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Objectives: The aim of this study was to assess the use of low tube potentials for coronary computed tomography angiography (CCTA) in worldwide clinical practice and its influence on radiation exposure, contrast agent volume, and image quality., Background: CCTA is frequently used in clinical practice. Lowering of tube potential is a potent method to reduce radiation exposure and to economize contrast agent volume., Methods: CCTAs of 4,006 patients from 61 international study sites were analyzed regarding very-low (≤80 kVp), low (90 to 100 kVp), conventional (110 to 120 kVp), and high (≥130 kVp) tube potentials. The impact on dose-length product (DLP) and contrast agent volume was analyzed. Image quality was determined by evaluation of the diagnostic applicability and assessment of the objective image parameters signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR)., Results: When compared with conventional tube potentials, low tube potentials were used in 56% of CCTAs (≤80 kVp: 9%; 90 to 100 kVp: 47%), which varied among sites from 0% to 100%. Tube potential reduction was associated with low-cardiovascular risk profile, low body mass index (BMI), and new-generation scanners. Median radiation exposure was lowered by 68% or 50% and median contrast agent volume by 25% or 13% for tube potential protocols of ≤80 kVp or 90 to 100 kVp when compared with conventional tube potentials, respectively (all p < 0.001). With the use of lower tube potentials, the frequency of diagnostic scans was maintained (p = 0.41), whereas SNR and CNR significantly improved (both p < 0.001). Considering BMI eligibility criteria, 58% (n = 946) of conventionally scanned patients would have been suitable for low tube potential protocols, and 44% (n = 831) of patients scanned with 90 to 100 kVp would have been eligible for very-low tube potential CCTA imaging of ≤80 kVp., Conclusions: This large international registry confirms the feasibility of tube potential reduction in clinical practice leading to lower radiation exposure and lower contrast volumes. The current registry also demonstrates that this strategy is still underused in daily practice. (PROspective multicenter registry on radiaTion dose Estimates of cardiac CT angIOgraphy iN daily practice in 2017 [PROTECTION-VI]; NCT02996903)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Symptom-based pretest probability scores that estimate the likelihood of obstructive coronary artery disease (CAD) in stable chest pain have moderate accuracy. We sought to develop a machine learning (ML) model, utilizing clinical factors and the coronary artery calcium score (CACS), to predict the presence of obstructive CAD on coronary computed tomography angiography (CCTA)., Methods and Results: The study screened 35 281 participants enrolled in the CONFIRM registry, who underwent ≥64 detector row CCTA evaluation because of either suspected or previously established CAD. A boosted ensemble algorithm (XGBoost) was used, with data split into a training set (80%) on which 10-fold cross-validation was done and a test set (20%). Performance was assessed of the (1) ML model (using 25 clinical and demographic features), (2) ML + CACS, (3) CAD consortium clinical score, (4) CAD consortium clinical score + CACS, and (5) updated Diamond-Forrester (UDF) score. The study population comprised of 13 054 patients, of whom 2380 (18.2%) had obstructive CAD (≥50% stenosis). Machine learning with CACS produced the best performance [area under the curve (AUC) of 0.881] compared with ML alone (AUC of 0.773), CAD consortium clinical score (AUC of 0.734), and with CACS (AUC of 0.866) and UDF (AUC of 0.682), P < 0.05 for all comparisons. CACS, age, and gender were the highest ranking features., Conclusion: A ML model incorporating clinical features in addition to CACS can accurately estimate the pretest likelihood of obstructive CAD on CCTA. In clinical practice, the utilization of such an approach could improve risk stratification and help guide downstream management., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guideline recommends risk enhancers in the borderline-risk and statin recommended/intermediate-risk groups. We determined the risk reclassification by the presence and severity of coronary computed tomography angiography (CCTA)-visualized coronary artery disease (CAD) according to statin eligibility groups. Of 35,281 individuals who underwent CCTA, 1,303 asymptomatic patients (age 59, 65% male) were identified. Patients were categorized as low risk, borderline risk, statin recommended/intermediate risk or statin recommended/high risk according to the guideline. CCTA-visualized CAD was categorized as no CAD, nonobstructive, or obstructive. Major adverse cardiovascular events (MACE) were defined as a composite outcome of all-cause mortality, nonfatal myocardial infarction, and late coronary revascularization (>90 days). We tested a reclassification wherein no CAD reclassifies downward, and the presence of any CAD reclassifies upward. During a median follow-up of 2.9 years, 93 MACE events (7.1%) were observed. Among the borderline-risk and statin-recommended/intermediate-risk groups eligible for risk enhancers, the presence or absence of any CCTA-visualized CAD led to a net increase of 2.3% of cases and 22.4% of controls correctly classified (net reclassification index [NRI] 0.27, 95% CI 0.13 to 0.41, p = 0.0002). The NRI was not significant among low- or statin-recommended/high-risk patients (all p >0.05). The presence or absence of CCTA-visualized CAD, including both obstructive and nonobstructive CAD, significantly improves reclassification in patients eligible for risk enhancers in 2018 ACC/AHA guidelines. Patients in low- and high-risk groups derive no significant improvement in risk reclassification from CCTA., (Copyright © 2019. Published by Elsevier Inc.)

Objectives: This study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS)., Background: Current risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification., Methods: A total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971)., Results: The mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort., Conclusions: The new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors used coronary computed tomography angiography (CTA) to determine plaque characteristics predicting individual late plaque events precipitating acute coronary syndromes (ACS) in a cohort of asymptomatic type 2 diabetic patients., Background: In patients with coronary artery disease, CTA plaque characteristics may predict mid-term patient events., Methods: Asymptomatic patients with diabetes 55 to 74 years of age with no history of coronary artery disease (N = 630) underwent baseline 64-slice CTA and detailed plaque level analysis. All subsequent clinical events were recorded and adjudicated. In patients who developed ACS, culprit plaque was identified at invasive angiography and its precursor located on the baseline CTA. Plaque characteristics predicting an ACS-associated culprit plaque event were analyzed by time to event accounting for inpatient clustering of plaques and competing events., Results: Among 2,242 plaques in 499 subjects, 24 ACS culprit plaques were identified in 24 subjects during median follow-up of 9.2 years (interquartile range: 8.4 to 9.8 years). Plaque volume (upper vs. lower quartile hazard ratio [HR]: 6.9; 95% confidence interval [CI]: 1.6 to 30.8; p = 0.011), percentage of low-density plaque content <50 Hounsfield units (HR: 14.2; 95% CI: 1.9 to 108; p = 0.010), and mild plaque calcification (HR vs. all other plaques 3.3 [95% CI: 1.5 to 7.3]; p = 0.004) predicted plaque events univariately and after adjustment by clinical risk score. A culprit plaque event occurred in 13 of 376 (3.5%) high-risk plaques (HRP) (plaques with ≥2 risk predictors) versus 11 of 1,866 (0.6%) in non-HRPs (p < 0.0001), at 12 of 343 (3.5%) stenotic sites (≥50%) versus 12 of 1,899 (0.6%) nonstenotic sites (p < 0.0001) and in 7 of 131 (5.3%) HRP with stenosis (p < 0.0001 vs. all others). In 130 (20.6%) subjects, no coronary plaque was present on baseline CTA., Conclusions: In asymptomatic patients with type 2 diabetes, CTA plaque volume, percent low-density plaque content, and mild calcification predicted late plaque events. The additional presence of luminal stenosis increased the probability of an acute event., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Non-statin therapy (NST) is used as second-line treatment when statin monotherapy is inadequate or poorly tolerated., Objective: To determine the association of NST with plaque composition, alone or in combination with statins, in patients undergoing coronary computed tomography angiography (coronary CTA)., Methods: From the multicenter CONFIRM registry, we analyzed individuals who underwent coronary CTA with known lipid-lowering therapy status and without prior coronary artery disease at baseline. We created a propensity score for being on NST, followed by stepwise multivariate linear regression, adjusting for the propensity score as well as risk factors, to determine the association between NST and the number of coronary artery segments with each plaque type (non-calcified (NCP), partially calcified (PCP) or calcified (CP)) and segment stenosis score (SSS)., Results: Of the 27,125 subjects in CONFIRM, 4,945 met the inclusion criteria; 371 (7.5%) took NST. At baseline, patients on NST had more prevalent risk factors and were more likely to be on concomitant cardiac medications. After multivariate and propensity score adjustment, NST was not associated with plaque composition: NCP (0.07 increase, 95% CI: -0.05, 0.20; p = 0.26), PCP (0.10 increase, 95% CI: -0.10, 0.31; p = 0.33), CP (0.18 increase, 95% CI: -0.10, 0.46; p = 0.21) or SSS (0.45 increase, 95% CI: -0.02,0.93; p = 0.06). The absence of an effect of NST on plaque type was not modified by statin use (p for interaction > 0.05 for all)., Conclusion: In this cross-sectional study, non-statin therapy was not associated with differences in plaque composition as assessed by coronary CTA., (Copyright © 2019. Published by Elsevier Inc.)

Objective: Data describing clinical relevance of chronic total occlusion (CTO) identified by coronary CT angiography (CCTA) have not been reported to date. We investigated the prognosis of CTO on CCTA., Methods: We identified 22 828 patients without prior known coronary artery disease (CAD), who were followed for a median of 26 months. Based on CCTA, coronary lesions were graded as normal (no atherosclerosis), non-obstructive (1%-49%), moderate-to-severe (50%-99%) or totally occluded (100%). All-cause mortality, and major adverse cardiac events defined as mortality, non-fatal myocardial infarction and late coronary revascularisation (≥90 days after CCTA) were assessed., Results: The distribution of patients with normal coronaries, non-obstructive CAD, moderate-to-severe CAD and CTO was 10 034 (44%), 7965 (34.9%), 4598 (20.1%) and 231 (1%), respectively. The mortality rate per 1000 person-years of CTO patients was non-significantly different from patients with moderate-to-severe CAD (22.95; 95% CI 12.71 to 41.45 vs 14.46; 95% CI 12.34 to 16.94; p=0.163), and significantly higher than of those with normal coronaries and non-obstructive CAD (p<0.001 for both). Among 14 382 individuals with follow-up for the composite end point, patients with CTO had a higher rate of events than those with moderate-to-severe CAD (106.56; 95% CI 76.51 to 148.42 vs 65.45; 95% CI 58.01 to 73.84, p=0.009). This difference was primarily driven by an increase in late revascularisations in CTO patients (27 of 35 events). After multivariable adjustment, compared with individuals with normal coronaries, the presence of CTO conferred the highest risk for adverse cardiac events (14.54; 95% CI 9.11 to 23.20, p<0.001)., Conclusions: The detection of CTO on non-invasive CCTA is associated with increased rate of late revascularisation but similar 2-year mortality as compared with moderate-to-severe CAD., Trial Registration Number: NCT01443637., Competing Interests: Competing interests: Dr JKM receives funding from the Dalio Foundation, National Institutes of Health and GE Healthcare. Dr JKM serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. All other coauthors have no relevant disclosures., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of 'age adjusted SIS' (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 ± 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C-statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26-0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification.

Introduction: Machine learning (ML) is a field in computer science that demonstrated to effectively integrate clinical and imaging data for the creation of prognostic scores. The current study investigated whether a ML score, incorporating only the 16 segment coronary tree information derived from coronary computed tomography angiography (CCTA), provides enhanced risk stratification compared with current CCTA based risk scores., Methods: From the multi-center CONFIRM registry, patients were included with complete CCTA risk score information and ≥3 year follow-up for myocardial infarction and death (primary endpoint). Patients with prior coronary artery disease were excluded. Conventional CCTA risk scores (conventional CCTA approach, segment involvement score, duke prognostic index, segment stenosis score, and the Leaman risk score) and a score created using ML were compared for the area under the receiver operating characteristic curve (AUC). Only 16 segment based coronary stenosis (0%, 1-24%, 25-49%, 50-69%, 70-99% and 100%) and composition (calcified, mixed and non-calcified plaque) were provided to the ML model. A boosted ensemble algorithm (extreme gradient boosting; XGBoost) was used and the entire data was randomly split into a training set (80%) and testing set (20%). First, tuned hyperparameters were used to generate a trained model from the training data set (80% of data). Second, the performance of this trained model was independently tested on the unseen test set (20% of data)., Results: In total, 8844 patients (mean age 58.0 ± 11.5 years, 57.7% male) were included. During a mean follow-up time of 4.6 ± 1.5 years, 609 events occurred (6.9%). No CAD was observed in 48.7% (3.5% event), non-obstructive CAD in 31.8% (6.8% event), and obstructive CAD in 19.5% (15.6% event). Discrimination of events as expressed by AUC was significantly better for the ML based approach (0.771) vs the other scores (ranging from 0.685 to 0.701), P < 0.001. Net reclassification improvement analysis showed that the improved risk stratification was the result of down-classification of risk among patients that did not experience events (non-events)., Conclusion: A risk score created by a ML based algorithm, that utilizes standard 16 coronary segment stenosis and composition information derived from detailed CCTA reading, has greater prognostic accuracy than current CCTA integrated risk scores. These findings indicate that a ML based algorithm can improve the integration of CCTA derived plaque information to improve risk stratification., (Published by Elsevier Inc.)

Background: The Coronary Artery Disease Reporting and Data System (CAD-RADS) provides a lexicon and standardized reporting system for coronary CT angiography., Objectives: To evaluate inter-observer agreement of the CAD-RADS among an panel of early career and expert readers., Methods: Four early career and four expert cardiac imaging readers prospectively and independently evaluated 50 coronary CT angiography cases using the CAD-RADS lexicon. All readers assessed image quality using a five-point Likert scale, with mean Likert score ≥4 designating high image quality, and <4 designating moderate/low image quality. All readers were blinded to medical history and invasive coronary angiography findings. Inter-observer agreement for CAD-RADS assessment categories and modifiers were assessed using intra-class correlation (ICC) and Fleiss' Kappa (κ).The impact of reader experience and image quality on inter-observer agreement was also examined., Results: Inter-observer agreement for CAD-RADS assessment categories was excellent (ICC 0.958, 95% CI 0.938-0.974, p < 0.0001). Agreement among expert readers (ICC 0.925, 95% CI 0.884-0.954) was marginally stronger than for early career readers (ICC 0.904, 95% CI 0.852-0.941), both p < 0.0001. High image quality was associated with stronger agreement than moderate image quality (ICC 0.944, 95% CI 0.886-0.974 vs. ICC 0.887, 95% CI 0.775-0.95, both p < 0.0001). While excellent inter-observer agreement was observed for modifiers S (stent) and G (bypass graft) (both κ = 1.0), only fair agreement (κ = 0.40) was observed for modifier V (high risk plaque)., Conclusion: Inter-observer reproducibility of CAD-RADS assessment categories and modifiers is excellent, except for high-risk plaque (modifier V) which demonstrates fair agreement. These results suggest CAD-RADS is feasible for clinical implementation., (Copyright © 2017. Published by Elsevier Inc.)

Background: Cardiac computed tomography angiography (cardiac CTA) is an increasingly used versatile imaging method to evaluate coronary and cardiac morphology. Owing to improvements in technology, image quality has continuously improved over the last 10-20 years. At the same time, numerous non-randomized and randomized studies have been performed to reduce the associated radiation exposure. Currently, it is unclear if the advances in technology and knowledge about radiation reduction translated into reduced levels of cardiac CTA radiation dose in daily clinical practice as well as a wide utilization of dose-saving strategies., Methods: The PROTECTION VI study is a multicenter, prospective, worldwide registry designed to evaluate radiation dose exposure, utilization of dose-saving strategies and diagnostic image quality during cardiac CTA in current daily practice. Assessment of image quality will be addressed by the evaluation of diagnostic image quality at the local study site and the calculation of quantitative image quality parameters in an imaging core laboratory. Above 4000 patients will be enrolled from approximately 70 sites in Europe, North America, South America, Asia and Australia. The study will analyze median radiation dose levels, image quality, frequency of use and efficacy of algorithms for dose reduction, and patient and study-related predictors associated with radiation dose., Conclusions: The PROTECTION VI study is designed to provide a reliable estimate of current radiation dose for cardiac CTA and to assess the potential for additional dose reductions., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess clinical outcomes associated with the novel Coronary Artery Disease-Reporting and Data System (CAD-RADS) scores used to standardize coronary computed tomography angiography (CTA) reporting and their potential utility in guiding post-coronary CTA care., Background: Clinical decision support is a major focus of health care policies aimed at improving guideline-directed care. Recently, CAD-RADS was developed to standardize coronary CTA reporting and includes clinical recommendations to facilitate patient management after coronary CTA., Methods: In the multinational CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, 5,039 patients without known coronary artery disease (CAD) underwent coronary CTA and were stratified by CAD-RADS scores, which rank CAD stenosis severity as 0 (0%), 1 (1% to 24%), 2 (25% to 49%), 3 (50% to 69%), 4A (70% to 99% in 1 to 2 vessels), 4B (70% to 99% in 3 vessels or ≥50% left main), or 5 (100%). Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality or myocardial infarction (MI). Receiver-operating characteristic (ROC) curves were used to compare CAD-RADS to the Duke CAD Index and traditional CAD classification. Referrals to invasive coronary angiography (ICA) after coronary CTA were also assessed., Results: Cumulative 5-year event-free survival ranged from 95.2% to 69.3% for CAD-RADS 0 to 5 (p < 0.0001). Higher scores were associated with elevations in event risk (hazard ratio: 2.46 to 6.09; p < 0.0001). The ROC curve for prediction of death or MI was 0.7052 for CAD-RADS, which was noninferior to the Duke Index (0.7073; p = 0.893) and traditional CAD classification (0.7095; p = 0.783). ICA rates were 13% for CAD-RADS 0 to 2, 66% for CAD-RADS 3, and 84% for CAD-RADS ≥4A. For CAD-RADS 3, 58% of all catheterizations occurred within the first 30 days of follow-up. In a patient subset with available medication data, 57% of CAD-RADS 3 patients who received 30-day ICA were either asymptomatic or not receiving antianginal therapy at baseline, whereas only 32% had angina and were receiving medical therapy., Conclusions: CAD-RADS effectively identified patients at risk for adverse events. Frequent ICA use was observed among patients without severe CAD, many of whom were asymptomatic or not taking antianginal drugs. Incorporating CAD-RADS into coronary CTA reports may provide a novel opportunity to promote evidence-based care post-coronary CTA., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined., Methods and Results: In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P <0.0001); men (24.6% versus 18.2%; P <0.0001). A significant interaction existed between sex and LM status for the composite outcome ( P =0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P =0.005) but not in men (adjusted hazard ratio, 0.98, P =0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P =0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque., Conclusion: Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts., (© 2017 American Heart Association, Inc.)

Background: Non-obstructive coronary artery disease (CAD) identified by coronary computed tomography angiography (CCTA) demonstrated prognostic value. CT-adapted Leaman score (CT-LeSc) showed to improve the prognostic stratification. Aim of the study was to evaluate the capability of CT-LeSc to assess long-term prognosis of patients with non-obstructive (CAD)., Methods: From 17 centers, we enrolled 2402 patients without prior CAD history who underwent CCTA that showed non-obstructive CAD and provided complete information on plaque composition. Patients were divided into a group without CAD and a group with non-obstructive CAD (<50% stenosis). Segment-involvement score (SIS) and CT-LeSc were calculated. Outcomes were non-fatal myocardial infarction (MI) and the combined end-point of MI and all-cause mortality., Results: Patient mean age was 56±12years. At follow-up (mean 59.8±13.9months), 183 events occurred (53 MI, 99 all-cause deaths and 31 late revascularizations). CT-LeSc was the only multivariate predictor of MI (HRs 2.84 and 2.98 in two models with Framingham and risk factors, respectively) and of MI plus all-cause mortality (HR 2.48 and 1.94 in two models with Framingham and risk factors, respectively). This was confirmed by a net reclassification analysis confirming that the CT-LeSc was able to correctly reclassify a significant proportion of patients (cNRI 0.28 and 0.23 for MI and MI plus all-cause mortality, respectively) vs. baseline model, whereas SIS did not., Conclusion: CT-LeSc is an independent predictor of major acute cardiac events, improving prognostic stratification of patients with non-obstructive CAD., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use., Methods and Results: Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age-sex percentiles of segment involvement score (SIS) at each year of life (40-79 years). The relationship between SIS age-sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (≤50th, 51-75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age-sex percentiles were well fitted to second-order polynomial curves (men: R 2 =0.86±0.12; women: R 2 =0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ≤50th, 51-75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%-2.7%], 3.9% [95% confidence interval: 3.0%-5.1%], and 7.2% [95% confidence interval: 5.4%-9.6%] in ≤50th, 51-75th, and >75th SIS% groups, respectively; P <0.001). Adjusted MACE risk was significantly increased among patients in SIS% groups above the median compared with patients below the median (hazard ratio [95% confidence interval]: 1.9 [1.3-2.8] for 51-75th SIS% group and 3.4 [2.3-5.0] for >75th SIS% group; P <0.01 for both)., Conclusions: We have developed clinically pragmatic age- and sex-specific nomograms of CAD prevalence using coronary computed tomography angiography findings. Global plaque burden measured using SIS% is predictive of cardiac events independent of traditional risk assessment., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443637., (© 2017 American Heart Association, Inc.)

In response to recent technological advancements in acquisition techniques as well as a growing body of evidence regarding the optimal performance of coronary computed tomography angiography (coronary CTA), the Society of Cardiovascular Computed Tomography Guidelines Committee has produced this update to its previously established 2009 "Guidelines for the Performance of Coronary CTA" (1). The purpose of this document is to provide standards meant to ensure reliable practice methods and quality outcomes based on the best available data in order to improve the diagnostic care of patients. Society of Cardiovascular Computed Tomography Guidelines for the Interpretation is published separately (2). The Society of Cardiovascular Computed Tomography Guidelines Committee ensures compliance with all existing standards for the declaration of conflict of interest by all authors and reviewers for the purpose ofclarity and transparency., (Copyright © 2016 Society of Cardiovascular Computed Tomography. All rights reserved.)

Objectives: The purpose of this study was to examine sex-specific associations, if any, between per-vessel coronary artery disease (CAD) extent and the risk of major adverse cardiovascular events (MACE) over a 5-year study duration., Background: The presence and extent of CAD diagnosed by coronary computed tomography angiography (CTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of sex on these findings., Methods: 5,632 patients (mean age 60.2 ± 11.8 years, 36.5% women) from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry were followed for 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction., Results: Obstructive CAD was more prevalent in men (42% vs. 26%; p < 0.001), whereas women were more likely to have normal coronary arteries (43% vs. 27%; p < 0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and nonobstructive CAD (HR: 2.16 for women, 2.56 for men; p < 0.001 for both), obstructive 1-vessel CAD (HR: 3.69 and 2.66; p < 0.001), 2-vessel CAD (HR: 3.92 and 3.55; p < 0.001), and 3-vessel/left main CAD (HR: 5.94 and 4.44; p < 0.001). Further exploratory analyses of atherosclerotic burden did not identify sex-specific patterns predictive of MACE., Conclusions: In a large prospective coronary CTA cohort followed long-term, we did not observe an interaction of sex for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by coronary CTA for the risk of MACE in both women and men., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite its well-established prognostic value, cardiorespiratory fitness (CRF) is not incorporated routinely in risk assessment tools. Whether low CRF provides additional predictive information in asymptomatic type 2 diabetics beyond conventional risk scores and coronary artery calcification (CAC) is unclear., Methods: We studied 600 type 2 diabetics aged 55-74 years without known coronary heart disease. CRF was quantified in metabolic equivalents (METs) by maximal treadmill testing and categorized as tertiles of percent predicted METs (ppMETs) achieved. CAC was calculated by non-enhanced computed tomography scans. The individual and joint association of both measures with an outcome event of all-cause mortality, myocardial infarction or stroke, was determined over a mean follow-up period of 80 ± 16 months., Results: There were 72 (12%) events during follow-up. Low CRF was independently associated with event risk after adjustment for traditional risk factors and CAC (HR 2.25, 95% CI 1.41-3.57, p = 0.001). CRF (unfit/fit) allowed further outcome discrimination both amongst diabetics with low CAC scores (9.5% versus 2.0% event rate), and amongst diabetics with high CAC scores (23.5% versus 12.4% event rate), p < 0.001. The addition of CRF to a model comprising UKPDS and CAC scores improved the area under the curve for event prediction from 0.66 to 0.71, p = 0.03, with a positive continuous net reclassification improvement (NRI) of 0.451, p = 0.002., Conclusions: CRF, quantified by ppMETs, provided independent prognostic information which was additive to CAC. Low CRF may identify asymptomatic diabetic subjects at higher risk for all-cause mortality, myocardial infarction or stroke, despite low CAC., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The purpose of this study was to evaluate the left main (LM) coronary artery anatomy using three-dimensional (3D) quantitative coronary angiography (QCA) software as compared to intravascular ultrasound (IVUS)., Background: Percutaneous intervention of the LM coronary artery is becoming more common in selected patients with LM coronary artery disease (CAD). Quantification of LM CAD by conventional angiography can be difficult. IVUS is considered the gold standard to evaluate LM anatomy and severity of CAD but entails additional steps, catheters, and expertise. Our objective was to compare a novel quantitative angiographic analysis system with IVUS for LM anatomy., Methods: Fifty five patients underwent both coronary angiography and IVUS of the LM. LM measurements were analyzed with 3D QCA (IC-PRO, Paieon, Israel) software using IVUS as the reference standard. The measurements included proximal, middle, distal minimal luminal diameter (MLD) and area. Additionally, lesion MLD, minimal luminal area were recorded by both systems. Bland-Altman plots were used to investigate agreement between the two imaging systems., Results: Of the 55 patients in our cohort, average age was 66 ± 11 years (25% female). By Bland-Altman analysis there was very good agreement between 3D QCA and IVUS for measures of MLD and minimal lumen area (MLA). However, there was poor concordance in the estimation of plaque burden between the two methods., Conclusions: Our data demonstrate that 3D QCA software has fair agreement when compared with IVUS for imaging of LM MLD and MLA. These results suggest that 3D QCA could potentially be helpful to guide intervention of the LM., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To assess the anatomic characteristics of the left main coronary artery (LM), and the relation between anatomic and clinical factors and the LM bifurcation angle (BA) using a novel, three dimensional quantitative coronary angiography (3D QCA) software., Background: Percutaneous intervention of the LM is a therapeutic option in selected patients with coronary artery disease (CAD). The anatomic features of the LM and its BA are determinants of procedural success and clinical outcome. However, those features and the factors that may affect the LM BA have not been fully described., Methods: The LM anatomy was evaluated from angiograms of 203 patients (age = 66 ± 11 years, 31% female) with and without LM CAD using 3D QCA analysis (IC-PRO, Paieon, Israel). LM size as well as the proximal BA (between LM and LCX) and the distal BA (between left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX)) were measured in end-diastole. Angiographic and clinical findings were also recorded., Results: 133/203 patients (65%) had no LM CAD. 3D QCA analysis demonstrated significant variability in the anatomy of the normal LM, including the LM branch vessels (LAD, LCX) diameter, and the LM BA. Among the 70 patients with LM CAD, 44 had distal LM disease. Importantly, patients with distal LM CAD had narrower proximal BA and a wider distal BA. Multivariate analysis (adjusted for clinical and anatomic variables) identified female sex (P = 0.02), trifurcation anatomy (P = 0.009), age > 75 years (P = 0.0009), and LM length > 12 mm (P = 0.001) as independent associates of the proximal BA. Independent associates of the distal BA were: trifurcation anatomy (P = 0.001), LM length > 12 mm (P < 0.0001), age > 75 years (P = 0.004), and a history of coronary bypass surgery (P = 0.04)., Conclusions: The current study demonstrates significant variability in the anatomy of the LM. The LM BA differs between patients with and without distal LM CAD, and both anatomic and clinical factors may affect the LM BA. Our findings also emphasize the possible usefulness of 3D QCA in the assessment of the LM., (Copyright © 2012 Wiley Periodicals, Inc.)

Aims: High-risk patients with severe aortic stenosis (AS) who are candidates for transcatheter valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) may additionally require revascularization of the unprotected left main coronary artery (UPLM). We aimed to assess the feasibility and procedural safety of UPLM stenting in such patients., Methods and Results: Ten cases of UPLM stenting prior to BAV or TAVI at three medical centers over a 2-year period were identified. Mean age was 84±4 years, aortic valve area was 0.70±0.12 cm(2), left ventricular ejection fraction was 58%±3%, and logistic EuroScore was 32±17. Intraaortic balloon counterpulsation was used in three patients. A single stent was used in seven patients, and two stents were used in three patients. One patient received a bare-metal stent, and the others received drug-eluting stents. No procedural complications occurred, and the patients were hemodynamically stable. Three patients subsequently underwent BAV, and seven underwent TAVI. During 6 months of follow-up, two patients died: one due to AS restenosis 6 months after BAV and one due to vascular complications 18 days after TAVI (34 days after UPLM stenting)., Conclusions: Stenting of the UPLM in patients with severe AS prior to percutaneous valve intervention seems feasible and safe. This approach may enable more patients to achieve comprehensive percutaneous therapy for severe coronary and valvular disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The relationship between coronary endothelial function and coronary calcification is not well established., Methods: Forty-six patients 17 men [37%]; age, 47.4+/-11.4 years prospectively underwent testing for coronary endothelial function and measurement of coronary artery calcification (CAC)., Results: Log CAC scores were not significantly different between patients with normal (n=31) and abnormal (n=15) response of epicardial coronary artery diameter to acetylcholine (%CAD(Ach)) (median (25, 75 percentile) 1.1 (0.0, 3.7) vs. 0.3 (0.0, 2.4), P=.32) and with normal (n=28) and abnormal (n=18) response of coronary blood flow to acetylcholine (%CBF(Ach)) (0.5 (0.0, 3.6) vs. 0.5 (0.0, 3.2), P=.76). Log CAC scores did not correlate with %CAD(Ach) (r=0.08, P=.59), %CBF(Ach) (r=0.14, P=.35)., Conclusions: In patients without significant coronary artery disease, coronary endothelial dysfunction showed no apparent association with coronary calcification. Our findings suggest that these 2 markers may represent separate, independent processes in the progression of coronary atherosclerosis.