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Objectives: The aim of the study was to determine the prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance (CMR) in reperfused ST-segment elevation myocardial infarction. Background: In acute myocardial infarction, CMR can retrospectively detect the myocardium at risk and the irreversible injury. This allows for quantifying the extent of salvaged myocardium after reperfusion as a potential strong end point for clinical trials and outcome. Methods: We analyzed 208 consecutive ST-segment elevation myocardial infarction patients undergoing primary angioplasty <12 h after symptom onset. T2-weighted and contrast-enhanced CMR was used to calculate the myocardial salvage index (MSI). Patients were categorized into 2 groups defined by the median MSI. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and occurrence of new congestive heart failure within 6 months after the index event. Results: The median MSI was 48 (interquartile range 27 to 73). Major adverse cardiovascular events were significantly lower in the MSI ≥ median group (2.9% vs. 22.1%, p < 0.001). The stepwise Cox proportional hazards model revealed that the MSI was the strongest predictor of major adverse cardiovascular events at 6-month follow-up (p < 0.001). All prognostic clinical (symptom onset to reperfusion), angiographic (Thrombolysis In Myocardial Infarction flow grade before angioplasty), and electrocardiographic (ST-segment resolution) parameters showed significant correlations with the MSI (p < 0.001 for all). Conclusions: This study for the first time demonstrates that the MSI assessed by CMR predicts the outcome in acute reperfused ST-segment elevation myocardial infarction. Therefore, MSI assessment has important implications for patient prognosis as well as for the design of future trials intended to test new reperfusion therapy efficacy. (Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance—Impact on Outcome; NCT00952224). [Copyright &y& Elsevier]

Objectives: The purpose of this study was to compare the characteristics and prevalence of late potentials (LP) in patients with nonischemic cardiomyopathy (NICM) and ischemic cardiomyopathy (ICM) etiologies and evaluate their value as targets for catheter ablation. Background: LP are frequently found in post-myocardial infarction scars and are useful ablation targets. The relative prevalence and characteristics of LP in patients with NICM is not well understood. Methods: Thirty-three patients with structural heart disease (NICM, n = 16; ICM, n = 17) referred for catheter ablation of ventricular tachycardia were studied. Electroanatomic mapping was performed endocardially (n = 33) and epicardially (n = 19). The LP were defined as low voltage electrograms (<1.5 mV) with onset after the QRS interval. Very late potentials (vLP) were defined as electrograms with onset >100 ms after the QRS. Results: We sampled an average of 564 ± 449 points and 726 ± 483 points in the left ventricle endocardium and epicardium, respectively. Mean total low voltage area in patients with ICM was 101 ± 55 cm2 and 56 ± 33 cm2, endocardial and epicardial, respectively, compared with NICM of 55 ± 41 cm2 and 53 ± 28 cm2, respectively. Within the total low voltage area, vLP were observed more frequently in ICM than in NICM in endocardium (4.1% vs. 1.3%; p = 0.0003) and epicardium (4.3% vs. 2.1%, p = 0.035). An LP-targeted ablation strategy was effective in ICM patients (82% nonrecurrence at 12 ± 10 months of follow-up), whereas NICM patients had less favorable outcomes (50% at 15 ± 13 months of follow-up). Conclusions: The contribution of scar to the electrophysiological abnormalities targeted for ablation of unstable ventricular tachycardia differs between ICM and NICM. An approach incorporating LP ablation and pace-mapping had limited success in patients with NICM compared with ICM, and alternative ablation strategies should be considered. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to assess the association of apolipoprotein(a) (apo[a]) isoforms with cardiovascular disease risk. Background: Although circulating lipoprotein(a) (Lp[a]) is likely to be a causal risk factor in coronary heart disease (CHD), the magnitude of this association is modest. Lipoprotein(a) particles with smaller, rather than larger, apo(a) isoforms may be stronger risk factors. Methods: Information was collated from 40 studies published between January 1970 and June 2009 that reported on associations between apo(a) isoforms and risk of CHD or ischemic stroke (involving a total of 11,396 patients and 46,938 controls). Results: Thirty-six studies used broadly comparable phenotyping and analytic methods to assess apo(a) isoform size. These studies yielded a combined relative risk for CHD of 2.08 (95% confidence intervals [CI]: 1.67 to 2.58) for individuals with smaller versus larger apo(a) isoforms (corresponding approximately to 22 or fewer kringle IV type 2 repeats vs. >22 repeats or analogously an apo[a] molecular weight of <640 kDa vs. ≥640 kDa). There was substantial heterogeneity among these studies (I2 = 85%, 80% to 89%), which was mainly explained by differences in the laboratory methods and analytic approaches used. In the 6 studies of ischemic stroke that used comparable phenotypic methods, the combined relative risk was 2.14 (1.85 to 2.97). Overall, however, only 3 studies made allowances for Lp(a) concentration. Conclusions: People with smaller apo(a) isoforms have an approximately 2-fold higher risk of CHD or ischemic stroke than those with larger proteins. Further studies are needed to determine whether the impact of smaller apo(a) isoforms is independent from Lp(a) concentration and other risk factors. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to investigate the prognostic implications of low-level increases in cardiac troponin I (cTnI) using a current-generation sensitive assay in patients with suspected acute coronary syndrome (ACS). Background: Recent enhancements in troponin assays have enabled resolution of the 99th percentile reference limit at progressively lower concentrations. However, the clinical significance of low-level increases with sensitive assays is still debated. Methods: We measured cTnI using a sensitive assay (TnI-Ultra, Siemens Healthcare Diagnostics, Deerfield, Illinois) at baseline in 4,513 patients with non–ST-segment elevation ACS randomly assigned to ranolazine or placebo. We applied decision limits at the 99th percentile reference limit (0.04 μg/l), the cut point of the predecessor assay (0.1 μg/l), and 1 equivalent to elevation of creatine kinase–myocardial band (1.5 ng/ml). Results: Patients with baseline cTnI ≥0.04 μg/l (n = 2,924) were at higher risk of death/myocardial infarction (MI) at 30 days than were patients with a negative cTnI (6.1% vs. 2.0%, p < 0.001). After adjusting for the TIMI (Thrombolysis In Myocardial Infarction) risk score, cTnI ≥0.04 μg/l was associated with a 3-fold (95% confidence interval: 2.0 to 4.4, p < 0.001) higher risk of death/MI at 30 days. Moreover, patients with low-level increases (0.04 μg/l to <0.1 μg/l), were at significantly higher risk of death/MI at 30 days (5.0% vs. 2.0%, p = 0.001) and death at 12 months (6.4% vs. 2.4%, p = 0.005) than were patients with cTnI <0.04 μg/l. Conclusions: Low-level increases in cTnI using a sensitive assay identify patients at higher risk of death or MI. These findings support current American College of Cardiology/American Heart Association recommendations defining MI, and the incremental value of newer, more sensitive assays in identifying high-risk patients with ACS. [Copyright &y& Elsevier]

Osteoprotegerin (OPG) is a glycoprotein that acts as a decoy receptor for receptor activator of nuclear factor κB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand. The OPG/RANKL/receptor activator of nuclear factor κB axis plays an important regulatory role in the skeletal, immune, and vascular systems. The protective role of OPG, in animal models, against vascular calcification has not been replicated in human trials; moreover, increased OPG levels have been consistently associated with the incidence and prevalence of coronary artery disease. There seems to be some dichotomy in the role of OPG, RANKL, and tumor necrosis factor-related apoptosis-inducing ligand in atherosclerosis and plaque stability. In this review, we integrate the findings from some of the important studies and try to draw conclusions with a view to gaining some insight into the complex interactions of the OPG/RANKL/receptor activator of nuclear factor κB axis and tumor necrosis factor-related apoptosis-inducing ligand in the pathophysiology of atherosclerosis. [Copyright &y& Elsevier]

Despite the wide contemporary availability of pharmacological and mechanical means of reperfusion, a very significant proportion of ST-segment elevation myocardial infarction (STEMI) patients are still not offered any reperfusion therapy, and some of them are considered “ineligible for reperfusion.” Spontaneous reperfusion and contraindications to the use of fibrinolytics and/or mechanical reperfusion methods account only for a small part of these clinical situations. The boundary between “timely” and “late” presentation in STEMI, the appropriateness of percutaneous intervention in patients presenting late after onset of symptoms, and the impact of sex and age on the eligibility and/or choice of reperfusion therapy continue to be challenged by the most recent published data. In the current invasive-driven reperfusion era, if scientific evidence and clinical guidelines are applied diligently, the vast majority of eligible STEMI patients should receive reperfusion therapy. Pharmacological nonlytic therapy of patients with STEMI, regardless of the choice of reperfusion strategy or the absence of it, is clearly defined by the current practice guidelines. Available data suggest that for patients who do not receive any form of reperfusion, anticoagulation therapy with low molecular weight heparin provides a clear additional mortality benefit versus placebo. Fondaparinux as compared with usual care (unfractionated heparin infusion or placebo) significantly reduces the composite of death or myocardial reinfarction without increasing severe bleeding or number of strokes. In the treatment of late-presenting patients with STEMI (beyond the first 12 h after onset of symptoms), clinical evaluation and risk stratification represent the crucial elements helping in decision making between therapeutic interventions. [Copyright &y& Elsevier]

Objectives: The aim of this study was to determine the impact of delay to angioplasty in patients with acute coronary syndromes (ACS). Background: There is a paucity of data on the impact of delays to percutaneous coronary intervention (PCI) in patients with non–ST-segment elevation acute coronary syndromes (NSTE-ACS) undergoing an invasive management strategy. Methods: Patients undergoing PCI in the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) trial were stratified according to timing of PCI after clinical presentation for outcome analysis. Results: Percutaneous coronary intervention was performed in 7,749 patients (median age 63 years; 73% male) with NSTE-ACS at a median of 19.5 h after presentation (<8 h [n = 2,197], 8 to 24 h [n = 2,740], and >24 h [n = 2,812]). Delay to PCI >24 h after clinical presentation was significantly associated with increased 30-day mortality, myocardial infarction (MI), and composite ischemia (death, MI, and unplanned revascularization). By multivariable analysis, delay to PCI of >24 h was a significant independent predictor of 30-day and 1-year mortality. The incremental risk of death attributable to PCI delay >24 h was greatest in those patients presenting with high-risk features. Conclusions: In this large-scale study, delaying revascularization with PCI >24 h in patients with NSTE-ACS was an independent predictor of early and late mortality and adverse ischemic outcomes. These findings suggest that urgent angiography and triage to revascularization should be a priority in NSTE-ACS patients. [Copyright &y& Elsevier]

Acute coronary syndrome encompasses a broad and heterogeneous population that challenges the clinician at each step of treatment in terms of: 1) diagnosis; 2) appropriate risk stratification; 3) therapeutic decision making; and 4) monitoring response to therapy. Although there are many established tools for diagnosis, prognosis, and clinical decision making, understanding the advantages and limitations of each tool according the clinical scenario is essential. Several emerging tools, such as novel biomarkers (e.g., high-sensitivity troponin and growth differential factor-15), ECG techniques (e.g., heart rate turbulence or T-wave alternans), and imaging modalities (computed tomography angiography and cardiac magnetic resonance) may potentially improve clinical care; however, they must be fully evaluated and validated in different scenarios and patient cohorts before they are incorporated into clinical practice. This review identifies promising new or emerging techniques, as well as established tools, and reviews their current or potential role in clinical practice. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to determine whether statin treatment is effective and safe in very elderly (80 years and older) acute myocardial infarction (AMI) patients. Background: Elderly individuals constitute an increasing percentage of patients admitted to hospitals for AMI. Despite that these patients have a higher mortality risk, the application of evidence-based medicine remains much lower than for younger patients. Methods: We included all patients 80 years and older who were admitted with the diagnosis of AMI in the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions between 1999 and 2003 (n = 21,410). Of these, complete covariate and follow-up data were available for 14,907 patients (study population A). To limit the bias related comorbidity on statin therapy, we also performed analyses excluding patients who died within 14 days of the acute event (study population B) and all patients who died within 365 days (study population C). A propensity score was used to adjust for initial differences between treatment groups. Results: All-cause mortality was significantly lower in patients receiving statin treatment at discharge in study population A (relative risk: 0.55, 95% confidence interval: 0.51 to 0.59), in study population B (relative risk: 0.65; 95% confidence interval: 0.60 to 0.71), and in study population C (relative risk: 0.66; 95% confidence interval: 0.59 to 0.76). Similar observations were made for cardiovascular mortality as well as for AMI mortality. There was no increase in cancer mortality in statin-treated patients. Conclusions: Statin treatment is associated with lower cardiovascular mortality in very elderly post-infarction patients without increasing the risk of the development of cancer. [Copyright &y& Elsevier]

Cardiovascular disease is the number 1 cause of death in the western world and 1 of the leading causes of death worldwide. The lifetime risk of atherosclerotic cardiovascular disease (CVD) for persons at age 50 years, on average, is estimated to be 52% for men and 39% for women, with a wide variation depending on risk factor burden. Assessing patients'' cardiovascular risk may be used for the targeting of preventive treatments of individual patients who are asymptomatic but at sufficiently high risk for the development of CVD. Risk stratifying patients for CVD remains challenging, particularly for those with low or intermediate short-term risk. Several algorithms have been described to facilitate the assessment of risk in individual patients. We describe 6 risk algorithms (Framingham Risk Score for coronary heart disease events and for cardiovascular events, Adult Treatment Panel III, SCORE [Systematic Coronary Risk Evaluation] project, Reynolds Risk Score, ASSIGN [Assessing Cardiovascular Risk to Scottish Intercollegiate Guidelines Network/SIGN to Assign Preventative Treatment], and QRISK [QRESEARCH Cardiovascular Risk Algorithm]) for outcomes, population derived/validated, receiver-operating characteristic, variables included, and limitations. Areas of uncertainty include 10-year versus lifetime risk, prediction of CVD or coronary heart disease end points, nonlaboratory-based risk scores, age at which to start, race and sex differences, and whether a risk score should guide therapy. We believe that the best high-risk approach to CVD evaluation and prevention lies in routine testing for cardiovascular risk factors and risk score assessment. We recommend that health care providers discuss the global cardiovascular risk and lifetime cardiovascular risk score assessment with each patient to better explain each patient''s future risk. Appropriate intervention, guided by risk assessment, has the potential to bring about a significant reduction in population levels of risk. [Copyright &y& Elsevier]

Objectives: We sought to assess the impact of renal function on platelet reactivity in patients with diabetes mellitus (DM) and coronary artery disease on aspirin and clopidogrel therapy. Background: Diabetes mellitus is a key risk factor for chronic kidney disease (CKD). In aspirin-treated DM patients the presence of moderate/severe CKD is associated with reduced clinical efficacy of adjunctive clopidogrel therapy. Whether these findings may be attributed to differences in clopidogrel-induced effects is unknown. Methods: This was a cross-sectional observational study in which DM patients taking maintenance aspirin and clopidogrel therapy were studied. Patients were categorized into 2 groups according to the presence or absence of moderate/severe CKD. Platelet aggregation after adenosine diphosphate (ADP) and collagen stimuli were assessed with light transmittance aggregometry and defined patients with high post-treatment platelet reactivity (HPPR). Markers of platelet activation, including glycoprotein IIb/IIIa activation and P-selectin expression, were also determined using flow cytometry. Results: A total of 306 DM patients were analyzed. Patients with moderate/severe CKD (n = 84) had significantly higher ADP-induced (60 ± 13% vs. 52 ± 15%, p = 0.001) and collagen-induced (49 ± 20% vs. 41 ± 20%, p = 0.004) platelet aggregation compared with those without (n = 222). After adjustment for potential confounders, patients with moderate/severe CKD were more likely to have HPPR after ADP (adjusted odds ratio: 3.8, 95% confidence interval: 1.7 to 8.5, p = 0.001) and collagen (adjusted odds ratio: 2.4; 95% confidence interval: 1.1 to 5.4; p = 0.029) stimuli. Markers of platelet activation were significantly increased in patients with HPPR. Conclusions: In DM patients with coronary artery disease taking maintenance aspirin and clopidogrel therapy, impaired renal function is associated with reduced clopidogrel-induced antiplatelet effects and a greater prevalence of HPPR. [Copyright &y& Elsevier]

Objectives: We sought to determine the prognostic and incremental value of coronary artery disease (CAD) severity, coronary atherosclerosis, and left ventricular ejection fraction (LVEF) measured with cardiac computed tomography angiography (CTA). Background: CTA is an emerging tool used for the detection of obstructive CAD. However, there are limited data supporting the prognostic value of 64-slice CTA and its ability to predict all-cause mortality and major adverse cardiac events such as cardiac death and nonfatal myocardial infarction. Methods: Consecutive patients (without history of revascularization, heart transplantation, and congenital heart disease) were prospectively enrolled. Each CTA was evaluated for CAD severity, total plaque score, and LVEF. Patients were followed, and all events were confirmed with death certificates or hospital or physician records and reviewed by a clinical events committee. Results: Between February 2006 and February 2008, 2,076 consecutive patients were prospectively enrolled and followed for a mean of 16 ± 8 months. At follow-up, a total of 31 (1.5%) patients had cardiac death or nonfatal myocardial infarction and 47 (2.3%) had all-cause mortality or nonfatal myocardial infarction. Multivariate analysis showed that CAD severity (hazard ratio [HR]: 3.02; 95% confidence interval [CI]: 1.89 to 4.83) was a predictor of major adverse cardiac events and that LVEF (HR: 1.47; 95% CI: 1.17 to 1.86) had incremental value over CAD severity. Total plaque score had incremental value over CAD severity and LVEF for all-cause mortality and nonfatal myocardial infarction (HR: 1.17; 95% CI: 1.06 to 1.29). Conclusions: Using CTA, CAD severity, LVEF, and total plaque score seems to have prognostic and incremental value over routine clinical predictors. Cardiac CTA seems to be a promising noninvasive modality with prognostic value. [Copyright &y& Elsevier]

Objectives: The aim of this study was to develop and validate a clinical decision rule (CDR) to predict 1-month serious outcome and all-cause death in patients presenting with syncope to the emergency department. Background: Syncope is a common, potentially serious condition accounting for many hospital admissions. Methods: This was a single center, prospective, observational study of adults presenting to the emergency department with syncope. A CDR was devised from 550 patients in a derivation cohort and tested in a validation cohort of a further 550 patients. Results: One-month serious outcome or all-cause death occurred in 40 (7.3%) patients in the derivation cohort. Independent predictors were brain natriuretic peptide concentration ≥300 pg/ml (odds ratio [OR]: 7.3), positive fecal occult blood (OR: 13.2), hemoglobin ≤90 g/l (OR: 6.7), oxygen saturation ≤94% (OR: 3.0), and Q-wave on the presenting electrocardiogram (OR: 2.8). One-month serious outcome or all-cause death occurred in 39 (7.1%) patients in the validation cohort. The ROSE (Risk stratification Of Syncope in the Emergency department) rule had a sensitivity and specificity of 87.2% and 65.5%, respectively, and a negative predictive value of 98.5%. An elevated B-type natriuretic peptide (BNP) concentration alone was a major predictor of serious cardiovascular outcomes (8 of 22 events, 36%) and all-cause deaths (8 of 9 deaths, 89%). Conclusions: The ROSE rule has excellent sensitivity and negative predictive value in the identification of high-risk patients with syncope. As a component, BNP seems to be a major predictor of serious cardiovascular outcomes and all-cause death. The ROSE rule and BNP measurement might be valuable risk stratification tools in patients with emergency presentations of syncope and should now be subjected to external validation. [Copyright &y& Elsevier]

Over the last 15 years, the use of invasive coronary physiology in the catheterization laboratory has demonstrated favorable outcomes for decision making in patients with intermediate single-vessel stenoses, complex bifurcation and ostial branch stenoses, multivessel coronary artery disease, and left main stenoses. A recent large multicenter study (FAME [FFR versus Angiography for Multivessel Evaluation]) found that a physiologically-guided approach was superior to the standard angiographically-guided approach for percutaneous revascularization in patients with multivessel coronary artery disease. This review addresses selected pertinent concepts and studies supporting the integration of coronary physiology in the catheterization laboratory for optimal patient outcomes. [Copyright &y& Elsevier]

In patients with known or suspected myocardial infarction (MI), cardiovascular magnetic resonance (CMR) provides a comprehensive, multifaceted view of the heart. The data, including that from a recent multicenter clinical trial, indicate that delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) is a well-validated, robust technique that can be easily implemented on scanners that are commonly available worldwide, with an effectiveness that clearly rivals the best available imaging techniques for the detection and assessment of acute and chronic MI. When patients present outside the diagnostic window of cardiac troponins, DE-CMR may be especially useful. Moreover, because DE-CMR can uniquely differentiate between ischemic and various nonischemic forms of myocardial injury, it may be helpful in cases of diagnostic uncertainty, such as in patients with classical features of MI in whom coronary angiography does not show a culprit lesion. Even after the diagnosis of MI has been made, CMR provides clinically relevant information by identifying residual viability, microvascular damage, stunning, and right ventricular infarction. In addition, post-MI sequelae, including left ventricular thrombus and pericarditis, are easily identified. Given that quantification of infarct size by DE-CMR is highly reproducible, this technique may provide a useful surrogate end point for clinical trials with appreciable reductions in sample size compared with alternative methods. [Copyright &y& Elsevier]

Objectives: This study examined myocardial microvascular emboli and obstruction, and related these to plaque in the epicardial coronary arteries supplying the affected microvessels. Background: Epicardial coronary thrombosis often causes microemboli and microvascular obstruction. The consequences of myocardial microvessel obstruction and myocyte necrosis are substantial, yet histopathologic characterization of epicardial coronary artery plaque has been incompletely characterized. This study examined myocardial microvascular emboli, and related these to plaque in the coronary arteries supplying the microvessels. Methods: Hearts from sudden coronary death patients underwent examination for coronary artery plaque type and cardiac microemboli. Results: Forty-four hearts were available for evaluation. Mean age at death was 51 ± 15 years. Coronary artery analysis found 26 plaque ruptures and 21 erosions, and a mean of 4.5 microemboli per heart. Microemboli and microvascular obstruction occurred most often from eroded plaques. Microemboli and occluded intramyocardial vessels were most common in the left anterior descending coronary artery, and all vessels contained fibrin and platelets. Mean stenoses of the culprit lesion was 74% in those with emboli and 75% in those without (p = NS). Intramyocardial microemboli were more common in plaque erosion than in rupture. Microvessels <200 μm were most often those that were occluded. Conclusions: Microemboli and microvascular obstruction are common in patients dying of acute coronary thrombosis. Plaque erosion is more likely to cause emboli in vessels <200 μm. These emboli and microvessel obstruction have a prominent clinical role since myonecrosis is often associated with these findings. [Copyright &y& Elsevier]

The risk of sudden death is highest early after myocardial infarction (MI) and progressively declines over the ensuing 6 to 12 months. Nevertheless, several randomized clinical trials have failed to show a survival benefit for implantable cardioverter-defibrillators when implanted early after MI in high-risk patients. The etiology of this acute MI–sudden cardiac death paradox is unclear, but may be related to the changing nature of the substrate over the several month period after acute MI. Further investigation is needed to delineate the actual causes of death in the early post-MI period and which interventions can be implemented to reduce the increased rate of sudden death that is observed. [Copyright &y& Elsevier]

Objectives: We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. Background: Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile. Methods: In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke. Results: Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin. Conclusions: Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin. [Copyright &y& Elsevier]

The topic of the J-curve relationship between blood pressure and coronary artery disease (CAD) has been the subject of much controversy for the past decades. An inverse relationship between diastolic pressure and adverse cardiac ischemic events (i.e., the lower the diastolic pressure the greater the risk of coronary heart disease and adverse outcomes) has been observed in numerous studies. This effect is even more pronounced in patients with underlying CAD. Indeed, a J-shaped relationship between diastolic pressure and coronary events was documented in treated patients with CAD in most large trials that scrutinized this relationship. In contrast to any other vascular bed, the coronary circulation receives its perfusion mostly during diastole; hence, an excessive decrease in diastolic pressure can significantly hamper perfusion. This adverse effect of too low a diastolic pressure on coronary heart disease leaves the practicing physician with the disturbing possibility that, in patients at risk, lowering blood pressure to levels that prevent stroke or renal disease might actually precipitate myocardial ischemia. However, these concerns should not deter physicians from pursuing a more aggressive control of hypertension, because currently blood pressure is brought to recommended target levels in only approximately one-third of patients. [Copyright &y& Elsevier]

Objectives: This study evaluates the effect of pre-operative angiotensin-converting enzyme inhibitor (ACEI) therapy on early clinical outcomes after coronary artery bypass grafting (CABG). Background: Therapy with ACEIs has been shown to reduce the rate of mortality and prevent cardiovascular events in patients with coronary artery disease. However, their pre-operative use in patients undergoing CABG is still controversial. Methods: A retrospective, observational, cohort study was undertaken of prospectively collected data on 10,023 consecutive patients undergoing isolated CABG between April 1996 and May 2008. Of these, 3,052 patients receiving pre-operative ACEI were matched to a control group by propensity score analysis. Results: Overall rate of mortality was 1%. Pre-operative ACEI therapy was associated with a doubling in the risk of death (1.3% vs. 0.7%; odds ratio [OR]: 2.00, 95% confidence interval [CI]: 1.17 to 3.42; p = 0.013). There was also a significant difference between the ACEI and control group in the risk of post-operative renal dysfunction (PRD) (7.1% vs. 5.4%; OR: 1.36, 95% CI: 1.1 to 1.67; p = 0.006), atrial fibrillation (AF) (25% vs. 20%; OR: 1.34, 95% CI: 1.18 to 1.51; p < 0.0001), and increased use of inotropic support (45.9% vs. 41.1%; OR: 1.22, 95% CI: 1.1 to 1.36; p < 0.0001). In a multivariate analysis, pre-operative ACEI treatment was an independent predictor of mortality (p = 0.04), PRD (p = 0.0002), use of inotropic drugs (p < 0.0001), and AF (p < 0.0001). Conclusions: Pre-operative therapy with ACEI is associated with an increased risk of mortality, use of inotropic support, PRD, and new onset of post-operative AF. [Copyright &y& Elsevier]

Objectives: Our aim was to assess the predictive value of myocardial infarct size assessed with late gadolinium-enhanced (LGE) magnetic resonance imaging (MRI) in medically treated patients with chronic myocardial infarction relative to contractile reserve on low-dose dobutamine magnetic resonance (DSMR) for long-term event-free survival. Background: Information on the relative merits of scar tissue and contractile reserve to predict long-term prognosis in patients with chronic myocardial infarction is lacking. Methods: A total of 177 patients with known coronary artery disease and scar tissue on LGE MRI were enrolled. Left ventricular (LV) functional parameters at rest and during low-dose DSMR were assessed, and the wall motion score index was calculated. Results: Eleven patients (6.2%) suffered an event during follow-up (average 20.3 months). Infarct size was a stronger predictor of events than LV ejection fraction and LV volumes at rest and during low-dose DSMR. Myocardial infarct size was used to separate patients at high risk (spatial extent ≥6 segments, n = 98) from those at low risk (spatial extent <6 segments, n = 79) for mortality. In the subgroup of patients at high risk, transmurality of infarct was not a predictor of events. However, the presence of contractile reserve (n = 63) was associated with a significantly higher number of events (12.7%) compared with no change in wall motion score index (6.7%; n = 15; p = 0.008). Conclusions: Myocardial infarct size on LGE MRI is a stronger predictor of clinical outcome than contractile reserve in medically treated patients with myocardial infarction. In patients with large myocardial scar, the presence of contractile reserve is more important for the prediction of events than scar tissue. [Copyright &y& Elsevier]

On the basis of the evidence obtained from observational studies, randomized controlled trials and their meta-analyses, current guidelines recommend initiating high-dose statin therapy pre-discharge regardless of the baseline low-density lipoprotein (LDL) level in patients with acute coronary syndromes (ACS). Careful review of the evidence indicates that early initiation of high-dose statin therapy reduces recurrent ischemia and may reduce revascularization, but does not confer benefit in terms of hard clinical outcomes such as death or myocardial infarction in any of the randomized controlled trials, and may be associated with increased liver and muscle-related adverse outcomes leading to increased withdrawal and suboptimal long-term adherence. A mortality benefit is apparent in pooled analyses of randomized controlled trials only at long-term (24-month) but not short-term (4-month) follow-up. The critical role of the timing of initiation of therapy (early vs. late) on the benefit-risk profile of statin treatment has not been systematically assessed. It is unclear whether the clinical benefits are attributable to lipid-lowering or lipid-lowering–independent effects. Finally, an optimal LDL threshold for initiating treatment or target LDL level for treatment in ACS remains yet to be defined. On the basis of these observations, and despite a compelling pathophysiologic rationale, the justification for current Class I, Level of Evidence: A recommendation for statin therapy in patients with ACS remains open to question. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the analytical and clinical performance of the novel hypersensitive cardiac troponin I (cTnI) prototype assay from Beckman Coulter (Fullerton, California). Background: Studies on patients with acute coronary syndromes and on seemingly healthy subjects have shown that even very minor elevations of cardiac troponins are associated with an increased risk of death. However, the normal plasma levels of cardiac troponins are still not known. Methods: cTnI plasma levels were measured in 542 healthy subjects, 319 men (age 59.9 ± 11.8 years) and 213 women (age 59.8 ± 13.1 years), and in 1,503 randomly selected patients of the GUSTO IV (Global Utilization of Strategies To open Occluded arteries IV) cohort with unstable angina and non–ST-segment elevation myocardial infarctions (MIs). Results: The cTnI levels at 10% coefficient of variation and 20% coefficient of variation imprecision were 0.0033 and 0.0016 μg/l, respectively. The cTnI levels were measurable in >95% of the healthy subjects. The median level of healthy subjects <60 years of age was 0.0032 μg/l (range 0.0011 to 0.0079 μg/l) with the 99th percentile being 0.010 μg/l. No sex differences were observed. A receiver-operator characteristic curve analysis showed an optimal discrimination between healthy subjects and patients at 0.0064 μg/l with a sensitivity of 84.8% (95% confidence interval: 82.8% to 86.6%) and specificity of 89.7% (95% confidence interval: 86.8% to 92.2%). Outcomes as to death and/or MI were significantly different at this level (p < 0.01) in the GUSTO IV cohort. Conclusions: The novel high-sensitivity cTnI prototype assay from Beckman Coulter allows for the first time the measurement of cTnI levels in almost all healthy subjects. Our data indicate that the assay may be a powerful aid in the diagnosis and outcome prediction of patients with suspected myocardial ischemia and question any definition of myocardial infarction. [Copyright &y& Elsevier]

Antithrombotic agents are an integral component of the medical regimens and interventional strategies currently recommended to reduce thrombotic complications in patients with acute coronary syndromes (ACS). Despite great advances with these therapies, associated high risks for thrombosis and hemorrhage remain as the result of complex interactions involving patient comorbidities, drug combinations, multifaceted dosing adjustments, and the intricacies of the care environment. As such, the optimal combinations of antithrombotic therapies, their timing, and appropriate targeted subgroups remain the focus of intense research. During the last several years a number of new antithrombotic treatments have been introduced, and new data regarding established therapies have come to light. Although treatment guidelines include the most current available data, subsequent findings can be challenging to integrate. This challenge is compounded by the complexity associated with different efficacy and safety measures and the variability in study populations, presenting syndromes, physician, and patient preferences. In this work we review recent data regarding clinically available antiplatelet and anticoagulation agents used in the treatment of patients with ACS. We address issues including relative efficacy, safety, and timing of therapies with respect to conservative and invasive treatment strategies. In specific cases we will highlight remaining questions and controversies and ongoing trials, which will hopefully shed light in these areas. In addition to reviewing existing agents, we take a look forward at the most promising new antithrombotics currently in late-stage clinical development and their potential role in the context of ACS management. [Copyright &y& Elsevier]

Objectives: The aim of this study was to evaluate the relative impact of spontaneously occurring and periprocedural myocardial infarction (MI) on survival after percutaneous coronary intervention (PCI). Background: The clinical significance of periprocedural MI after PCI remains uncertain. Methods: Outcomes during a 1-year follow-up were evaluated among 7,773 patients enrolled in the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial with a non–ST-segment elevation acute coronary syndrome in whom PCI was performed. Results: Periprocedural MI developed in 466 patients (6.0%), and spontaneous MI unrelated to PCI subsequently developed in 200 patients (2.6%). Patients developing spontaneous and periprocedural MI compared with those patients without MI had significantly greater unadjusted rates of mortality at 30 days (5.0% vs. 3.2% vs. 0.8%, respectively, p < 0.0001) and at 1 year (16.0% vs. 6.0% vs. 2.6%, respectively, p < 0.0001). In a time-updated multivariable analysis, after adjusting for differences in baseline and procedural characteristics between the groups, we found that spontaneous MI was a powerful independent predictor of subsequent mortality (hazard ratio: 7.49, 95% confidence interval: 4.95 to 11.33, p < 0.0001), whereas periprocedural MI was not a significant predictor of mortality (hazard ratio: 1.30, 95% confidence interval: 0.85 to 1.98, p = 0.22). Conclusions: Among patients with acute coronary syndrome undergoing PCI, the spontaneous development of an MI unrelated to PCI is a powerful predictor of subsequent mortality. In contrast, periprocedural MI is a marker of baseline risk, atherosclerosis burden, and procedural complexity but in most cases does not have independent prognostic significance. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158) [Copyright &y& Elsevier]

Objectives: We aimed to evaluate the efficacy and safety of ranolazine in a larger and more diverse group of patients with angina than previously studied. Background: Ranolazine is an antianginal shown to reduce angina and improve exercise performance in selected patients with early-positive exercise testing and those with frequent angina. Methods: We investigated the antianginal effects of ranolazine in the subgroup of patients with prior chronic angina (n = 3,565, 54%) enrolled in the randomized, double-blind, placebo-controlled MERLIN–TIMI (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) 36 trial of patients with acute coronary syndrome. Follow-up was a median of 350 days. Results: Patients with prior angina received evidence-based therapy (95% aspirin, 78% statins, 89% beta-blockers, average 2.9 antianginal agents). The primary end point (cardiovascular death, myocardial infarction, recurrent ischemia) was less frequent with ranolazine (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.75 to 0.97; p = 0.017), due entirely to a significant reduction in recurrent ischemia (HR: 0.78; 95% CI: 0.67 to 0.91; p = 0.002). Ranolazine also reduced worsening angina (HR: 0.77; 95% CI: 0.59 to 1.00; p = 0.048) and intensification of antianginal therapy (HR: 0.77; 95% CI: 0.64 to 0.92, p = 0.005). Exercise duration at 8 months was greater with ranolazine (514 s vs. 482 s, p = 0.002). Cardiovascular death or myocardial infarction did not differ between treatment groups (HR: 0.97; 95% CI: 0.80 to 1.16; p = 0.71). Symptomatic documented arrhythmias (2.9% vs. 2.9%, p = 0.92) and total mortality (6.2% vs. 6.4%, p = 0.96) were similar with ranolazine or placebo. Conclusions: In this largest study of ranolazine in patients with established coronary artery disease, ranolazine was effective in reducing angina with favorable safety in a substantially broader group of patients with angina than previously studied. (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes; NCT00099788) [Copyright &y& Elsevier]

Objectives: This study was designed to determine whether imaging myocardial edema would identify acute myocardial ischemia before irreversible injury takes place. Background: Early identification of acute myocardial ischemia is a diagnostic challenge. Methods: We studied 15 dogs with serial T2-weighted and cine imaging at baseline, during transient coronary occlusion of up to 35 min, and after reperfusion in a 1.5-T magnetic resonance imaging system. Late gadolinium enhancement and troponin measurements were used to assess for the presence of irreversible injury. Myocardial water content was measured to assess myocardial edema. Results: We consistently observed a transmural area of high T2 signal intensity matching areas with new onset regional akinesia 28 ± 4 min after experimental coronary artery occlusion. At this time, the contrast-to-noise ratio between the ischemic and remote myocardium had significantly increased from 1.0 ± 2.0 to 12.8 ± 9.6 (p < 0.003), which further increased after reperfusion to 15.8 ± 10.3 (p < 0.004 compared with baseline). Neither myocardial late gadolinium enhancement nor troponin elevation were noted at this time window. Myocardial water content of the ischemic segments was consistently higher (68.9 ± 2% vs. 67.0 ± 2%; p < 0.004) than in remote segments and the difference correlated significantly to the contrast-to-noise ratio in T2 images (p < 0.04). Conclusions: We provide the first evidence that T2-weighted cardiovascular magnetic resonance imaging of edema detects acute ischemic myocyte injury before the onset of irreversible injury. T2-weighted cardiovascular magnetic resonance imaging may serve as a very useful diagnostic marker in clinical settings such as unstable angina or evolving infarction. [Copyright &y& Elsevier]

Objectives: We sought to evaluate the utility of T-wave alternans (TWA) assessment in the immediate post-exercise period to identify and validate cutpoints for the modified moving average (MMA) assessment method. Background: The presence of TWA is associated with an increased risk of cardiovascular death (CVD). The immediate post-exercise period, where increased physiologic stress and minimal surface artifact coexist, appears ideal to implement the MMA method. Methods: A test (n = 322) and validation cohort (n = 681) provided 1,003 patients with coronary artery disease (CAD). We assessed TWA immediately after exercise. The outcomes, CVD and mortality, were adjudicated independent of the TWA results. Results: During 48 months of follow-up 85 deaths, 54 categorized as CVD (64%), were observed. A linear relationship between the magnitude of TWA and the risk of CVD was identified. As a continuous measure TWA voltage was equivalent to ejection fraction in predicting the risk of CVD. To facilitate clinical application, a sensitive, modest predictive accuracy (20 μV) and a specific, greater predictive accuracy MMA cutpoint (60 μV) were identified and validated. Each cutpoint was associated with a 2.5-fold greater risk of CVD, independent of other important variables, including ejection fraction. Conclusions: Post-exercise assessment of TWA using the MMA method is a strong, independent predictor of risk in patients with CAD. The 20-μV cutpoint (87% sensitivity) appears to be most suitable in higher-risk patients, whereas the 60-μV cutpoint (95% specificity) appears more appropriate when TWA is used as a single screening test in those at lower risk. (Assessment of Noninvasive Methods to Identify Patients at Risk of Serious Arrhythmias After a Heart Attack; NCT00399503) [Copyright &y& Elsevier]

Objectives: We sought to examine the combined effect of hospital and physician volume of primary percutaneous coronary intervention (PCI) on in-hospital mortality. Background: An inverse relationship between volume and outcome has been observed for both hospitals and physicians after primary PCI for acute myocardial infarction. Methods: Using the New York State PCI registry, we examined yearly hospital volume, physician volume, and risk-adjusted mortality in 7,321 patients undergoing primary PCI for acute myocardial infarction. Risk-adjusted mortality rates for high-volume hospitals (>50 cases/year) and high-volume physicians (>10 cases/year) were compared with their respective low-volume counterparts. Results: Primary PCI by high-volume hospitals (odds ratio [OR]: 0.58; 95% confidence interval [CI]: 0.38 to 0.88) and high-volume physicians (OR: 0.66; 95% CI: 0.48 to 0.92) was associated with lower odds of mortality. Furthermore, there was a significant interaction between hospital and physician volume on adjusted mortality (p = 0.02). Although unadjusted mortality was lower when primary PCI was performed by high-volume physicians in high-volume hospitals compared with low-volume physicians in low-volume hospitals (3.2% vs. 6.7%, p = 0.03), the risk-adjusted mortality rate was not statistically significant (3.8% vs. 8.4%, p = 0.09). In low-volume hospitals, the average risk-adjusted mortality rate for low-volume physicians was 8.4% versus 4.8% for high-volume physicians (OR: 1.44; 95% CI: 0.68 to 3.03). However, in high-volume hospitals, the risk-adjusted mortality rate for high-volume physicians was 3.8% versus 6.5% for low-volume physicians (OR: 0.58; 95% CI: 0.39 to 0.86). Conclusions: During primary PCI, physician experience significantly modifies the hospital volume-outcome relationship. Therefore, policymakers need to consider physician experience when developing strategies to improve access to primary PCI. [Copyright &y& Elsevier]

Acute heart failure syndromes (AHFS) have emerged as a leading public health problem worldwide, accounting for a substantial number of hospitalizations and a high utilization of resources. Although in-hospital mortality rates are relatively low, patients with AHFS have very high early after-discharge mortality and rehospitalization rates. The majority of patients admitted with AHFS have coronary artery disease (CAD), which independently has an adverse impact on prognosis. The initial in-hospital and after-discharge management of AHFS may be dependent on clinical presentation: AHFS in patients with underlying CAD or acute coronary syndromes (ACS) complicated by heart failure. In addition, the extent and severity of CAD and the presence of ischemia and/or stunned/hibernating myocardium should be assessed for optimal management. Although the overall management of AHFS with CAD may be similar to that in patients with ACS complicated by heart failure, for which specific guidelines exist, management of the former is less well defined. Prospective studies of the assessment and treatment of CAD in patients with AHFS are urgently needed. [Copyright &y& Elsevier]

Objectives: We studied whether an increase in adenosine dose overcomes caffeine antagonism on adenosine-mediated coronary vasodilation. Background: Caffeine is a competitive antagonist at the adenosine receptors, but it is unclear whether caffeine in coffee alters the actions of exogenous adenosine, and whether the antagonism can be surmounted by increasing the adenosine dose. Methods: Myocardial perfusion scintigraphy (MPS) was used to assess adenosine-induced hyperemia in 30 patients before (baseline) and after coffee ingestion (caffeine). At baseline, patients received 140 μg/kg/min of adenosine combined with low-level exercise. For the caffeine study, 12 patients received 140 μg/kg/min of adenosine (standard) and 18 patients received 210 μg/kg/min (high dose) after caffeine intake (200 mg). Myocardial perfusion was assessed semiquantitatively and quantitatively, and perfusion defect was characterized according to the presence of reversibility. Results: Caffeine reduced the magnitude of perfusion abnormality induced by standard adenosine as measured by the summed difference score (SDS) (12.0 ± 4.4 at baseline vs. 4.1 ± 2.1 after caffeine, p < 0.001) as well as defect size (18% [3% to 38%] vs. 8% [0% to 22%], p < 0.01), whereas it had no effect on the abnormalities caused by high-dose adenosine (SDS, 7.7 ± 4.0 at baseline vs. 7.8 ± 4.2 after caffeine, p = 0.7). There was good agreement between baseline and caffeine studies for segmental defect category (kappa = 0.72, 95% confidence interval: 0.65 to 0.79) in the high-dose group. An increase in adenosine after caffeine intake was well tolerated. Conclusions: Caffeine in coffee attenuates adenosine-induced coronary hyperemia and, consequently, the detection of perfusion abnormality by adenosine MPS. This can be overcome by increasing the adenosine dose without compromising test tolerability. [Copyright &y& Elsevier]

Objectives: The purpose of this study was to evaluate the role of heart rate reduction with beta-blockers on the risk of cardiovascular events in patients with hypertension. Background: Resting heart rate has been shown to be a risk factor for cardiovascular morbidity and mortality in the general population and in patients with heart disease such as hypertension, myocardial infarction, and heart failure. Conversely, pharmacological reduction of heart rate is beneficial for patients with heart disease. However, the role of pharmacological reduction of heart rate using beta-blockers in preventing cardiovascular events in patients with hypertension is not known. Methods: We conducted a MEDLINE/EMBASE/CENTRAL database search of studies from 1966 to May 2008. We included randomized controlled trials that evaluated beta-blockers as first-line therapy for hypertension with follow-up for at least 1 year and with data on heart rate. We extracted the baseline characteristics, the blood pressure response, heart rate at the baseline and end of trial, and cardiovascular outcomes from each trial. Results: Of 22 randomized controlled trials evaluating beta-blockers for hypertension, 9 studies reported heart rate data. The 9 studies evaluated 34,096 patients taking beta-blockers against 30,139 patients taking other antihypertensive agents and 3,987 patients receiving placebo. Paradoxically, a lower heart rate (as attained in the beta-blocker group at study end) was associated with a greater risk for the end points of all-cause mortality (r = −0.51; p < 0.0001), cardiovascular mortality (r = −0.61; p < 0.0001), myocardial infarction (r = −0.85; p < 0.0001), stroke (r = −0.20; p = 0.06), or heart failure (r = −0.64; p < 0.0001). The same was true when the heart rate difference between the 2 treatment modalities at the end of the study was compared with the relative risk reduction for cardiovascular events. Conclusions: In contrast to patients with myocardial infarction and heart failure, beta-blocker–associated reduction in heart rate increased the risk of cardiovascular events and death for hypertensive patients. [Copyright &y& Elsevier]

Objectives: Transplant coronary artery disease (TCAD) limits long-term survival after heart transplantation (HTX). We hypothesized that contrast-enhanced magnetic resonance imaging (CE-MRI) detects chronic TCAD-related myocardial infarctions (MIs), even in patients with angiographically classified mild TCAD. Background: Coronary angiography underestimates the TCAD-degree, subsequently missing occluded small coronary arteries and resulting MI. CE-MRI as a noninvasive imaging technique identifies infarct-typical MI and myocardial fibrosis. Methods: CE-MRI (gadolinium: 0.2 mmol/kg/bw) was performed in 53 HTX patients on a 1.5-T MRI scanner (Philips, Best, the Netherlands). Infarct-typical CE-MRI areas were classified as: I = ≤25%, II = 25% to 50%, III = 50% to 75% and IV = ≥75%. Infarct-atypical forms were divided into diffuse, spotted, intramural, and infero-septal. Coronary angiography results were reviewed qualitatively with the TCAD score (TCAD I = mild evidence; II = 30% to 75%, III = ≥75% stenosis). Groups were compared with analysis of variance (statistically significant p values ≤0.05). Results: Infarct-typical CE-MRI was already present in TCAD I + II, increased significantly between groups (I = 23%, II = 33%, III = 84%, p < 0.05), and involved only single coronary territories in TCAD I but multiple vessels in TCAD II + III. Infarct-atypical CE-MRI was equally distributed across all TCAD stages (I = 50% vs. II = 58% vs. III = 42%, p = NS) without relation to a coronary territory. Patients with only infarct-atypical CE-MRI were associated with significantly better left ventricular function compared with patients with infarct-typical or combined CE-MRI patterns (ejection fraction = 66 ± 6% vs. 45 ± 16% or 60 ± 13%; end-diastolic volume = 139 ± 32 ml vs. 148 ± 27 ml or 164 ± 43 ml; end-systolic volume = 47 ± 15 ml vs. 81 ± 27 ml or 69 ± 38 ml, p ≤ 0.05). Conclusions: CE-MRI allows identification of silent MI in apparently event-free HTX patients and is able to disclose myocardial fibrosis already in patients with absent or mild angiographic TCAD. CE-MRI might be helpful to establish an earlier TCAD diagnosis and to intensify medical treatment. Future studies are necessary to test prognostic implications associated with CE-MRI patterns. [Copyright &y& Elsevier]

Objectives: The aim of this study was to evaluate the correlation of point-of-care measurement of platelet inhibition with clinical outcome in patients undergoing percutaneous coronary intervention (PCI). Background: Individual variability of clopidogrel response might influence results of PCI. Methods: A total of 160 patients receiving clopidogrel before PCI were prospectively enrolled. Platelet reactivity was measured by the VerifyNow P2Y12 assay (Accumetrics Inc., San Diego, California). Primary end point was 30-day occurrence of major adverse cardiac events (MACE) according to quartile distribution of P2Y12 reaction units (PRU). Results: Primary end point occurred more frequently in patients with pre-procedural PRU levels in the fourth quartile versus those in the lowest quartile (20% vs. 3%; p = 0.034), and it was entirely due to periprocedural myocardial infarction (MI). Mean PRU absolute levels were higher in patients with periprocedural MI (258 ± 53 vs. 219 ± 69 in patients without; p = 0.030). On multivariable analysis pre-PCI PRU levels in the fourth quartile were associated with 6-fold increased risk of 30-day MACE (odds ratio: 6.1; 95% confidence interval: 1.1 to 18.3, p = 0.033). By receiver-operating characteristic curve analysis, the optimal cut-off for the primary end point was a pre-PCI PRU value ≥240 (area under the curve: 0.69; 95% confidence interval: 0.56 to 0.81, p = 0.016). Conclusions: This study indicates that high pre-PCI platelet reactivity might predict 30-day events. Use of a rapid point-of-care assay for monitoring residual platelet reactivity after clopidogrel administration might help identify patients in whom individualized antiplatelet strategies might be indicated with coronary intervention. [Copyright &y& Elsevier]

Objectives: Because excess adiposity is one of the most important determinants of adipokines and inflammatory factors associated with coronary plaque rupture, we hypothesized that obesity was associated with myocardial infarction at earlier ages. Background: The developing obesity pandemic of the past 50 years has gained considerable attention as a major public health threat. Methods: The CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) registry was a voluntary observational data collection and quality improvement initiative that began in November 2001, with retrospective data collection from January 2001 to January 2007. The CRUSADE initiative included high-risk patients with unstable angina and non–ST-segment elevation myocardial infarction (NSTEMI). We retrospectively examined, among 189,065 patients with acute coronary syndrome (between January 2001 and September 2006) in the CRUSADE initiative, the relationship of body mass index (BMI) with patient age of first NSTEMI. Results: A total of 111,847 patients with NSTEMI were included in the final analysis. There was a strong, inverse linear relationship between BMI and earlier age of first NSTEMI. The mean patient ages (± SD) of first NSTEMI were 74.6 ± 14.3 years and 58.7 ± 12.5 years for the leanest (BMI ≤18.5 kg/m2) and most obese (BMI >40.0 kg/m2) cohorts, respectively (p < 0.0001). After adjustment for baseline demographic data, cardiac risk factors, and medications, the age of first NSTEMI occurred 3.5, 6.8, 9.4, and 12.0 years earlier with ascending levels of adiposity (BMI 25.1 to 30.0, 30.1 to 35.0, 35.1 to 40.0, and >40.0 kg/m2, respectively; referent 18.6 to 25.0 kg/m2) (p < 0.0001 for each estimate). Conclusions: Excess adiposity is strongly related to first NSTEMI occurring prematurely. [Copyright &y& Elsevier]

Objectives: The aim of this study was to compare the effectiveness of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM). Background: Drug-eluting stent implantation significantly improved the angiographic and clinical outcomes compared with bare-metal stent implantation in diabetic patients. However, comparison of SES with PES in diabetic patients has not been sufficiently evaluated. Methods: This prospective, multicenter, randomized study compared SES (n = 200) and PES implantation (n = 200) for diabetic patients (n = 400). The primary end point was in-segment restenosis at 6 months according to intention-to-treat principle. Results: The 2 groups had similar baseline clinical and angiographic characteristics. Six-month in-stent (3.4% vs. 18.2%, p < 0.001) and in-segment restenosis (4.0% vs. 20.8%, p < 0.001) and 9-month target lesion revascularization (2.0% vs. 7.5%, p = 0.017) were significantly lower in the SES versus the PES group. The incidence of death (0% in SES vs. 0.5% in PES, p = 0.999) or myocardial infarction (0.5% in SES vs. 0.5% in PES, p = 0.999) at 9-month follow-up was not statistically different between the 2 groups. Major adverse cardiac events including death, myocardial infarction, and target lesion revascularization at 9 months (2.0% vs. 8.0%, p = 0.010) were lower in the SES versus the PES group. Conclusions: Sirolimus-eluting stent implantation is superior in reducing angiographic restenosis and improving 9-month clinical outcomes in patients with DM and coronary artery disease compared with PES implantation. [Copyright &y& Elsevier]

Objectives: The aim of the study was to assess the relationship between baseline and post-procedural Thrombolysis In Myocardial Infarction (TIMI) epicardial blood flow grade and mortality in patients with acute coronary syndromes (ACS) who were treated with early percutaneous coronary intervention (PCI). Background: The impact of baseline and post-procedural TIMI flow grade on mortality in patients with ACS has been insufficiently studied. Methods: This prospective registry included 10,455 patients with ACS who underwent coronary angiography and PCI: 2,853 patients with ST-segment elevation acute myocardial infarction, 3,060 patients with non–ST-segment elevation acute myocardial infarction, and 4,542 patients with unstable angina. The primary outcome was 1-year mortality. Results: At 1 year, there were 976 deaths: 117 deaths among patients with TIMI flow grade 0 to 1, 105 deaths among patients with TIMI flow grade 2, and 754 deaths among patients with TIMI flow grade 3 (Kaplan-Meier estimates of mortality 28.3%, 18.4%, and 8.0%, respectively; odds ratio: 1.66, 95% confidence interval [CI]: 1.57 to 1.76, p < 0.001, for TIMI flow grade 0 to 1 vs. TIMI flow grade 2 and odds ratio: 2.51, 95% CI: 2.06 to 3.06, p < 0.001, for TIMI flow grade 2 vs. TIMI flow grade 3). By using the Cox proportional hazards survival model, we identified post-PCI TIMI flow grade (hazard ratio: 0.60, 95% CI: 0.52 to 0.70; p < 0.001, for 1 grade increase in TIMI flow grade) but not baseline TIMI grade (hazard ratio: 1.08, 95% CI: 0.96 to 1.22; p = 0.20, for 1 grade increase in TIMI flow grade) as an independent correlate of 1-year mortality. Conclusions: In patients with ACS treated with early PCI, post-procedural TIMI flow grade but not baseline TIMI flow grade is an independent correlate of 1-year mortality. [Copyright &y& Elsevier]

Antianginal and lipid-lowering medications may modify the results of stress myocardial perfusion imaging. Several studies have shown the beneficial potential of these agents in suppressing myocardial ischemia in patients with known coronary artery disease. The effects of nitrates, calcium-channel blockers, beta-blockers, and statins on myocardial perfusion imaging are likely attributable to changes in myocardial blood flow and myocardial oxygen supply–demand ratio. This comprehensive review examines relevant experimental and clinical published data. Technical issues in image interpretation specific to myocardial perfusion imaging and implications of use of cardiac medications to results of myocardial perfusion imaging are discussed. [Copyright &y& Elsevier]

Objectives: This study sought to evaluate the day–night variation of acute myocardial infarction (MI) in patients with obstructive sleep apnea (OSA). Background: Obstructive sleep apnea has a high prevalence and is characterized by acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of MI during the night. Methods: We prospectively studied 92 patients with MI for which the time of onset of chest pain was clearly identified. The presence of OSA was determined by overnight polysomnography. Results: For patients with and without OSA, we compared the frequency of MI during different intervals of the day based on the onset time of chest pain. The groups had similar prevalence of comorbidities. Myocardial infarction occurred between 12 am and 6 am in 32% of OSA patients and 7% of non-OSA patients (p = 0.01). The odds of having OSA in those patients whose MI occurred between 12 am and 6 am was 6-fold higher than in the remaining 18 h of the day (95% confidence interval: 1.3 to 27.3, p = 0.01). Of all patients having an MI between 12 am and 6 am, 91% had OSA. Conclusions: The diurnal variation in the onset of MI in OSA patients is strikingly different from the diurnal variation in non-OSA patients. Patients with nocturnal onset of MI have a high likelihood of having OSA. These findings suggest that OSA may be a trigger for MI. Patients having nocturnal onset of MI should be evaluated for OSA, and future research should address the effects of OSA therapy for prevention of nocturnal cardiac events. [Copyright &y& Elsevier]

Objectives: We studied the relation between presence and severity of microvascular obstruction (MO), measured by cardiovascular magnetic resonance (CMR) and intracoronary Doppler flow measurements, for assessment of myocardial reperfusion in patients with acute anterior myocardial infarction (MI) treated by primary percutaneous coronary intervention (PCI). Background: Cardiovascular magnetic resonance has been used to detect and quantify MO in patients after acute MI but has never been compared with coronary blood flow velocity patterns. Methods: Twenty-seven patients with first anterior ST-segment elevation MI successfully treated with primary PCI were included. Coronary blood flow velocity was measured during recatheterization 4 to 8 days after primary PCI. These measurements were related to MO determined by late gadolinium-enhanced (LGE) CMR performed the day before recatheterization. Results: Early systolic retrograde flow was observed in 0 of 8 patients without MO on LGE CMR and in 10 (53%) of 19 patients with MO (p = 0.01). The extent of MO correlated with the diastolic-systolic velocity ratio (r = 0.44; p = 0.02), diastolic deceleration time (r = −0.61; p = 0.001), diastolic deceleration rate (r = 0.75; p < 0.0001), and coronary flow velocity reserve of the infarct-related artery (r = −0.44; p = 0.02). Furthermore, multivariate regression analyses, including extent of MO, infarct size, and transmural necrosis on LGE CMR, revealed that extent of MO was the only independent factor related to early systolic retrograde flow and diastolic deceleration rate. Conclusions: Assessment of microvascular injury by LGE CMR corresponds well to evaluation by intracoronary Doppler flow measurements. By means of CMR, quantification of myocardial function, infarct size, and microvascular injury can accurately be performed with a single noninvasive technique in patients with acute MI. [Copyright &y& Elsevier]

Objectives: We sought to evaluate the association between physical activity levels and the clinical outcome at presentation, as well as the 30-day prognosis of hospitalized patients with acute coronary syndromes (ACS). Background: Regular physical activity has been associated with decreased risk of coronary heart disease. However, less is known about the effects of life-long physical activity on ACS prognosis. Methods: From October 2003 to September 2004, a sample of 6 hospitals located in urban and rural Greek regions were selected, and almost all of their ACS patients were enrolled into the study (2,172 patients were included in the study; 76% men and 24% women). Logistic regression models were applied to evaluate the effect of physical activity status (as assessed using the International Physical Activity Questionnaire) on in-hospital mortality and the 30-day outcome of cardiovascular events (death or rehospitalization due to cardiovascular disease). Results: An inverse association was observed between the level of physical activity and troponin I levels at presentation (p = 0.01). Moreover, after taking into account various potential confounders, physical activity was associated with a 0.56-fold (95% confidence interval [CI] 0.32 to 0.90) lower odds of in-hospital mortality and a 0.80-fold (95% CI 0.50 to 0.99) lower odds of cardiovascular events within the first month after discharge. Conclusion: In conclusion, physical activity is associated with a reduced severity of ACS, reduced in-hospital mortality rates, and improved short-term prognosis. [Copyright &y& Elsevier]

Objectives: Our purpose was to evaluate the long-term use of sirolimus-eluting stents (SES) and bare-metal stents (BMS) in patients with complex coronary artery lesions. Background: Although the use of SES has proved to be effective in patients with simple coronary artery lesions, there are limited data of the long-term outcome of patients with complex coronary artery lesions. Methods: We randomly assigned 322 patients with total coronary occlusions or lesions located in bifurcations, ostial, or angulated segments of the coronary arteries to have SES or BMS implanted. Results: At 3 years, major adverse cardiac events had occurred in 20 patients (12%) in the SES group and in 59 patients (38%) in the BMS group (p < 0.001). Four versus 2 patients suffered a cardiac death (p = NS), and 5 versus 1 died of a noncardiac disease (p = NS) in the SES versus the BMS group. Six patients in the SES group versus 15 patients in the BMS group suffered a myocardial infarction (p < 0.05) during the 3-year observation period, and target lesion revascularization was performed in 8 patients (4.9%) versus 53 patients (33.8%), respectively (p < 0.001); of these, 4 in the SES versus 7 in the BMS group were performed between 1 and 3 years after the index treatment (p = NS). According to revised definitions, stent thrombosis occurred in 5 patients (3.1%) in the SES group and in 7 patients (4.4%) in the BMS group (p = NS); very late stent thrombosis was observed in 4 versus 1 patient. Conclusions: A continued benefit was observed up to 3 years after implantation of SES in patients with complex coronary artery lesions. The rate of late adverse events was similar in the 2 groups, and stent thromboses occurred rarely after 1 year. (Sirolimus Eluting Stents in Complex Coronary Lesions [SCANDSTENT]; NCT00151658) [Copyright &y& Elsevier]

Objectives: The aim of this post hoc analysis from the TNT (Treating to New Targets) trial is to determine whether patients with previous coronary artery bypass grafting (CABG) surgery achieved clinical benefit from intensive low-density lipoprotein (LDL)-cholesterol lowering. Background: The development and progression of atherosclerosis is accelerated in coronary venous bypass grafts. Methods: A total of 10,001 patients with documented coronary disease, including 4,654 with previous CABG, were randomized to atorvastatin 80 or 10 mg/day and were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event (cardiac death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke). Results: A first major cardiovascular event occurred in 11.4% of the patients with prior CABG and 8.5% of those without prior CABG (p < 0.001). In CABG patients, mean LDL-cholesterol levels at study end were 79 mg/dl in the 80-mg arm and 101 mg/dl in the 10-mg arm, and the primary event rate was 9.7% in the 80-mg arm and 13.0% in the 10-mg arm (hazard ratio 0.73, 95% confidence interval 0.62 to 0.87, p = 0.0004). Repeat revascularization during follow-up, either CABG or percutaneous coronary intervention, was performed in 11.3% of the CABG patients in the 80-mg arm and 15.9% in the 10-mg arm (hazard ratio 0.70, 95% confidence interval 0.60 to 0.82, p < 0.0001). Conclusions: Intensive LDL-cholesterol lowering to a mean of 79 mg/dl with atorvastatin 80 mg/day in patients with previous CABG reduces major cardiovascular events by 27% and the need for repeat coronary revascularization by 30%, compared with less intensive cholesterol-lowering to a mean of 101 mg/dl with atorvastatin 10 mg/day. (A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [TNT]; NCT00327691) [Copyright &y& Elsevier]

Objectives: We investigated whether the loss of function CYP2C19 681G>A *2 polymorphism is associated with high (>14%) residual platelet aggregation (RPA) on clopidogrel and whether high on-clopidogrel RPA impacts clinical outcome after elective coronary stent placement. Background: The cytochrome P450 (CYP)–dependent conversion of clopidogrel to its active metabolite may contribute to the variability in antiplatelet effect of clopidogrel. Methods: The study included 797 consecutive patients undergoing percutaneous coronary intervention, who were followed-up for 1 year. Adenosine-diphosphate–induced (5 μmol/l) RPA was assessed after a 600-mg loading dose and after the first 75-mg maintenance dose of clopidogrel before discharge. CYP2C19 genotype was analyzed by real-time polymerase chain reaction. Results: Of the patients included, 552 (69.3%) were CYP2C19 wild-type homozygotes (*1/*1) and 245 (30.7%) carried at least one *2 allele. Residual platelet aggregation at baseline did not differ significantly between genotypes. On clopidogrel, RPA was significantly (p < 0.001) higher in *2 carriers than in wild-type homozygotes (23.0% [interquartile range (IQR) 8.0% to 38.0%] vs. 11.0% [IQR 3.0% to 28.0%] after loading; 11.0% [IQR 5.0% to 22.0%] vs. 7.0% [IQR 3.0% to 14.0%] at pre-discharge). Between *2 carriers and wild-type homozygotes, we found significant (p < 0.001) differences in the proportion of patients with RPA >14%, both after loading (62.4% vs. 43.4%) and at pre-discharge (41.3% vs. 22.5%). Residual platelet aggregation >14% at pre-discharge incurred a 3.0-fold increase (95% confidence interval 1.4 to 6.8; p = 0.004) in the 1-year incidence of death and myocardial infarction. Conclusions: Patients carrying at least one CYP2C19*2 allele are more prone to high-on clopidogrel platelet reactivity, which is associated with poor clinical outcome after coronary stent placement (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236). [Copyright &y& Elsevier]

Perioperative myocardial infarctions are the predominant cause of morbidity and mortality in patients undergoing noncardiac surgery. The pathophysiology of perioperative myocardial infarction is complex. Prolonged myocardial ischemia due to the stress of surgery in the presence of a hemodynamically significant coronary lesion, leading to subendocardial ischemia, and acute coronary artery occlusion after plaque rupture and thrombus formation contribute equally to these devastating events. Perioperative management aims at optimizing the patient''s condition by identification and modification of underlying cardiac risk factors and diseases. During recent decades there has been a shift from the assessment and treatment of the underlying culprit coronary lesion toward a systemic medical therapy aiming at prevention of myocardial oxygen supply demand mismatch and coronary plaque stabilization. Beta-blockers, statins, and aspirin are widely used in this setting. The role of prophylactic coronary revascularization has been restricted to the same indications as the nonoperative setting. Therefore pre-operative cardiac testing is recommended only if test results will change perioperative management. In addition to the limited perioperative period, physicians should benefit from this opportunity to initiate lifestyle changes and medical therapy to lessen the impact of cardiac risk factors, as patients should live long enough after the operation to enjoy the benefits of surgery. [Copyright &y& Elsevier]

Objectives: African Americans have a high incidence of heart failure (HF). Limited retrospective observational subgroup analyses of patients with left ventricular systolic dysfunction (LVSD) suggest marginal benefit of angiotensin-converting enzyme inhibitors in the prevention of HF hospitalizations or total mortality in African Americans. Background: Very few data exist concerning the effectiveness of angiotensin receptor blockers in this population. Methods: Baseline characteristics, treatments, and outcomes of patients from the U.S. (3,390 white and 340 African-American patients) in the VALIANT (VALsartan In Acute myocardial iNfarcTion) trial were compared. This trial included patients with an acute myocardial infarction (MI) after initial stabilization and documented LVSD and/or HF. Patients were randomly assigned to receive treatment with valsartan, captopril, or the combination; follow-up continued for up to 3 years (median 24.7 months). Results: African Americans had more coronary risk factors, more markers of poor outcome after MI, and were less likely to be revascularized when compared with white patients. After adjusting for treatment assignment, baseline characteristics, and post-infarction parameters, no difference was found in the 3-year rate of all-cause mortality, cardiovascular mortality, rehospitalization for HF, recurrent MI, or stroke between the 2 groups. Conclusions: African Americans sustaining an acute MI with LVSD and/or HF had similar clinical outcomes compared with white Americans. Valsartan, captopril, or the combination had comparable effects on cardiovascular morbidity and mortality in African Americans and white Americans. [Copyright &y& Elsevier]

Objectives: Our aim was to assess the prognostic value of midregional proatrial natriuretic peptide (MR-proANP) in patients after acute myocardial infarction (AMI). Background: Multimarker strategies may assist risk stratification after AMI. Midregional proatrial natriuretic peptide is a newly described stable fragment of N-terminal proatrial natriuretic peptide. We compared the prognostic value of MR-proANP and an established marker, N-terminal pro-B-type natriuretic peptide (NT-proBNP), after AMI. Methods: We recruited 983 consecutive post-AMI patients (720 men, median age 65 [range 24 to 95] years) in a prospective study with follow-up over 343 (range 0 to 764) days. Results: Plasma MR-proANP was raised in patients who died (n = 101) compared with that seen in survivors (median 310 [range 48 to 1,150] pmol/l vs. 108 [range 4.9 to 1,210] pmol/l, p < 0.0001). Using Cox modeling, log10MR-proANP (hazard ratio 3.87) and log10NT-proBNP (hazard ratio 3.25) were significant independent predictors of death. In patients stratified by NT-proBNP in the highest quartile (>∼5,900 pmol/l), MR-proANP in the top quartile (∼330 pmol/l) was associated with poorer outcome (p < 0.0001). Findings were similar for heart failure as an individual end point. However, neither marker predicted recurrent AMI. Conclusions: The A- and B-type natriuretic systems are activated after AMI. Midregional proatrial natriuretic peptide is a powerful predictor of adverse outcome, especially in those with an elevated NT-proBNP. Midregional proatrial natriuretic peptide may represent a clinically useful marker of prognosis after an AMI as part of a multimarker strategy targeting the natriuretic neurohormonal pathway. [Copyright &y& Elsevier]

Cardiac rehabilitation is increasingly recognized as an integral component of the continuum of care for patients with cardiovascular disease. Its application is a class I recommendation in most contemporary cardiovascular clinical practice guidelines. Despite the documentation of substantial morbidity and mortality benefits, cardiac rehabilitation services are vastly underutilized. The core components of cardiac rehabilitation have been detailedly delineated. Implementation of newly available performance measures offers the potential to enhance referral to, enrollment in, and completion of cardiac rehabilitation. [Copyright &y& Elsevier]

Objectives: This study was designed to compare the long-term outcomes of patients with peripheral arterial disease (PAD) with a risk factor matched population of coronary artery disease (CAD) patients, but without PAD. Background: The PAD is considered to be a risk factor for adverse late outcome. Methods: A total of 2,730 PAD patients undergoing vascular surgery were categorized into groups: 1) carotid endarterectomy (n = 560); 2) elective abdominal aortic surgery (AAA) (n = 923); 3) acute AAA surgery (r-AAA) (n = 200), and 4) lower limb reconstruction procedures (n = 1,047). All patients were matched using the propensity score, with 2,730 CAD patients who underwent coronary angioplasty. Survival status of all patients was obtained. In addition, the cause of death and complications after surgery in PAD patients were noted. The Kaplan-Meier method was used to compare survival between the matched PAD and CAD population and the different operation groups. Prognostic risk factors and perioperative complications were identified with the Cox proportional hazards regression model. Results: The PAD patients had a worse long-term prognosis (hazard ratio 2.40, 95% confidence interval 2.18 to 2.65) and received less medication (beta-blockers, statins, angiotensin-converting enzyme inhibitors, aspirin, nitrates, and calcium antagonists) than CAD patients did (p < 0.001). Cerebro-cardiovascular complications were the major cause of long-term death (46%). Importantly, no significant difference in long-term survival was observed between the AAA and lower limb reconstruction groups (log rank p = 0.70). After vascular surgery, perioperative cardiac complications were associated with long-term cardiac death, and noncardiac complications were associated with all-cause death. Conclusions: Long-term prognosis of vascular surgery patients is significantly worse than for patients with CAD. The vascular surgery patients receive less cardiac medication than CAD patients do, and cerebro-cardiovascular events are the major cause of late death. [Copyright &y& Elsevier]

Objectives: The aim was to compare safety and effectiveness of the CoStar drug-eluting stent (DES) (Conor MedSystems, Menlo Park, California) with those of the Taxus DES (Boston Scientific, Maple Grove, Minnesota) in de novo single- and multivessel percutaneous coronary intervention (PCI). Background: Paclitaxel elution from a stent coated with biostable polymer (Taxus) reduces restenosis after PCI. The CoStar DES is a novel stent with laser-cut reservoirs containing bioresorable polymer loaded to elute 10 μg paclitaxel/30 days. Methods: Patients undergoing PCI for a single target lesion per vessel in up to 3 native epicardial vessels were randomly assigned 3:2 to CoStar or Taxus. Primary end point was 8-month major adverse cardiac events (MACE), defined as adjudicated death, myocardial infarction (MI), or clinically driven target vessel revascularization (TVR). Protocol-specified 9-month angiographic follow-up included 457 vessels in 286 patients. Results: Of the 1,700 patients enrolled, 1,675 (98.5%) were evaluable (CoStar = 989; Taxus = 686), including 1,330 (79%) single-vessel and 345 (21%) multivessel PCI. The MACE rate at 8 months was 11.0% for CoStar versus 6.9% for Taxus (p < 0.005), including adjudicated death (0.5% vs. 0.7%, respectively), MI (3.4% vs. 2.4%, respectively), and TVR (8.1% vs. 4.3%, respectively). Per-vessel 9-month in-segment late loss was 0.49 mm with CoStar and 0.18 mm with Taxus (p < 0.0001). Findings were consistent across pre-specified subgroups. Conclusions: The CoStar DES is not noninferior to the Taxus DES based on per-patient clinical and per-vessel angiographic analyses. The relative benefit of Taxus is primarily attributable to reduction in TVR. Follow-up to 9 months showed no apparent difference in death, MI, or stent thrombosis rates. [Copyright &y& Elsevier]