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Objectives: To validate published prediction models for the presence of obstructive coronary artery disease (CAD) in patients with new onset stable typical or atypical angina pectoris and to assess the incremental value of the CT coronary calcium score (CTCS).Methods: We searched the literature for clinical prediction rules for the diagnosis of obstructive CAD, defined as ≥50% stenosis in at least one vessel on conventional coronary angiography. Significant variables were re-analysed in our dataset of 254 patients with logistic regression. CTCS was subsequently included in the models. The area under the receiver operating characteristic curve (AUC) was calculated to assess diagnostic performance.Results: Re-analysing the variables used by Diamond & Forrester yielded an AUC of 0.798, which increased to 0.890 by adding CTCS. For Pryor, Morise 1994, Morise 1997 and Shaw the AUC increased from 0.838 to 0.901, 0.831 to 0.899, 0.840 to 0.898 and 0.833 to 0.899. CTCS significantly improved model performance in each model.Conclusions: Validation demonstrated good diagnostic performance across all models. CTCS improves the prediction of the presence of obstructive CAD, independent of clinical predictors, and should be considered in its diagnostic work-up. [ABSTRACT FROM AUTHOR]

Cardiovascular diagnostic imaging tests are increasingly used in everyday clinical practice, but are often imperfect, just like any other diagnostic test. The performance of a cardiovascular diagnostic imaging test is usually expressed in terms of sensitivity and specificity compared with the reference standard (gold standard) for diagnosing the disease. However, evidence-based application of a diagnostic test also requires knowledge about the pre-test probability of disease, the benefit of making a correct diagnosis, the harm caused by false-positive imaging test results, and potential adverse effects of performing the test itself. To assist in clinical decision making regarding appropriate use of cardiovascular diagnostic imaging tests, we reviewed quantitative concepts related to diagnostic performance (e.g., sensitivity, specificity, predictive values, likelihood ratios), as well as possible biases and solutions in diagnostic performance studies, Bayesian principles, and the threshold approach to decision making., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The optimal imaging strategy for patients with stable chest pain is uncertain., Objective: To determine the cost-effectiveness of different imaging strategies for patients with stable chest pain., Design: Microsimulation state-transition model., Data Sources: Published literature., Target Population: 60-year-old patients with a low to intermediate probability of coronary artery disease (CAD)., Time Horizon: Lifetime., Perspective: The United States, the United Kingdom, and the Netherlands., Intervention: Coronary computed tomography (CT) angiography, cardiac stress magnetic resonance imaging, stress single-photon emission CT, and stress echocardiography., Outcome Measures: Lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios., Results of Base-Case Analysis: The strategy that maximized QALYs and was cost-effective in the United States and the Netherlands began with coronary CT angiography, continued with cardiac stress imaging if angiography found at least 50% stenosis in at least 1 coronary artery, and ended with catheter-based coronary angiography if stress imaging induced ischemia of any severity. For U.K. men, the preferred strategy was optimal medical therapy without catheter-based coronary angiography if coronary CT angiography found only moderate CAD or stress imaging induced only mild ischemia. In these strategies, stress echocardiography was consistently more effective and less expensive than other stress imaging tests. For U.K. women, the optimal strategy was stress echocardiography followed by catheter-based coronary angiography if echocardiography induced mild or moderate ischemia., Results of Sensitivity Analysis: Results were sensitive to changes in the probability of CAD and assumptions about false-positive results., Limitations: All cardiac stress imaging tests were assumed to be available. Exercise electrocardiography was included only in a sensitivity analysis. Differences in QALYs among strategies were small., Conclusion: Coronary CT angiography is a cost-effective triage test for 60-year-old patients who have nonacute chest pain and a low to intermediate probability of CAD., Primary Funding Source: Erasmus University Medical Center.

Several non-invasive imaging techniques are currently in use for the diagnostic workup of adult patients with stable chest pain suspected of having coronary artery disease (CAD). In this paper, we present a systematic overview of the evidence on diagnostic performance and comparative cost-effectiveness of new modalities in comparison to established technologies. A literature search for English language studies from 2009 to 2013 was performed, and two investigators independently extracted data on patient and study characteristics. The reviewed published evidence on diagnostic performance and cost-effectiveness support a strategy of CTCA as a rule out (gatekeeper) test of CAD in low- to intermediate-risk patients since it has excellent diagnostic performance and as initial imaging test is cost-effective under different willingness-to-pay thresholds. More cost-effectiveness research is needed in order to define the role and choice of cardiac stress imaging tests.

Background: To determine the comparative effectiveness and costs of a CT-strategy and a stress-electrocardiography-based strategy (standard-of-care; SOC-strategy) for diagnosing coronary artery disease (CAD)., Methods: A decision analysis was performed based on a well-documented prospective cohort of 471 outpatients with stable chest pain with follow-up combined with best-available evidence from the literature. Outcomes were correct classification of patients as CAD- (no obstructive CAD), CAD+ (obstructive CAD without revascularization) and indication for Revascularization (using a combination reference standard), diagnostic costs, lifetime health care costs, and quality-adjusted life years (QALY). Parameter uncertainty was analyzed using probabilistic sensitivity analysis., Results: For men (and women), diagnostic cost savings were €245 (€252) for the CT-strategy as compared to the SOC-strategy. The CT-strategy classified 82% (88%) of simulated men (women) in the appropriate disease category, whereas 83% (85%) were correctly classified by the SOC-strategy. The long-term cost-effectiveness analysis showed that the SOC-strategy was dominated by the CT-strategy, which was less expensive (-€229 in men, -€444 in women) and more effective (+0.002 QALY in men, +0.005 in women). The CT-strategy was cost-saving (-€231) but also less effective compared to SOC (-0.003 QALY) in men with a pre-test probability of ≥ 70%. The CT-strategy was cost-effective in 100% of simulations, except for men with a pre-test probability ≥ 70% in which case it was 59%., Conclusions: The results suggest that a CT-based strategy is less expensive and equally effective compared to SOC in all women and in men with a pre-test probability <70%., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To compare the diagnostic performance and radiation exposure of 128-slice dual-source CT coronary angiography (CTCA) protocols to detect coronary stenosis with more than 50 % lumen obstruction., Methods: We prospectively included 459 symptomatic patients referred for CTCA. Patients were randomized between high-pitch spiral vs. narrow-window sequential CTCA protocols (heart rate below 65 bpm, group A), or between wide-window sequential vs. retrospective spiral protocols (heart rate above 65 bpm, group B). Diagnostic performance of CTCA was compared with quantitative coronary angiography in 267 patients., Results: In group A (231 patients, 146 men, mean heart rate 58 ± 7 bpm), high-pitch spiral CTCA yielded a lower per-segment sensitivity compared to sequential CTCA (89 % vs. 97 %, P = 0.01). Specificity, PPV and NPV were comparable (95 %, 62 %, 99 % vs. 96 %, 73 %, 100 %, P > 0.05) but radiation dose was lower (1.16 ± 0.60 vs. 3.82 ± 1.65 mSv, P < 0.001). In group B (228 patients, 132 men, mean heart rate 75 ± 11 bpm), per-segment sensitivity, specificity, PPV and NPV were comparable (94 %, 95 %, 67 %, 99 % vs. 92 %, 95 %, 66 %, 99 %, P > 0.05). Radiation dose of sequential CTCA was lower compared to retrospective CTCA (6.12 ± 2.58 vs. 8.13 ± 4.52 mSv, P < 0.001). Diagnostic performance was comparable in both groups., Conclusion: Sequential CTCA should be used in patients with regular heart rates using 128-slice dual-source CT, providing optimal diagnostic accuracy with as low as reasonably achievable (ALARA) radiation dose.

Objective: Echocardiography, radionuclide myocardial perfusion imaging (MPI), and coronary CT angiography (CTA) are the three main imaging techniques used in the emergency department for the diagnosis of acute coronary syndrome (ACS). The purpose of this article is to quantitatively examine existing evidence about the diagnostic performance of these imaging tests in this setting., Conclusion: Our systematic search of the medical literature showed no significant difference between the modalities for the detection of ACS in the emergency department. There was a slight, positive trend favoring coronary CTA. Given the absence of large differences in diagnostic performance, practical aspects such as local practice, expertise, medical facilities, and individual patient characteristics may be more important.

Unlabelled: The performance of a diagnostic test is often expressed in terms of sensitivity and specificity compared with the reference standard. Calculations of sensitivity and specificity commonly involve multiple observations per patient, which implies that the data are clustered. Whether analysis of sensitivity and specificity per patient or using multiple observations per patient is preferable depends on the clinical context and consequences. The purpose of this article was to discuss and illustrate the most common statistical methods that calculate sensitivity and specificity of clustered data, adjusting for the possible correlation between observations within each patient. This tutorial presents and illustrates the following methods: (a) analysis at different levels ignoring correlation, (b) variance adjustment, (c) logistic random-effects models, and (d) generalized estimating equations. The choice of method and the level of reporting should correspond with the clinical decision problem. If multiple observations per patient are relevant to the clinical decision problem, the potential correlation between observations should be explored and taken into account in the statistical analysis., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12120509/-/DC1., (© RSNA, 2012.)

Background: Transcatheter aortic valve replacement (TAVR) offers a new treatment option for patients with aortic stenosis, but costs may play a decisive role in decision making. Current studies are evaluating TAVR in an intermediate-risk population. We assessed the in-hospital and 1-year follow-up costs of patients undergoing TAVR and surgical aortic valve replacement (SAVR) at intermediate operative risk and identified important cost components., Methods: We prospectively collected clinical data on 141 patients undergoing TAVR and 405 undergoing SAVR. Propensity score matching yielded 42 matched pairs at intermediate risk. Costs were assessed using a detailed resource-use approach and compared using bootstrap methods., Results: In-hospital costs were higher in TAVR patients than in SAVR patients (€40802 vs €33354, respectively; p=0.010). The total costs at 1 year were €46217 vs €35511, respectively (p=0.009). The TAVR was less costly with regard to blood products, operating room use, and length-of-stay., Conclusions: For intermediate-risk patients with severe aortic stenosis the costs at 1 year are higher for TAVR than for SAVR. The difference was mainly caused by the higher costs of the transcatheter valve and was not compensated by the lower costs for blood products and hospital stay in TAVR patients. Therefore, SAVR remains a clinically and economically attractive treatment option., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine and compare the diagnostic performance of stress myocardial perfusion imaging (MPI) for the diagnosis of obstructive coronary artery disease (CAD), using conventional coronary angiography (CCA) as the reference standard., Methods: We searched Medline and Embase for literature that evaluated stress MPI for the diagnosis of obstructive CAD using magnetic resonance imaging (MRI), contrast-enhanced echocardiography (ECHO), single-photon emission computed tomography (SPECT) and positron emission tomography (PET)., Results: All pooled analyses were based on random effects models. Articles on MRI yielded a total of 2,970 patients from 28 studies, articles on ECHO yielded a sample size of 795 from 10 studies, articles on SPECT yielded 1,323 from 13 studies. For CAD defined as either at least 50 %, at least 70 % or at least 75 % lumen diameter reduction on CCA, the natural logarithms of the diagnostic odds ratio (lnDOR) for MRI (3.63; 95 % CI 3.26-4.00) was significantly higher compared to that of SPECT (2.76; 95 % CI 2.28-3.25; P = 0.006) and that of ECHO (2.83; 95 % CI 2.29-3.37; P = 0.02). There was no significant difference between the lnDOR of SPECT and ECHO (P = 0.52)., Conclusion: Our results suggest that MRI is superior for the diagnosis of obstructive CAD compared with ECHO and SPECT. ECHO and SPECT demonstrated similar diagnostic performance.

Objectives: To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations., Design: Retrospective pooled analysis of individual patient data., Setting: 18 hospitals in Europe and the United States., Participants: Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively)., Main Outcome Measures: Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined., Results: We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory., Conclusions: Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Purpose: To determine and compare the prognostic value of cardiac computed tomographic (CT) angiography, coronary calcium scoring, and exercise electrocardiography (ECG) in patients with chest pain who are suspected of having coronary artery disease (CAD)., Materials and Methods: This study complied with the Declaration of Helsinki, and the local ethics committee approved the study. Patients (n = 471) without known CAD underwent exercise ECG and dual-source CT at a rapid assessment outpatient chest pain clinic. Coronary calcification and the presence of 50% or greater coronary stenosis (in one or more vessels) were assessed with CT. Exercise ECG results were classified as normal, ischemic, or nondiagnostic. The primary outcome was a major adverse cardiac event (MACE), defined as cardiac death, nonfatal myocardial infarction, or unstable angina requiring hospitalization and revascularization beyond 6 months. Univariable and multivariable Cox regression analysis was used to determine the prognostic values, while clinical impact was assessed with the net reclassification improvement metric., Results: Follow-up was completed for 424 (90%) patients; the mean duration of follow-up was 2.6 years. A total of 44 MACEs occurred in 30 patients. Four of the MACEs were cardiac deaths and six were nonfatal myocardial infarctions. The presence of coronary calcification (hazard ratio [HR], 8.22 [95% confidence interval {CI}: 1.96, 34.51]), obstructive CAD (HR, 6.22 [95% CI: 2.77, 13.99]), and nondiagnostic stress test results (HR, 3.00 [95% CI: 1.26, 7.14]) were univariable predictors of MACEs. In the multivariable model, CT angiography findings (HR, 5.0 [95% CI: 1.7, 14.5]) and nondiagnostic exercise ECG results (HR, 2.9 [95% CI: 1.2, 7.0]) remained independent predictors of MACEs. CT angiography findings showed incremental value beyond clinical predictors and stress testing (global χ(2), 37.7 vs 13.7; P < .001), whereas coronary calcium scores did not have further incremental value (global χ(2), 38.2 vs 37.7; P = .40)., Conclusion: CT angiography findings are a strong predictor of future adverse events, showing incremental value over clinical predictors, stress testing, and coronary calcium scores., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110744/-/DC1., (RSNA, 2011)

Aims: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort., Methods and Results: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence., Conclusion: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

Objectives: The purpose of this study was to critically appraise guidelines on imaging of asymptomatic coronary artery disease (CAD)., Background: Various imaging tests exist to detect CAD in asymptomatic persons. Because randomized controlled trials are lacking, guidelines that address the use of CAD imaging tests may disagree., Methods: Guidelines in English published between January 1, 2003, and February 26, 2010, were retrieved using MEDLINE, Cumulative Index to Nursing and Allied Health Literature, the National Guideline Clearinghouse, the National Library for Health, the Canadian Medication Association Infobase, and the Guidelines International Network International Guideline Library. Guidelines developed by national and international medical societies from Western countries, containing recommendations on imaging of asymptomatic CAD were included. Rigor of development was scored by 2 independent reviewers using the Appraisal of Guidelines Research and Evaluation (AGREE) instrument. One reviewer performed full extraction of recommendations, which was checked by a second reviewer., Results: Of 2,415 titles identified, 14 guidelines met our inclusion criteria. Eleven of 14 guidelines reported relationship with industry. The AGREE scores varied across guidelines from 21% to 93%. Two guidelines considered cost effectiveness. Eight guidelines recommended against or found insufficient evidence for testing of asymptomatic CAD. The other 6 guidelines recommended imaging patients at intermediate or high CAD risk based on the Framingham risk score, and 5 considered computed tomography calcium scoring useful for this purpose., Conclusions: Guidelines on risk assessment by imaging of asymptomatic CAD contain conflicting recommendations. More research, including randomized controlled trials, evaluating the impact of imaging on clinical outcomes and costs is needed., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the effectiveness and cost-effectiveness of state-of-the-art noninvasive diagnostic imaging strategies in patients with a transient ischemic attack (TIA) or minor stroke who are suspected of having carotid artery stenosis (CAS)., Materials and Methods: All prospectively evaluated patients provided informed consent, and the local ethics committee approved this study. Diagnostic performance, treatment, long-term events, quality of life, and costs resulting from strategies employing duplex ultrasonography (US), computed tomographic (CT) angiography, contrast material-enhanced magnetic resonance (MR) angiography, and combinations of these modalities were modeled in a decision tree and Markov model. Data sources included a prospective diagnostic cohort study, a meta-analysis, and a review of the literature. Outcomes were costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net health benefits (QALY-equivalents), with a willingness-to-pay threshold of euro 50,000 per QALY and a societal perspective. The strategy with the highest net health benefit was considered the most cost effective. Extensive one-way, two-way, and probabilistic sensitivity analyses to explore the effect of varying parameter values were performed. The reference case analysis assumed that patients underwent surgery 2-4 weeks after the first symptoms, and the effect of earlier intervention was explored., Results: The reference case analysis showed that duplex US combined with CT angiography and surgery for 70%-99% stenoses was the most cost-effective strategy, with a net health benefit of 13.587 and 15.542 QALY-equivalents in men and women, respectively. In men, the CT angiography strategy with a 70%-99% cutoff yielded slightly more QALYs, at an incremental cost of euro 71,419 per QALY, compared with duplex US combined with CT angiography. In patients with a high-risk profile, in patients with a high prior probability of disease, and when patients could be treated within 2 weeks after the first symptoms, the CT angiography strategy with surgery for 50%-99% stenoses was the most cost-effective strategy., Conclusion: In diagnosing CAS, duplex US should be the initial test, and, if its results are positive, CT angiography should be performed; patients with 70%-99% stenoses should then undergo carotid endarterectomy. In patients with a high-risk profile, a high probability of CAS, or who can undergo surgery without delay, immediate CT angiography and surgery for 50%-99% stenoses is indicated.

Purpose: To determine the cost-effectiveness of computed tomographic (CT) coronary angiography as a triage test, performed prior to conventional coronary angiography, by using a Markov model., Materials and Methods: A Markov model was used to analyze the cost-effectiveness of CT coronary angiography performed as a triage test prior to conventional coronary angiography from the perspective of the patient, physician, hospital, health care system, and society by using recommendations from the United Kingdom, the United States, and the Netherlands for cost-effectiveness analyses. For CT coronary angiography, a range of sensitivities (79%-100%) and specificities (63%-94%) were used to help diagnose significant coronary artery disease (CAD). Optimization criteria (ie, outcomes considered) were: revised posttest probability of CAD, life-years, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analysis was performed., Results: For a prior probability of CAD of less than 40%, the probability of CAD after CT coronary angiography with negative results was less than 1%. The Markov model calculations from the patient/physician perspective suggest that CT coronary angiography maximizes life-years respectively in 60-year-old men and women at a prior probability of less than 38% and 24% and maximizes QALYs at a prior probability of less than 17% and 11%. From the hospital/health care perspective, CT coronary angiography helps reduce health care and direct nonhealth care-related costs (according to UK/U.S. recommendations), regardless of prior probability, and lowers all costs, including production losses (Netherlands recommendations) at a prior probability of less than 87%-92%. Analysis performed from a societal perspective by using a willingness-to-pay threshold level of euro 80,000/QALY suggests that CT coronary angiography is cost-effective when the prior probability is lower than 44% and 37% in men and women, respectively. Sensitivity analyses showed that results changed across the reported range of sensitivity of CT coronary angiography., Conclusion: The optimal diagnostic work-up depends on the optimization criterion, prior probability of CAD, and the diagnostic performance of CT coronary angiography.