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Objectives: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone., Methods: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis., Results: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities., Conclusion: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone., Clinical Relevance Statement: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic., Key Points: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders., (© 2023. The Author(s).)

Objectives: To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting., Methods: Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA., Results: In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1-90.6%), updated D+F 47.3% (34.2-59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70-0.76 versus AUC of 0.70 CI 0.67-0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29-1.86, net reclassification index 0.11 CI 0.05-0.16, p < 0.001)., Conclusions: Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed., Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT02400229 KEY POINTS: • Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT. • Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F. • Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe.

To evaluate computer-aided stenosis detection for computed tomography coronary angiography (CTA) in comparison with human reading and conventional coronary angiography (CCA) as the reference standard. 50 patients underwent CTA and CCA and out of these 44 were evaluable for computer-aided stenosis detection. The diagnostic performance of the software and of human reading were compared and quantitative coronary angiography (QCA) served as the reference standard for the detection of significant stenosis (>50 %). Overall, three readers with high (reader 1), intermediate (reader 2) and low (reader 3) experience in cardiac CT imaging performed the manual CTA evaluation on a commercially available workstation, whereas the automated software processed the datasets without any human interaction. The prevalence of coronary artery disease was 41 % (18/44) and QCA indicated significant stenosis (>50 %) in 33 coronary vessels. The automated software accurately diagnosed 18 individuals with significant coronary artery disease (CAD), and correctly ruled out CAD in 10 patients. In summary the sensitivity of computer-aided detection was 100 %/94 % (per-patient/per-vessel) and the specificity was 38 %/70 %, the positive predictive value (PPV) was 53 %/42 % and the negative predictive value (NPV) was 100 %/98 %. In comparison, reader 1-3 showed per-patient sensitivities of 100/94/89 %, specificities of 73/69/50 %, PPVs of 72/68/55 % and NPVs of 100/95/87 %. Computer-aided detection yields a high NPV that is comparable to more experienced human readers. However, PPV is rather low and in the range of an unexperienced reader.

Aims: To evaluate the diagnostic power of integrating the results of computed tomography angiography (CTA) and CT myocardial perfusion (CTP) to identify coronary artery disease (CAD) defined as a flow limiting coronary artery stenosis causing a perfusion defect by single photon emission computed tomography (SPECT)., Methods and Results: We conducted a multicentre study to evaluate the accuracy of integrated CTA-CTP for the identification of patients with flow-limiting CAD defined by ≥50% stenosis by invasive coronary angiography (ICA) with a corresponding perfusion deficit on stress single photon emission computed tomography (SPECT/MPI). Sixteen centres enroled 381 patients who underwent combined CTA-CTP and SPECT/MPI prior to conventional coronary angiography. All four image modalities were analysed in blinded independent core laboratories. The prevalence of obstructive CAD defined by combined ICA-SPECT/MPI and ICA alone was 38 and 59%, respectively. The patient-based diagnostic accuracy defined by the area under the receiver operating characteristic curve (AUC) of integrated CTA-CTP for detecting or excluding flow-limiting CAD was 0.87 [95% confidence interval (CI): 0.84-0.91]. In patients without prior myocardial infarction, the AUC was 0.90 (95% CI: 0.87-0.94) and in patients without prior CAD the AUC for combined CTA-CTP was 0.93 (95% CI: 0.89-0.97). For the combination of a CTA stenosis ≥50% stenosis and a CTP perfusion deficit, the sensitivity, specificity, positive predictive, and negative predicative values (95% CI) were 80% (72-86), 74% (68-80), 65% (58-72), and 86% (80-90), respectively. For flow-limiting disease defined by ICA-SPECT/MPI, the accuracy of CTA was significantly increased by the addition of CTP at both the patient and vessel levels., Conclusions: The combination of CTA and perfusion correctly identifies patients with flow limiting CAD defined as ≥50 stenosis by ICA causing a perfusion defect by SPECT/MPI.

Purpose: To evaluate very small superparamagnetic iron oxide particles (VSOP-C184) as blood-pool contrast agent for coronary MR angiography (CMRA) in humans., Materials and Methods: Six healthy volunteers and 14 patients with suspected coronary artery disease underwent CMRA after administration of VSOP-C184 at the following doses: 20 μmol Fe/kg (4 patients), 40 μmol Fe/kg (5 patients), 45 μmol Fe/kg (6 healthy volunteers), and 60 μmol Fe/kg (5 patients). In healthy volunteers, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), and vessel edge definition (VED) of contrast-enhanced CMRA were compared with non-contrast-enhanced CMRA. In patients, a per-segment intention-to-diagnose evaluation of contrast-enhanced CMRA for detection of significant coronary stenosis (≥50%) was performed., Results: Three healthy volunteers (45 μmol Fe/kg VSOP-C184) and two patients (60 μmol Fe/kg VSOP-C184) had adverse events of mild or moderate intensity. VSOP-C184 significantly increased CNR (15.1 ± 4.6 versus 6.9 ± 1.9; P = 0.010), SNR (21.7 ± 5.3 versus 15.4 ± 1.6; P = 0.048), and VED (2.3 ± 0.6 versus 1.2 ± 0.2; P < 0.001) compared with non-contrast-enhanced CMRA. In patients, contrast-enhanced CMRA yielded sensitivity, specificity, and diagnostic accuracy for detection of significant coronary stenosis of 86.7%, 71.0%, 73.1%, respectively., Conclusion: CMRA using VSOP-C184 was feasible and yielded moderate diagnostic accuracy for detection of significant coronary stenosis within this proof-of-concept setting., (Copyright © 2011 Wiley-Liss, Inc.)

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.

Background: Noninvasive angiography using multislice computed tomography (MSCT) is superior to magnetic resonance imaging (MRI) for detection of coronary stenoses. We compared patient acceptance of these two noninvasive diagnostic tests and invasive conventional coronary angiography (Angio)., Methods and Findings: A total of 111 consecutive patients with suspected coronary artery disease underwent MSCT, MRI, and Angio. Subsequently, patient acceptance of the three tests was evaluated with questionnaires in all patients. The main acceptance variables were preparation and information prior to the test, degree of concern, comfort, degree of helplessness, pain (on visual analog scales), willingness to undergo the test again, and overall satisfaction. Preparation for each test was not rated significantly differently, whereas patients were significantly more concerned about Angio than the two noninvasive tests (p<0.001). No pain during MSCT, MRI, and Angio as assessed on visual analog scales (0 to 100) was reported by 99, 93, and 31 patients, respectively. Among the 82 patients who felt pain during at least one procedure, both CT (0.9+/-4.5) and MRI (5.2+/-16.6) were significantly less painful than Angio (24.6+/-23.4, both p<0.001). MSCT was considered significantly more comfortable (1.49+/-0.64) than MRI (1.75+/-0.81, p<0.001). In both the no-revascularization (55 patients) and the revascularization group (56 patients), the majority of the patients (73 and 71%) would prefer MSCT to MRI and Angio for future imaging of the coronary arteries. None of the patients indicated to be unwilling to undergo MSCT again. The major advantages patients attributed to MSCT were its fast, uncomplicated, noninvasive, and painless nature., Conclusions: Noninvasive coronary angiography with MSCT is considered more comfortable than MRI and both MSCT and MRI are less painful than Angio. Patient preference for MSCT might tip the scales in favor of this test provided that the diagnostic accuracy of MSCT can be shown to be high enough for clinical application.

Background: Multislice computed tomography (CT) and magnetic resonance imaging (MRI) are the main candidates for noninvasive coronary angiography; however, multislice CT, unlike MRI, exposes patients to radiation and an iodinated intravenous contrast agent., Objective: To compare the diagnostic accuracy of multislice CT and MRI for noninvasive detection of clinically significant coronary stenoses (> or =50%)., Design: Prospective intention-to-diagnose study., Setting: Single tertiary referral center, Berlin, Germany., Patients: 129 consecutive patients with suspected coronary artery disease., Interventions: Multislice CT and MRI were both performed within a median of 1 day before conventional coronary angiography, which served as the reference standard., Measurements: Diagnostic performance of multislice CT and MRI., Results: 129 patients completed the study. Altogether, 108 patients with 430 vessels could be examined with both multislice CT and MRI and were used for analysis. In the per-patient analysis, the sensitivity of multislice CT (92% [95% CI, 82% to 96%]) was significantly higher than that of MRI (74% [CI, 61% to 83%]; P = 0.013). The sensitivity for detecting clinically significant stenoses was 82% for multislice CT and 54% for MRI (P < 0.001). Specificity and negative predictive value of multislice CT and MRI in the per-vessel analysis were 90% versus 87% (P = 0.73) and 95% versus 90% (P = 0.032), respectively. The effective radiation dose used with multislice CT (mean, 12.3 mSv [SD, 1.4]) in a consecutive subgroup of 73 patients was not significantly different from that used with diagnostic cardiac catheterization (11.4 mSv [SD, 4.8]) (P = 0.169). Most patients (74%) indicated that they would prefer multislice CT for future diagnostic imaging (P < 0.001)., Limitations: This was a single-center study with 129 patients., Conclusions: In patients referred for conventional coronary angiography, multislice CT compares favorably with MRI for noninvasive detection of coronary stenoses.

Purpose: To analyze the incremental diagnostic value of a combination of two approaches (free-breathing and breathhold) vs. the sole free-breathing approach to coronary magnetic resonance angiography (CMRA) for detection of significant stenoses., Materials and Methods: Thirty patients were consecutively included in this prospective trial. CMRA was performed on a 1.5-T MR scanner (Magnetom Sonata, Siemens) using a balanced steady-state free precession (SSFP) sequence during free-breathing (2.4 x 0.9 x 0.7 mm3). Breathholding acquisitions (3.0 x 1.5 x 0.7 mm3) were only performed in cases in which the quality of free-breathing CMRA precluded assessment. Patients with contraindications to CMRA, claustrophobia, or nonassessable images were not excluded from the assessment of diagnostic accuracy (intention-to-diagnose design)., Results: In 60% of all free-breathing coronary acquisitions the image quality was adequate for diagnostic assessment. For the remaining 40% of the cases, breathhold acquisitions were obtained. The sensitivity, specificity, nonassessable rate, and accuracy in identifying main coronary branches with significant stenoses using the combination of both breathing approaches and the free-breathing approach alone were 65% vs. 32%, 73% vs. 53%, 24% vs. 52%, and 71% vs. 46%, respectively (P < 0.001)., Conclusion: In this consecutive cohort of patients, the combination of free-breathing and breathhold CMRA significantly improved diagnostic accuracy. Nevertheless, even this combination did not reach accuracies sufficient for routine clinical application., (Copyright 2006 Wiley-Liss, Inc.)

Rationale and Objectives: To compare the diagnostic accuracy and image quality of 2 reconstruction algorithms (multisegment and halfscan) for computed tomography (CT) coronary angiography in patients without beta-blocker medication., Materials and Methods: Thirty-four patients with 42 significant coronary stenoses in 136 main coronary branches were examined using a 16-slice CT scanner (Aquilion, Toshiba, Otawara, Japan). Twenty-seven patients (79%) had heart rates above 65 beats/min., Results: Without exclusion of branches the sensitivity, specificity, accuracy, and rate of nonassessable segments with multisegment versus halfscan reconstruction were 88 versus 74%, 91 versus 71%, 90 versus 72%, and 2 versus 21% (P < 0.01), respectively. Multisegment reconstruction improved the average vessel length free of motion artifacts by 56% compared with halfscan reconstruction (P < 0.01). Image quality in terms of vessel continuity and visibility of side branches (P < 0.005) was significantly better using multisegment reconstruction., Conclusions: Multisegment reconstruction has superior diagnostic accuracy and image quality compared with halfscan reconstruction in patients with normal heart rates.