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
Authors: Mohamed Mahmoud , Bosserdt Maria , Wieske Viktoria , Dubourg Benjamin , Alkadhi Hatem , Garcia Mario J. , Leschka Sebastian , Zimmermann Elke , Shabestari Abbas A. , Nørgaard Bjarne L. , Meijs Matthijs F. L. , Øvrehus Kristian A. , Diederichsen Axel C. P. , Knuuti Juhani , Halvorsen Bjørn A. , Mendoza-Rodriguez Vladymir , Wan Yung-Liang , Bettencourt Nuno , Martuscelli Eugenio , Buechel Ronny R. , Mickley Hans , Sun Kai , Muraglia Simone , Kaufmann Philipp A. , Herzog Bernhard A. , Tardif Jean-Claude , Schütz Georg M. , Laule Michael , Newby David E. , Achenbach Stephan , Budoff Matthew , Haase Robert , Biavati Federico , Mézquita Aldo Vásquez , Schlattmann Peter , Dewey Marc ,   COME-CCT
Published: October 2023

Abstract
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.