year. Compared with no CAD/complete revascularization, TAVR and SAVR patients undergoing incomplete revascularization had significantly higher 1-year cardiovascular death rates (adj HR: 2.80; 95% CI: 1.07 to 7.36; p = 0.037).ConclusionsAmong LEF-LG severe AS patients, SAVR and TAVR improved survival compared with MT. CAD severity was associated with worse outcomes and incomplete revascularization predicted 1-year cardiovascular mortality among TAVR and SAVR patients.     

Long-Term Efficacy and Safety of Paclitaxel-Eluting Balloon for the Treatment of Drug-Eluting Stent Restenosis: 3-Year Results of a Randomized Controlled Trial

ObjectivesThis study sought to investigate the long-term comparative efficacy and safety of paclitaxel-eluting balloon (PEB), paclitaxel-eluting stent (PES), or balloon angioplasty (BA) for the treatment of drug-eluting stent restenosis.BackgroundThe optimal treatment of drug-eluting stent restenosis remains unknown. Although PEB has shown encouraging results, the long-term clinical efficacy and safety of PEB remains poorly defined.MethodsA total of 402 patients with clinically significant restenosis in limus-eluting stents were randomly assigned to receive PEB (n = 137), PES (n = 131), or BA (n = 134). For this analysis, PEB versus PES and PEB versus BA were compared. The primary efficacy and safety endpoints were target lesion revascularization and the composite of death or myocardial infarction.ResultsAt a median follow-up of 3 years, the risk of target lesion revascularization was comparable with PEB versus PES (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 0.91 to 2.33; p = 0.11) and lower with PEB versus BA (HR: 0.51, 95% CI: 0.34 to 0.74; p < 0.001). The risk of death/myocardial infarction tended to be lower with PEB versus PES (HR: 0.55, 95% CI: 0.28 to 1.07; p = 0.08), due to a lower risk of death (HR: 0.38, 95% CI: 0.17 to 0.87; p = 0.02). The risk of death/myocardial infarction was similar with PEB versus BA (HR: 0.96, 95% CI: 0.46 to 2.0; p = 0.91).ConclusionsAt 3 years, the use of PEB as compared with PES to treat patients with limus-eluting stent restenosis has similar efficacy and safety. PEB remains superior to BA. The sustained efficacy without trade-off in safety supports the role of PEB as treatment option for patients with drug-eluting stent restenosis. (Intracoronary Stenting and Angiographic Results: Drug Eluting Stent In-Stent Restenosis: 3 Treatment Approaches [ISAR-DESIRE 3]; NCT00987324)     

Progression to Overt or Silent CAD in Asymptomatic Patients With Diabetes Mellitus at High Coronary Risk: Main Findings of the Prospective Multicenter BARDOT Trial With a Pilot Randomized Treatment Substudy

ObjectivesThe purpose of this study was to evaluate prevalence, progression, treatment, and outcome of silent coronary artery disease (CAD) in asymptomatic patients with diabetes (DM) at high coronary risk.BackgroundDespite the close association of diabetes and CAD, general CAD screening in asymptomatic patients with DM is discouraged even though outcome data in patients at high coronary risk are lacking.MethodsProspective multicenter outcome study—with a pilot randomized treatment substudy. The study comprised 400 asymptomatic patients with DM (type 2) without history or symptoms of CAD at high CAD risk. They underwent clinical evaluation and myocardial perfusion single-photon emission computed tomography (MPS) at baseline and after 2 years. Patients with normal MPS received usual care; those with abnormal MPS received medical or combined invasive and medical management.ResultsAn abnormal MPS was found in 87 of 400 patients (22%). In patients with normal MPS, MACE occurred in 2.9% and ischemia or new scar in 3.2%. Patients with abnormal MPS had more MACE (9.8%; hazard ratio: 3.44; 95% confidence interval [CI]: 1.32 to 8.95; p = 0.011) and ischemia or new scar (34.2%; odds ratio: 15.91; 95% CI: 7.24 to 38.03; p < 0.001) despite therapy, resulting in “overt or silent CAD progression” of 35.6% versus 4.6% (odds ratio: 11.53; 95% CI: 5.63 to 24.70; p < 0.001). Patients with abnormal MPS randomized to medical versus invasive-medical strategies had similar event rates (p = 0.215), but more ischemic or new scar findings (54.3% vs. 15.8%; p < 0.001).ConclusionsHigh-risk asymptomatic patients with DM and normal MPS (78%) have a low rate of first manifestations of CAD. Patients with abnormal MPS at baseline (22%) have a 7-fold higher rate of progression to “overt or silent CAD,” despite therapy. Randomized patients’ outcomes suggest that a combined invasive and medical strategy for silent CAD may reduce scintigraphic but not symptomatic CAD progression versus medical therapy alone. (Trial of Invasive versus Medical therapy of Early coronary artery disease in Diabetes Mellitus ISRCTN87953632).     

Coronary Vessel Wall Contrast Enhancement Imaging as a Potential Direct Marker of Coronary Involvement: Integration of Findings From CAD and SLE Patients

ObjectivesThis study investigated the feasibility of visual and quantitative assessment of coronary vessel wall contrast enhancement (CE) for detection of symptomatic atherosclerotic coronary artery disease (CAD) and subclinical coronary vasculitis in autoimmune inflammatory disease (systemic lupus erythematosus [SLE]), as well as the association with aortic stiffness, an established marker of risk.BackgroundCoronary CE by cardiac magnetic resonance (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake within the coronary artery vessel wall.MethodsA total of 75 subjects (CAD: n = 25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical scanner. Coronary arteries were visualized by a T2-prepared steady state free precession technique. Coronary wall CE was visualized using inversion-recovery T1 weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg gadobutrol. Proximal coronary segments were visually examined for distribution of CE and quantified for contrast-to-noise ratio (CNR) and total CE area.ResultsCoronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for SLE and a patchy/regional distribution in CAD patients. Compared with control subjects, CNR values and total CE area in patients with CAD and SLE were significantly higher (mean CNR: 3.9 ± 2.5 vs. 6.9 ± 2.5 vs. 6.8 ± 2.0, respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR): 0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p < 0.001). Both measures were positively associated with aortic stiffness (CNR: r = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68, p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p < 0.05).ConclusionsWe demonstrate that quantification of coronary CE by CNR and total CE area is feasible for detection of subclinical and clinical uptake of gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an instrumental novel direct marker of vessel wall injury and remodeling in subpopulations at risk.     

Epicardial adipose tissue volume as a marker of coronary artery disease severity in patients with diabetes independent of coronary artery calcium: Findings from the CTRAD study

AimsThe association between epicardial adipose tissue (EAT) volume and coronary artery disease (CAD) severity was evaluated, independent of traditional risk factors and coronary artery calcium (CAC) scores, in patients with diabetes type 2 (DM-2) using cardiac computed tomography angiography (CTA).MethodsA multivariate analysis was utilized to assess for an independent association after calculating EAT volume, CAD severity, and calcium scores in 92 patients with DM-II from the CTRAD study. We graded CAD severity as none (normal coronaries), mild-moderate (<70% stenosis), and severe (70% or greater stenosis).ResultsA total of 39 (42.3%) asymptomatic patients with diabetes did not have CAD; 30.4% had mild/moderate CAD; and 27.1% had severe CAD. Mean EAT volume was highest in patients with severe CAD (143.14 cm³) as compared to mild/moderate CAD (112.7 cm³), and no CAD (107.5 cm³) (p = 0.003). After adjustment of clinical risk factors, notably, CAC score, multivariate regression analysis showed EAT volume was an independent predictor of CAD severity in this sample (odds ratio 11.2, 95% confidence interval 1.7–73.8, p = 0.01).ConclusionsIncreasing EAT volume in asymptomatic patients with DM-II is associated with presence of severe CAD, independent of BMI and CAC, as well as traditional risk factors.