Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780

Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography

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

Comparative effectiveness of initial computed tomography and invasive coronary angiography in women and men with stable chest pain and suspected coronary artery disease: multicentre randomised trial

To assess the comparative effectiveness of computed tomography and invasive coronary angiography in women and men with stable chest pain suspected to be caused by coronary artery disease

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: Meta-analysis of individual patient data

Objective To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. Design Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. Data sources Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. Eligibility criteria for selecting studies Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. Results Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). Conclusions In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. Systematic review registration PROSPERO CRD42012002780

Coronary computed tomography and coronary artery calcium score for diagnosis of coronary artery disease in chronic coronary syndrom: individual patient date meta-analysis of the International Collaborative COME-CCT consortium

Einleitung: Kardiovaskuläre Erkrankungen und allen voran hierunter die koronare Herzerkrankung (KHK) sind weiterhin die häufigste Todesursache weltweit. Der Gold-standard zur Diagnose der KHK bei Patient*innen mit stabilen Brustschmerzen ist wei-terhin die invasive Koronarangiographie (ICA). Im Laufe der letzten Jahre hat sich die sich die Computertomographie der Koronargefäße (CTA) als geeignete nicht-invasive diagnostische Methode zum KHK-Ausschluss entwickelt und bekleidet in den aktuel-len internationalen Leitlinien bereits einen großen Stellenwert. Eine einheitliche Im-plementierung der CTA auch unter besonderer Berücksichtigung des Kalziumscores (CAC Score) fehlt bislang. Ziel dieser Arbeit war es, die diagnostische Genauigkeit der CTA versus CAC Score, sowie die diagnostische Genauigkeit der CTA in Abhängig-keit der Kalziumscorehöhe im Rahmen des internationalen kollaborativen COME-CCT Konsortiums mittels Individualpatientendaten Meta-Analyse zu untersuchen. Methoden: Insgesamt 28 diagnostische Genauigkeitsstudien aus 14 Ländern konnten im Rahmen dieser Subanalyse des COME-CCT Konsortiums eingeschlossen werden. 2452 Patient*innen mit stabilen Brustschmerzen und Verdacht auf das Vorliegen einer KHK aus dem weltweiten kollaborativen COME-CCT Konsortium mit vollständigem Agatston Score wurden zur Analyse eingeschlossen. Bei allen Patient*innen lag eine Indikation zur ICA vor und alle Patient*innen erhielten sowohl eine CTA als auch eine ICA zur KHK-Evaluation. Der CAC Score wurde auf Patientenebene mittels Agatston Score bestimmt. Eine obstruktive KHK wurde als mindesten 50 % Diameterstenose basierend auf der ICA definiert, ein CAC Score > 400 wurde als positiv gewertet. Di-agnostische Genauigkeitswerte wurden für die CTA sowie den Agatston Score be-rechnet und unter Verwendung eines logistischen Regressionsmodells miteinander verglichen. Darüber hinaus wurde die diagnostische Genauigkeit der CTA in Abhän-gigkeit der Kalziumscorehöhe. Ergebnisse: Eine obstruktive KHK wurde bei 45 % der Patient*innen diagnostiziert (1100/2452). Die diagnostische Genauigkeit der CTA war nicht signifikant unter-schiedlich bei Patient*innen mit niedrig bis moderat erhöhtem (CAC Score 1 bis mit 100, 100 bis 400) versus deutlich bis stark erhöhtem (CAC Score 401 bis 1000, > 1000) CAC Score. Die CTA war in der Diagnose der KHK dem CAC Score überlegen mit einer diagnostischen Genauigkeit von 81,1 % (95 % Konfidenzintervall [CI]: 77,5 – 84,1 %) versus 68,8 % (95 %CI: 64,2 to 73,1 %, p < 0,001). 16,8 % der Patient*innen mit Fehlen von koronaren Verkalkungen zeigten eine obstruktive KHK in der Korona-rangiographie. Diskussion: Die diagnostische Genauigkeit der CTA zeigt unabhängig von der beo-bachteten Kalziumscorehöhe eine gute diagnostische Performance und sollte daher bei allen Patient*innen mit entsprechender Indikationsstellung durchgeführt werden ungeachtet des CAC Score. In unserer weltweiten kollaborativen IPD Meta-Analyse zeigt die CTA eine überlegene diagnostische Genauigkeit verglichen mit dem CAC Score. Das Fehlen von koronaren Verkalkungen schließt das Vorhandensein einer obstruktiven KHK nicht zuverlässig aus und ist nicht zum KHK-Ausschluss geeignet.Introduction: Cardiovascular diseases, with coronary artery disease (CAD) leading, are the most common causes of death worldwide. Still, invasive angiography is the reference standard for diagnosis of CAD. Over the last years, CTA has evolved as a reliable non-invasive diagnostic imaging method for evaluation of CAD and is imple-mented centrally in the most recent European as well as US American and interna-tional guidelines. However, a consistent guideline implementation of the use of CTA with special focus also on the coronary artery calcium score (CAC score) is still miss-ing. In our internal collaborative IPD meta-analysis setting, the aim of this study was to investigate first, the diagnostic accuracy of CTA versus CAC score for diagnosis of CAD, and second, diagnostic accuracy of CTA in different CAC score subgroups for evaluation of diagnostic performance according to elevated CAC score. Methods: Overall, 28 diagnostic accuracy studies from 14 countries were included in the current pre-defined subgroup analysis of the COME-CCT Consortium with 2452 stable chest pain patients included. Patients had complete CAC score data by Agat-ston Score on the per-patient level and an indication for ICA, and received both diag-nostic tests, CTA and ICA. Obstructive CAD was defined as at least 50 % diameter stenosis by ICA, positive CAC score was defined as an Agatston Score > 400. Diag-nostic accuracy values were calculated for CTA and ICA and compared by using lo-gistic regression model. Further, diagnostic accuracy of CTA in different CAC score subgroups were calculated. Results: Obstructive CAD was present in 45 % of the patients (1100/2452). Diagnostic accuracy of CTA was not significantly different in low to intermediate (CAC score 1 to 1000) CAC score. When compared to CAC score, CTA was superior for diagnosis of CAD with overall diagnostic accuracy of 81.1 % (95 % confidence interval [CI]: 77.5 - 84.1 %) versus CAC score with 68.8 % (95 % CI: 64.2 to 73.1 %, p < 0.001). In patients with CAC score of zero CAD was diagnosed in 16,8 % by ICA. Discussion: Diagnostic accuracy of CTA showed good overall diagnostic accuracy independent from the amount of CAC score and thus, and should pe always preferred in stable chest pain patients with respective imaging indication. By using data from our worldwide collaborative IPD meta-analysis we demonstrate CTA to be superior to the CAC score for diagnosis of CAD and should be the preferred non-invasive imaging test. Absence of CAC does not sufficiently exclude obstructive CAD and should not be used in this regard

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium

OBJECTIVES There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p 1000). CONCLUSIONS Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease

Applicability and accuracy of pretest probability calculations implemented in the NICE clinical guideline for decision making about imaging in patients with chest pain of recent onset

OBJECTIVES To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset. METHODS The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT). RESULTS 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models. CONCLUSIONS Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations. KEY POINTS • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT

Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

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 &lt; 0.001), likelihood ratio test 236.3, df: 1, p &lt; 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 &lt; 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