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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.)

Objective: Patients with inflammatory rheumatic diseases have an increased risk of developing coronary atherosclerosis. However, outcomes of surgical revascularization in these patients have been rarely studied. We aimed to determine whether, or which, inflammatory rheumatic diseases may pose effects on mortality and adverse cardiac outcomes after coronary artery bypass grafting., Methods: By using the National Health Insurance Research Database of Taiwan, we identified 40,639 adult patients who underwent first-time coronary artery bypass grafting between 2000 and 2010. Among these patients, 101 had rheumatoid arthritis, 56 had systemic lupus erythematosus, and 73 had ankylosing spondylitis. The odds ratios (ORs) of operative mortality and hazard ratios (HRs) of overall mortality and adverse cardiac outcomes after coronary artery bypass grafting (ie, myocardial infarction and repeat revascularization) in relation to rheumatoid arthritis, systemic lupus erythematosus, and ankylosing spondylitis were estimated., Results: With adjustment for potential confounders including patient characteristics, hospital levels, and combined surgery, systemic lupus erythematosus was an independent predictor for operative mortality (adjusted OR, 2.63; 95% confidence interval [CI], 1.04-6.65; P = .04) and ankylosing spondylitis was marginally associated with operative mortality (adjusted OR, 2.41; 95% CI, 0.99-5.88; P = .054). Systemic lupus erythematosus was a significantly independent predictor for overall mortality during the follow-up period (adjusted HR, 2.23; 95% CI, 1.51-3.31; P < .0001) and might increase the risk of repeat revascularization (adjusted HR, 1.89; 95% CI, 0.97-3.68; P = .06). Neither rheumatoid arthritis nor ankylosing spondylitis was significantly associated with overall mortality and adverse cardiac outcomes., Conclusions: Our study may help surgeons and physicians recognize the potential risks inherent to systemic lupus erythematosus and ankylosing spondylitis when conducting coronary artery bypass grafting and providing follow-up care., (Copyright © 2015 The American Association for Thoracic Surgery. Published by 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.)

Objective: Patients undergoing cardiac surgery with a history of untreated atrial fibrillation have reduced survival compared with similar patients without atrial fibrillation. We sought to compare the midterm survival of patients who received concomitant surgical ablation treatment for atrial fibrillation (atrial fibrillation ablated) with that of matched patients without a history of atrial fibrillation (no atrial fibrillation)., Methods: We evaluated 3262 consecutive patients (813 [25%] with atrial fibrillation and 2449 [75%] without preoperative atrial fibrillation) undergoing cardiac surgery at a single institution from April 2004 to April 2009. Of patients with atrial fibrillation, 565 (70%) were treated with a concomitant surgical ablation procedure. Propensity scores were calculated on the basis of 37 known preoperative risk factors and yielded 744 patients. Midterm survival was compared between patients with atrial fibrillation ablation (n = 372) and patients without atrial fibrillation (n = 372). Survival was also compared between patients with successful vs unsuccessful ablation, and a matched analysis was performed at 1 year between the 2 groups., Results: Mean follow-up was 2.7 ± 1.6 years. Patients without atrial fibrillation and patients with treated atrial fibrillation had similar early 30-day mortality (1.2% vs 0.3%, P = .37) and overall mortality rates (11.6% vs 9.4%, P = .344), respectively. Survival analysis showed no differences at 1, 3, and 5 years between the 2 groups (log-rank P = .22). At last follow-up, 78% of treated patients were free of atrial fibrillation. At 1 year, 68% of patients were free of atrial fibrillation and antiarrhythmic medication. Freedom from atrial fibrillation and antiarrhythmic medication at 1 year predicted improved midterm survival (P = .03) compared with patients in atrial fibrillation or taking antiarrhythmic medication. Propensity-matched analysis after 1 year demonstrated improved survival for patients who were successfully treated (P = .016)., Conclusions: Patients undergoing surgical treatment of atrial fibrillation had survival similar to that of patients without a history of atrial fibrillation. Those with successful sinus restoration had improved survival compared with those who were treated but remained in atrial fibrillation., (Copyright © 2012 The American Association for Thoracic Surgery. Published by 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.)

Study Objective: Coronary artery calcium scoring (CACS) is a simple and readily available test for identifying coronary artery disease. Our objective is to evaluate whether a CACS of zero will identify chest pain patients who can be safely discharged home, without need for further cardiac testing., Methods: This was a prospective observational cohort study conducted at an urban tertiary care hospital of stable patients presenting to the emergency department (ED) with chest pain of uncertain cardiac cause. Patients with a normal initial troponin level, nonischemic ECG, and no history of coronary artery disease had stress myocardial perfusion imaging (SPECT) and CACS within 24 hours of ED admission. Cardiac events were defined as an acute coronary syndrome during the index hospitalization or in follow-up. CACS results were assessed in relation to SPECT findings and cardiac events., Results: The 1,031 patients enrolled (mean [SD] age 54 [13] years) had a median CACS of 0 (61% with CACS of 0). The frequency of an abnormal SPECT ranged from 0.8% (CACS of 0) to17% (CACS>400). Cardiac events occurred in 32 patients (3.1%) during the index hospitalization (N=28) or after hospital discharge (N=4) (mean 7.4 [3.3] months). Only 2 events occurred in 625 patients with a CACS of 0 (0.3%; 95% confidence interval 0.04% to 1.1%). Thus, 2 of 32 patients with a cardiac event had a CACS of 0 (6%; 95% confidence interval 0.8% to 21%). Both of these patients developed increased troponin levels during their index visit but had normal serial ECG and SPECT study results and no cardiac events at 6-month follow-up., Conclusion: A majority of patients (61% in our sample) evaluated for chest pain of uncertain cardiac cause have a CACS of 0, which predicts both a normal SPECT result and an excellent short-term outcome. Our results suggest that patients with a CACS of 0 can be discharged home, without further cardiac testing., (Copyright (c) 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Older patients account for up to a quarter of all emergency department (ED) visits. Atypical clinical presentation of illness, a high prevalence of cognitive disorders, and the presence of multiple comorbidities complicate their evaluation and management. Increased frailty, delayed diagnosis, and greater illness severity contribute to a higher risk of adverse outcomes. This article will review the most common conditions encountered in older patients, including delirium, dementia, falls, and polypharmacy, and suggest simple and efficient strategies for their evaluation and management. It will discuss age-related changes in the signs and symptoms of acute coronary events, abdominal pain, and infection, examine the yield of different diagnostic approaches in this population, and list the underlying medical problems present in half of all "social" admission cases. Complete geriatric assessments are time consuming and beyond the scope of most EDs. We propose a strategy based on the targeting of high-risk patients and provide examples of simple and efficient tools that are appropriate for ED use., (Copyright (c) 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Study Objective: Current recommendations indicate that emergency physicians should activate cardiac catheterization laboratory personnel by a single page for ST-segment elevation myocardial infarction (STEMI) patients. We assessed the accuracy of emergency physician cardiac catheterization laboratory activations, angiographic findings, outcomes, and treatment times among patients with and without STEMI., Methods: We classified the appropriateness and outcomes of consecutive emergency physician STEMI pages between June 2006 and September 2008. Emergency physician activations of the cardiac catheterization laboratory were classified according to the findings of the initial ECG compared with cardiology interpretation for the presence of STEMI and presence of coronary disease., Results: During a 27-month period, emergency physician activation of the cardiac catheterization laboratory occurred 249 times. There were 188 (76%) patients with a true STEMI, of whom 13 did not receive emergency angiography. Of the 37 (15%) patients who had ECG findings meeting STEMI criteria and who ultimately did not have myocardial necrosis and underwent emergency angiography, 12 had significant disease and 5 had revascularization performed. Eleven patients had ECGs concerning for but not meeting STEMI criteria; all had emergency angiography (n=11) or received a diagnosis of non-STEMI (n=6). Only 13 patients were considered as having received unnecessary cardiac catheterization laboratory activations (5.2%) in which emergency angiography was not performed and myocardial infarction was excluded., Conclusion: A significant number of emergency physician STEMI cardiac catheterization laboratory activations are for patients who did not meet standard STEMI criteria. However, most had ECG findings and symptoms that lead to emergency angiography, had significant disease, or were diagnosed with non-STEMI. Only a small percentage of patients received unnecessary cardiac catheterization laboratory activations. Our findings support current recommendations for emergency physician cardiac catheterization laboratory activation for potential STEMI patients., (Copyright 2009 American College of Emergency Physicians. Published by 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.

Objectives: We hypothesized that a large number of patients with diabetic retinopathy who could benefit greatly from early coronary artery bypass grafting would not be identified., Methods: Patients with diabetic retinopathy receiving ophthalmologic care as outpatients in our hospital in whom coronary artery disease was not previously suspected were referred randomly to the diabetic retinocoronary clinic and were asked to participate in diagnostic tests, including an exercise treadmill test and exercise thallium scintigraphy or coronary computed tomography. Patients who had type 1 diabetes mellitus, required hemodialysis, or both were excluded from this study. A definitive diagnosis of coronary artery disease was confirmed by means of coronary angiography., Results: Of 214 patients with diabetic retinopathy, 55 (25.7%) were confirmed as having significant stenotic coronary artery disease. Patients with angiographically confirmed coronary disease were older than those with negative results on diagnostic tests (62.2 + or - 9.8 vs 57.9 + or - 10.3 years, P = .01). Fifteen had 1-vessel disease, 17 had 2-vessel disease, 14 had 3-vessel disease, 1 had left main trunk plus 1-vessel disease, 2 had left main trunk plus 2-vessel disease, and 5 had left main trunk plus 3-vessel disease. Eight patients had left main trunk disease, and 18 patients with non-left main trunk disease had proximal left anterior descending coronary artery (LAD) disease. Forty-two patients showed indications of coronary revascularization (coronary artery bypass grafting in 17 and percutaneous coronary intervention in 25). During the entire follow-up (287.6 + or - 183.2 days) of 39 patients undergoing coronary revascularization, all were alive without myocardial infarction, but 8 experienced vitreous hemorrhage., Conclusions: Approximately 25% of patients with diabetic retinopathy receiving ophthalmologic care as outpatients have a significant stenotic coronary artery disease. Of the total diabetic population, a large number of patients with diabetic retinopathy who show strong indications for early coronary artery bypass grafting might well go unrecognized., (Copyright 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

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.

Objectives: To relate cardiovascular magnetic resonance-derived segmental wall motion and myocardial scarring and determine whether they are associated with postoperative mitral regurgitation following coronary artery bypass grafting and annuloplasty for severe functional ischemic mitral regurgitation., Methods: From January 2001 to October 2006, 29 patients with grade >or=3+ chronic functional ischemic mitral regurgitation were studied using cardiovascular magnetic resonance. Wall motion abnormality was graded for 17 standard left ventricular myocardial segments (0 = none, 1+ = hypokinesis, 2+ = severe hypokinesis, 3+ = akinesis, 4+ = dyskinesis), as was degree of hyperenhancement (scarring). Postoperative mitral regurgitation was assessed longitudinally by 71 transthoracic echocardiograms., Results: Wall motion abnormalities grade >or=2+ were present in most myocardial segments (median 13). Scar >25% was present in a median of 3 segments, and 44% of those were in the territory of the posterior papillary muscle. Nearly all segments (95%) with >25% scar had >or=2+ wall motion abnormality. Although 90% of patients had no mitral regurgitation at hospital discharge, by 6 months, 34% had mitral regurgitation grade >or=2+. There was little association between wall motion abnormality and recurrence of mitral regurgitation (P > .1). Seventy percent of patients with scar >25% in the posterior papillary muscle region exhibited postoperative mitral regurgitation of grade >or=2+ by 6 months, compared with 15% with score

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.

Objective: Boussignac continuous positive airway pressure (BCPAP) delivered by face mask is useful for patients with acute cardiogenic pulmonary edema (ACPE). Although BCPAP is medically effective, we observed that not all suitable patients received it. In this descriptive, prospective, cohort study, we explored the experiences and attitudes of both patients and staff with BCPAP., Methods: Patients were interviewed 12 to 48 hours after treatment with BCPAP. Nurses on the coronary care unit were interviewed on their knowledge, skills, experiences, and opinions concerning BCPAP., Results: Of 117 patients with ACPE, 87 patients (74%) received BCPAP treatment. It was decided not to administer BCPAP in 30 patients with ACPE (26%). Patients who received BCPAP found that the reduction of dyspnea outweighed any discomfort. Barriers for the use of BCPAP were not related to nurses' skills but to the following: the nurses' belief that BCPAP created major discomfort, the lack of guidelines, the ultimate improvement of oxygenation without BCPAP, and the more labor-intensive treatment., Conclusion: Overestimation of patient discomfort by nurses and system-related factors impeded the use of BCPAP for all patients with ACPE.

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: Anxiety and depression are frequently observed in patients with coronary artery disease. Because emotional distress is of prognostic importance in these patients, screening is recommended., Objective: We compared the Short Form 36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS) in measuring emotional distress in patients admitted for elective coronary angiography., Methods: A total of 587 patients were consecutively included (mean age 62 years, 75% were male). Gender-specific partial correlations were calculated for the associations between their SF-36 and HADS scores, whereas subgroup differences were evaluated using t tests or analysis of variance., Results: In both genders, the HADS subscales for anxiety and depression were significantly related to all SF-36 subscales and most strongly related to the Mental Health subscale. Both HADS and the Mental Health subscale demonstrated a high occurrence of emotional distress and discriminated significantly between patients with and without severe angina. The HADS, but not the SF-36, demonstrated high levels of emotional distress (anxiety) among men without verified coronary artery disease., Conclusion: Both instruments seem appropriate as screening instruments for emotional distress in patients with suspected coronary artery disease. Although the Mental Health subscale has the advantage of being shorter, we recommend the HADS because it shows anxiety more specifically.

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.

Study Objective: The emergency department (ED) evaluation of chest pain patients with potential acute coronary syndrome is limited by the initial sensitivity of cell injury markers. BNP is increased during myocardial ischemia and is associated with adverse outcomes. We determine whether the addition of B-type natriuretic peptide (BNP) to troponin I, creatine kinase-MB (CK-MB), and myoglobin increases the sensitivity and negative predictive value (NPV) for acute myocardial infarction, acute coronary syndrome, and 30-day adverse events among chest pain patients with potential acute coronary syndrome., Methods: A convenience sample of patients aged 30 years or older and presenting to an urban academic ED with nontraumatic chest pain, thus prompting an ECG, was enrolled, and consent was obtained. Blood samples were drawn at 0 and 90 minutes. Thirty-day follow-up was performed for all enrolled patients. Main outcomes were acute myocardial infarction, acute coronary syndrome, and 30-day events (death, acute myocardial infarction, or revascularization). BNP cutoffs were derived from receiver operator characteristics curves. The sensitivity, specificity, positive predictive value (PPV), and NPV with 95% confidence intervals (CIs) were calculated with and without BNP. Differences in sensitivity and specificity with the addition of BNP were calculated with 95% CIs, and McNemar's test was performed to compare sensitivities and specificities., Results: Four hundred twenty-six patients were enrolled and analyzed. The cohort was 54.7+/-13.9 years old, 47.7% men, and 63.5% black. The outcomes were acute myocardial infarction, 39 (9.2%), acute coronary syndrome, 101 (23.7%), and 30-day adverse cardiovascular events 52 (12.2%). BNP cutoffs derived were 51, 31, and 31 pg/mL for acute myocardial infarction, acute coronary syndrome, and 30-day events, respectively. The addition of BNP showed increased sensitivity at the cost of decreased specificity for all 3 outcomes, as follows: (1) acute myocardial infarction: sensitivity: 87.2% (95% CI 72.6% to 95.7%) to 97.4% (95% CI 86.5% to 100%), difference 10.3% (95% CI-0.2% to 24.6%), P=.125; specificity: 62.3% (95% CI 57.2% to 67.1%) to 47.8% (95% CI 42.7% to 52.9%), difference 14.5% (95% CI 11.1% to %18.4), P<.0001; (2) acute coronary syndrome: sensitivity: 75.2% (95% CI 65.7% to 83.3%) to 88.1% (95% CI 80.2% to 93.7%), difference 12.9% (95% CI 7.0% to 21.0%), P=.0002; specificity: 68.0% (95% CI 62.6% to 73.0%) to 48.6% (95% CI 43.1% to 54.2%), difference 19.4% (95% CI 15.2% to 24.1%), P<.0001; (3) 30-day events: sensitivity: 71.2% (95% CI 56.9% to 82.9%) to 88.5% (95% CI 76.6% to 95.7%), difference 17.3% (95% CI 7.7% to 30.3%), P=.004; specificity: 61.8% (95% CI 56.6% to 66.7%) to 43.9% (95% CI 38.8% to 49.0%), difference 17.9% (95% CI 14.2% to 22.2%), P<.0001. There were trends toward increased NPV and decreased PPV for all outcomes, and the addition of BNP achieved a NPV of 99.5% (95% CI 97.0% to 100%) compared with 98.0% (95% CI 95.3% to 99.3%) for acute myocardial infarction., Conclusion: The addition of BNP as a dichotomous test to troponin I, CK-MB, and myoglobin produces increased sensitivity at a cost of decreased specificity for acute myocardial infarction, acute coronary syndrome, and 30-day adverse events. Because of this tradeoff, BNP cannot be recommended for use among all ED chest pain patients. However, the improved sensitivity may make this test useful in selected cohorts when the decreased specificity is less important.

Objective: Prediction of surgical site infection and mortality after cardiac surgery might allow for interventions to reduce adverse outcomes. We sought to evaluate existing risk scores., Methods: We included 809 consecutive patients undergoing coronary artery bypass surgery. Data were collected prospectively. Infections were defined as deep sternal wound infection or mediastinitis by using established criteria and evaluated 60 days after surgical intervention. All-cause mortality was assessed at 30 days and 6 months. We assessed the ability of the National Nosocomial Infections Surveillance risk index, the EuroSCORE, and the Society of Thoracic Surgeons risk score to predict infection and mortality. Discrimination was assessed using the area under the receiver operating curve., Results: The rate of surgical site infection was 3.6% (29/809 patients). The National Nosocomial Infections Surveillance risk index showed moderate discrimination for infection (area under the receiver operating curve of 0.64) and poor ability to stratify patients into infection risk groups. The EuroSCORE predicted infection and 30-day and 6-month mortality with good discrimination (area under the receiver operating curve of 0.72, 0.78, and 0.77, respectively). Ranking patients by the EuroSCORE and dividing the cohort into 3 roughly equal risk groups yielded an ascending risk for infection of 0.7%, 3.0%, and 7.2%. The preoperative and intraoperative Society of Thoracic Surgeons risk scores showed good discrimination for surgical site infection (area under the receiver operating curve of 0.72 and 0.76, respectively) and excellent discrimination for early and late mortality (area under the receiver operating curve of >0.80). Risk grouping based on the Society of Thoracic Surgeons score yielded an ascending risk for infection of 0.7%, 3.6%, and 6.4%., Conclusions: The EuroSCORE and the Society of Thoracic Surgeons risk score can be used for joint risk stratification for surgical site infection and mortality. Both scores performed better than the National Nosocomial Infections Surveillance risk index.

Study Objective: We seek to determine whether cardiac risk factor burden (defined as the number of conventional cardiac risk factors present) is useful for the diagnosis of acute coronary syndromes in the emergency department (ED) setting., Methods: This was a post hoc analysis of the Internet Tracking Registry of Acute Coronary Syndromes (i*trACS) registry, which had 17,713 ED visits for suspected acute coronary syndromes. First visit for US patients who were not cocaine or amphetamine users, who did not leave against medical advice, and for whom ECG and demographic data were complete were included. Acute coronary syndrome was defined by 30-day revascularization, diagnostic-related group codes, or death within 30 days, with positive cardiac biomarkers at index hospitalization. Cardiac risk factors were diabetes, hypertension, smoking, hypercholesterolemia, and family history of coronary artery disease. Cardiac risk factor burden was defined as the number of risk factors present. Because multiple logistic regression analysis revealed that age modified the relationship between cardiac risk factor burden and acute coronary syndromes, a stratified analysis was performed for 3 age categories: younger than 40, 40 to 65, and older than 65 years. Positive likelihood ratios and negative likelihood ratios with their 95% confidence intervals (CIs) were calculated for each total risk factor cutoff., Results: Of 10,806 eligible patients, 871 (8.1%) had acute coronary syndromes. In patients younger than 40 years, having no risk factors had a negative likelihood ratio of 0.17 (95% CI 0.04 to 0.66), and having 4 or more risk factors had a positive likelihood ratio of 7.39 (95% CI 3.09 to 17.67). In patients between 40 and 65 years of age, having no risk factors had a negative likelihood ratio of 0.53 (95% CI 0.40 to 0.71), and having 4 or more risk factors had a positive likelihood ratio of 2.13 (95% CI 1.66 to 2.73). In patients older than 65 years, having no risk factors had a negative likelihood ratio of 0.96 (95% CI 0.74 to 1.23), and having 4 or more risk factors had a positive likelihood ratio of 1.09 (95% CI 0.64 to 1.62)., Conclusion: Cardiac risk factor burden has limited clinical value in diagnosing acute coronary syndromes in the ED setting, especially in patients older than 40 years.

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.

Study Objective: We evaluate associations between pairs of discordant cardiac biomarkers (positive MB band of creatine kinase [CKMB] with negative creatine kinase, positive CKMB with negative cardiac troponin, and positive troponin with negative CKMB) and the presence of acute coronary syndromes in emergency department (ED) chest pain patients., Methods: This was a secondary analysis of a prospective registry. Data were obtained from the multicenter Internet Tracking Registry of Acute Coronary Syndromes, which included 17,713 ED visits for possible acute coronary syndrome between June 1999 and August 2001. First visits and first ED cardiac biomarker results from the 9 sites, 8 in the United States and 1 in Singapore, were included. Subjects were excluded for incomplete information or an initial ECG consistent with ST-segment elevation myocardial infarction. Acute coronary syndrome was defined by diagnosis-related group code indicating myocardial infarction, positive invasive or noninvasive diagnostic testing, revascularization, or death during hospitalization or within 30 days., Results: Of 8,769 eligible patients, 1,614 (18.4%) had acute coronary syndrome. The CKMB and cardiac troponin results were discordant in 7% of patients (CKMB+/cardiac troponin-, 4.9%, CKMB-/cardiac troponin+ 2.1%), whereas increased CKMB with normal creatine kinase levels occurred in 239 (3.1%) patients. The unadjusted odds ratios with 95% confidence intervals for acute coronary syndrome in patients with and without discordant markers were: CKMB+/CK- 5.7 (4.4-7.4), CKMB+/CK+ 4.4 (3.6-5.2), CKMB-/cTn+ 4.8 (3.4-6.8), CKMB+/cTn- 2.2 (1.7-2.8), CKMB+/cTn+ 26.6 (18.0-39.3). For the group with cardiac troponin, the reference category was negative troponin and negative CKMB; for the group with creatine kinase, the reference category was negative CKMB but either a positive or negative creatine kinase., Conclusion: Among the spectrum of ED patients with chest pain, an increased CKMB level with a normal creatine kinase level identifies patients at increased risk for acute coronary syndrome. Similarly, an increased troponin level regardless of CKMB level and an increased CKMB level regardless of troponin level identify patients at higher risk for acute coronary syndrome than those with uniformly normal cardiac biomarker levels. Our data suggest that discordant cardiac biomarkers may identify patients at increased risk for acute coronary syndrome.

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.

Study Objective: Observational studies of well-described patient populations presenting to emergency departments (EDs) with suspicion of acute coronary syndrome are necessary to understand the relationships between patients' signs and symptoms, cardiac risk profile, test results, practice patterns, and outcomes. We describe the methods for data collection and the ED population enrolled in a multicenter registry of patients with chest pain., Methods: Patients older than 18 years, presenting to one of 8 EDs in the United States or 1 ED in Singapore, and with possible acute coronary syndrome were enrolled in the Internet Tracking Registry of Acute Coronary Syndromes between June 1999 and August 2001. Prospective data, including presenting signs and symptoms, ECG findings, and the ED physician's initial impression of risk, were systematically collected. Medical record review or daily follow-up was used to obtain cardiac biomarker results, invasive and noninvasive testing, treatments, procedures, and inhospital outcomes. Thirty-day outcomes were determined by telephone follow-up and medical record review., Results: The registry includes 15,608 patients, with 17,713 visits. Chest pain was the chief complaint in 71% of visits. The ECG was diagnostic of ischemia or infarction in 10.1% and positive cardiac biomarkers were observed in 10% of visits. Forty-three percent of patients were sent home directly from the ED. Of admitted patients, 5% died by 30 days, and 3% had documented coronary artery disease or had undergone percutaneous coronary intervention or coronary artery bypass grafting within 30 days. For patients discharged directly from the ED, 0.4% died or had a documented myocardial infarction within 30 days. Coronary artery bypass graft surgery, percutaneous coronary intervention, or a diagnosis of coronary artery disease was found in 0.5% of discharged patients., Conclusion: A unique description of undifferentiated ED chest pain patients with suspected acute coronary syndrome is provided. The data set can be used to generate and explore hypotheses to improve understanding of the complex relationships between presentation, treatment, testing, intervention and outcomes.

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.

Study Objective: We compare the diagnostic accuracy of 3 methods--attribute matching, physician's written unstructured estimate, and a logistic regression formula (Acute Coronary Insufficiency-Time Insensitive Predictive Instrument, ACI-TIPI)--of estimating a very low pretest probability (< or = 2%) for acute coronary syndromes in emergency department (ED) patients evaluated in chest pain units., Methods: We prospectively studied 1,114 consecutive patients from 3 academic EDs, evaluated for acute coronary syndrome. Physicians collected data required for pretest probability assessment before protocol-driven chest pain unit testing. A pretest probability greater than 2% was considered "test positive." The criterion standard was the outcome of acute coronary syndrome (death, myocardial infarction, revascularization, or > 60% stenosis prompting new treatment) within 45 days, adjudicated by 3 independent reviewers., Results: Fifty-one of 1,114 enrolled patients (4.5%; 95% confidence interval [CI] 3.4% to 6.0%) developed acute coronary syndrome within 45 days, including 4 of 991 (0.4%; 95% CI 0.1% to 1.0%) patients, discharged after a negative chest pain unit evaluation result, who developed acute coronary syndrome. Unstructured estimate identified 293 patients with pretest probability less than or equal to 2%, 2 had acute coronary syndrome, yielding sensitivity of 96.1% (95% CI 86.5% to 99.5%) and specificity of 27.4% (95% CI 24.7% to 30.2%). Attribute matching identified 304 patients with pretest probability less than or equal to 2%; 1 had acute coronary syndrome, yielding a sensitivity of 98.0% (95% CI 89.6% to 99.9%) and a specificity of 26.1% (95% CI 23.6% to 28.7%). ACI-TIPI identified 56 patients; none had acute coronary syndrome, yielding sensitivity of 100% (95% CI 93.0% to 100%) and specificity of 6.1% (95% CI 4.7% to 7.9%)., Conclusion: In a low-risk ED population with symptoms suggestive of acute coronary syndrome, patients with a quantitative pretest probability less than or equal to 2%, determined by attribute matching, unstructured estimate, or logistic regression, may not require additional diagnostic testing.

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.