Search

Chronic exposure to fine particulate matter (PM 2.5 ) is accepted as a causal risk factor for coronary heart disease (CHD). However, most of the evidence for this hypothesis is based upon cohort studies in whites, comprised of either only males or females who live in urban areas. It is possible that many estimates of the effect of chronic exposure to PM 2.5 on risk for CHD do not generalize to more diverse samples., Methods: Therefore, we estimated the relationship between chronic exposure to PM 2.5 and risk for CHD in among participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort who were free from CHD at baseline (n=17,126). REGARDS is a sample of whites and blacks of both genders living across the continental United States. We fit Cox proportional hazards models for time to CHD to estimate the hazard ratio for baseline 1-year mean PM 2.5 exposure, adjusting for environmental variables, demographics, and other risk factors for CHD including the Framingham Risk Score., Results: The hazard ratio (95% CI) for a 2.7-μg/m 3 increase (interquartile range) 1-year mean concentration of PM 2.5 was 0.94 (0.83-1.06) for combined CHD death and nonfatal MI, 1.13 (0.92-1.40) for CHD death, and 0.85 (0.73-0.99) for nonfatal MI. We also did not find evidence that these associations depended upon overall CHD risk factor burden., Conclusions: Our results do not provide strong evidence for an association between PM 2.5 and incident CHD in a heterogeneous cohort, and we conclude that the effects of chronic exposure to fine particulate matter on CHD require further evaluation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The purpose of the study was to determine the long-term prognostic value of normal adenosine stress cardiac magnetic resonance imaging (CMR) in patients referred for evaluation of myocardial ischemia., Methods: We reviewed 300 consecutive patients (age 65 ± 11 years, 74% male) with suspected or known coronary disease and normal wall motion who had undergone adenosine stress CMR negative for ischemia and scar. Most patients were at intermediate risk of coronary artery disease. The end points studied were all causes of mortality and major adverse cardiac events, including cardiac death, myocardial infarction, revascularization, and hospitalization for unstable angina., Results: During a mean follow-up of 5.5 years (mean = 5.4 ± 1.1), 16 patients died because of various causes (cardiac death in 5 patients). Three patients had a nonfatal myocardial infarction, 7 patients were hospitalized for revascularization, and 11 were medically treated for unstable angina. The annual cardiac event rate was 1.3% (0.78% in the first 3 years and 1.9% between the fourth and sixth years). The predictors of major adverse cardiac events in a multivariate analysis model were as follows: advanced age (hazard ratio [HR] 1.15, 95% confidence interval [95% CI] 1.02-1.30), diabetes (HR 17.5, 95% CI 2.2-140), and the habit of smoking (HR 5.9, 95% CI 1.0-35.5). For all causes of mortality, the only predictor was diabetes (HR 11.4, 95% CI 1.76-74.2). Patients with normal stress CMR had an excellent outcome during the 3 years after the study. The cardiac event rate was higher between the fourth and sixth years., Conclusion: Over a 5.5-year period, a low event rate and excellent prognosis occurred in patients with normal adenosine stress CMR. Low- to intermediate-risk patients with a normal CMR are at low risk for subsequent cardiac events., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: While the process of informed consent is designed to transfer knowledge of the risks and benefits of treatment and to engage patients in shared medical decision-making, this is poorly done in routine clinical care. We assessed the impact of a novel informed consent form for percutaneous coronary intervention (PCI) that is more simply written, includes images of the procedure, and embeds individualized estimates of outcomes on multiple domains of successful informed consent and shared decision-making., Methods: We interviewed 590 PCI patients receiving traditional consent documents and 527 patients receiving novel ePRISM consents at 9 US centers and compared patients' perceptions, knowledge transfer, and engagement in medical decision-making. Heterogeneity across sites was assessed and adjusted for using hierarchical models., Results: Site-adjusted analyses revealed more frequent review (72% for ePRISM vs 45% for original consents) and better understanding of the ePRISM consents (ORs=1.8-3.0, depending upon the outcome) with marked heterogeneity across sites (median relative difference [MRD] in the ORs of ePRISM's effect =2-3.2). Patients receiving ePRISM consents better understood the purposes and risks of the procedure (ORs=1.9-3.9, MRDs=1.1-6.2), engaged more in shared decision-making (proportional OR=2.1 [95% CI=1.02-4.4], MRD=2.2) and discussed stent options with their physicians (58% vs. 31%; site-adjusted odds ratio=2.7 [95% CI=1.2, 6.3], MRD=2.6) more often., Conclusions: A personalized consent document improved the process of informed consent and shared decision-making. Marked heterogeneity across hospitals highlights that consent documents are but one aspect of engaging patients in understanding and participating in treatment., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A number of investigative strategies exist for the diagnosis of coronary heart disease (CHD). Despite the widespread availability of noninvasive imaging, invasive angiography is commonly used early in the diagnostic pathway. Consequently, approximately 60% of angiograms reveal no evidence of obstructive coronary disease. Reducing unnecessary angiography has potential financial savings and avoids exposing the patient to unnecessary risk. There are no large-scale comparative effectiveness trials of the different diagnostic strategies recommended in international guidelines and none that have evaluated the safety and efficacy of cardiovascular magnetic resonance., Trial Design: CE-MARC 2 is a prospective, multicenter, 3-arm parallel group, randomized controlled trial of patients with suspected CHD (pretest likelihood 10%-90%) requiring further investigation. A total of 1,200 patients will be randomized on a 2:2:1 basis to receive 3.0-T cardiovascular magnetic resonance-guided care, single-photon emission computed tomography-guided care (according to American College of Cardiology/American Heart Association appropriate-use criteria), or National Institute for Health and Care Excellence guidelines-based management. The primary (efficacy) end point is the occurrence of unnecessary angiography as defined by a normal (>0.8) invasive fractional flow reserve. Safety of each strategy will be assessed by 3-year major adverse cardiovascular event rates. Cost-effectiveness and health-related quality-of-life measures will be performed., Conclusions: The CE-MARC 2 trial will provide comparative efficacy and safety evidence for 3 different strategies of investigating patients with suspected CHD, with the intension of reducing unnecessary invasive angiography rates. Evaluation of these management strategies has the potential to improve patient care, health-related quality of life, and the cost-effectiveness of CHD investigation., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Coronary calcifications are a marker of coronary atherosclerosis. The role of coronary calcium scoring (CS) as part of the initial evaluation of patients with suspected coronary heart disease (CHD) is controversially discussed. The primary goal of this study was to characterize the coronary calcium distribution in this particular patient population. In a second step, we aimed to establish a possible clinical implication using CS for the diagnosis of CHD., Methods: Calcium scoring procedure was performed by either using a multidetector or a dual-source computed tomographic scanner. All patients underwent invasive coronary angiography (ICA) as the current criterion standard for CHD detection. A total of 4,137 (2,780 men, mean age 60.5 ± 12.4 years) consecutive patients were included., Results: Mean CS was 288 ± 446 (range 0-5,252). Overall coronary artery calcifications significantly increased with patients' age. In 2,048 patients (mean CS 101 ± 239, range 0-5252), significant CHD (≥50% stenosis) was excluded by ICA (1,939 patients without calcifications). In remaining 2,089 patients (51%, mean CS 607 ± 821, range 0-5,252), significant CHD was documented leading to intervention in 732 patients. A threshold of zero calcifications (existence of calcified tissue) had the best overall sensitivity and negative predictive value with 99%. Overall specificity with 34% and overall positive predictive value with 24% were rather low., Conclusion: Coronary calcium scoring is able to exclude significant CHD in patients with suspected CHD with a high negative predictive value and, therefore, possibly reduce the number of invasive diagnostic examinations. Because of the low specificity and positive predictive value, CS cannot be used to indicate ICA., (Copyright © 2014 Mosby, Inc. All rights reserved.)

dal-PLAQUE is a placebo-controlled multicenter study designed to assess the effect of dalcetrapib on imaging measures of plaque inflammation and plaque burden. dal-PLAQUE is a multimodality imaging study in the context of the large dal-HEART Program. Decreased high-density lipoprotein cholesterol is linked to increased risk of coronary heart disease (CHD). Dalcetrapib, a compound that increases high-density lipoprotein cholesterol by modulating cholesteryl ester transfer protein, is being studied to assess if it can reduce the progression of atherosclerotic disease and thereby decrease cardiovascular morbidity and mortality. Patients with CHD or CHD-risk equivalents were randomized to receive 600 mg dalcetrapib or placebo daily for 24 months, in addition to conventional lipid-lowering medication and other medications for cardiovascular risk factors. The primary outcomes are the effect of dalcetrapib on 18F-fluorodeoxyglucose positron emission tomography target-to-background ratio after 6 months and magnetic resonance imaging (MRI) plaque burden (wall area, wall thickness, total vessel area, and wall area/total vessel area ratio) after 12 months. Secondary objectives include positron emission tomography target-to-background ratio at 3 months and MRI plaque burden at 6 and 24 months; plaque composition at 6, 12, and 24 months; and aortic compliance at 6 months. A tertiary objective is to examine the dynamic contrast-enhanced MRI parameters of plaque neovascularization. In total, 189 subjects entered screening, and 130 were randomized. dal-PLAQUE will provide important information on the effects of dalcetrapib on markers of inflammation and atherosclerotic plaque burden and, thereby, on the safety of cholesteryl ester transfer protein modulation with dalcetrapib. Results are expected in 2011., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Myocardial perfusion imaging (MPI) is a useful method for risk assessment in patients with diabetes mellitus (DM) and chronic kidney disease (CKD), but these patients have a residual risk that is not accounted for by MPI. The objective of this study is to determine whether the heart rate response (HRR) to adenosine has an incremental prognostic value to MPI in high-risk patients., Methods: The study group included 879 (age 61 ± 13 years, 48% women, 58% white, 40% DM, 49% CKD) consecutive patients who underwent adenosine MPI. Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min per 1.73 m(2) or dialysis replacement therapy. An HRR <10% (change from baseline) was considered blunted. The outcome of interest was overall mortality., Results: During a follow-up period of 40 ± 14 months, 212 patients (24%) died. Patients with DM (23.4% ± 16.3% vs 29.4% ± 21.4%, P < .0001) and CKD (22.7% ± 17.6% vs 30.5% ± 20.4%, P < .0001) had lower HRR as compared with patients without DM and CKD, respectively. A blunted HRR was associated with increased mortality in the overall population and in those with DM and CKD and helped in risk stratification when added to traditional MPI findings. In a Cox regression model, a blunted HRR was the strongest predictor of mortality (hazard ratio 2.8, P < .0001) and provided additional prognostic data to MPI (hazard ratio 1.9, P < .0001) after controlling for age, gender, race, history of myocardial infarction, DM, CKD, β-blocker use, and presence of chest pain., Conclusions: A blunted HRR to adenosine is an independent predictor of poor outcome, adds incremental value to MPI, and helps in better risk stratification in high-risk patient groups., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Central aortic systolic blood pressures (SBPs) differ from and are preferable to cuff pressures when calculating cardiac work, left ventricular wall stress, and rate-pressure product. Despite the widespread use of dobutamine, differences between aortic and brachial SBP (pulse amplification) and pulse transmission during dobutamine infusion have not been previously studied. This study assessed these differences and used applanated radial pulses with the Sphygmocor (AtCor Medical, Sydney, Australia) device to investigate the effects of dobutamine on arterial pulse transmission and pulse amplification., Methods: Using a cuff oscillometer, brachial arterial pressures were measured simultaneously with directly recorded aortic pressures at rest and during increasing dobutamine infusion rates in 25 patients. In 15 of those patients, applanated radial pulses were fed into the Sphygmocor device and calibrated in 2 ways to predict aortic pressures., Results: At peak dobutamine infusion, SBP amplification averaged 14.9 mm Hg, with a maximum difference of 43 mm Hg. When radial artery pulses were calibrated using cuff pressures, the Sphygmocor underestimated the aortic SBP at all dobutamine doses. However, when radial artery pulses were calibrated using the more accurate aortic mean and diastolic BPs, the Sphygmocor accurately predicted the aortic SBP at baseline, but not at the higher dobutamine doses., Conclusions: Similar to exercise, dobutamine induced cuff SBPs and pulse pressures higher than those measured in the aorta-uncorrected by the cuff-calibrated Sphygmocor. This increasing pulse amplification was explained by the effects of dobutamine on the properties of the conduit arterial walls, on changes in pulse wave velocity, on increasing heart rate, and on reflected waves.

Background: Identifying persons at risk for sudden cardiac death (SCD) is challenging. A comprehensive evaluation may reveal clues about the clinical, anatomical, genetic, and metabolic risk factors for SCD., Methods: Seventy-one patients who had SCD (25-60 years old) without an initially apparent cause of death were evaluated at the Hennepin County Medical Examiner's office (Minneapolis, MN) from August 2001 to July 2004. We reviewed their clinic records conducted next-of-kin interviews and performed autopsy, laboratory testing, and genetic analysis for mutations in genes associated with the long QT syndrome., Results: Mean age was 49.5 +/- 7 years, 86% were male, and 2 subjects had history of coronary heart disease (CHD). Coronary risk factors were highly prevalent in comparison to individuals of the same age group in this community (eg, smoking 61%, hypertension 27%, hyperlipidemia 25%) but inadequately treated. On autopsy, 80% of the subjects had high-grade coronary stenoses. Acute coronary lesions and previous silent myocardial infarction (MI) were found in 27% and 34%, respectively. Furthermore, 32% of the subjects had recently smoked cigarettes, and 50% had ingested analgesics. Possible deleterious mutations of the ion channel genes were detected in 5 subjects (7%). Of these, 4 were in the sodium channel gene SCN5A., Conclusions: Most of the persons who had SCD in the community had severe subclinical CHD, including undetected previous MI. Traditional coronary risk factors were prevalent and undertreated. Mutations in the long QT syndrome genes were detected in a few subjects. These findings imply that improvements in the detection and treatment of subclinical CHD in the community are needed to prevent SCD., (Copyright 2010 Mosby, Inc. All rights reserved.)

Background: Advances in high-throughput genomics facilitate the identification of novel genetic susceptibility variants for coronary heart disease (CHD). This may improve CHD risk prediction. The aim of the present simulation study was to investigate to what degree CHD risk can be predicted by testing multiple genetic variants (genetic profiling)., Methods: We simulated genetic profiles for a population of 100,000 individuals with a 10-year CHD incidence of 10%. For each combination of model parameters (number of variants, genotype frequency and odds ratio [OR]), we calculated the area under the receiver operating characteristic curve (AUC) to indicate the discrimination between individuals who will and will not develop CHD., Results: The AUC of genetic profiles could rise to 0.90 when 100 hypothetical variants with ORs of 1.5 and genotype frequencies of 50% were simulated. The AUC of a genetic profile consisting of 10 established variants, with ORs ranging from 1.13 to 1.42, was 0.59. When 2, 5, and 10 times as many identical variants would be identified, the AUCs were 0.63, 0.69, and 0.76., Conclusion: To obtain AUCs similar to those of conventional CHD risk predictors, a considerable number of additional common genetic variants need to be identified with preferably strong effects.

Background: Adenosine and regadenoson increase heart rate (HR) when used as stress agents to produce coronary hyperemia due to direct sympathetic stimulation. We hypothesized that the HR response will be lower in patients with than in those without diabetes mellitus (DM)., Methods: We studied the HR response (percentage maximal increase) in 2,000 patients in The ADenoscan Versus regAdenosoN Comparative Evaluation for Myocardial Perfusion Imaging (ADVANCE MPI 1 and 2) Trials with known DM status., Results: There were 643 patients with a history of DM (65.4 +/- 0.4 years, 32% women) and 1,357 patients with no DM (65.5 +/- 0.3 years, 29% women). Compared with non-DM, the DM group had higher HR at baseline (68.4 +/- 0.48 vs 65.2 +/- 0.31 beat/min, P < .001) and smaller HR response after adenosine or regadenoson administration (29.4% +/- 0.64% vs 36.1% +/- 0.54%, P < .001). Insulin therapy was associated with further blunting in the HR response (25.9% +/- 1.0% vs 31.2% +/- 0.8%, P < .001). After adjusting for beta-blocker intake, baseline HR, age, gender, renal function, systolic blood pressure, and left ventricular systolic function, DM independently accounted for a decrease in the HR response., Conclusions: The HR response to adenosine and regadenoson in patients with DM is blunted. If additional studies confer an agreement between traditional tests for determination of autonomic neuropathy and this measure, then examination of HR response to these agents during myocardial perfusion imaging might add prognostic power.

Background: Controversy remains regarding whether gender differences exist in clinical management after exercise treadmill testing (ETT)., Methods: We studied 7,506 patients (49.8% women) without documented coronary heart disease referred for ETT from July 2001 to June 2004 in a community-based setting. We assessed the relationship between gender and subsequent diagnostic testing (secondary stress testing or coronary angiography) within 6 months after ETT. Secondary outcomes included subsequent stress testing, coronary angiography, and new cardiology visits in the 6-month interval. Multivariable analyses assessed the relationship between gender and these outcomes adjusting for demographic, clinical, and stress test characteristics. In subsequent analyses, patients were stratified by Duke Treadmill Scores (Duke University, Durham, NC)., Results: Compared with men, women referred for ETT were older, had a higher prevalence of some cardiac risk factors, achieved lower peak workloads, and, more often, experienced chest pain or ST-segment changes. After accounting for differences in clinical and ETT parameters, gender was not associated with any subsequent diagnostic testing in the 6 months after ETT (OR 1.0, 95% CI 0.85-1.18). In secondary analyses, women were less likely to undergo angiography (OR 0.63, 95% CI 0.47-0.83) with a trend toward more subsequent stress testing. Stratified analyses revealed less subsequent testing in high-to-intermediate Duke Treadmill Score women compared with men (OR 0.61, 95% CI 0.48-0.79). Women and men were equally likely to die (hazards ratio 0.93, 95% CI 0.61-1.44) in the adjusted survival analysis., Conclusions: Overall, women and men equally underwent subsequent diagnostic testing after ETT. Although women were less likely to undergo angiography and higher-risk women were less likely to undergo subsequent testing, adverse events were not higher in women. Given these findings, assumptions regarding gender disparities in clinical management after ETT should be reevaluated in other settings.

Background: It is unknown if contemporary preventive treatments such as statins or primary percutaneous coronary intervention in patients with coronary heart disease (CHD) have rendered obsolete the use of measured exercise capacity for assessment of future risk and prognosis. Using a sample of patients from 2 clinical sites, most of whom were taking beta-blockade, antiplatelet, and statin therapy, we hypothesized that peak oxygen consumption (Vo(2)) would remain a strong and independent predictor of all-cause and cardiovascular-specific mortality in men and women with CHD., Methods: We studied 2,812 patients with CHD between 1996 and 2004. All-cause and cardiovascular disease-specific mortality served as end points., Results: In all men and women and in a subgroup of patients following evidence-based care, peak Vo(2) remained a strong predictor of all-cause death, with every 1 mL x kg(-1) x min(-1) increase in peak Vo(2) associated with an approximate 15% decrease in risk of death. Among men, a peak Vo(2) (mL x kg(-1) x min(-1)) below approximately 15 was associated with the highest risk, whereas a peak Vo(2) above approximately 19 was associated with a low rate and risk for annual all-cause mortality. Among women, a peak Vo(2) below approximately 12 was associated with the highest risk, whereas a peak Vo(2) above approximately 16.5 was associated with the lowest rate and risk for annual all-cause mortality., Conclusions: In men and women with CHD, peak Vo(2) remains an independent predictor of all-cause and cardiovascular-specific mortality.

Background: To compare the relative value of metabolic syndrome (MetS) and cardiovascular risk score estimates in patients with acute coronary syndromes (ACS) aged <45 years., Patients and Methods: Two hundred consecutive patients (183 men, mean age 40.8 +/- 3.5 years) presented with a first-ever ACS, and 200 age-and sex-matched controls were evaluated. Metabolic syndrome diagnostic criteria, European Risk SCORE estimation function, and the Framingham Risk Score (FRS) were assessed in all participants., Results: The prevalence of the MetS was significantly higher in the patients' group compared with the control group (51.5% vs 26.0%, P < .001). No subjects with a SCORE >1.0% were identified. The mean 10-year FRS for patients and controls was 13.03% +/- 7.96% and 10.02 +/- 8.10%, respectively (P < .001), whereas only 22.5% of ACS patients had a 10-year risk >20.0% compared with 14.5% of controls (P = .04). After controlling for potential confounders, MetS was associated with 1.93 (95% CI 1.13-3.28, P = .01) higher odds of having an ACS. Moreover, the odds had a positive association with the increasing cumulative number of MetS components. Crude and adjusted ORs for the FRS were 1.05 (95% CI 1.029-1.08, P = .001) and 0.98 (95% CI 0.92-1.05, P = NS), respectively., Conclusion: Metabolic syndrome is highly associated with ACS in subjects <45 years of age and seems to be more valuable than established cardiovascular risk calculators.

Background: Multivessel (MV) coronary artery disease (CAD) frequently exists in patients presenting with non-ST-elevation (NSTE) acute coronary syndromes (ACSs). Although an early invasive strategy improves outcome in these patients, there are limited data on culprit-only, single-vessel (SV) percutaneous coronary intervention (PCI) or MV PCI in the NSTE ACS setting., Methods: To identify the predictors of SV versus MV PCI in patients with ACS and compare their outcomes up to hospital discharge, we analyzed the records of 105,866 patients undergoing PCI with ACS and MV CAD from 402 centers reported to the American College of Cardiology National Cardiovascular Database Registry between 2000 and 2004. Demographic, clinical, and angiographic characteristics of the patients were used to create a propensity score for SV versus MV PCI., Results: Single-vessel PCI was performed in 68% (72,048 patients), whereas the remaining 32% (33,818 patients) had MV PCI. Factors independently associated with the performance of SV versus MV PCI were presentation with NSTE infarction (vs unstable angina), adjusted odds ratio (OR) of 1.29 (95% CI 1.24-1.34); being older, adjusted OR of 1.09 (95% CI 1.08-1.11) per decade; and presence of total occlusion, adjusted OR of 1.25 (95% CI 1.16-1.36). The c-statistic for the model was 0.70. Procedural success was achieved in 91% of SV PCI and 88% of MV PCI (P < .001). Inhospital mortality was 1.3% and 1.2%, respectively (P = .09; adjusted OR 1.11 [95% CI 0.97-1.27], P = .13). Rates of morbidity, such as bleeding, development of renal failure, or nonfatal cardiogenic shock, were similar for both groups., Conclusions: In patients with MV CAD, presenting with ACS and selected for PCI, performance of MV PCI appears to be associated with at least as successful an inhospital outcome as SV PCI.

Background: The objective of this study was to evaluate risk-adjusted sequential probability ratio test control charts for the detection of significant discrepancies between institution or individual interventional cardiologist postprocedural mortality rates and national or local event rate expectations., Methods: Eight thousand nine hundred forty-two percutaneous coronary interventional procedures were performed by 27 operators between January 1, 2002, and November 30, 2006. The institution-based evaluation included all procedures, and the individual-based evaluations included 8750 procedures performed by 18 operators who had each done at least 100 PCI procedures. Risk-adjusted sequential probability ratio test control charts were developed to assess whether the odds ratios (ORs) for death were >2.0 for alpha = beta = 0.10. The American College of Cardiology 1.1 prediction model was used to risk-adjust both the institution and individuals, and an additional local model was used for individuals., Results: After national risk adjustment, the local institution did not show mortality of more than a 1.5 OR. Two operators had a >2.0 mortality OR after national risk adjustment, and one of those remained elevated after local risk adjustment. Of 18 operators, 10 had insufficient data to allow us to accept or reject the hypothesis of increased risk., Conclusions: The local institution performed within national expectations, but 1 operator was identified as having poor performance, which prompted an in-depth review of that operator's cases. The review revealed that the operator had an unusually high number of patients who presented with risk factors not included in the risk-adjustment models. This study highlights the utility of risk-adjusted sequential probability ratio test as a method for outcomes monitoring and quality control in interventional cardiology.

Background: Although its limitations for diagnosing critical coronary artery disease are well described, coronary angiography remains the predominant method for guiding decisions about stent implantation in patients with multivessel coronary artery disease. However, some have suggested that invasive physiologic guidance may improve decision making., Trial Design: The objective of this multicenter, randomized clinical trial is to compare the efficacy of 2 strategies, one based on angiographic guidance to one based on physiologic guidance with fractional flow reserve (FFR), for deciding which coronary lesions to stent in patients with multivessel coronary disease. Eligible patients must have coronary narrowings > 50% diameter stenosis in > or = 2 major epicardial vessels, > or = 2 of which the investigator feels require drug-eluting stent placement. Patients with previous coronary bypass surgery or left main coronary disease are excluded. Based on angiographic evaluation, the investigator notes the lesions that require stenting. The patient is then randomly assigned to either angiographic guidance or FFR guidance. Patients assigned to angiographic guidance undergo stenting as planned. Patients assigned to FFR guidance first have FFR measured in each diseased vessel and only undergo stenting if the FFR is < or = 0.80. The primary end point of the study is a composite of major adverse cardiac events, including death, myocardial infarction, and repeat coronary revascularization, at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, 2-year, and 5-year outcomes., Conclusion: The FAME study will examine for the first time in a large, multicenter, randomized fashion the role of measuring FFR in patients undergoing multivessel percutaneous coronary intervention.

Background: Limited data suggest that ST elevation (ST elevation) in aVR is associated with higher mortality and more extensive coronary artery disease in the setting of non-ST elevation acute coronary syndromes (ACS)., Methods: In the prospective Global Registry of Acute Coronary Events (GRACE) electrocardiographic substudy, the admission electrocardiograms were analyzed by a blinded core laboratory. We performed multivariable analysis to determine (1) the independent prognostic significance of ST elevation in aVR and (2) its association with significant (> or = 50% stenosis) left main or 3-vessel disease (LM/3-vd)., Results: Among 5064 patients with non-ST elevation ACS, 4696 had no ST elevation in aVR, 292 (5.8%) had minor (0.5-1 mm) ST elevation in aVR, and 76 (1.5%) had major (>1 mm) ST elevation in aVR; their in-hospital mortality rates were 4.2%, 6.2%, and 7.9%, respectively (P for trend =.03). At 6 months follow-up, the cumulative mortality rates were 7.6%, 12.7%, and 18.3%, respectively (log-rank P for trend <.001). However, minor and major ST elevation in aVR were not independent predictors of in-hospital or 6-month death after adjusting for other validated prognosticators in the GRACE risk model. Of the 2416 patients without prior coronary bypass surgery who underwent cardiac catheterization, the prevalence of LM/3-vd was 26.1%, 36.2%, and 55.9% for the groups with no, minor, and major ST elevation in aVR, respectively (P for trend <.001). After adjusting for other clinical characteristics, major ST elevation in aVR remained an independent predictor of LM/3-vd (adjusted odds ratio, 2.68; 95% confidence interval, 1.29-5.58; P = .008)., Conclusion: ST elevation in aVR is less prevalent than reported in previous smaller studies. Although it is associated with higher unadjusted in-hospital and 6-month mortality, it does not provide incremental prognostic value beyond comprehensive risk stratification using the validated GRACE risk model. However, ST elevation greater than 1 mm in aVR may be useful in the early identification of LM/3-vd in ACS patients with ST depression.

Aims: The aim of this study is to compare the anti-inflammatory effect of the dexamethasone preloaded stent (Dexamet, Abbott, Galway, Ireland) with the bare metal stent (BMS; BiodivYsio, Biocompatibles Cardiovascular LTD, Galway, Ireland) in patients with acute coronary syndrome (ACS) assessed by angiographic (QCA) and intracoronary ultrasound (ICUS)., Methods and Results: One hundred twenty patients with ACS were randomly assigned to revascularization using the Dexamet stent (n = 60) or BMS (n = 60). Serial QCA analysis and ICUS analysis were performed during long-term follow-up (2.9 F; 20 MHz transducer; Volcano Corp, Brussels, Belgium). Power calculations were performed for QCA-derived differences of lumen loss. In addition, statistical analysis was performed (SPSS for Windows 12.0.1). The target lesion revascularization rate was lower in the Dexamet group (10 [16.67%] vs 20 [33.33%] patients; P = .031). The QCA revealed improved lumen restoration in the Dexamet stent group (lumen loss, 0.55 +/- 0.65 vs 1.07 +/- 0.92 mm [P = .001]; loss index, 0.20 +/- 0.23 vs 0.46 +/- 0.42 [P < .001]). The ICUS revealed greater neointimal proliferation in the BMS versus the Dexamet stent group (3.36 +/- 1.03 vs 3.05 +/- 1.38 mm2; P < .001). Death (n = 1) and the number of total occlusions of the stent segment (n = 1) were identical in both groups., Conclusion: Dexamet stents, in comparison with the BMS stents, reduced the target lesion revascularization rate in patients with ACS and lead to better lumen restoration during long-term follow-up.

Background: Uncertainty exists about the performance of the Framingham risk score when applied in different populations., Objective: We assessed calibration of the Framingham risk score (ie, relationship between predicted and observed coronary event rates) in US and non-US populations free of cardiovascular disease., Methods: We reviewed studies that evaluated the performance of the Framingham risk score to predict first coronary events in a validation cohort, as identified by Medline, EMBASE, BIOSIS, and Cochrane library searches (through August 2005). Two reviewers independently assessed 1496 studies for eligibility, extracted data, and performed quality assessment using predefined forms., Results: We included 25 validation cohorts of different population groups (n = 128,000) in our main analysis. Calibration varied over a wide range from under- to overprediction of absolute risk by factors of 0.57 to 2.7. Risk prediction for 7 cohorts (n = 18658) from the United States, Australia, and New Zealand was well calibrated (corresponding figures: 0.87-1.08; for the 5 biggest cohorts). The estimated population risks for first coronary events were strongly associated (goodness of fit: R2 = 0.84) and in good agreement with observed risks (coefficient for predicted risk: beta = 0.84; 95% CI 0.41-1.26). In 18 European cohorts (n = 109499), the corresponding figures indicated close association (R2 = 0.72) but substantial overprediction (beta = 0.58, 95% CI 0.39-0.77). The risk score was well calibrated on the intercept for both population clusters., Conclusion: The Framingham score is well calibrated to predict first coronary events in populations from the United States, Australia, and New Zealand. Overestimation of absolute risk in European cohorts requires recalibration procedures.

Background: Diabetes and prediabetic conditions are growing cardiovascular risk factors. Better understanding and earlier recognition and treatment of dysglycemia-related risk are health priorities. We assessed the predictive value of 3 proposed new markers for diabetes and cardiovascular risk. We tested whether the plasma levels of (1) asymmetric dimethylarginine (ADMA), (2) cortisol/cortisone (Cl/Cn) ratio, and (3) C-peptide predicted glycemic status, coronary artery disease, and death or myocardial infarction (MI) in a nested case-control cohort (N = 850) with normal fasting glucose (< 110 mg/dL), impaired fasting glucose (110-125), or diabetic (> or = 126) status., Methods: High-sensitivity C-reactive protein (hsCRP) served as a control risk marker. Follow-up averaged 2.6 +/- 1.4 years. High-pressure liquid chromatography with pre-column derivitization and fluorescence was used to assay ADMA, liquid chromatography/tandem mass spectrometry for Cl and Cn, and chemiluminescent immunoassay for C-peptide., Results: Asymmetric dimethylarginine levels were positively associated with glycemic category (P < .001). Quartiles 2 to 4 ADMA also conferred increased risk of death/MI independent of hsCRP and other risk factors (adjusted hazard ratio, 2.1; P = .002). Cortisol/Cortisone ratios (P = .013) and C-peptide (P = .047) were associated with glycemic categories but less strongly than ADMA. Quartiles 2 to 4 Cl/Cn were protective against incident death/MI (adjusted hazard ratio, 0.48; P < .001), whereas C-peptide did not predict outcomes., Conclusions: Among a high coronary risk case-control cohort, ADMA (strongly), Cl/Cn (moderately), and C-peptide (weakly) predicted glycemic categories. Asymmetric dimethylarginine and Cl/Cn also predicted clinical outcome independent of and more strongly than hsCRP. Asymmetric dimethylarginine and Cl/Cn represent promising new candidate markers of dysglycemia and associated cardiovascular risk.

Background: The association of plaques with outward arterial remodeling and acute coronary syndromes (ACS) has been mostly investigated by cross-sectional intravascular ultrasound studies. Magnetic resonance imaging (MRI) has made it possible to noninvasively assess the coronary vessels of patients with chronic coronary artery disease, but no study has been done in patients with ACS. We sought to serially investigate changes in coronary vessel walls of patients with ACS using noninvasive serial MRI., Methods: A total of 42 segments of coronary arteries from 22 patients presenting with non-ST-segment elevation ACS were studied at baseline in the acute phase and at 6 months after stabilization and optimization of medical therapy. Patients received routine medical treatment during this period with control of risk factors. Vessel wall area, maximum wall thickness, mean wall thickness, and lumen area were analyzed longitudinally using MRI., Results: Vessel wall area (38.8 +/- 20.0 vs 27.7 +/- 10.4 mm2; P = .001), maximum wall thickness (2.9 +/- 0.7 vs 2.5 +/- 0.6 mm; P < .001), and mean wall thickness (2.0 +/- 0.7 vs 1.6 +/- 0.5 mm; P < .001) were significantly reduced at 6 months compared with baseline, whereas lumen area did not show significant changes (11.5 +/- 4.8 vs 10.9 +/- 5.0 mm2; P = .52). The wall/lumen ratio was significantly reduced from 3.7 +/- 1.7 to 2.9 +/- 1.3 (P = .01), suggesting a regression of outward remodeling., Conclusion: Patients with ACS have increased coronary vessel wall thickness and area that can regress with stabilization and medical therapy over the period of 6 months. Magnetic resonance imaging can detect and serially follow these changes, monitoring coronary vascular remodeling from the acute to the chronic phase of the disease.

Background: Preclinical data suggest beneficial effects of angiotensin II receptor blockers (ARBs) on neointima formation after vascular injury. Preliminary clinical data, however, revealed conflicting results. The AACHEN trial was a double-blind, randomized, placebo-controlled clinical multicenter trial to evaluate the effects of candesartan cilexetil on intimal hyperplasia after coronary stent implantation., Methods: A total of 120 patients (61 +/- 9 years, 83% male) were randomized to receive either 32 mg candesartan cilexetil (active) or placebo starting 7 to 14 days before elective coronary stent implantation. A follow-up angiography including intravascular ultrasound assessment of the target lesion was performed 24 +/- 2 weeks after stent implantation. The primary end point was defined as the difference in neointimal area between groups as assessed by intravascular ultrasound. Secondary end points included differences in angiographic parameters (ie, restenosis rate) and incidence of major cardiac events., Results: The mean stent length measured 15.0 +/- 4.9 mm in the active and 14.6 +/- 5.7 mm in the placebo group (P = .81). There was no significant difference in neointimal area between groups (2.1 +/- 1.0 vs 2.1 +/- 1.5 mm2, P = 1.00), nor were there differences in angiographic end point parameters. Major cardiac event rates were not significantly different between treatment groups (8% vs 11%, P = .75)., Conclusions: High-dose candesartan cilexetil therapy in patients with symptomatic coronary artery disease undergoing coronary stent implantation does not reduce clinical event rates, restenosis rates, or neointimal proliferation after elective stent implantation.

Background: A variety of imaging modalities have implicated impaired myocardial perfusion in the pathogenesis of acute coronary syndromes (ACSs)., Methods: We hypothesized that an abnormal TIMI myocardial perfusion grade (TMPG 0/1/2) and an impaired coronary flow reserve (CFR) as assessed angiographically using the TIMI frame count would be associated with biomarker release, ischemia on Holter monitoring, and adverse clinical outcomes in the PROTECT-TIMI 30 trial of patients with non-ST-elevation ACS undergoing percutaneous coronary intervention (PCI)., Results: The pre-PCI TMPG was correlated with the baseline as well as peak levels of troponin I (P < .001) and creatine kinase-MB (P < .001) and the post-PCI rise in troponin I (P = .03). The incidence of an ischemic event on Holter by 48 hours was more common among patients with an abnormal post-PCI TMPG (12.5% vs 7.0%, P = .013), and the mean normalized duration of ischemia by 24 hours after PCI on Holter monitoring trended longer among patients with an abnormal post-PCI TMPG (8.9 vs 3.2 minutes, P = .068). In multivariable analyses, an abnormal post-PCI TMPG was the strongest correlate of death, myocardial infarction, or an ischemic event by 48 hours after randomization. In contrast, the post-PCI CFR as assessed angiographically using the TIMI frame count was not associated with the baseline, peak, or absolute rise of any biomarker, Holter findings, or clinical events., Conclusions: An abnormal TMPG, but not an angiographic CFR, is associated with biomarker status, the occurrence and duration of Holter ischemia, and adverse clinical outcomes among patients with moderate- to high-risk non-ST-elevation ACS undergoing PCI.

Background: We sought to assess the influence of emergency department (ED) structure and care processes on adherence to practice guidelines for the treatment of patients with non-ST-segment elevation acute coronary syndromes., Methods: We surveyed emergency physicians and nurses from 316 hospitals participating in the CRUSADE Quality Improvement Initiative and used multivariable modeling to correlate ED-specific characteristics with guidelines adherence., Results: Factors that were significantly associated with improved guidelines adherence included collaboration between emergency physicians and hospital administration, northeast region, adequate nursing support, use of locum tenens physicians, an independent ED (not a division of another clinical department), and use of a care algorithm for acute coronary syndromes., Conclusions: Quality improvement strategies that have the full support of hospital administration, focus on increasing collaboration between emergency physicians and other health care providers, and specified protocol-driven management algorithm may be the most successful methods for improving the care and outcomes of patients with non-ST-segment elevation acute coronary syndromes.

Background: The pathophysiology of the apical ballooning syndrome (ABS) is poorly understood. This study evaluated myocardial perfusion abnormalities at the time of presentation in patients with ABS and examined whether abnormal microvascular blood flow predicts the extent of myocardial injury., Methods: We evaluated 42 consecutive patients, all women, with a diagnosis of ABS and technically adequate angiograms for the assessment of the TIMI myocardial perfusion grade (TMPG), an index of myocardial perfusion., Results: Abnormal myocardial perfusion was present in 29 (69%) patients. There were no differences in age, frequency of conventional coronary atherosclerosis risk factors, left ventricular ejection fraction at either presentation or follow-up, congestive heart failure at presentation, or length of hospital stay between patients with normal versus those with abnormal TMPG. Patients with abnormal TMPG had higher peak troponin level compared with patients with normal TMPG (0.84 +/- 0.68 vs 0.42 +/- 0.33 ng/mL, P = .047). Similarly, ST elevation or deep T-wave inversion on the electrocardiogram was more common in patients with abnormal perfusion (86% vs 46%, P = .006)., Conclusion: Impaired myocardial perfusion due to abnormal microvascular blood flow is frequently present in patients with ABS and correlates with the extent of myocardial injury. Microvascular dysfunction likely play a pivotal role in the pathogenesis of myocardial stunning in ABS.

Background: Heparin is ubiquitously used in cardiac catheterization but predisposes to the development of heparin-induced thrombocytopenia. The objective was to examine prospectively the prevalence of anti-platelet factor 4 (PF4)/heparin antibodies and heparin-induced thrombocytopenia in the population undergoing cardiac catheterization., Methods: This is a prospective study of 500 consecutive patients presenting for cardiac catheterization at our institution who were enrolled over the course of 1 year. Anti-PF4/heparin antibodies and concurrent platelet counts were measured at catheterization and 5 days thereafter. Thrombotic complications were assessed 30 days after the procedure via telephone interview. All patients presenting for cardiac catheterization at our institution were screened. Inclusion criteria were (a) males and nonpregnant females with age >18 years and (b) patients scheduled to undergo cardiac catheterization. Patients with a known history of heparin-induced thrombocytopenia, with documented bleeding or hypercoagulability, and those at high risk for bleeding were excluded., Results: Of 500 patients, 15 (3%) had anti-PF4/heparin antibodies before catheterization. After catheterization, the prevalence of anti-PF4/heparin antibodies increased to 10.1% (36 of 357) of the patients. Overall rates of thrombotic complications were low (4 of 445, 0.9%) and did not correlate with anti-PF4/heparin antibody status. Patients with an initial positive test for anti-PF4/heparin antibodies were more likely to have prior coronary disease (73.3% vs 45.2%; P < .05). Patients who developed anti-PF4/heparin antibodies after catheterization were more likely to have increased length of stay (3.7 vs 2.4 days; P = .02). The platelet count at the time of catheterization was lower in the cohort of patients who developed the second positive anti-PF4/heparin antibody test versus patients without a second positive antibody test (mean values of 191,800/microL vs 222,300/microL; P = .008)., Conclusions: The prevalence of antibodies to PF4/heparin is low in the population presenting for cardiac catheterization. However, a significant proportion of patients develop antibodies to PF4/heparin after a small exposure to heparin during catheterization. Clinically significant thrombotic complications were rare and did not correlate with antibody status.

Background: Percutaneous coronary intervention (PCI) is known to induce atherosclerotic plaque rupture, which may affect resting distal microvascular perfusion either through distal microvascular spasm or through embolization. We evaluated the effect of PCI on resting microvascular flow., Methods: We performed cardiovascular magnetic resonance imaging to assess left ventricular systolic function and microvascular perfusion in 15 patients with stable coronary artery disease before and within 24 hours after PCI and in 10 control subjects without obstructive coronary artery disease on a clinical 1.5-T CMR scanner. Microvascular perfusion was evaluated at rest after injecting a bolus of gadolinium-diethylenetriamine pentaacetic acid (0.1 mmol/kg) by calculating the time to 50% maximum myocardial enhancement (T50% max), as well as the relative upslope, of the myocardial signal intensity curve. Regional perfusion and systolic thickening were evaluated using a 16-segment left ventricular model with the slice locations matched anatomically pre-PCI and post-PCI. The relative contrast delay in the region of myocardium subtended by the PCI artery was calculated by subtracting the T50% max of a remote region from the PCI region., Results: In subjects with coronary artery disease, PCI resulted in a regional contrast delay (mean delay 0.6 +/- 0.2 seconds post-PCI vs 0.0 +/- 0.2 seconds pre-PCI, P < .05) and a reduction in the relative upslope (8.6 +/- 0.5 post-PCI vs 10.1 +/- 0.7 pre-PCI, P = .02), consistent with reduced microvascular perfusion. This was unaccompanied by any change in regional systolic thickening (54% +/- 7% pre-PCI vs 53% +/- 5% post-PCI, P = NS)., Conclusions: The data show PCI-induced impairment of resting microvascular perfusion in the area of myocardium subtended by the treated artery after PCI, a likely consequence of iatrogenic atherosclerotic plaque rupture.

Background: Patients referred for stress echocardiography may differ significantly from those referred for stress myocardial perfusion imaging (MPI). Such differences, if present, should be considered when comparing the accuracy and discriminatory performance of these tests., Methods: We prospectively collected demographic and clinical information on all stress imaging studies performed at our institution between 1998 and 2001. The data were reviewed, summarized, and compared using the t test and chi2 test where appropriate., Results: Of 5320 stress imaging studies performed, 3383 were stress echocardiographies and 1937 were MPI studies. Patients referred for MPI were older (59 vs 54, P < .0001), and more likely to have diabetes (32% vs 20%, P < .0001), prior myocardial infarction (39% vs 15%, P < .0001), and prior revascularization (38% vs 12%, P < .0001). Pharmacologic stress testing was much more common in the MPI group (66% vs 17%, P < .0001). More patients referred for MPI had decreased left ventricular function (23% vs 7%, P < .0001) and abnormal stress test results (41% vs 18%, P < .0001)., Conclusions: Patients with a history of myocardial infarction, revascularization, or higher risk profiles are more likely to be referred for MPI compared to stress echocardiography at our institution. These differences in referral patterns are likely to exist in other centers, and it is reasonable to assume that systematic differences in test selection occur, resulting in patient populations with differing clinical risk profiles. Caution in interpreting analyses comparing the accuracy of stress imaging modalities is appropriate.

Background: Evaluated the efficacy of reducing the risk of cardiac events by a preclinical diagnosis of CAD in subjects with type 2 diabetes mellitus with 2 or more cardiovascular risk factors., Methods: One hundred forty-one subjects with type 2 diabetes mellitus without known cardiac disease and asymptomatic, aged >45 to <76 years, were randomized into the screening arm for CAD (71 patients) or to the control arm (70 patients). The screening consisted in performing an exercise electrocardiogram test and dipyridamole stress echocardiography; if 1 test was abnormal, coronary angiography is done. Screening was positive in 15 subjects (21.4%). At coronary angiography, which was performed in 14 of 15 patients, stenoses > or =50% of vessel diameter were present in 9 patients, of these 4 underwent coronary artery bypass grafting and 4 underwent percutaneous transluminal coronary angioplasty. Stenoses <50% of vessel diameter were present in 5 patients., Results: Mean follow-up was 53.5 months (range, 42-54 months). During this period, 1 major (myocardial infarction) and 3 minor events (angina) occurred in the screening arm. Eleven major and 4 minor events occurred in the control arm. In the screened arm, the proportion of all events was significantly less (P = .018) (RR .226, 95% CI 0.707-0.719, P = .012); the proportion of major to minor events was significantly less (P = .006) (RR .07, 95% CI 0.0087-0.565, P = .013)., Conclusions: The preclinical diagnosis of CAD is effective in reducing the risk of cardiac events, especially major events, in subjects with type 2 diabetes mellitus at high cardiovascular risk.

Background: The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction., Methods: Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 101) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. RESULTS; Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients. Subclinical disease could not be predicted by BNP., Conclusions: Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Background: Low-level cardiac troponin-I (cTn-I) elevations predict adverse cardiovascular outcomes in patients with definite acute coronary syndromes (ACS), as defined by the presence of chest pain accompanied by ischemic electrocardiographic changes. However, their prognostic value in other clinical situations remains unclear., Methods: We studied 366 patients with suspected myocardial infarction (MI) but without definite ACS, including 57 patients with low-level cTn-I elevations (1.0 to 3.0 ng/mL) and 309 patients with cTn-I <1.0 ng/mL. All cTn-I measurements were made with the Dade Stratus II analyzer. We determined the adjusted 1-year risk of nonfatal MI or death from coronary heart disease (CHD death) in each group by using Cox proportional hazards models., Results: Among patients with cTn-I elevations between 1.0 and 3.0 ng/mL, 6 (11%) had a nonfatal MI or CHD death at 1 year compared with 12 (4%) patients in the cTn-I <1.0 ng/mL group [hazard ratio (HR), 3.5; 95% CI, 1.4 to 8.8]. After adjusting for baseline clinical characteristics, cTn-I levels between 1.0 and 3.0 ng/mL remained strongly associated with nonfatal MI or CHD death (adjusted HR, 3.4; 95% CI, 1.3 to 9.4). This association persisted even in the 215 patients who presented without chest pain (adjusted HR, 4.3; 95% CI, 1.4 to 13)., Conclusions: Low-level cTn-I elevations identify a subset of patients at increased risk for future cardiovascular events, even when obtained outside the context of definite ACS or presentation with chest pain.

Background: Major depressive disorder (MDD) disproportionately affects patients with coronary artery disease (CAD). Evidence of myocardial ischemia with electrocardiography (ECG) or single-photon-emission-computed-tomography (SPECT) assessments during exercise testing is an important determinant of CAD prognosis. However, many key symptoms of MDD, such as reduced interest in daily activities, lack of energy, and fatigue, may affect exercise performance and the detection of ischemia in patients with MDD. This study evaluated the extent to which MDD and depressive symptomatology moderate exercise test performance and compared the ability of ECG versus SPECT for detecting ischemia in 1367 consecutive patients who underwent exercise testing., Methods: All patients underwent a brief, structured psychiatric interview (PRIME-MD) and completed the Beck Depression Inventory (BDI) on the day of their exercise (treadmill) test., Results: A total of 183 patients (13%) met diagnostic criteria for MDD. Patients with MDD achieved a significantly lower percent of maximal predicted heart rate (%MPHR), exhibited lower peak exercise mets, and spent less time exercising compared with patients without MDD (all P values <.05). BDI scores were also negatively correlated with all 3 indices of exercise performance (all P values <.01). There were no differences in rates of SPECT ischemia in patients with MDD (40%) versus patients without MDD (45%; P =.23); however, rates of ECG ischemia were significantly lower (30%) in patients with MDD than in patients without MDD (48%; P <.0001)., Conclusions: Results suggest that patients with CAD who have MDD, depressive symptomatology, or both exhibit poor exercise tolerance and performance and that ECG, as compared with SPECT, may not be as reliable in detecting ischemia in patients who are depressed.

Background: B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are elevated in patients with acute coronary syndromes and are closely linked to prognosis. Because there is only a small amount of data available concerning NT-proBNP in patients with stable angina pectoris, we aimed to determine whether NT-proBNP is of additional diagnostic value in these patients., Methods and Results: Ninety-four patients with stable angina pectoris were prospectively included. All patients underwent exercise testing and coronary angiography, and 91 patients received thallium-201 single-photon emission computed tomography myocardial scintigraphy. NT-proBNP was analyzed at rest and after exercise testing. NT-proBNP was elevated in patients with inducible myocardial ischemia shown by single-photon emission computed tomography (396 +/- 80 pg/mL vs 160 +/- 101 pg/mL; P <.01) closely linked to the extent of coronary artery disease (CAD) (no CAD, 148 +/- 29 pg/mL; 1- or 2-vessel disease, 269 +/- 50 pg/mL; 3-vessel disease 624 +/- 186 pg/mL; P <.01). In a multivariate analysis, NT-proBNP was an independent predictor for CAD. The area under the curve of the receiver operating characteristic curve was 0.72 for NT-proBNP to predict CAD. Using an optimized cut off level of 214 pg/mL, CAD can be predicted with high accuracy. The total test efficiency of exercise testing can be improved from 1.46 to 1.52 when combined with NT-proBNP measurement., Conclusion: NT-proBNP is elevated in patients with stable angina pectoris and has a close correlation to disease severity. Combining the measurement of NT-proBNP with exercise testing, the test accuracy for predicting severe CAD can be improved. Our data show an incremental value of NT-proBNP in the diagnostic process of stable angina pectoris.

Background: Abnormalities in endothelium-dependent vasodilation may be detected in arteries before the development of overt atherosclerosis, and their presence may predict stress-induced ischemia as assessed by ST-segment depression and/or perfusion defects. Brachial artery ultrasound during reactive hyperemia is a noninvasive method of assessing peripheral vasomotion, measured by flow-mediated vasodilation (FMD). The purpose of the current study was to assess whether endothelium-dependent FMD of the brachial artery, by ultrasound imaging, predicts the presence of angiographically assessed coronary artery disease (CAD)., Methods: One hundred ninety-eight in-hospital patients (age, 59 +/- 9 years; 78 women) with chest pain syndrome and without previous myocardial infarction or revascularization procedures were enrolled in the present study. All of the patients, at testing time, were not receiving nitrate therapy and underwent, on different days, coronary angiography and endothelium-dependent FMD testing of the brachial artery by high-resolution ultrasound. The result of the flow-mediated dilation (%FMD) is defined as the percent change in the internal diameter of the brachial artery during reactive hyperemia related to baseline. A coronary vessel was considered to have a significant obstruction if its diameter was narrowed by 50% or more on quantitative computer-assisted analysis. A prognostically validated angiographic Duke score (from 0 = normal to 100 = severe left main disease) was calculated., Results: The %FMD was lower in patients with (n = 69) compared with those without (n = 129) CAD (4.64% +/- 4.36% vs 7.39% +/- 5.68%; P =.01). By multivariate analysis, the %FMD (P =.01; odds ratio [OR], 1.13; 95% confidence interval [CI], 1.05 to 1.23), male sex (P =.01; OR, 3.47; 95% CI, 1.64 to 7.36), and cigarette smoking habit (P <.01; OR, 4.00; 95% CI, 2.50 to 6.35) were independent predictors of CAD. %FMD was poorly albeit significantly correlated with the severity of CAD (%FMD Duke score, P <.01, r = -0.25). The receiver operator characteristic curve showed the %FMD optimal cutoff value as < or =8.84, with sensitivity of 90%, specificity of 37%, negative predictive value of 90%, and positive predictive value of 43%., Conclusions: In patients with chest pain, a depressed FMD of the brachial artery was a sensitive indicator of CAD, but it showed poor specificity, and it appeared to be unable to predict both the extent and the severity of angiographically assessed CAD.

Background: We hypothesized that imaging of regional myocardial function (RF) and perfusion (PER) will add incremental value for both diagnosis and short-term prognosis to routine demographic, clinical, and electrocardiographic findings in patients presenting to the emergency department (ED) with chest pain and without ST-segment elevation on the electrocardiogram., Methods: We compared contrast echocardiography (CE) with gated single-photon emission computed tomography (SPECT) for this purpose. Both CE and SPECT readings included separate and composite assessments of both RF and PER. Adverse events in the first 48 hours after ED presentation included acute myocardial infarction, emergent revascularization, and cardiac-related death., Results: Concordance between CE and SPECT was 77% (73% to 82%) for all territories, with a higher concordance for the anterior wall of 84% (78% to 89%). Of the 203 patients recruited for the study, 38 (19%) had a cardiac event within 48 hours of ED presentation: 21 had acute myocardial infarction, 16 underwent an urgent revascularization procedure, and 1 died. In multivariate logistic regression models, the number of abnormal segments on CE and SPECT were significant predictors (P <.05) of cardiac events. The composite scores on CE provided 17% incremental information (P =.009, n = 203) and gated SPECT provided 23.5% additional information (P =.020, n = 163) for predicting cardiac events compared with routine demographic, clinical, and electrocardiographic variables. RF and composite evaluation was superior on SPECT compared with CE, whereas PER alone was not., Conclusions: Cardiac imaging of RF and PER at the time of ED presentation offers substantially greater diagnostic and prognostic information for early cardiac events in patients presenting to the ED with chest pain and no ST elevation than does the routine demographic, clinical, and electrocardiographic assessment.

Background: Recently revised American College of Cardiology/American Heart Association guidelines have suggested that exercise test scores be used in decisions concerning patients with suspected coronary artery disease (CAD). Pretest and exercise test scores derived for use in women without known CAD have not been tested in women with a low prevalence of CAD., Methods: Within the Women's Ischemia Syndrome Evaluation (WISE) study, we evaluated 563 women undergoing coronary angiography for suspected myocardial ischemia. The prevalence of angiographic CAD was 26%. Overall, 189 women underwent treadmill exercise testing. Prognostic end points included death, myocardial infarction, stroke, and revascularization., Results: Each score stratified women into 3 probability groups (P <.001) according to the prevalence of coronary disease: Pretest: low 20/164 (12%), intermediate 53/245 (22%), high 75/154 (49%); Exercise test: low 11/83 (13%), intermediate 22/74 (30%), high 17/32 (53%). However, the Duke score did not stratify as well: low 7/46 (15%), intermediate 36/126 (29%), high 6/17 (35%); P =.44. When pretest and exercise scores were considered together, the best stratification with the exercise test score was in the intermediate pretest group (P <.03). The Duke score did not stratify this group at all (P =.98). Pretest and exercise test scores also stratified women according to prognostic end points: pretest--low 7/164 (4.3%), intermediate 28/245 (11.4%), high 27/154 (17.5%), P <.01; exercise test--low 4/83 (4.8%) and intermediate-high 17/106 (16%), P =.014., Conclusion: Both pretest and exercise test scores performed better than the Duke score in stratifying women with a low prevalence of angiographic CAD. The exercise test score appears useful in women with an intermediate pretest score, consistent with American College of Cardiology/American Heart Association guidelines.

Background: No previous studies have compared myocardial contrast echocardiography (MCE) and single-photon emission computerized tomography (SPECT) for the detection of coronary artery disease (CAD) in patients with a medium likelihood of CAD. This study was developed to test the hypothesis that MCE is superior to SPECT for the detection of CAD., Methods: Fifty-five patients with a medium probability of CAD and no previous myocardial infarction were recruited. Results of MCE and SPECT were compared to quantitative coronary arteriography, where CAD was defined as >50% stenosis. Each patient was examined for the anterior and posterior circulations., Results: On a coronary circulation basis (n = 110), the sensitivity of MCE was significantly greater than that of SPECT for the detection of CAD (86% vs 43%, P <.0001). However, the specificities were similar (88% and 93%, P =.52). Both techniques were marginally more accurate in the anterior compared to the posterior circulation (88% vs 76%, P =.07 for MCE and 79% vs 63%, P =.19, for SPECT). On a patient basis (n = 55), MCE had a higher sensitivity than SPECT for the detection of CAD (83% vs 49%, P <.05). Although specificity tended to be higher for SPECT than MCE (92% vs 58%), it was not significant (P =.33). When CAD was defined as >40% coronary stenosis, the specificity of MCE increased to 83% without any change in sensitivity., Conclusion: In this preliminary study, MCE was found to be superior to SPECT during dipyridamole stress for the diagnosis of CAD in patients with a medium pretest probability of CAD. Larger studies are required to confirm these findings.

Background: Exercise treadmill testing has limited sensitivity for the detection of coronary artery disease, frequently requiring the addition of imaging modalities to enhance the predictive value of the test. Recently, there has been interest in using nonstandard electrocardiographic (ECG) leads during exercise testing., Methods: We consecutively enrolled all patients undergoing exercise myocardial imaging with four additional leads recorded (V4R, V7, V8, and V9). The test characteristics of the 12-lead, the 15-lead (12-lead, V7, V8, V9), and the 16-lead (12-lead, V4R, V7, V8, V9) ECGs were compared with stress imaging in all patients. In the subset of patients who underwent angiography within 60 days of stress testing, these lead arrays were compared with the catheterization findings., Results: There were 727 subjects who met entry criteria. The mean age was 58.5 +/- 12.3 years, and 366 (50.3%) were women. Pretest probability for disease was high in 241 (33.1%), intermediate in 347 (47.7%), and low in 139 (19.1%). A total of 166 subjects had an abnormal 12-lead ECG during exercise. The addition of 3 posterior leads to the standard 12-lead ECG resulted in 7 additional subjects having an abnormal electrocardiographic response to exercise. The addition of V4R resulted in only 1 additional patient having an abnormal ECG during exercise. The sensitivity of the ECG for detecting ischemia as determined by stress imaging was 36.6%, 39.2%, and 40.0% (P = NS) for the 12-lead, 15-lead, and 16-lead ECGs, respectively. In those with catheterization data (n = 123), the sensitivity for determining obstructive coronary artery disease was 43.5%, 45.2%, and 45.2% (P = NS) for the 12-lead, 15-lead, and 16-lead ECGs, respectively. The sensitivity of imaging modalities was 77.4% when compared with catheterization., Conclusions: In patients undergoing stress imaging studies, the addition of right-sided and posterior leads did not significantly increase the sensitivity of the ECG for the detection of myocardial ischemia. Additional leads should not be used to replace imaging modalities for the detection of coronary artery disease.

Background: Coronary artery disease (CAD) is the leading cause of death and a leading cause of disability in the developed world. Early onset (premature) coronary artery disease (EOCAD) is known to have a particularly strong genetic component. However, the actual genes leading to this increased risk of CAD remain obscure., Methods: The primary goal of the Genetics of Early Onset Cardiovascular Disease (GENECARD) study is to perform a genetic linkage study in 920 families with at least 1 sibling pair having EOCAD. The study sites include a US network of 15 cardiology practices and 5 additional sites located in Europe and the United States. We propose to identify chromosomal regions associated with increased susceptibility to EOCAD in this large sample of affected sibling pairs and nuclear families, where EOCAD is defined on the basis of having acute coronary syndrome (unstable angina or myocardial infarction), a revascularization procedure, or a positive functional imaging study at or before the age of 50 years in men or 55 years in women. To identify which genomic regions and genes are associated with increased susceptibility to EOCAD, we will use a comprehensive strategy comprising genomic screening, fine mapping, candidate gene analysis, and family-based association studies., Results: Herein we describe the clinical characteristics, family history, and risk factor profiles of the 1168 members from 438 nuclear families included in the first, exploratory analysis. Analysis of the study population revealed a strong concordance of known cardiac risk factors among affected sibling pairs. There was significant concordance (P <. 01) among siblings with EOCAD for presence of diabetes (78% concordance), dyslipoproteinemia (67%), obesity (63%), and hypertension (56%). This level of concordance of risk factors among siblings might be expected, given the significant genetic components demonstrated for these metabolic susceptibility traits. However, there was also substantial sibling pair concordance (P <.01) for smoking history (74%), regular alcohol consumption (81%), and sedentary lifestyle (63%), environmental traits without known inherited predisposition., Conclusions: Analyses such as these will have implications for stratifying populations for the statistical analysis of the genome scan and on the choice of covariates for the follow-up studies of the initial genome screen analysis.

Background: Depression has been associated with higher mortality and morbidity rates after acute coronary syndromes (ACS), but little is known about the association between depression, angina burden, and quality of life. We evaluated the association between a history of depression and patient-reported angina frequency, physical limitation, and quality of life 7 months after discharge from the hospital for ACS., Methods: Patients were enrolled in the Department of Veterans Affairs Access to Cardiology Study, a cohort study of all patients with acute myocardial infarction or unstable angina who were discharged from 24 Veterans Affairs medical centers between March 1998 and February 1999. Data from 1957 patients who completed a 7-month postdischarge Seattle Angina Questionnaire were analyzed. Multivariate logistic regression was used to evaluate a history of depression as an independent predictor of angina frequency, physical limitation, and quality of life 7 months after ACS, as measured with the Seattle Angina Questionnaire., Results: A total of 526 patients (26.7%) had a history of depression. After adjustment for a wide array of demographic, cardiac, and comorbid factors, a history of depression was significantly associated with more frequent angina (odds ratio [OR] 2.40, 95% CI 1.86-3.10, P <.001), greater physical limitation (OR 2.89, 95% CI 2.17-3.86, P <.001), and worse quality of life (OR 2.84, 95% CI 2.16-3.72, P <.001) after ACS., Conclusion: We found a strong association between a history of depression and both heavier angina burden and worse health status after ACS. These findings further support the importance of depression as a risk marker for adverse outcomes after ACS.

Background: Improved patient selection may optimize the efficiency of cardiac catheterization in both high- and low-rate regions. The purpose of this study was to develop and validate a clinical model for predicting high-risk coronary artery disease (CAD) after myocardial infarction (MI) and to examine the model's potential impact on the use rate of both US and Canadian catheterization practices., Methods and Results: By the use of baseline clinical variables from 1122 patients in the angiographic substudy of the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-1) trial, we developed a model that was predictive of severe CAD (left main or triple-vessel disease). The final model, which included prior MI, age, sex, hyperlipidemia, and decreased left ventricular ejection fraction (C-index = 0.70), was externally validated in 781 patients in the GUSTO IIb trial. Although the probability of severe CAD predicted 5-year survival, the frequency of catheterization in both Canada and the United States bore no relationship to severe CAD risk in the GUSTO-1 trial. By use of the model, we estimated that as much as 15% of US catheterizations from both GUSTO-1 and GUSTO IIb might have been avoided, without significantly compromising the number of patients with severe CAD who were identified (sensitivity = 0.94). By applying the model to Canadian practices, an additional 30 cases of severe CAD might have been identified per every 1000 catheterizations performed, without increasing the catheterization rate., Conclusions: The likelihood of severe CAD after ST-elevation MI may be predicted from simple baseline clinical variables. The use of a severe CAD predictive model to guide patient selection might enhance the cost-effectiveness of both aggressive and conservative catheterization practices.

Background: The utility of exercise echocardiography for evaluating remote ischemia due to noninfarct-related artery (n-IRA) lesions in patients with prior myocardial infarction has not been established., Methods: Quantitative coronary angiography and treadmill exercise echocardiography were performed within 2 weeks in 115 patients with prior myocardial infarction (>6 weeks) and 224 patients without myocardial infarction. Coronary lumen diameter stenosis > or =50% (by angiography) and the lack of a hyperdynamic response on exercise echocardiography were considered significant. Myocardial infarction size was defined as the number of myocardial segments with severe hypokinesis, akinesis, or dyskinesis on echocardiography at rest., Results: For detection of n-IRA lesions in patients with prior myocardial infarction, the sensitivity of exercise echocardiography was similar (78% vs 79%, P = not significant), however, the specificity was significantly lower (77% vs 91%, P <.01) than for detection of significant stenoses in patients without prior myocardial infarction. Angiographic percent-diameter stenosis, presence of collateral vessel, achieved exercise level, and presence of peri-infarct ischemia did not affect the specificity of exercise echocardiography. However, the specificity of exercise echocardiography was significantly lower (69% vs 84%, P <.05) in patients with echocardiographically large infarction (infarction size > or =2) than in patients with small infarction (infarction size <2)., Conclusion: In patients with prior myocardial infarction, exercise echocardiography showed low specificity for detection of noninfarct-related artery lesions, especially in patients with echocardiographically large myocardial infarction. These characteristics of treadmill exercise echocardiography should be considered when this technique is applied for patients with healed myocardial infarction.

Background: Recently revised American College of Cardiology/American Heart Association guidelines for exercise electrocardiography (ExECG) have suggested that ExECG scores be used to assist in management decisions in patients with suspected coronary artery disease (CAD)., Methods: We used 442 women who underwent both ExECG and coronary angiography (CAD > or =1 lesion with > or =50% stenosis; CAD prevalence was 32%) to derive an ExECG score including clinical and ExECG variables. By use of logistic regression analysis, variables were selected and relative weights were determined. Variable codes multiplied by respective weights were summed to produce a final ExECG score. The score was validated in separate populations concerning angiographic as well as prognostic end points., Results: Clinical variables selected and their weights included age (5), symptoms (2), diabetes (2), smoking (2), and estrogen status (1). ExECG variables selected and their weights included ST depression (2), exercise heart rate (4), and Duke Angina Index (3). For the validation group, score ranges are shown with the prevalence of CAD: <20 = 0/5 or 0%, 20-29 = 3/26 or 11%, 30-39 = 20/56 or 36%, 40-49 = 33/81 or 41%, 50-59 = 24/49 or 49%, 60-69 = 22/32 or 69%, and >70 = 7/7 or 100%. Frequency of death within 3 predetermined subgroups was as follows: low <40 = 3/1237 (0.2%), intermediate 40-60 = 9/383 (2.3%), high >60 = 4/54(7%); P<.0001., Conclusion: A simple ExECG score was developed for use specifically in women. When evaluated in separate cohorts, the score stratified women with suspected coronary disease into groups with a gradually increasing frequency of coronary disease and death.

Objectives: We sought to determine the value of electrophysiology (EP) testing in patients with ventricular fibrillation (VF), ventricular tachycardia (VT) with syncope, or sustained VT in the setting of left ventricular dysfunction., Background: Traditionally, EP testing is part of the workup of patients with sustained VT or VF. Recently, some have suggested that EP testing is unnecessary in these patients, many of whom are likely to receive an implantable cardioverter-defibrillator (ICD)., Methods: Within a multicenter trial (Antiarrhythmics Versus Implantable Defibrillators) designed to evaluate whether drugs or ICD resulted in a better outcome, data were analyzed regarding EP testing. Although this testing was not required, it was performed in >50% of patients. Information regarding the results of EP testing was correlated to baseline clinical characteristics and outcome., Results: Of 572 patients subjected to an EP test, 384 (67%) had inducible sustained VT or VF. Inducible patients were more likely to have coronary artery disease, previous infarction, and VT as their index arrhythmic event. Inducibility of VT or VF did not predict death or recurrent VT or VF., Conclusions: Information derived from EP testing in this patient population, particularly those with VF, is of limited value and may not be worth the risks and costs of the procedure, particularly in those patients likely to receive an ICD.

Background: Diastolic dysfunction induced by ischemia may alter transmitral blood flow, but this reflects global ventricular function, and pseudonormalization may occur with increased preload. Tissue Doppler may assess regional diastolic function and is relatively load-independent, but limited data exist regarding its application to stress testing. We sought to examine the stress response of regional diastolic parameters to dobutamine echocardiography (DbE)., Methods: Sixty-three patients underwent study with DbE: 20 with low probability of coronary artery disease (CAD) and 43 with CAD who underwent angiography. A standard DbE protocol was used, and segments were categorized as ischemic, scar, or normal. Color tissue Doppler was acquired at baseline and peak stress, and waveforms in the basal and mid segments were used to measure early filling (Em), late filling (Am), and E deceleration time. Significant CAD was defined by stenoses >50% vessel diameter., Results: Diastolic parameters had limited feasibility because of merging of Em and Am waves at high heart rates and limited reproducibility. Nonetheless, compared with normal segments, segments subtended with significant stenoses showed a lower Em velocity at rest (6.2 +/- 2.6 cm/s vs 4.8 +/- 2.2 cm/s, P <.0001) and peak (7.5 +/- 4.2 cm/s vs 5.1 +/- 3.6 cm/s, P <.0001). Abnormal segments also showed a shorter E deceleration time (51 +/- 27 ms vs 41 +/- 27 ms, P =.0001) at base and peak. No changes were documented in Am. The same pattern was seen with segments identified as ischemic with wall motion score. However, in the absence of ischemia, segments of patients with left ventricular hypertrophy showed a lower Em velocity, with blunted Em responses to stress., Conclusion: Regional diastolic function is sensitive to ischemia. However, a number of practical limitations limit the applicability of diastolic parameters for the quantification of stress echocardiography.

Background: Patients at high risk of sudden cardiac death, yet at low risk of nonsudden death, might be ideal candidates for antiarrhythmic drugs or devices. Most previous studies of prognostic markers for sudden cardiac death have ignored the competitive risk of nonsudden cardiac death. The goal of the present study was to evaluate the ability of clinical factors to distinguish the risks of sudden and nonsudden cardiac death., Methods: We identified all deaths during a 3.3-year follow-up of 30,680 patients discharged alive after admission to the cardiac care unit of a Seattle hospital. Detailed chart reviews were conducted on 1093 subsequent out-of-hospital sudden deaths, 973 nonsudden cardiac deaths, and 442 randomly selected control patients., Results: Patients who died in follow-up (suddenly or nonsuddenly) were significantly different for many clinical factors from control patients. In contrast, patients with sudden cardiac death were insignificantly different for most clinical characteristics from patients with nonsudden cardiac death. The mode of death was 20% to 30% less likely to be sudden in women, patients who had angioplasty or bypass surgery, and patients prescribed beta-blockers. The mode of death was 20% to 30% more likely to be sudden in patients with heart failure, frequent ventricular ectopy, or a discharge diagnosis of acute myocardial infarction. A multivariable model had only modest predictive capacity for mode of death (c-index of 0.62)., Conclusion: Standard clinical evaluation is much better at predicting overall risk of death than at predicting the mode of death as sudden or nonsudden.

Background: In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding., Objective: Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with enoxaparin plus ASA., Methods: Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days., Results: The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively)., Conclusions: Combination therapy with tirofiban plus enoxaparin appears safe, relative to therapy with tirofiban plus UFH.