Aortic valve chordae tendineae: A rare cause of aortic stenosis.

We describe a rare case of severe low-flow, low-gradient aortic stenosis due to a calcified aortic valve chordae tendineae. The chordae was captured on cardiac computed tomography (CT) using advanced 3-dimensional image reconstruction to reveal the fibrous strand tethering the non-coronary cusp to the left ventricular outflow tract, rendering it functionally immobile. This is one of the first reported cases of severe aortic stenosis from an aortic valve chordae tendineae which highlights the utility of advanced image processing techniques in cardiac CT.

Controversies in Diagnostic Imaging of Patients With Suspected Stable and Acute Chest Pain Syndromes.

There has been a tremendous growth quantity of high-quality imaging evidence in the area of acute and stable ischemic heart disease (SIHD). A number of recent comparative effectiveness trials have spurned significant controversies in the field of cardiovascular imaging. The result of this evidence is that many health care policies and national guidelines have undergone significant revisions. With all of this evidence, many challenges remain and the optimal evaluation strategy for evaluation of patients presenting with chest pain remains ill-defined. This paper enlisted the guidance of numerous experts in the field of cardiovascular imaging to garner their perspective on available imaging research in chest pain syndromes. Each of these vignettes represent editorial perspectives and diverse opinions as to which, if any, should be the primary test in the evaluation of stable chest pain. These perspectives are not meant to be all inclusive but to highlight many of the commonly discussed controversies in the evaluation of chest pain symptoms. These perspectives are presented as a pre-amble to an upcoming American College of Cardiology/American Heart Association clinical practice guideline that is undergoing revision from the previous report published in 2012. The evidence has changed considerably since the 2012 SIHD guideline, and the current perspectives represent the diversity of available evidence as to the optimal imaging strategy for evaluation of the symptomatic patient.

Pretest probability for patients with suspected obstructive coronary artery disease: re-evaluating Diamond-Forrester for the contemporary era and clinical implications: insights from the PROMISE trial.

AIMS: To update pretest probabilities (PTP) for obstructive coronary artery disease (CAD ≥ 50%) across age, sex, and clinical symptom strata, using coronary computed tomography angiography (CTA) in a large contemporary population of patients with stable chest pain referred to non-invasive testing. METHODS AND RESULTS: We included patients enrolled in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial and randomized to CTA. Exclusively level III-certified readers, blinded to demographic and clinical data, assessed the prevalence of CAD ≥ 50% in a central core lab. After comparing the recent European Society of Cardiology-Diamond and Forrester PTP (ESC-DF) with the actual observed prevalence of CAD ≥ 50%, we created a new PTP set by replacing the ESC-DF PTP with the observed prevalence of CAD ≥ 50% across strata of age, sex, and type of angina. In 4415 patients (48.3% men; 60.5 ± 8.2 years; 78% atypical angina; 11% typical angina; 11% non-anginal chest pain), the observed prevalence of CAD ≥ 50% was 13.9%, only one-third of the average ESC-DF PTP (40.6; P < 0.001 for difference). The PTP in the new set ranged 2-48% and were consistently lower than the ESC-DF PTP across all age, sex, and angina type categories. Initially, 4284/4415 (97%) patients were classified as intermediate-probability by the ESC-DF (PTP 15-85%); using the PROMISE-PTP, 50.2% of these patients were reclassified to the low PTP category (PTP < 15%). CONCLUSION: The ESC-DF PTP overestimate vastly the actual prevalence of CAD ≥ 50%. A new set of PTP, derived from results of non-invasive testing, may substantially reduce the need for non-invasive tests in stable chest pain.

The External Validity of Prediction Models for the Diagnosis of Obstructive Coronary Artery Disease in Patients With Stable Chest Pain: Insights From the PROMISE Trial.

OBJECTIVES: This study sought to externally validate prediction models for the presence of obstructive coronary artery disease (CAD). BACKGROUND: A better assessment of the probability of CAD may improve the identification of patients who benefit from noninvasive testing. METHODS: Stable chest pain patients from the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial with computed tomography angiography (CTA) or invasive coronary angiography (ICA) were included. The authors assumed that patients with CTA showing 0% stenosis and a coronary artery calcium (CAC) score of 0 were free of obstructive CAD (≥50% stenosis) on ICA, and they multiply imputed missing ICA results based on clinical variables and CTA results. Predicted CAD probabilities were calculated using published coefficients for 3 models: basic model (age, sex, chest pain type), clinical model (basic model + diabetes, hypertension, dyslipidemia, and smoking), and clinical + CAC score model. The authors assessed discrimination and calibration, and compared published effects with observed predictor effects. RESULTS: In 3,468 patients (1,805 women; mean 60 years of age; 779 [23%] with obstructive CAD on CTA), the models demonstrated moderate-good discrimination, with C-statistics of 0.69 (95% confidence interval [CI]: 0.67 to 0.72), 0.72 (95% CI: 0.69 to 0.74), and 0.86 (95% CI: 0.85 to 0.88) for the basic, clinical, and clinical + CAC score models, respectively. Calibration was satisfactory although typical chest pain and diabetes were less predictive and CAC score was more predictive than was suggested by the models. Among the 31% of patients for whom the clinical model predicted a low (≤10%) probability of CAD, actual prevalence was 7%; among the 48% for whom the clinical + CAC score model predicted a low probability the observed prevalence was 2%. In 2 sensitivity analyses excluding imputed data, similar results were obtained using CTA as the outcome, whereas in those who underwent ICA the models significantly underestimated CAD probability. CONCLUSIONS: Existing clinical prediction models can identify patients with a low probability of obstructive CAD. Obstructive CAD on ICA was imputed for 61% of patients; hence, further validation is necessary.

The Quantitative Science of Evaluating Imaging Evidence.

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.

Comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic review.

Coronary artery disease (CAD) remains one of the leading causes of morbidity and mortality globally. The most cost-effective imaging strategy to diagnose CAD in patients with stable chest pain is however uncertain. To review the evidence on comparative cost-effectiveness of different imaging strategies for patients presenting with stable chest pain symptoms suggestive for CAD. Systematic review. Studies performing a formal economic evaluation or decision analysis in the English language published between January 1995 and December 2015 were identified using PubMed, Medline (OvidSP), Embase, Web of Science, Cochrane economic evaluations library, and EconLit. Reviews and meta-analyses were excluded. Two independent reviewers assessed titles and abstracts. Of the 4498 titles identified, 70 met our selection criteria. One reviewer used a modified version of the CHEERS checklist to assess study quality. One reviewer extracted data on study details, which were checked by a second reviewer. There is a major heterogeneity between the available cost-effectiveness studies included in this study. The included studies compared very different testing strategies in very different ways and provided mostly short-term results. Strategies of no-testing and xECG were underrepresented. Nonetheless, the findings from this systematic review suggest that for patients with a low to intermediate prior probability of having obstructive CAD, computed tomography coronary angiography (CTCA) may be cost-effective as an initial diagnostic imaging test in comparison with CAG or other non-invasive diagnostic tests. If functional testing is required, stress echocardiography (SE) or single-photon emission computed tomography (SPECT) are suggested to be cost-effective initial strategies in patients with intermediate prior probability of CAD. Yet, other functional testing strategies such as xECG and positron-emission tomography (PET) scanning have not been studied as intensely. Immediate CAG is suggested to be a cost-effective strategy for patients at a high prior probability of having obstructive CAD whom may benefit from revascularization. The study emphasizes the inextricable link between clinical effectiveness and economic efficiency. Evidence suggests that the optimal diagnostic imaging strategy for individuals suspected of having CAD is CTCA for low and intermediate disease probability, followed by SE or SPECT as necessary, and invasive CAG for high disease probability. Further studies are needed to evaluate the cost-effectiveness of alternative non-invasive tests, including a no-testing strategy.

The optimal imaging strategy for patients with stable chest pain: a cost-effectiveness analysis.

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.

Diagnostic performance and comparative cost-effectiveness of non-invasive imaging tests in patients presenting with chronic stable chest pain with suspected coronary artery disease: a systematic overview.

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.

Coronary computed tomography versus exercise testing in patients with stable chest pain: comparative effectiveness and costs.

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%.

Diagnostic accuracy of 128-slice dual-source CT coronary angiography: a randomized comparison of different acquisition protocols.

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.

Methods for calculating sensitivity and specificity of clustered data: a tutorial.

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.

Costs of transcatheter versus surgical aortic valve replacement in intermediate-risk patients.

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.

Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts.

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.

Diagnostic performance of stress myocardial perfusion imaging for coronary artery disease: a systematic review and meta-analysis.

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.

Stable angina pectoris: head-to-head comparison of prognostic value of cardiac CT and exercise testing.

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.

Systematic review of guidelines on imaging of asymptomatic coronary artery disease.

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.

A clinical prediction rule for the diagnosis of coronary artery disease: validation, updating, and extension.

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.