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Aims: We sought to compare the complementary prognostic value of exercise treadmill testing (ETT) and coronary computed tomographic angiography (CTA) among patients referred for both exams., Methods and Results: We studied 582 patients without known coronary artery disease (CAD) who were clinically referred for ETT and CTA within 6 months. Patients were followed for cardiovascular (CV) death, non-fatal myocardial infarction (MI), or late revascularization (>90 days), stratified by Duke Treadmill Score (DTS) and CAD severity (≥50% stenosis). Mean age was 54 ± 13 years (63% male). In median follow-up of 40 months, there were 3 CV deaths, 7 non-fatal MIs, and 26 late revascularizations. ETT was inconclusive in 23%, positive in 31%, and negative in 46%. CTA demonstrated no CAD in 37%, non-obstructive CAD in 28%, and obstructive CAD in 35%. Among low-risk ETT patients (n = 326), there were 3 MI, 10 late revascularizations, and the frequent presence of non-obstructive (32%, n = 105) and obstructive CAD (27%, n = 88). When present, ETT features (i.e., angina, DTS, ischaemic electrocardiogram changes, and exercise capacity) individually failed to predict CV death/MI after adjustment for Morise score. Conversely, both obstructive CAD [HR 4.9 (1.0-23.3), P = 0.048] and CAD extent by segment involvement score >4 [HR 3.9 (1.0-15.2), P = 0.049] predicted increased risk for CV death or MI., Conclusion: Patients with a low-risk ETT have an excellent prognosis at 40 months, despite the frequent presence of non-obstructive (32%) and obstructive (27%) CAD. In patients with an intermediate- to high-risk ETT (DTS <5), CTA can provide incremental risk stratification for future CV events., (Published by Oxford University Press on behalf of the European Society of Cardiology 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

In the >40 years since planar myocardial imaging with(43)K-potassium was introduced into clinical research and management of patients with coronary artery disease (CAD), diagnosis and treatment have undergone profound scientific and technological changes. One such innovation is the current state-of-the-art hardware and software for positron emission tomography myocardial perfusion imaging, which has advanced it from a strictly research-oriented modality to a clinically valuable tool. This review traces the evolving role of quantitative positron emission tomography measurements of myocardial blood flow in the evaluation and management of patients with CAD. It presents methodology, currently or soon to be available, that offers a paradigm shift in CAD management. Heretofore, radionuclide myocardial perfusion imaging has been primarily qualitative or at best semiquantitative in nature, assessing regional perfusion in relative terms. Thus, unlike so many facets of modern cardiovascular practice and CAD management, which depend, for example, on absolute values of key parameters such as arterial and left ventricular pressures, serum lipoprotein, and other biomarker levels, the absolute levels of rest and maximal myocardial blood flow have yet to be incorporated into routine clinical practice even in most positron emission tomography centers where the potential to do so exists. Accordingly, this review focuses on potential value added for improving clinical CAD practice by measuring the absolute level of rest and maximal myocardial blood flow. Physiological principles and imaging fundamentals necessary to understand how positron emission tomography makes robust, quantitative measurements of myocardial blood flow possible are highlighted. [ABSTRACT FROM AUTHOR]

Aims We sought to compare the complementary prognostic value of exercise treadmill testing (ETT) and coronary computed tomographic angiography (CTA) among patients referred for both exams. Methods and results We studied 582 patients without known coronary artery disease (CAD) who were clinically referred for ETT and CTA within 6 months. Patientswere followed for cardiovascular (CV) death, non-fatal myocardial infarction (MI), or late revascularization (.90 days), stratified by Duke Treadmill Score (DTS) and CAD severity (≥50% stenosis). Mean age was 54+13 years (63% male). In median follow-up of 40 months, therewere 3 CV deaths, 7 non-fatal MIs, and 26 late revascularizations. ETTwas inconclusive in 23%, positive in 31%, and negative in 46%.CTAdemonstrated noCADin 37%, nonobstructive CADin 28%, and obstructive CADin 35%. Among low-risk ETT patients (n ¼ 326), therewere 3 MI, 10 late revascularizations, and the frequent presence of non-obstructive (32%, n ¼ 105) and obstructive CAD (27%, n ¼ 88). When present, ETT features (i.e. angina, DTS, ischaemic electrocardiogram changes, and exercise capacity) individually failed to predict CV death/MI after adjustment for Morise score. Conversely, both obstructive CAD [HR 4.9 (1.0-23.3), P ¼ 0.048] and CAD extent by segment involvement score .4 [HR 3.9 (1.0-15.2), P ¼ 0.049] predicted increased risk for CV death or MI. Conclusion Patients with a low-risk ETT have an excellent prognosis at 40 months, despite the frequent presence of non-obstructive (32%) and obstructive (27%) CAD. In patients with an intermediate- to high-risk ETT (DTS ,5), CTA can provide incremental risk stratification for future CV events. [ABSTRACT FROM AUTHOR]

Background Left main disease (LMD) and three-vessel disease (3VD) have important prognostic value in patients with coronary artery disease. However, uncertainties still exist about their prevalence and predictors in patients with acute coronary syndrome (ACS) and also in patients with stable coronary disease. Thus the aim of this study was to perform an international collaborative systematic review and metaanalysis to appraise the prevalence and predictors of LMD and 3VD. Methods Medline/PubMed were systematically searched for eligible studies published up to 2010, reporting multivariate predictors of LMD or 3VD. Study features, patient characteristics, and prevalence and predictors of LMD and 3VD were abstracted and pooled with random-effect methods (95% CIs). Results 17 studies (22 740 patients) were included, 11 focusing on ACS (17 896 patients) and six on stable coronary disease (4844 patients). In the ACS subgroup, LMD or 3VD occurred in 20% (95% CI 7.2% to 33.4%), LMD in 12% (95% CI 10.5% to 13.5%), and 3VD in 25% (95% CI 23.1% to 27.0%). Heart failure at admission and extent of ST-segment elevation in lead aVR on 12-lead ECG were the most powerful predictors of LMD or 3VD. In the stable disease subgroup, LMD or 3VD was found in 36% (95% CI 18.5% to 48.8%), with the most powerful predictors being transient ischaemic dilation during the imaging stress test, extent of ST-segment elevation in aVR and V1 during the stress test, and hyperlipidaemia. Conclusions This meta-analysis demonstrated that severe coronary diseasedthat is, LMD or 3VDdis more common in patients with ACS or stable coronary disease than generally perceived, and that simple and low-cost tools may help in the selection of the most appropriate therapeutic approach. [ABSTRACT FROM AUTHOR]

Objectives: The authors tested the hypothesis that exercise treadmill testing (ETT)–induced ST-segment elevation (STE) in electrocardiographic lead aVR is an important indicator of significant left main coronary artery (LMCA) or ostial left anterior descending coronary artery (LAD) stenosis. Background: Although STE in lead aVR is an indicator of LMCA or very proximal LAD occlusion in acute coronary syndromes, its predictive power in the setting of ETT is uncertain. Methods: Rest and stress electrocardiograms, clinical and stress test parameters, and single photon-emission computed tomographic myocardial perfusion imaging (MPI) data, when available, were obtained in 454 subjects (378 with MPI) who underwent cardiac catheterization and standard Bruce ETT ≤ 6 months before catheterization. Patients were selected for LMCA or ostial LAD disease (≥50% stenosis) with or without other coronary artery disease (CAD), CAD (≥70% stenosis) without significant LMCA or ostial LAD, or no significant CAD. Univariate followed by multivariate logistic regression analyses of clinical, electrocardiographic, stress test, and single photon-emission computed tomographic MPI variables were used to identify significant correlates of LMCA or ostial LAD stenosis. Bayesian analysis of the data also was performed. Results: LMCA (n = 38) or ostial LAD (n = 42) stenosis occurred in 75 patients (5 patients had both). The remainder had CAD without LMCA or ostial LAD stenosis (n = 276) or no CAD (n = 103). In multivariate analysis, the strongest predictor was stress-induced STE in lead aVR (p < 0.0001, area under the curve 0.82). Both left ventricular ejection fraction (after stress) and percent reversible LAD ischemia on single photon-emission computed tomographic MPI also contributed significantly in multivariate analysis (p < 0.005 and p < 0.05, respectively, areas under the curve 0.60 and 0.64, respectively). Although additional electrocardiographic, stress test, and MPI variables were significant univariate predictors, none was statistically significant in multivariate analysis. At 1-mm STE in lead aVR, sensitivity for LMCA or ostial LAD stenosis was 75%, specificity was 81%, overall predictive accuracy was 80%, and post-test probability increased nearly 3 times from 17% to 45%. Conclusions: Stress (ETT)–induced STE in lead aVR is an important indicator of significant LMCA or ostial LAD stenosis and should not be ignored. [Copyright &y& Elsevier]

Objectives: This study tests the hypothesis that absolute measurement of adenosine (Ado)-stimulated myocardial blood flow (MBFado) is superior to measurement of relative tracer uptake for identification of hemodynamically significant coronary artery disease (CAD). Background: Positron emission tomography measurement of absolute myocardial blood flow (MBF) (13N-ammonia) with Ado has the capability to more accurately assess hemodynamic severity of CAD than measurement of relative tracer content (TC) (nCi/ml) during Ado, which by definition depends on at least 1 normal zone to which others are compared. Methods: A total of 27 patients (20 male, 58 ± 11 years, mean ± SD) with known or suspected CAD and 21 normal subjects (13 male, 38 ± 10 years) were studied. Parametric (K1) MBF images and TC sum images were analyzed. A stenosis ≥70% defined significant CAD. The receiver-operator characteristic curve (ROC) analysis area under the curve (AUC) compared MBF and TC results. Cut-point analysis for sensitivity, specificity, and accuracy showed the best MBF criteria for CAD as MBFado <1.85 ml/min/g and the best TC as <70% maximum. The myocardial blood flow reserve ratio (MBFR) (optimal <2.0×) also was studied. Results: The ROC analysis of PET parameters showed that MBFado was superior to <70% maximum uptake for CAD detection (n = 144 vessels; AUC 0.900 vs. 0.690, respectively, p < 0.0001) and was marginally greater than MBFR (0.856; p = 0.10). For CAD cut-point analysis, MBFado accuracy exceeded TC (0.84 vs. 0.72, respectively, p = 0.005), as did sensitivity (0.81 vs. 0.48, respectively; p = 0.001). Specificity of MBFado for CAD classification (0.85) was comparable to TC (0.82; p = NS). Sensitivity, specificity, and predictive accuracy for MBFR were 0.62, 0.85, and 0.79, respectively. The difference in specificity was not significant versus MBFado. However, MBFado was more sensitive than MBFR (p = 0.01). The difference in predictive accuracy was borderline (p = 0.06) in favor of MBFado. Conclusions: Measurement of Ado-stimulated absolute MBF is superior to relative measurement of myocardial tracer retention for identification of CAD and can be accomplished with a single MBFado measurement. [Copyright &y& Elsevier]

Objectives: This study sought to determine the feasibility of performing a comprehensive cardiac computed tomographic (CT) examination incorporating stress and rest myocardial perfusion imaging together with coronary computed tomography angiography (CTA). Background: Although cardiac CT can identify coronary stenosis, very little data exist on the ability to detect stress-induced myocardial perfusion defects in humans. Methods: Thirty-four patients who had a nuclear stress test and invasive angiography were included in the study. Dual-source computed tomography (DSCT) was performed as follows: 1) stress CT: contrast-enhanced scan during adenosine infusion; 2) rest CT: contrast-enhanced scan using prospective triggering; and 3) delayed scan: acquired 7 min after rest CT. Images for CTA, computed tomography perfusion (CTP), and single-photon emission computed tomography (SPECT) were each read by 2 independent blinded readers. Results: The DSCT protocol was successfully completed for 33 of 34 subjects (average age 61.4 ± 10.7 years; 82% male; body mass index 30.4 ± 5 kg/m2) with an average radiation dose of 12.7 mSv. On a per-vessel basis, CTP alone had a sensitivity of 79% and a specificity of 80% for the detection of stenosis ≥50%, whereas SPECT myocardial perfusion imaging had a sensitivity of 67% and a specificity of 83%. For the detection of vessels with ≥50% stenosis with a corresponding SPECT perfusion abnormality, CTP had a sensitivity of 93% and a specificity of 74%. The CTA during adenosine infusion had a per-vessel sensitivity of 96%, specificity of 73%, and negative predictive value of 98% for the detection of stenosis ≥70%. Conclusions: Adenosine stress CT can identify stress-induced myocardial perfusion defects with diagnostic accuracy comparable to SPECT, with similar radiation dose and with the advantage of providing information on coronary stenosis. [Copyright &y& Elsevier]

: ObjectivesWe sought to use positron emission tomography (PET) to test the hypothesis that hyperhomocysteinemia adversely effects coronary microvascular dilator function.: BackgroundHyperhomocysteinemia is associated with abnormal endothelium-dependent vasodilation in peripheral human arteries. However, its effect on the coronary circulation is not known.: MethodsEighteen healthy humans, age 24 to 56 years, were enrolled in a double-blind, crossover trial. Basal and adenosine-stimulated myocardial blood flow (MBF) was determined by PET: after ingestion of placebo and after methionine-induced hyperhomocysteinemia. Further, brachial ultrasonography was used to assess flow-mediated vasodilation. Additionally, to assess the role of nitric oxide (NO) in adenosine-mediated vasodilation, the MBF response to adenosine was measured in the presence and absence of the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA) (0.3 mg/kg/min intravenously).: ResultsHyperhomocysteinemia resulted in a reduction in the MBF dose-response curve to adenosine (p < 0.05). This was most apparent with low dose adenosine, where MBF augmentation was significantly blunted during hyperhomocysteinemia (1.06 ± 1.00 ml/min/g vs. 0.58 ± 0.78 ml/min/g, placebo vs. methionine, p < 0.05). Similarly, flow-mediated brachial artery vasodilation was impaired during hyperhomocysteinemia (4.4 ± 2.6% vs. 2.6 ± 2.3%, placebo vs. methionine, p < 0.05). In a separate series of experiments, MBF during adenosine was reduced in the presence of l-NMMA (p < 0.05 analysis of variance). This was most apparent at the low dose of adenosine, where MBF response to adenosine was blunted in the presence of l-NMMA (2.08 ± 1.34 ml/min/g vs. 1.48 ± 1.32 ml/min/g, placebo vs. l-NMMA, p < 0.05).: ConclusionsThe data, therefore, support the hypothesis that acute hyperhomocysteinemia impairs microvascular dilation in the human coronary circulation as a result of reduced NO bioavailability. [Copyright &y& Elsevier]