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Objectives: A proof-of-concept study was undertaken to determine whether differences in corrected coronary opacification (CCO) within coronary lumen can identify arteries with abnormal resting coronary flow. Background: Although computed tomographic coronary angiography can be used for the detection of obstructive coronary artery disease, it cannot reliably differentiate between anatomical and functional stenoses. Methods: Computed tomographic coronary angiography patients (without history of revascularization, cardiac transplantation, and congenital heart disease) who underwent invasive coronary angiography were enrolled. Attenuation values of coronary lumen were measured before and after stenoses and normalized to the aorta. Changes in CCO were calculated, and CCO differences were compared with severity of coronary stenosis and Thrombolysis In Myocardial Infarction (TIMI) flow at the time of invasive coronary angiography. Results: One hundred four coronary arteries (n = 52, mean age = 60.0 ± 9.5 years; men = 71.2%) were assessed. Compared with normal arteries, the CCO differences were greater in arteries with computed tomographic coronary angiography diameter stenoses ≥50%. Similarly, CCO differences were greater in arteries with TIMI flow grade <3 (0.406 ± 0.226) compared with those with normal flow (TIMI flow grade 3) (0.078 ± 0.078, p < 0.001). With CCO differences, abnormal coronary flow (TIMI flow grade <3) was identified with a sensitivity and specificity, positive predictive value, and negative predictive value of 83.3% (95% confidence interval [CI]: 57.7 to 95.6%), 91.2% (95% CI: 75.2% to 97.7%), 83.3% (95% CI: 57.7% to 95.6%), and 91.2% (95% CI: 75.2% to 97.7%), respectively. Accuracy of this method was 88.5% with very good agreement (kappa = 0.75, 95% CI: 0.55 to 0.94). Conclusions: Changes in CCO across coronary stenoses seem to predict abnormal (TIMI flow grade <3) resting coronary blood flow. Further studies are needed to understand its incremental diagnostic value and its potential to measure stress coronary blood flow. [Copyright &y& Elsevier]

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

Objectives: The objective was to determine the prognostic value of rubidium-82 (82Rb) positron emission tomography (PET) myocardial perfusion imaging (MPI). Background: 82Rb PET MPI accurately diagnoses coronary artery disease (CAD). However, there are limited data evaluating its prognostic value. Methods: Follow-up (3.1 ± 0.9 years) was obtained in 367 patients who underwent dipyridamole 82Rb PET MPI. Patients were divided into groups based on their summed stress score (SSS): group I, normal (<4); group II, mild (4 to 7); and group III, moderate (8 to 11) to severe (≥12). Results: There were significant differences among patients in the 3 SSS groups for hard events (cardiac death and myocardial infarction [MI]) (p < 0.001) and total cardiac events (hard events, revascularization and hospitalization) (p < 0.001). The annual hard events rates were 0.4%, 2.3%, and 7.0% in the normal, mild, and moderate-severe groups, respectively. In adjusted survival models, 82Rb PET SSS was the strongest predictor of total cardiac events and a significant predictor of hard events. Among patients referred for PET after 99mTc single-photon emission computed tomography, the annual total event rate was higher with abnormal versus normal SSS on PET (15.2% vs. 1.3%, p < 0.001). In patients with obesity, the annual total event rate was 11.1% with an abnormal scan and 1.5% with a normal scan (p < 0.001). Conclusions: This study shows that 82Rb PET MPI has significant prognostic value for predicting cardiac events, including death and MI. It also seems to have prognostic value in patients whose diagnosis remains uncertain after single-photon emission computed tomography MPI and in obese patients. The prognostic value of PET MPI may improve the management of cardiac patients. [Copyright &y& Elsevier]

Objectives: The aim of this study was to compare treadmill exercise (TEX) and dipyridamole stress on the uptake and retention of N-13 ammonia. Background: Size and severity of stress-induced myocardial perfusion defects are clinically important. Because ammonia uptake and retention seems to be related to perfusion, viability, and metabolism, exercise stress might induce larger perfusion defects than dipyridamole stress. Methods: Twenty-six patients underwent TEX and dipyridamole stress N-13 ammonia positron emission tomography (PET). Images were assessed with a 17-segment model and a five-point score. Summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) were calculated. Left ventricular (LV) defect sizes were measured quantitatively with a 70% threshold for abnormal perfusion. Results: Compared with dipyridamole stress, TEX yielded larger SSS (9.1 ± 5.7 vs. 6.9 ± 5.9; p < 0.01), SDS (5.8 ± 4.7 vs. 3.7 ± 4.6; p < 0.02), and percentage of LV stress defect (19.3 ± 11.5% vs. 13.8 ± 13.6%; p < 0.02). Conclusions: In patients achieving adequate exercise, TEX N-13 ammonia PET myocardial perfusion imaging (MPI) yields larger stress perfusion defects than dipyridamole stress and might reflect the true myocardial ischemic burden. Treadmill exercise might be the preferred method of stress for routine N-13 ammonia PET MPI. [Copyright &y& Elsevier]

Objectives: This study assessed the feasibility of treadmill exercise rubidium-82 (82Rb) positron emission tomography (PET) and compared image quality and diagnostic content with dipyridamole 82Rb PET in patients referred for evaluation of coronary artery disease (CAD). Background: Dipyridamole stress 82Rb PET myocardial perfusion imaging (MPI) is an accurate imaging modality used to diagnose CAD and determine prognosis. Although pharmacologic stress is used routinely, exercise treadmill stress may be an alternative and provide clinical information helpful to decision making, particularly for patients unwilling or unable to tolerate pharmacologic stress. Methods: Fifty patients (mean age, 60 ± 10 years; 47 men) underwent treadmill exercise and dipyridamole 82Rb PET. Images were assessed: 1) qualitatively using a 17-segment model and a semiquantitative visual score on a five-point scale and with calculation of summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS); and 2) quantitatively with a 70% threshold for abnormal perfusion and expressed as extent of abnormal perfusion (% left ventricular). Results: Treadmill exercise was preferred by 74% of patients (37 of 50, p < 0.001). The exercise and dipyridamole 82Rb PET summed scores and quantitative extent of abnormal perfusion were very similar and highly correlated. Results of Bland-Altman analysis showed no significant bias. Image quality was superior with exercise stress with greater myocardial uptake and higher target to background ratios. Conclusions: Treadmill exercise 82Rb PET is feasible and provides imaging results of similar diagnostic content and superior image quality compared with dipyridamole stress. Treadmill exercise is a reasonable alternative to pharmacologic stress with 82Rb PET MPI. [Copyright &y& Elsevier]

Whether initial invasive management in older vs younger adults with chronic coronary disease and moderate or severe ischemia improves health status or clinical outcomes is unknown. The goal of this study was to examine the impact of age on health status and clinical outcomes with invasive vs conservative management in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. One-year angina-specific health status was assessed with the 7-item Seattle Angina Questionnaire (SAQ) (score range 0-100; higher scores indicate better health status). Cox proportional hazards models estimated the treatment effect of invasive vs conservative management as a function of age on the composite clinical outcome of cardiovascular death, myocardial infarction, or hospitalization for resuscitated cardiac arrest, unstable angina, or heart failure. Among 4,617 participants, 2,239 (48.5%) were aged <65 years, 1,713 (37.1%) were aged 65 to 74 years, and 665 (14.4%) were aged ≥75 years. Baseline SAQ summary scores were lower in participants aged <65 years. Fully adjusted differences in 1-year SAQ summary scores (invasive minus conservative) were 4.90 (95% CI: 3.56-6.24) at age 55 years, 3.48 (95% CI: 2.40-4.57) at age 65 years, and 2.13 (95% CI: 0.75-3.51) at age 75 years (P interaction = 0.008). Improvement in SAQ Angina Frequency was less dependent on age (P interaction = 0.08). There were no age differences between invasive vs conservative management on the composite clinical outcome (P interaction = 0.29). Older patients with chronic coronary disease and moderate or severe ischemia had consistent improvement in angina frequency but less improvement in angina-related health status with invasive management compared with younger patients. Invasive management was not associated with improved clinical outcomes in older or younger patients. (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches [ISCHEMIA]; NCT01471522) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: The association of atherosclerotic features with first acute coronary syndromes (ACS) has not accounted for plaque burden.Objectives: The purpose of this study was to identify atherosclerotic features associated with precursors of ACS.Methods: We performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CTA) with follow-up over 3.4 ± 2.1 years. Patients with ACS and nonevent patients with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and coronary CTA-evaluated obstructive (≥50%) CAD. Separate core laboratories performed blinded adjudication of ACS and culprit lesions and quantification of baseline coronary CTA for percent diameter stenosis (%DS), percent cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibrofatty, and necrotic core), and presence of high-risk plaques (HRPs).Results: We identified 234 ACS and control pairs (age 62 years, 63% male). More than 65% of patients with ACS had nonobstructive CAD at baseline, and 52% had HRP. The %DS, cross-sectional PB, fibrofatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI]: 1.005 to 1.015; 1.008 per percent cross-sectional PB, 95% CI: 1.003 to 1.013; 1.002 per mm3 fibrofatty plaque, 95% CI: 1.000 to 1.003; 1.593 per mm3 necrotic core, 95% CI: 1.219 to 2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by coronary CTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP.Conclusions: Although ACS increases with %DS, most precursors of ACS cases and culprit lesions are nonobstructive. Plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate plaque burden. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the current analysis was to compare sex differences in the prognostic accuracy of stress myocardial perfusion rubidum-82 (Rb-82) positron emission tomography (PET). Background: The diagnostic evaluation of women presenting with suspected cardiac symptoms is challenging with reported reduced accuracy, attenuation artifact, and more recent concerns regarding radiation safety. Stress myocardial perfusion Rb-82 PET is a diagnostic alternative with improved image quality and radiation dosimetry. Currently, the prognostic accuracy of stress Rb-82 PET in women has not been established. Methods: A total of 6,037 women and men were enrolled in the PET Prognosis Multicenter Registry. Patients were followed for the occurrence of coronary artery disease (CAD) mortality, with a median follow-up of 2.2 years. Cox proportional hazards modeling was used to estimate CAD mortality. The net re-classification improvement index (NRI) was calculated. Results: The 5-year CAD mortality was 3.7% for women and 6.0% for men (p < 0.0001). Unadjusted CAD mortality ranged from 0.9% to 12.9% for women (p < 0.0001) and from 1.5% to 17.4% for men (p < 0.0001) for 0% to ≥15% abnormal myocardium at stress. In multivariable models, the percentage of abnormal stress myocardium was independently predictive of CAD mortality in women and men. An interaction term of sex by the percentage of abnormal stress myocardium was nonsignificant (p = 0.39). The categorical NRI when Rb-82 PET data was added to a clinical risk model was 0.12 for women and 0.17 for men. Only 2 cardiac deaths were reported in women <55 years of age; accordingly the percentage of abnormal myocardium at stress was of borderline significance (p = 0.063), but it was highly significant for women ≥55 years of age (p < 0.0001), with an increased NRI of 0.21 (95% confidence interval: 0.09 to 0.34), including 17% of CAD deaths and 3.9% of CAD survivors that were correctly re-classified in this older female subset. Conclusions: Stress Rb-82 PET provides significant and clinically meaningful effective risk stratification of women and men, supporting this modality as an alternative to comparative imaging modalities. Rb-82 PET findings were particularly helpful at identifying high-risk, older women. [Copyright &y& Elsevier]

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology-pressure and flow-as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements. [ABSTRACT FROM AUTHOR]

Angiographic severity of coronary artery stenosis has historically been the primary guide to revascularization or medical management of coronary artery disease. However, physiologic severity defined by coronary pressure and/or flow has resurged into clinical prominence as a potential, fundamental change from anatomically to physiologically guided management. This review addresses clinical coronary physiology—pressure and flow—as clinical tools for treating patients. We clarify the basic concepts that hold true for whatever technology measures coronary physiology directly and reliably, here focusing on positron emission tomography and its interplay with intracoronary measurements. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to evaluate the potential of serum heat shock protein 27 (HSP27) as a therapeutic target in coronary artery disease. Background: Expression of HSP27 in human coronary arteries diminishes with the progression of atherosclerosis, whereas ubiquitous HSP27 overexpression in apolipoprotein E−/− (ApoE−/−) mice attenuates atherogenesis. However, it remains unclear whether increasing serum HSP27 levels alone is sufficient for atheroprotection. Methods: Low- and intermediate-risk patients undergoing coronary or computed tomography angiography had serum HSP27 levels measured. Elevated serum HSP27 levels in female atheroprone ApoE−/− mice were achieved by transplantation with HSP27 overexpressing bone marrow or by administering recombinant HSP27. Results: Patients with >50% stenosis in any major epicardial artery had lower HSP27 levels compared with those free of atherosclerosis (median [interquartile range]: 2,176 pg/ml [551–5,475] vs. 6,200 pg/ml [2,575–9,560]; p < 0.001). After a 5-year period of clinical follow-up, low serum HSP27 levels (<50th percentile) were predictive of subsequent major adverse cardiovascular events (hazard ratio: 2.93, 95% confidence interval: 1.06 to 8.12; p = 0.04). In experimental murine models of atherosclerosis, increasing serum HSP27 levels both reduced de novo atherosclerotic lesion formation and enhanced features of plaque stability. Conclusions: In humans, low serum HSP27 levels are associated with the presence of coronary artery disease and prognostic of future adverse clinical events. In mouse models of atherosclerosis, increasing HSP27 levels reduced lesion progression and promoted features of plaque stability. Serum HSP27 levels may represent a potential therapeutic target for atherosclerosis. [Copyright &y& Elsevier]

Objectives: The aim of this study was to analyze the predictive value of coronary computed tomography angiography (CCTA) and to model and validate an optimized score for prognosis of 2-year survival on the basis of a patient population with suspected coronary artery disease (CAD). Background: Coronary computed tomography angiography carries important prognostic information in addition to the detection of obstructive CAD. But it is still unclear how the results of CCTA should be interpreted in the context of clinical risk predictors. Methods: The analysis is based on a test sample of 17,793 patients and a validation sample of 2,506 patients, all with suspected CAD, from the international CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry. On the basis of CCTA data and clinical risk scores, an optimized score was modeled. The endpoint was all-cause mortality. Results: During a median follow-up of 2.3 years, 347 patients died. The best CCTA parameter for prediction of mortality was the number of proximal segments with mixed or calcified plaques (C-index 0.64, p < 0.0001) and the number of proximal segments with a stenosis >50% (C-index 0.56, p = 0.002). In an optimized score including both parameters, CCTA significantly improved overall risk prediction beyond National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) score as best clinical score. According to this score, a proximal segment with either a mixed or calcified plaque or a stenosis >50% is equivalent to a 5-year increase in age or the risk of smoking. Conclusions: In CCTA, both plaque burden and stenosis, particularly in proximal segments, carry incremental prognostic value. A prognostic score on the basis of this data can improve risk prediction beyond clinical risk scores. [Copyright &y& Elsevier]

Objectives: The primary objective of this multicenter registry was to study the prognostic value of positron emission tomography (PET) myocardial perfusion imaging (MPI) and the improved classification of risk in a large cohort of patients with suspected or known coronary artery disease (CAD). Background: Limited prognostic data are available for MPI with PET. Methods: A total of 7,061 patients from 4 centers underwent a clinically indicated rest/stress rubidium-82 PET MPI, with a median follow-up of 2.2 years. The primary outcome of this study was cardiac death (n = 169), and the secondary outcome was all-cause death (n = 570). Net reclassification improvement (NRI) and integrated discrimination analyses were performed. Results: Risk-adjusted hazard of cardiac death increased with each 10% myocardium abnormal with mildly, moderately, or severely abnormal stress PET (hazard ratio [HR]: 2.3 [95% CI: 1.4 to 3.8; p = 0.001], HR: 4.2 [95% CI: 2.3 to 7.5; p < 0.001], and HR: 4.9 [95% CI: 2.5 to 9.6; p < 0.0001], respectively [normal MPI: referent]). Addition of percent myocardium ischemic and percent myocardium scarred to clinical information (age, female sex, body mass index, history of hypertension, diabetes, dyslipidemia, smoking, angina, beta-blocker use, prior revascularization, and resting heart rate) improved the model performance (C-statistic 0.805 [95% CI: 0.772 to 0.838] to 0.839 [95% CI: 0.809 to 0.869]) and risk reclassification for cardiac death (NRI 0.116 [95% CI: 0.021 to 0.210]), with smaller improvements in risk assessment for all-cause death. Conclusions: In patients with known or suspected CAD, the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors. [Copyright &y& Elsevier]

Objectives: This study sought to examine patterns of follow-up invasive coronary angiography (ICA) and revascularization (REV) after coronary computed tomography angiography (CCTA). Background: CCTA is a noninvasive test that permits direct visualization of the extent and severity of coronary artery disease (CAD). Post-CCTA patterns of follow-up ICA and REV are incompletely defined. Methods: We examined 15,207 intermediate likelihood patients from 8 sites in 6 countries; these patients were without known CAD, underwent CCTA, and were followed up for 2.3 ± 1.2 years for all-cause mortality. Coronary artery stenosis was judged as obstructive when ≥50% stenosis was present. A multivariable logistic regression was used to estimate ICA use. A Cox proportional hazards model was used to estimate all-cause mortality. Results: During follow-up, ICA rates for patients with no CAD to mild CAD according to CCTA were low (2.5% and 8.3%), with similarly low rates of REV (0.3% and 2.5%). Most ICA procedures (79%) occurred ≤3 months of CCTA. Obstructive CAD was associated with higher rates of ICA and REV for 1-vessel (44.3% and 28.0%), 2-vessel (53.3% and 43.6%), and 3-vessel (69.4% and 66.8%) CAD, respectively. For patients with <50% stenosis, early ICA rates were elevated; over the entirety of follow-up, predictors of ICA were mild left main, mild proximal CAD, respectively, or higher coronary calcium scores. In patients with <50% stenosis, the relative hazard for death was 2.2 (p = 0.011) for ICA versus no ICA. Conversely, for patients with CAD, the relative hazard for death was 0.61 for ICA versus no ICA (p = 0.047). Conclusions: These findings support the concept that CCTA may be used effectively as a gatekeeper to ICA. [Copyright &y& Elsevier]

Objectives: This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging. Background: Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on subsequent patient management are unclear. Methods: We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography. Results: Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results. Conclusions: Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomy''s Role in Coronary Artery [CAD] [SPARC]; NCT00321399) [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA). Background: The frequency and clinical relevance of CAD in patients without CAC are unclear. Methods: We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed. Results: Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84). Conclusions: In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA. [Copyright &y& Elsevier]

Objectives: We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA). Background: Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes. Methods: We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models. Results: At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men. Conclusions: Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis. [Copyright &y& Elsevier]

Objectives: We evaluated the prognostic value of myocardial flow reserve (MFR) using rubidium-82 (82Rb) positron emission tomography (PET) in patients assessed for ischemia. Background: The clinical value of MFR quantification using 82Rb PET beyond relative myocardial perfusion imaging remains uncertain. Methods: We prospectively enrolled 704 consecutive patients; 677 (96%) completed follow-up (median 387 days [interquartile range: 375 to 416 days]). Patients were divided into 4 groups: I, normal summed stress score (SSS) (<4) and normal myocardial flow reserve (MFR) (>2); II, normal SSS and MFR <2; III, SSS ≥4 and MFR ≥2; IV, SSS ≥4 and MFR <2. Results: For patients with a normal SSS and those with an abnormal SSS, there were significant differences in outcomes for hard events (cardiac death and myocardial infarction) between patients with MFR ≥2 and those with MFR <2 (I: 1.3% vs. II: 2% [p = 0.029]; III: 1.1% vs. IV: 11.4% [p = 0.05]) and for major adverse cardiac events (MACE) (p = 0.003 and p < 0.001, respectively). In the adjusted Cox model, MFR was an independent predictor of hard events (hazard ratio: 3.3; 95% confidence interval: 1.1 to 9.5; p = 0.029) and MACE (hazard ratio: 2.4, 95% confidence interval: 1.4 to 4.4, p = 0.003). The incremental prognostic value of the MFR over the SSS was demonstrated by comparing the adjusted SSS model with and without the MFR for hard events (p = 0.0197) and MACE (p = 0.002). Conclusions: MFR quantified using 82Rb PET predicts hard cardiac events and MACE independent of the SSS and other parameters. Routine assessment of 82Rb PET–quantified MFR could improve risk stratification for patients being investigated for ischemia. [ABSTRACT FROM AUTHOR]

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

Objectives: We sought to determine the incidence, clinical significance, and potential financial impact of noncardiac incidental findings (IF) identified with cardiac computed tomography (CT). Background: Cardiac CT is gaining acceptance and may lead to the frequent discovery of extracardiac IF. Methods: Consecutive patients undergoing cardiac CT had noncardiac structures evaluated after full field of view (32 to 50 cm) reconstruction. IF were categorized as clinically significant (CS), indeterminate, or clinically insignificant. Patient follow-up was performed by telephone, and verified with hospital records and/or communication with physicians. Results: Of 966 patients (58 ± 16 years of age, 55.4% men, >98% outpatients), 401 (41.5%) patients had noncardiac IF. A total of 12 (1.2%) patients had CS findings, and 68 (7.0%) patients had indeterminate findings. At follow-up (18.4 ± 7.6 months), none of the indeterminate findings became CS. Although 3 patients with indeterminate findings were diagnosed with malignant lesions, they were unrelated to the IF. After adjusting for age, IF were not an independent predictor of noncardiac death. Noncardiac death and cancer death in patients with and without IF were not statistically different. One patient suffered a major complication related to the investigation of an IF. The total direct cost associated with investigating IF was Canadian $57,596 (U.S. $83,035). Conclusions: Although noncardiac IF are common, clinically significant or indeterminate IF are less prevalent. Rates of death were similar in patients with and without IF, and IF was not an independent predictor of noncardiac death. The investigation of IF is not without cost or risk. Larger studies are required to assess the potential mortality benefit of identifying IF. [Copyright &y& Elsevier]