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Objectives: The size of the heart may predict major cardiovascular events (MACE) in patients with stable chest pain. We aimed to evaluate the prognostic value of 3D whole heart volume (WHV) derived from non-contrast cardiac computed tomography (CT)., Methods: Among participants randomized to the CT arm of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE), we used deep learning to extract WHV, defined as the volume of the pericardial sac. We compared the WHV across categories of cardiovascular risk factors and coronary artery disease (CAD) characteristics and determined the association of WHV with MACE (all-cause death, myocardial infarction, unstable angina; median follow-up: 26 months)., Results: In the 3798 included patients (60.5 ± 8.2 years; 51.5% women), the WHV was 351.9 ± 57.6 cm 3 /m 2 . We found smaller WHV in no- or non-obstructive CAD, women, people with diabetes, sedentary lifestyle, and metabolic syndrome. Larger WHV was found in obstructive CAD, men, and increased atherosclerosis cardiovascular disease (ASCVD) risk score (p < 0.05). In a time-to-event analysis, small WHV was associated with over 4.4-fold risk of MACE (HR (per one standard deviation) = 0.221; 95% CI: 0.068-0.721; p = 0.012) independent of ASCVD risk score and CT-derived CAD characteristics. In patients with non-obstructive CAD, but not in those with no- or obstructive CAD, WHV increased the discriminatory capacity of ASCVD and CT-derived CAD characteristics significantly., Conclusions: Small WHV may represent a novel imaging marker of MACE in stable chest pain. In particular, WHV may improve risk stratification in patients with non-obstructive CAD, a cohort with an unmet need for better risk stratification., Key Points: • Heart volume is easily assessable from non-contrast cardiac computed tomography. • Small heart volume may be an imaging marker of major adverse cardiac events independent and incremental to traditional cardiovascular risk factors and established CT measures of CAD. • Heart volume may improve cardiovascular risk stratification in patients with non-obstructive CAD., (© 2021. European Society of Radiology.)

Objectives: To evaluate whether iterative reconstruction algorithms improve the diagnostic accuracy of coronary CT angiography (CCTA) for detection of lipid-core plaque (LCP) compared to histology., Methods and Materials: CCTA and histological data were acquired from three ex vivo hearts. CCTA images were reconstructed using filtered back projection (FBP), adaptive-statistical (ASIR) and model-based (MBIR) iterative algorithms. Vessel cross-sections were co-registered between FBP/ASIR/MBIR and histology. Plaque area <60 HU was semiautomatically quantified in CCTA. LCP was defined by histology as fibroatheroma with a large lipid/necrotic core. Area under the curve (AUC) was derived from logistic regression analysis as a measure of diagnostic accuracy., Results: Overall, 173 CCTA triplets (FBP/ASIR/MBIR) were co-registered with histology. LCP was present in 26 cross-sections. Average measured plaque area <60 HU was significantly larger in LCP compared to non-LCP cross-sections (mm(2): 5.78 ± 2.29 vs. 3.39 ± 1.68 FBP; 5.92 ± 1.87 vs. 3.43 ± 1.62 ASIR; 6.40 ± 1.55 vs. 3.49 ± 1.50 MBIR; all p < 0.0001). AUC for detecting LCP was 0.803/0.850/0.903 for FBP/ASIR/MBIR and was significantly higher for MBIR compared to FBP (p = 0.01). MBIR increased sensitivity for detection of LCP by CCTA., Conclusion: Plaque area <60 HU in CCTA was associated with LCP in histology regardless of the reconstruction algorithm. However, MBIR demonstrated higher accuracy for detecting LCP, which may improve vulnerable plaque detection by CCTA., Key Points: • A low attenuation plaque area is associated with the presence of lipid-core plaque • MBIR leads to higher diagnostic accuracy for detecting lipid-core plaque • The benefit of MBIR is mainly due to increased sensitivity at high specificities • Semiautomated CCTA assessment can detect vulnerable plaques non-invasively.