Search

Coronary CT angiography (CCTA) has been gradually adopted into clinical practice over the last two decades. CCTA has high diagnostic accuracy, prognostic value, and unique features such as assessment of plaque composition. CCTA-derived functional assessment techniques such as fractional flow reserve and CT perfusion are also available and can increase the diagnostic specificity of the modality. These properties propound CCTA as a competitor of functional testing in diagnosis of obstructive CAD, however, utilizing CCTA in a concomitant fashion to potentiate the performance of the latter can lead to better patient care and may provide more accurate prognostic information. Although multiple diagnostic challenges such as evaluation of calcified segments, stents, and small distal vessels still exist, the technologic developments in hardware as well as growing incorporation of artificial intelligence to daily practice are all set to augment the diagnostic and prognostic role of CCTA in cardiovascular disorders., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Coronary computed tomography angiography (CCTA) is an important non-invasive tool for the assessment of coronary artery disease and the delivery of information incremental to coronary anatomy. CCTA measured left ventricular (LV) mid-diastolic volume (LV MDV ) and LV mass (LV Mass ) have important prognostic information but the utility of prospectively ECG-triggered CCTA to predict reduced left ventricular ejection fraction (LVEF) is unknown. The objective of this study was to determine if indexed LV MDV (LV MDVi ) and the LV MDV :LV Mass ratio on CCTA can identify patients with reduced LVEF., Materials/methods: 8179 patients with prospectively ECG-triggered CCTA between November 2014 and December 2019 were reviewed. A subset derivation cohort of 4352 healthy patients was used to define normal LV MDVi and LV MDV :LV Mass . Sex-specific thresholds were tested in a validation cohort of 1783 patients, excluded from the derivation cohort, with cardiac disease and known LVEF. The operating characteristics for 1 SD above the mean were tested for the identification of abnormal LVEF, LVEF≤35 ​% and ≤30 ​%., Results: The derivation cohort had a mean LV MDVi of 61.0 ​± ​13.7 ​mL/m 2 and LV MDV :LV Mass of 1.11 ​± ​0.24 ​mL/g. LV MDVi and LV MDV :LV Mass were both higher in patients with reduced LVEF than those with normal LVEF (98.8 ​± ​40.8 ​mL/m 2 vs. 63.3 ​± ​19.7 ​mL/m 2 , p ​< ​0.001, and 1.32 ​± ​0.44 ​mL/g vs. 1.05 ​± ​0.28 ​mL/g, p ​< ​0.001). Both mean LV MDVi and LV MDV :LV Mass increased with the severity of LVEF reduction. Sex-specific LV MDVi thresholds were 79 ​% and 80 ​% specific for identifying abnormal LVEF in females (LV MDVi  ​≥ ​69.9 ​mL/m 2 ) and males (LV MDVi  ​≥ ​78.8 ​mL/m 2 ), respectively. LV MDV :LV Mass thresholds had high specificity (87 ​%) in both females (LV MDVi :LV Mass  ​≥ ​1.39 ​mL/g) and males (LV MDVi :LV Mass  ​≥ ​1.30 ​mL/g)., Conclusion: Our study provides reference thresholds for LV MDVi and LV MDV :LV Mass on prospectively ECG-triggered CCTA, which may identify patients who require further LV function assessment., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Benjamin Chow reports a relationship with TD Bank that includes: funding grants. Benjamin Chow reports a relationship with SIEMENS that includes: funding grants. Benjamin Chow reports a relationship with Artrya that includes: equity or stocks and funding grants. Daniel Juneau reports a relationship with Advanced Accelerator Applications that includes: consulting or advisory. Daniel Juneau reports a relationship with Pfizer Inc that includes: consulting or advisory. Daniel Juneau reports a relationship with AbbVie Inc that includes: consulting or advisory., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We sought to assess the prognostic value of coronary computed tomographic angiography (CCTA) in patients with coronary artery bypass graft (CABG) by meta-analysis. MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus were searched for relevant original articles published up to July 2021. CCTA prognostic studies enrolling patients with CABG were screened and included if outcomes included all-cause mortality or major adverse cardiac events. Maximally adjusted hazard ratios (HRs) were extracted for CCTA-derived prognostic factors. HRs were log-transformed and pooled across studies using the DerSimonian-Laird random-effects model and statistical heterogeneity was assessed using the I 2 statistic. Of 1,576 screened articles, 4 retrospective studies fulfilled all inclusion criteria. Collectively, a total of 1,809 patients with CABG underwent CCTA (mean [SD] age 67.0 [8.5] years across 3 studies, 81.5% male across 4 studies). Coronary artery disease severity and revascularization were categorized using 2 models: unprotected coronary territories and coronary artery protection score. The pooled HRs from the random-effects models using the most highly adjusted study estimate were 3.64 (95% confidence interval 2.48 to 5.34, I 2  = 57.8%, p <0.001; 4 studies) and 4.85 (95% confidence interval 3.17 to 7.43, I 2  = 39.9%, p <0.001; 2 studies) for unprotected coronary territories and coronary artery protection score, respectively. In conclusion, in a limited number of studies, CCTA is an independent predictor of adverse events in patients with CABG. Larger studies using uniform models and endpoints are needed., Competing Interests: Declaration of Competing Interest Dr. Chow holds the Saul and Edna Goldfarb Chair in Cardiac Imaging Research; and receives research support from TD Bank, AusculSciences, Siemens Healthineers, and Artrya. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Abnormalities in computed tomography myocardial perfusion has been associated with coronary artery disease and major adverse cardiovascular events (MACE). We sought to investigate if subendocardial attenuation using coronary computed tomography angiography predicts MACE 30 days postelective noncardiac surgery., Methods: Using a 17-segment model, coronary computed tomography angiography images were analyzed for subendocardial and transmural attenuation and the corresponding blood pool. The segment with the lowest subendocardial attenuation and transmural attenuation were normalized to the segment with the highest subendocardial and transmural attenuation, respectively (SUB normalized , and TRANS normalized , respectively). We evaluated the independent and incremental value of myocardial attenuation to predict the composite of cardiovascular death or nonfatal myocardial infarction., Results: Of a total of 995 coronary CTA VISION (Coronary Computed Tomographic Angiography and Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) patients, 735 had available images and complete data for these analyses. Among these patients, 60 had MACE. Based on Revised Cardiovascular Risk Index, 257, 302, 138, and 38 patients had scores of 0, 1, 2, and ≥3, respectively. On coronary computed tomography angiography, 75 patients had normal coronary arteries, 297 patients had nonobstructive coronary artery disease, 264 patients had obstructive disease, and 99 patients had extensive obstructive coronary artery disease. SUB normalized was an independent and incremental predictor of events in the model that included Revised Cardiovascular Risk Index and coronary artery disease severity. Compared with patients in the highest tertile of SUB normalized , patients in the second and first tertiles had an increased hazards ratio for events (2.23 [95% CI, 1.091-4.551] and 2.36 [95% CI, 1.16-4.81], respectively). TRANS normalized , as a continuous variable, was also found to be a predictor of MACE ( P =0.027)., Conclusions: Our study demonstrates that SUB normalized and TRANS normalized are independent and incremental predictors of MACE 30 days after elective noncardiac surgery. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01635309.

Objective: We sought to determine the prognostic value of coronary computed tomography angiography (CCTA) in patients with a history of percutaneous coronary intervention (PCI)., Background: Although the prognostic value of CCTA has been well studied, its incremental value in patients with previous PCI has not been robustly investigated., Methods: Consecutive patients with previous PCI were prospectively enrolled and CCTA images were evaluated for coronary artery disease (CAD) severity. Patients were followed for major adverse cardiovascular events (MACE) which was a composite of cardiac death and non-fatal myocardial infarction. All-cause death was assessed as a secondary endpoint., Results: A total of 501 patients were analyzed with a mean follow-up time of 59.5 ± 32.0 months and 52 patients (10.4%) experienced MACE. Multivariable Cox regression analysis showed that CAD severity was a predictor of MACE with 0, 1, 2, and 3 vessel disease having annual rates of 1.3%, 2.2%, 2.2%, and 5.3%, respectively. All-cause death was similar in all categories of CAD., Conclusions: In patients with previous PCI, CAD severity as measured with CCTA has independent and incremental prognostic value., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary CT angiography (CCTA) is increasing seen as a first line investigation in patients with suspected coronary artery disease. Heart-rate control improves the image quality and diagnostic accuracy of CCTA. Typically, beta-blockers are administered to induce sinus bradycardia. Sinus bradycardia may also be induced by ivabradine. We hypothesized that in a real-world population ivabradine would be an effective alternative to metoprolol at heart rate lowering for CCTA., Methods: This was a retrospective analysis of consecutive patients who were exposed to an ivabradine-based (IB) versus a metoprolol-only (MO) protocol to achieve a target heart rate 65 and received heart-rate lowering medication: 1958 patients had MO, and 718 received IB protocol. Target heart rate of

Aims: This large prospective cohort study sought to confirm the incremental prognostic value of coronary computed tomographic angiography (CCTA) measured over a prolonged follow-up duration. CCTA has diagnostic and prognostic value but data supporting its long-term prognostic value in a large prospectively recruited cohort with suspected coronary artery disease (CAD) has been limited., Methods and Results: Consecutive patients (without history of myocardial infarction, revascularization, cardiac transplantation, and congenital heart disease) were prospectively enrolled. CCTA was evaluated for CAD severity, total plaque score (TPS), and left ventricular ejection fraction. Patients were followed for major adverse events (MAE) and major adverse cardiac events (MACE).Over a total of 99 months, 8667 consecutive CCTA patients (mean age = 57.1 ± 11.1 years, 52.9% men) were prospectively enrolled and followed for a mean duration of 7.0 ± 2.6 years. At follow-up, there were a total of 723 MAE, 278 MACE, 547 all-cause deaths, 110 cardiac deaths, and 104 non-fatal myocardial infarction. Patients without coronary atherosclerosis at the time of CCTA had a very low annual event rate for both MAE and MACE (0.45%/year and 0.19%/year, respectively). Both MAE and MACE increased with increasing TPS and severity of CAD. In patients with non-obstructive CAD and who were statin-naive, TPS ≥5 had MACE rates >0.75%/year. Patients with high-risk CAD had an annual MAE and MACE rates of 3.52%/year and 2.58%/year, respectively. Adjusted hazard ratio of the severity of CAD based on multivariable analyses indicated that the prognostic values were incremental., Conclusion: CCTA has independent and incremental prognostic value that is durable over time. The absence of coronary atherosclerosis portends an excellent prognosis. Patients with increasing non-obstructive plaque burden have worse prognosis and a TPS threshold ≥5 may identify a population that may benefit from statin therapy., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Low-attenuation plaques (LAPs) are associated with an increased risk of cardiovascular mortality and morbidity. South Asians experience poorer cardiovascular outcomes compared to Caucasian populations. We hypothesised that South Asian population has a higher prevalence of LAP compared to Caucasians and this difference predicts major adverse cardiovascular events. 72 Caucasian and 72 Morise score-matched South Asian patients were identified from a cardiac computed tomography angiography (CCTA) registry. Coronary artery plaque subtypes in proximal major epicardial and left main arteries were analysed from CCTA images using pre-determined attenuation ranges in Hounsfield units (HUs): 1 to 30 HU (low attenuation), 31 to 70 HU (intermediate attenuation), 71 to 150 HU (high attenuation), and mean coronary lumen + 2 standard deviations to 1000 HU (calcified). For each analysis, data comparison was performed for plaque volumes after normalising for the corresponding coronary artery outer vessel wall volume. The baseline characteristics and total plaque score of the two cohorts were similar. There were no statistically significant differences in low, intermediate, and high- attenuation, or calcified normalised plaque volumes between Caucasian and Morise score-matched South Asian cohorts. After a mean follow up of 32 months, major adverse cardiovascular events were similar between Caucasians and South Asians. In a Morise score-matched ethnicity study, we found no significant differences in plaque subtypes including LAP in South Asians compared to a Caucasian cohort. Other factors accounting for poor outcomes in South Asians should be investigated.

Background: The incremental value and optimal utilization of non-invasive testing for prediction of peri-operative cardiac events during non-cardiac surgery are not clear., Methods: A sub-study of VISION-CTA was performed using patients who underwent both coronary computed tomography angiography (CCTA) and nuclear myocardial perfusion imaging (MPI) as part of their pre-operative assessment. CCTA images were compared with MPI to determine the correlation between ischemia and obstructive coronary artery disease (CAD). Patients were followed post-operatively for 30 days and primary outcomes were all-cause death and non-fatal myocardial infarction. The predictive capacity of CCTA and nuclear MPI in predicting peri-operative major adverse cardiac event (MACE) was analyzed., Results: A total of 55 patients (mean age 68.5 ± 8.4 years, 80.0% male) were analyzed. There was a strong correlation between the degree of obstructive CAD and the severity of perfusion abnormalities. Patients with severe CAD (≥ 70% stenosis) had a higher summed stress score than those without severe CAD [4.88 ± 1.22 and 1.30 ± 0.62, respectively (P < .05)]. Similarly summed difference score was significantly higher in patients with severe CAD [1.33 ± 0.46 and 0.17 ± 0.17 (P < .05)]. At 30 days there was a total of 8 (14.5%) MACE. The rate of MACE was higher in patients with severe CAD than those without (20.7% and 7.7%, respectively). Myocardial ischemia appeared to be predictive of MACE with an unadjusted odds ratio of 14.63 (P = .003). The predictive capacity of MPI further improved when only those patients with severe CAD were included (33.00) with a sensitivity, specificity, positive predictive value, and negative predictive value of 100% (79.4-100.0), 72.7% (49.8-89.3), 50.0% (21.1-78.9), and 100% (79.4-100.0), respectively., Conclusion: Although patients with significant obstructive disease are at risk of peri-operative MACE, the absolute event rate is low. Our data, albeit hypothesis generating, suggest that the peri-operative risk may be refined further by employing nuclear MPI in those with obstructive disease on CCTA.

Background: There is conflicting data on early left ventricle (LV) remodeling in diabetes mellitus (DM) and hypertension (HTN). This study examines the feasibility of cardiac computed tomography angiography (CCTA) to detect early LV geometric changes in patients with DM and HTN., Methods: Consecutive patients (n = 5,992) who underwent prospective electrocardiography (ECG)-triggered (mid-diastolic) CCTA were screened. Patients with known structural heart disease or known LV dysfunction were excluded. Left ventricular mass (LVM), left ventricular mid-diastolic volume (LVMDV), and LV concentricity (LVM/LVMDV) were measured and indexed to body surface area., Results: A total of 4,283 patients were analyzed (mean age 57 ± 10.69 years, female 46.7%). DM, HTN, and HTN + DM were present in 4.1%, 35.8% and 10.6% of patients, respectively. Compared to normal patients, HTN and HTN + DM patients had increased LVM indexed to body surface area (LVMi) (56.87 ± 17.24, 59.26 ± 13.62, and 58.56 ± 13.09, respectively; P < 0.05). There was no difference in LVMi between normal subjects and patients with DM (56.39 ± 11.50, P = 0.617).Concentricity indices were higher in patient with HTN (1.0456 ± 0.417; P < 0.001), DM (1.109 ± 0.638; P = 0.004), and HTN + DM (1.083 ± 0.311, P < 0.001) than normal individuals (0.9671 ± 0.361). There was no overlap of the 95% confidence intervals in the composite of concentricity indices and LVMi between the different groups., Conclusions: CCTA measures of LVM and concentricity index may discriminate patients with HTN and DM before overt structural heart disease., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Aims: We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores - which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) - and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders., Methods: Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability., Results: A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265)., Conclusion: Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone., Competing Interests: Declaration of competing interest Dr. James K. Min receives funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare. Dr. Min serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly. The Department of Cardiology of the Leiden University Medical Center received research grants from Biotronik, Medtronic, Boston Scientific and Edwards Lifesciences. Arthur J.H.A. Scholte received consulting fees from GE Healthcare and Canon., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: While an assessment of the right ventricular (RV) size remains challenging, the entire RV is can be imaged on coronary computed tomography angiography (CCTA) studies. With prospective ECG-triggering, the RV end diastolic volume (RVEDV) cannot be measured; however, the RV mid-diastolic volume (RVMDV) can still be measured accurately from routine CCTA data sets. The objective of this study is to establish normal reference values for RVMDV., Methods: Right ventricular mid-diastolic volumes were measured in 4855 consecutive patients undergoing prospectively ECG-triggered coronary CTA. All patients with known cardiac or pulmonary disease (coronary artery disease, myocardial infarction, revascularization, heart failure, pulmonary hypertension, congenital heart disease, valvular heart disease, atrial fibrillation, implantable cardiac defibrillator implantation, cardiac transplant, or cardiac surgery) or smoking history (3313 patients) were excluded., Results: 1542 patients were analyzed (mean age 56.4 ± 11.1 years, mean BSA 1.96 ± 0.26 and 47% male). The mean RVMDV for men and women was 168.6 ± 37.6 mL and 117.6 ± 26.4 mL, respectively. Mean BSA-indexed RVMDV was 80.0 ± 15.3 mL/m 2 and 64.1 ± 12.2 mL/m 2 for men and women, respectively. The presence of hypertension and diabetes did not have an impact on these values. RVMDV and BSA-indexed RVMDV were lower in women and in older individuals., Conclusion: Normal reference ranges for RVMDV were established using prospectively ECG-triggered coronary CTA studies. This data can be used to identify patients with abnormal RV volumes and potentially RV dysfunction, adding incremental diagnostic value to routine CCTA studies., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: There are significant sex-specific differences in left ventricular ejection fraction (LVEF), with a higher LVEF being observed in women. We sought to assess the clinical relevance of an increased LVEF in women and men., Methods and Results: A total of 4632 patients from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry (44.8% women; mean age 58.7 ± 13.2 years in men and 59.5 ± 13.3 years in women, P = 0.05), in whom LVEF was measured by cardiac computed tomography, were categorized according to LVEF (low <55%, normal 55-65%, and high >65%). The prevalence of high LVEF was similar in both sexes (33.5% in women and 32.5% in men, P = 0.46). After 6 years of follow-up, no difference in mortality was observed in patients with high LVEF in the overall cohort (P = 0.41). When data were stratified by sex, women with high LVEF died more often from any cause as compared to women with normal LVEF (8.6% vs. 7.1%, log rank P = 0.032), while an opposite trend was observed in men (5.8% vs. 6.8% in normal LVEF, log rank P = 0.89). Accordingly, a first order interaction term of male sex and high LVEF was significant (hazard ratios 0.63, 95% confidence intervals 0.41-0.98, P = 0.043) in a Cox regression model of all-cause mortality adjusted for age, cardiovascular risk factors, and severity of coronary artery disease (CAD)., Conclusion: Increased LVEF is highly prevalent in patients referred for evaluation of CAD and is associated with an increased risk of death in women, but not in men. Differentiating between normal and hyperdynamic left ventricles might improve risk stratification in women with CAD., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01443637., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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.)

Background: Randomized trials have shown favorable clinical outcomes for coronary CT angiography (CTA) in patients with suspected acute coronary syndrome (ACS). Our goal was to estimate the cost-effectiveness of coronary CTA as compared to alternative management strategies for ACP patients over lifetime., Methods: Markov microsimulation model was developed to compare cost-effectiveness of competitive strategies for ACP patients: 1) coronary CTA, 2) standard of care (SOC), 3) AHA/ACC Guidelines, and 4) expedited emergency department (ED) discharge protocol with outpatient testing. ROMICAT-II trial was used to populate the model with low to intermediate risk of ACS patient data, whereas diagnostic test-, treatment effect-, morbidity/mortality-, quality of life- and cost data were obtained from the literature. We predicted test utilization, costs, 1-, 3-, 10-year and over lifetime cardiovascular morbidity/mortality for each strategy. We determined quality adjusted life years (QALY) and incremental cost-effectiveness ratio. Observed outcomes in ROMICAT-II were used to validate the short-term model., Results: Estimated short-term outcomes accurately reflected observed outcomes in ROMICAT-II as coronary CTA was associated with higher costs ($4,490 vs. $2,513-$4,144) and revascularization rates (5.2% vs. 2.6%-3.7%) compared to alternative strategies. Over lifetime, coronary CTA dominated SOC and ACC/AHA Guidelines and was cost-effective compared to expedited ED protocol ($49,428/QALY). This was driven by lower cardiovascular mortality (coronary CTA vs. expedited discharge: 3-year: 1.04% vs. 1.10-1.17; 10-year: 5.06% vs. 5.21-5.36%; respectively)., Conclusion: Coronary CTA in patients with suspected ACS renders affordable long-term health benefits as compared to alternative strategies., (Copyright © 2020 Society of Cardiovascular Computed Tomography. All rights reserved.)

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.)

Aims: The long-term prognostic value of coronary computed tomography angiography (CCTA)-identified coronary artery disease (CAD) has not been evaluated in elderly patients (≥70 years). We compared the ability of coronary CCTA to predict 5-year mortality in older vs. younger populations., Methods and Results: From the prospective CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry, we analysed CCTA results according to age <70 years (n = 7198) vs. ≥70 years (n = 1786). The severity of CAD was classified according to: (i) maximal stenosis degree per vessel: none, non-obstructive (1-49%), or obstructive (>50%); (ii) segment involvement score (SIS): number of segments with plaque. Cox-proportional hazard models assessed the relationship between CCTA findings and time to mortality. At a mean 5.6 ± 1.1 year follow-up, CCTA-identified CAD predicted increased mortality compared with patients with a normal CCTA in both <70 years [non-obstructive hazard ratio (HR) confidence interval (CI): 1.70 (1.19-2.41); one-vessel: 1.65 (1.03-2.67); two-vessel: 2.24 (1.21-4.15); three-vessel/left main: 4.12 (2.27-7.46), P < 0.001] and ≥70 years [non-obstructive: 1.84 (1.15-2.95); one-vessel: HR (CI): 2.28 (1.37-3.81); two-vessel: 2.36 (1.33-4.19); three-vessel/left main: 2.41 (1.33-4.36), P = 0.014]. Similarly, SIS was predictive of mortality in both <70 years [SIS 1-3: 1.57 (1.10-2.24); SIS ≥4: 2.42 (1.65-3.57), P < 0.001] and ≥70 years [SIS 1-3: 1.73 (1.07-2.79); SIS ≥4: 2.45 (1.52-3.93), P < 0.001]. CCTA findings similarly predicted long-term major adverse cardiovascular outcomes (MACE) (all-cause mortality, myocardial infarction, and late revascularization) in both groups compared with patients with no CAD., Conclusion: The presence and extent of CAD is a meaningful stratifier of long-term mortality and MACE in patients aged <70 years and ≥70 years old. The presence of obstructive and non-obstructive disease and the burden of atherosclerosis determined by SIS remain important predictors of prognosis in older populations., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Coronary artery calcification is a marker of underlying atherosclerotic vascular disease. The absence of coronary artery calcification is associated with a low prevalence of obstructive coronary artery disease (CAD), but it cannot be ruled out completely. We sought to develop a clinical tool that can be added to Agatston score of zero to rule out obstructive CAD with high accuracy., Methods: We developed a clinical score retrospectively from a cohort of 4903 consecutive patients with an Agatston score of zero. Patients with prior diagnosis of CAD, coronary percutaneous coronary intervention, or surgical revascularization were excluded. Obstructive CAD was defined as any epicardial vessel diameter narrowing of ≥50%. The score was validated using an external cohort of 4290 patients with an Agatston score of zero from a multinational registry., Results: The score consisted of 7 variables: age, sex, typical chest pain, dyslipidemia, hypertension, family history, and diabetes mellitus. The model was robust with an area under the curve of 0.70 (95% CI, 0.65-0.76) in the derivation cohort and 0.69 (95% CI, 0.65-0.72) in the validation cohort. Patients were divided into 3 risk groups based on the score: low (≤6), intermediate (7-13), and high (≥14). Patients who score ≤6 have a negative likelihood ratio of 0.42 for obstructive CAD, whereas those who score ≥14 have a positive likelihood ratio of >5.5 for obstructive CAD. The outcome was ruled out in >98% of patients with a score ≤6 in the validation cohort., Conclusions: We developed a score that may be used to identify the likelihood of obstructive CAD in patients with an Agatston score of zero, which may be used to direct the need for additional testing. However, the results of this retrospective analysis are hypothesis generating and before clinical implementation should be validated in a trial with a prospectively collected data.

Background: Coronary computed tomography angiography (CCTA) left ventricle (LV) volumes have prognostic value. LV measurements however can differ depending on post-processing software. Two common methods are the contour (CON) or attenuation (ATT) based methods. This study aims to determine differences in LV volume measurements using the 2 methods., Methods: LV mid-diastolic volumes (LVMDV) were measured using both ATT and CON from 2 vendors in 750 consecutive patients undergoing CCTA. 500 were measured in a derivation cohort to establish a linear regression equation that would correct for any detected differences between the two methods. The equation was then assessed in 250 cases in the validation cohort. Comparisons were made between intra-vendor LVMDV CON and LVMDV ATT as well as inter-vendor LVMDV ATT ., Results: In the derivation cohort, the correlation between the two methods and vendors were very good (0.98 and 0.97 respectively). LVMDV CON was 20.4 ± 7.4% greater than LVMDV ATT . LVMDV ATT was 9.2 ± 6.6% greater with one vendor compared to the other. Validation cohort corrected LVMDV ATT was not statistically different to measured LVMDV ATT (p = 0.45)., Conclusion: A systematic difference was found between ATT and CON measuring methods. Using a derived linear regression equation, we were able to correct for differences in measurement techniques. The method of LVMDV measurement requires careful consideration when establishing reference values and extrapolating published study results., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

The prognostic performance of coronary artery calcium score (CACS) for predicting adverse outcomes in patients with decreased renal function remains unclear. We aimed to examine whether CACS improves risk stratification by demonstrating incremental value beyond a traditional risk score according to renal function status. 9,563 individuals without known coronary artery disease were enrolled. Estimated glomerular filtration rate (eGFR, ml/min/1.73 m 2 ) was ascertained using the modified Modification of Diet in Renal Disease formula, and was categorized as: ≥90, 60 to 89, and <60. CACS was categorized as 0, 1 to 100, 101 to 400, and >400. Multivariable Cox regression was used to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) for major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, and late revascularization (>90 days). Mean age was 55.8 ± 11.5 years (52.8% male). In total, 261 (2.7%) patients experienced MACE over a median follow-up of 24.5 months (interquartile range: 16.9 to 41.1). Incident MACE increased with higher CACS across each eGFR category, with the highest rate observed among patients with CACS >400 and eGFR <60 (95.1 per 1,000 person-years). A CACS >400 increased MACE risk with HR 4.46 (95% CI 1.68 to 11.85), 6.63 (95% CI 4.03 to 10.92), and 6.14 (95% CI 2.85 to 13.21) for eGFR ≥90, 60 to 89, and <60, respectively, as compared with CACS 0. Further, CACS improved discrimination and reclassification beyond Framingham 10-year risk score (FRS) (AUC: 0.70 vs 0.64; category free-NRI: 0.51, all p <0.001) for predicting MACE in patients with impaired renal function (eGFR < 90). In conclusion, CACS improved risk stratification and provided incremental value beyond FRS for predicting MACE, irrespective of eGFR status., (Published by Elsevier Inc.)

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.

Aims: Advances of cardiac computed tomography angiography (CTA) have been developed for dose reduction, but their efficacy in clinical practice is largely unknown. This study was designed to evaluate radiation dose exposure and utilization of dose-saving strategies for contrast-enhanced cardiac CTA in daily practice., Methods and Results: Sixty one hospitals from 32 countries prospectively enrolled 4502 patients undergoing cardiac CTA during one calendar month in 2017. Computed tomography angiography scan data and images were analysed in a central core lab and compared with a similar dose survey performed in 2007. Linear regression analysis was performed to identify independent predictors associated with dose. The most frequent indication for cardiac CTA was the evaluation of coronary artery disease in 89% of patients. The median dose-length product (DLP) of coronary CTA was 195 mGy*cm (interquartile range 110-338 mGy*cm). When compared with 2007, the DLP was reduced by 78% (P < 0.001) without an increase in non-diagnostic coronary CTAs (1.7% in 2007 vs. 1.9% in 2017 surveys, P = 0.55). A 37-fold variability in median DLP was observed between the hospitals with lowest and highest DLP (range of median DLP 57-2090 mGy*cm). Independent predictors for radiation dose of coronary CTA were: body weight, heart rate, sinus rhythm, tube voltage, iterative image reconstruction, and the selection of scan protocols., Conclusion: This large international radiation dose survey demonstrates considerable reduction of radiation exposure in coronary CTA during the last decade. However, the large inter-site variability in radiation exposure underlines the need for further site-specific training and adaptation of contemporary cardiac scan protocols.

Aims: Coronary computed tomography angiography (CCTA) and coronary artery calcium score (CACS) have prognostic value for coronary artery disease (CAD) events beyond traditional risk assessment. Age is a risk factor with very high weight and little is known regarding the incremental value of CCTA over CAC for predicting cardiac events in older adults., Methods and Results: Of 27 125 individuals undergoing CCTA, a total of 3145 asymptomatic adults were identified. This study sample was categorized according to tertiles of age (cut-off points: 52 and 62 years). CAD severity was classified as 0, 1-49, and ≥50% maximal stenosis in CCTA, and further categorized according to number of vessels ≥50% stenosis. The Framingham 10-year risk score (FRS) and CACS were employed as major covariates. Major adverse cardiovascular events (MACE) were defined as a composite of all-cause death or non-fatal MI. During a median follow-up of 26 months (interquartile range: 18-41 months), 59 (1.9%) MACE occurred. For patients in the top age tertile, CCTA improved discrimination beyond a model included FRS and CACS (C-statistic: 0.75 vs. 0.70, P-value = 0.015). Likewise, the addition of CCTA improved category-free net reclassification (cNRI) of MACE in patients within the highest age tertile (e.g. cNRI = 0.75; proportion of events/non-events reclassified were 50 and 25%, respectively; P-value <0.05, all). CCTA displayed no incremental benefit beyond FRS and CACS for prediction of MACE in the lower age tertiles., Conclusion: CCTA provides added prognostic value beyond cardiac risk factors and CACS for the prediction of MACE in asymptomatic older adults.

Our objective was to assess the prognostic value of symptom typicality in patients without obstructive coronary artery disease (CAD), determined by coronary computed tomographic angiography (CCTA). We identified 4215 patients without prior history of CAD and without obstructive CAD (<50% CCTA stenosis). CAD severity was categorized as nonobstructive (1%-49%) and none (0%). Based upon the Diamond-Forrester criteria for angina pectoris, symptom typicality was classified as asymptomatic, nonanginal, atypical, and typical. Multivariable Cox proportional hazards models were used to assess the risk of major adverse cardiac events (MACE), comprising all-cause mortality, myocardial infarction, unstable angina, and late revascularization, according to symptom typicality. Mean patient age was 57.0 ±12.0 years (54.9% male). During a median follow-up of 5.3 years (interquartile range, 4.6-5.9 years), MACE were reported in 312 (7.4%) patients. Among patients with nonobstructive CAD, there was an association between symptom typicality and MACE (P for interaction = 0.05), driven by increased risk of MACE among those with typical angina and nonobstructive CAD (hazard ratio: 1.62, 95% confidence interval: 1.06-2.48, P = 0.03). No consistent relationship was found between symptom typicality and MACE among patients without any CAD (hazard ratio: 0.73, 95% confidence interval: 0.34-1.57, P = 0.08). In the CONFIRM registry, patients who presented with concomitant typical angina and nonobstructive CAD had a higher rate of MACE than did asymptomatic patients with nonobstructive CAD. However, the presence of typical angina did not appear to portend worse prognosis in patients with no CAD., (© 2018 Wiley Periodicals, Inc.)

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.)

Purpose: Cardiac imaging expenditures have come under scrutiny, and a focus on appropriate use criteria (AUC) has arisen to ensure cost-effective resource utilization. Although AUC has been developed by clinical experts, it has not undergone rigorous quality assurance testing to ensure that inappropriate indications for testing yield little clinical benefit. The objective of the study was to evaluate the potential incremental prognostic value of coronary computed tomographic angiography (CCTA) in the different AUC categories., Materials and Methods: Consecutive patients enrolled into a cardiac CT Registry were collated. Patient indications were reviewed and based on the 2010 AUC (appropriate, uncertain, and inappropriate). Patients were followed-up for death, myocardial infarction (MI), and late revascularization, with the primary composite endpoint being cardiac death, nonfatal MI, and late revascularization. The prognostic value of CCTA over clinical variables in each of the AUC categories was assessed., Results: Indications for CCTA were appropriate, uncertain, and inappropriate in 1284 (66.5%), 312 (16.2%), and 334 (17.3%) patients, respectively. Rates of all-cause of death, cardiac death, nonfatal MI, and late revascularization were similar across patients with appropriate, uncertain, and inappropriate indications for CCTA. Moreover, in each AUC category, CCTA had incremental prognostic value over a routine clinical risk score (National Cholesterol Education Program) with hazard ratios of 9.98, 7.39, and 5.61., Conclusions: CCTA has incremental prognostic value in all AUC categories, even when the reason for the study was deemed "inappropriate." This suggests that CCTA may still have clinical value in "inappropriate" indications and that further quality assurance AUC studies are needed.

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: Left ventricular (LV) volumetric and functional parameters measured with cardiac computed tomography (cardiac CT) augment risk prediction and discrimination for future mortality. Gender- and age-specific standard values for LV dimensions and systolic function obtained by 64-slice cardiac CT are lacking., Methods and Results: 1155 patients from the Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry (54.5% males, mean age 53.1 ± 12.4 years, range: 18-92 years) without known coronary artery disease (CAD), structural heart disease, diabetes, or hypertension who underwent cardiac CT for various indications were categorized according to age and sex. A cardiac CT data acquisition protocol was used that allowed volumetric measuring of LV function. Image interpretation was performed at each site. Patients with significant CAD (>50% stenosis) on cardiac CT were excluded from the analysis. Overall, mean left ventricular ejection fraction (LVEF) was higher in women when compared with men (66.6 ± 7.7% vs. 64.6 ± 8.1%, P < 0.001). This gender-difference in overall LVEF was caused by a significantly higher LVEF in women ≥70 years when compared with men ≥70 years (69.95 ± 8.89% vs. 65.50 ± 9.42%, P = 0.004). Accordingly, a significant increase in LVEF was observed with age (P = 0.005 for males and P < 0.001 for females), which was more pronounced in females (5.21%) than in males (2.6%). LV end-diastolic volume decreased in females from 122.48 ± 27.87 (<40 years) to 95.56 ± 23.17 (>70 years; P < 0.001) and in males from 155.22 ± 35.07 (<40 years) to 130.26 ± 27.18 (>70 years; P < 0.001)., Conclusion: Our findings indicate that the LV undergoes a lifelong remodelling and highlight the need for age and gender adjusted reference values., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

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.)

Hypertension is an atherosclerosis factor and is associated with cardiovascular risk. We investigated the relationship between hypertension and the presence, extent, and severity of coronary atherosclerosis in coronary computed tomographic angiography and cardiac events risk. Of 17 181 patients enrolled in the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry) who underwent ≥64-detector row coronary computed tomographic angiography, we identified 14 803 patients without known coronary artery disease. Of these, 1434 hypertensive patients were matched to 1434 patients without hypertension. Major adverse cardiac events risk of hypertension and non-hypertensive patients was evaluated with Cox proportional hazards models. The prognostic associations between hypertension and no-hypertension with increasing degree of coronary stenosis severity (nonobstructive or obstructive ≥50%) and extent of coronary artery disease (segment involvement score of 1-5, >5) was also assessed. Hypertension patients less commonly had no coronary atherosclerosis and more commonly had nonobstructive and 1-, 2-, and 3-vessel disease than the no-hypertension group. During a mean follow-up of 5.2±1.2 years, 180 patients experienced cardiac events, with 104 (2.0%) occurring in the hypertension group and 76 (1.5%) occurring in the no-hypertension group (hazard ratios, 1.4; 95% confidence intervals, 1.0-1.9). Compared with no-hypertension patients without coronary atherosclerosis, hypertension patients with no coronary atherosclerosis and obstructive coronary disease tended to have higher risk of cardiac events. Similar trends were observed with respect to extent of coronary artery disease. Compared with no-hypertension patients, hypertensive patients have increased presence, extent, and severity of coronary atherosclerosis and tend to have an increase in major adverse cardiac events., (© 2017 American Heart Association, Inc.)

Background: The segment involvement score (SIS) is a semiquantitative measure of the extent of atherosclerosis burden by coronary computed tomography angiography (CTA). We sought to evaluate by meta-analysis the prognostic value of SIS, and to compare it with other CTA measures of coronary artery disease (CAD)., Methods: Electronic databases from 1946 to January 2016 were searched. Studies reporting SIS, or an equivalent measure by coronary CTA, and clinical outcomes were included. Maximally adjusted hazard ratios (HR), predominantly for clinical variables, were extracted for SIS, obstructive CAD, Agatston coronary artery calcium score, and plaque composition. These were pooled using DerSimonian-Laird random effects models., Results: Eleven nonrandomized studies with good methodological quality enrolling 9777 subjects (mean age 61 ± 11 years, 57% male, mean follow up 3.3 years) who had 472 (4.8%) MACE (cardiac or all cause death, non-fatal myocardial infarction or late revascularization), were included. SIS (per segment increase) had pooled HR of 1.25 (95% CI: 1.16,1.35; I 2  = 71.4%, p < 0.001) for MACE. HR for MACE was 1.37 (95% CI: 1.32,1.42; I 2  = 95.6%, p < 0.001) for number of segments with stenosis (per segment increase), 3.39 (95% CI: 1.65,6.99; I 2  = 87.8%, p = 0.001) for obstructive CAD (binary variable) and 1.00 (95% CI: 1.00,1.01; I 2  = 75.0%, p = 0.490) for Agatston score (per unit increase). HRs by plaque composition (calcified, non-calcified and mixed; per segment change) were 1.24 (95% CI: 1.10,1.39; I 2  = 81.6%, p = 0.001), 1.20 (95% CI: 0.97,1.48; I 2  = 92.9%, p = 0.093) and 1.27 (95% CI: 1.03,1.58; I 2  = 89.8%, p = 0.029), respectively., Conclusion: Despite heterogeneity in endpoints, extent of CAD as quantified by SIS on coronary CTA is a strong, independent predictor of cardiovascular events., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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.)

Introduction: Aortic valve calcification (AVC) has been associated with major adverse cardiovascular events and all-cause mortality. We sought to develop and validate a method to quantify AVC using coronary CT angiography (CTA)., Methods: Of 59 patients who underwent both non-contrast and contrast enhanced coronary CTA, 25 patients served as the derivation cohort and 34 patients served as the validation cohort. For non-contrast enhanced CT, quantification of AVC was performed using the Agatston method for coronary artery calcification (CAC). For contrast enhanced coronary CTA, a region of interest (ROI) was placed in the ascending aorta and the mean aortic attenuation value (HU Aorta ) and standard deviation (SD) were measured. Using a calcium threshold of mean HU Aorta  + 2SD, the AVC CTA was calculated. All other Agatston score parameters (weighting factors and area calculations) remained unchanged., Results: In the derivation cohort, the correlation between AVC CAC and AVC CTA was excellent (r = 0.982). Using the line of best fit, a correction factor was calculated enabling the conversion of AVC CTA results to a AVC CAC equivalent (AVC Corrected  = 1.868 × AVC CTA ). Using this correction in the validation cohort, the correlation and agreement between AVC CAC and AVC Corrected were good (ICC = 0.939; 95% CI: 0.881-0.969; kappa = 0.700; 95% CI: 0.469-0.931)., Conclusion: The quantification of AVC Corrected using contrast enhanced CTA is feasible using a systematic approach with very good reliability and good agreement with AVC CAC . Larger-scale validation studies are needed to determine whether the use of AVC CAC can be eliminated in favour of AVC Corrected ., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The adoption of prospectively ECG-triggered acquisition coronary computed tomography angiography (CTA) has resulted in the inability to measure left ventricle (LV) end-diastolic volume and LV ejection fraction. However other prognostic measures such as LV mass and LV mid-diastolic volume (LVMDV) can still be assessed. The objective of this study is to establish normal reference values for LVMDV and LV mass., Methods: Left ventricular mid-diastolic volumes and LV mass were prospectively measured in 2647 consecutive 'normal' patients undergoing prospectively ECG-triggered coronary CTA. Patients with known coronary artery disease (prior myocardial infarction or prior revascularization), heart failure, congenital heart disease, heart transplant or prior cardiac surgery were excluded. Commercially available software was used to calculate the LVMDV and LV mass., Results: Among the 2647 patient cohort (mean age = 58 years, 54% men), the mean LVMDV indexed for body surface area was 57.5 ± 15.3 mL/m 2 and 64.5 ± 20.2 mL/m 2 for women and men, respectively. The mean indexed LV mass was 52.2 ± 10.9 g/m 2 for women and 63.6 ± 13.7 g/m 2 for men. Indexed LVMDV decreased with increasing age. The presence of hypertension, diabetes and obstructive coronary artery disease did not have a clinically relevant impact on these values. Age and sex specific upper limits of normal were defined., Conclusion: We establish normal reference ranges for LVMDV and LV mass using prospectively ECG-triggered coronary CTA. These benchmarks may identify patients at increased risk of adverse events, supporting the potential for clinical reporting of these metrics., (Copyright © 2017 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the long-term performance of the CONFIRM score for prediction of all-cause mortality in a large patient cohort undergoing coronary computed tomography angiography (CCTA)., Methods and Results: Patients with a 5-year follow-up from the international multicentre CONFIRM registry were included. The primary endpoint was all-cause mortality. The predictive value of the CONFIRM score over clinical risk scores (Morise, Framingham, and NCEP ATP III score) was studied in the entire patient population as well as in subgroups. Improvement in risk prediction and patient reclassification were assessed using categorical net reclassification index (NRI) and integrated discrimination improvement (IDI). During a median follow-up period of 5.3 years, 982 (6.5%) of 15 219 patients died. The CONFIRM score outperformed the prognostic value of the studied three clinical risk scores (c-indices: CONFIRM score 0.696, NCEP ATP III score 0.675, Framingham score 0.610, Morise score 0.606; c-index for improvement CONFIRM score vs. NCEP ATP III score 0.650, P < 0.0001). Application of the CONFIRM score allowed reclassification of 34% of patients when compared with the NCEP ATP III score, which was the best clinical risk score. Reclassification was significant as revealed by categorical NRI (0.06 with 95% CI 0.02 and 0.10, P = 0.005) and IDI (0.013 with 95% CI 0.01 and 0.015, P < 0.001). Subgroup analysis revealed a comparable performance in a variety of patient subgroups., Conclusions: The CONFIRM score permits a significantly improved prediction of mortality over clinical risk scores for >5 years after CCTA. These findings are consistent in a large variety of patient subgroups., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

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.)

Background The accuracy of coronary computed tomography angiography (CCTA) is sub-optimal in patients with coronary stents. Methods that can increase its diagnostic accuracy are desirable. Objective A proof-of-concept study was undertaken to determine if corrected coronary opacification (CCO) differences can improve the accuracy of CCTA in stented coronary arteries. Methods PCI patients who underwent both CCTA and invasive coronary angiography (ICA) within 3 months were analyzed. Coronary luminal attenuation values (normalized to the aorta) were measured proximally and distally to coronary stents. CCO differences were evaluated for ability to predict (i) stenosis on invasive angiography, (ii) abnormal resting coronary flow as measured by the corrected thrombolysis in myocardial infarction (TIMI) frame count (cTFC), and (iii) the combination of abnormal resting flow and significant stenosis on invasive angiography. Results Twenty-nine stented coronary arteries (n = 25, mean age =61.4 years, men =80.0%) were assessed. In stented coronary vessels, CCO identified stenosis (≥ 70%) with an area under the curve of 0.767 (P = 0.021). CCO predicted abnormal resting coronary flow with high accuracy (AUC =0.867, P = 0.002). Combined CCTA/CCO identified both abnormal cTFC and stenosis ≥70% on ICA (functionally significant stenosis) with diagnostic accuracy of 92.3%. In contrast, CCTA visual assessment alone had lower diagnostic accuracy of 66.7% for identifying functionally significant stenosis. Conclusion CCO differences are predictive of abnormal resting flow and consequently, in-stent restenosis. Incorporation of this technique may improve the specificity of CCTA in PCI patients.

Background: Downstream resource utilization and its impact on outcomes after a canceled CCTA have not been well studied. We sought to understand downstream resource utilization and patient outcomes after canceled CCTA., Methods and Results: Consecutive patients were prospectively enrolled into an institutional cardiac CT registry. Patients who had the CCTA study canceled because of severe coronary calcification were followed for downstream resource utilization and the composite of all-cause mortality and non-fatal myocardial infarction (MI). 463 patients had their CCTA canceled due to severe coronary calcification and follow-up was available for 453 (97.8%) patients (median follow-up=36.0months). There were a total of 62 events (41 all-cause deaths and 21 non-fatal MI) with an annualized event rate of 4%. Three hundred and twenty patients underwent downstream CAD (ICA or MPI or EST) investigations. Age, NCEP/ATP III risk, beta-blocker use, Agatston and downstream CAD testing were associated with the primary outcome. There were fewer events in those that received downstream CAD testing (30 (9.7%) versus 32 (22.4%)). The annualized event rates for those who did and did not receive downstream CAD testing were 2.8% and 6.2%, respectively. Multivariable analysis confirmed that downstream CAD testing was an independent predictor of event-free survival and that the absence of additional CAD testing was associated with worse outcome (HR: 2.58 (95% CI: 1.54-4.31))., Conclusions: Patients with canceled CCTA due to severe and/or extensive CAC have high rates of death and non-fatal MI. The use of additional CAD testing appears to be associated with improved outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Total plaque score (TPS) on coronary computed tomography angiography (CCTA) has been validated as a surrogate measure of coronary artery disease (CAD) burden and is prognostic. We propose a novel measure, percentage TPS adjusted to age (%TPS/age), that may reflect vascular age and potentially more rapidly progressive atherosclerosis and evaluate its potential prognostic value., Methods: %TPS/age was calculated for consecutive patients prospectively enrolled into our institutional CCTA registry and evaluated for primary composite outcome of cardiac death, nonfatal myocardial infarction, and late revascularization., Results: Of 1896 patients identified (mean age 57.7 ± 11.4 years, 50.1% male, median follow-up 18.6 months [interquartile range: 15.3, 32.4]), 552 (29%) had %TPS/age = 0 (no atherosclerosis), with 1 (0.2%) primary outcome observed (annual event rate [AER] = 0.1%). Two events (0.4%, AER = 0.3%) were observed in %TPS/age < 0.314 category, 22 (5.0%, AER = 2.2%) in %TPS/age 0.314 to 0.699 category, and 54 (12.0%, AER = 5.7%) in %TPS/age ≥ 0.700 category. After adjusting for clinical predictors and obstructive CAD, higher %TPS/age category was associated with hazard ratio 1.95 (1.31-2.88, P < .001) for primary outcome on multivariable analysis, Harrell-C-Statistic 0.87 (confidence interval 95%: 0.84-0.90), and net reclassification improvement of 0.71 ( P < .001)., Conclusion: %TPS/Age has incremental prognostic value to traditional risk factors and CCTA measures of CAD and improves evaluation of burden of coronary atherosclerosis and clinical risk.

Background: Coronary computed tomography (CT) angiography (CCTA) has the ability to detect, characterize, and quantify atherosclerotic plaques. The aim of our study was to evaluate the prognostic power of CCTA-quantified plaque subtypes., Materials and Methods: A total of 36 patients with adverse events and 36 Morise score-matched patients who remained event free on follow-up were identified. Using CCTA images, plaque subtype volumes in the major epicardial arteries were analyzed using predetermined attenuation ranges in Hounsfield units (HU): 1 to 30 HU (low attenuating), 31 to 70 HU (intermediate attenuating), 71 to 150 HU (high attenuating), and mean coronary lumen+2 SD to 1000 HU (calcified). Each epicardial artery was divided into proximal, mid, and distal segments, and plaque volumes were normalized for arterial segment length., Results: The baseline characteristics of the 2 cohorts were similar. Low-attenuation and intermediate-attenuation plaque volumes were greater in the proximal segments as well as in the entire length in the adverse event compared with the event-free group. High-attenuation plaque volume was increased only in the proximal segments in the adverse event group. There was no difference in the volume of calcified plaque between the 2 groups. The log rank test using a cutoff of 3.99 mm/mm for combined intermediate and low plaque volume showed more adverse events in patients with a plaque volume of ≥3.99 mm/mm., Conclusions: Adverse events appear to be associated with greater volumes of low-attenuation and intermediate-attenuation plaques that reflect lipid and fibrous atherosclerosis. The difference between the 2 groups is most apparent in the proximal epicardial arteries.

Objectives: The goal of this study was to determine the long-term prognostic value of coronary computed tomography angiography (CTA) among patients with diabetes mellitus (DM) compared with nondiabetic subjects., Background: The long-term prognostic value of coronary CTA in patients with DM is not well established., Methods: Patients enrolled in the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry with 5-year follow-up data were identified. The extent and severity of coronary artery disease (CAD) were analyzed at baseline coronary CTA and in relation to outcomes between diabetic and nondiabetic patients. CAD according to coronary CTA was defined as none (0% stenosis), nonobstructive (1% to 49% stenosis), or obstructive (≥50% stenosis). Time to death (and in a subgroup, time to major adverse cardiovascular event) was estimated by using multivariable Cox proportional hazards models., Results: A total of 1,823 patients were identified as having DM with 5-year clinical follow-up and were propensity-matched to 1,823 patients without DM (mean age 61.8 ± 10.9 years; 54.4% male). Patients with DM did not exhibit a heightened risk of death compared with the propensity-matched nondiabetic subjects in the absence of CAD on coronary CTA (risk-adjusted hazard ratio [HR] of DM: 1.32; 95% confidence interval [CI]: 0.78 to 2.24; p = 0.296). Patients with DM were at increased risk of dying compared with nondiabetic subjects in the setting of nonobstructive CAD (in the propensity-matched cohort: HR, 2.10; 95% CI: 1.43 to 3.09; p < 0.001) with a mortality risk greater than nondiabetic subjects with obstructive disease (p < 0.001). In a risk-adjusted hazard analysis among patients with DM, both per-patient obstructive CAD and nonobstructive CAD conferred an increase in all-cause mortality risk compared with patients without atherosclerosis on coronary CTA (nonobstructive disease-HR: 2.07; 95% CI: 1.33 to 3.24; p = 0.001; obstructive disease-HR: 2.22; 95% CI: 1.47 to 3.36; p < 0.001)., Conclusions: Among patients with DM, nonobstructive and obstructive CAD according to coronary CTA were associated with higher rates of all-cause mortality and major adverse cardiovascular events at 5 years, and this risk was significantly higher than in nondiabetic subjects. Importantly, patients with DM without CAD according to coronary CTA were at a risk comparable to that of nondiabetic subjects., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Previous studies have demonstrated that left atrial (LA) volume has incremental prognostic value in predicting major adverse cardiac events (MACE). However, the predictive ability of LA volume in mid diastasis has not been investigated. We determined the incremental predictive value of LA volume indexed to body surface area (LAVi) measured in mid ventricular diastasis., Materials and Methods: A total of 96 patients with MACE (all-cause mortality and nonfatal myocardial infarction) were matched to 96 controls without adverse events on follow-up. Coronary computed tomographic angiography images were reconstructed at the 75% phase (mid ventricular diastasis). LA volumes were measured and indexed to the body surface area. The predictive value of LAVi was assessed using Cox proportional hazard models for the MACE., Results: LAVi was significantly larger (P<0.001) in the cases with adverse clinical outcomes (63.8±2.1 mL/m) versus the controls (50.3±1.2 mL/m). In a multivariate analysis, both significant coronary artery disease (defined as >70% stenosis in at least 1 coronary artery) and LAVi emerged as significant predictors of MACE with P-values of 0.0022 and 0.0001, respectively., Conclusions: A significantly larger LAVi was associated with MACE. LAVi was an incremental predictor to traditional clinical variables for MACE. The assessment of LAVi may be considered during coronary computed tomographic angiography and could potentially be incorporated into risk stratification and decision-making strategies.

AIMS: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes. METHODS AND RESULTS: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004). CONCLUSION: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity.

AimObstructive coronary artery disease (CAD) in proximal coronary segments is associated with a poor prognosis. However, the relative importance of plaque location regarding the risk for major adverse cardiovascular events (MACE) in patients with non-obstructive CAD has not been well defined.Methods and resultsFrom the Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter (CONFIRM) registry, 4644 patients without obstructive CAD were included in this study. The degree of stenosis was classified as 0 (no) and 1-49% (non-obstructive). Proximal involvement was defined as any plaque present in the left main or the proximal segment of the left anterior descending artery, left circumflex artery, and right coronary artery. Extensive CAD was defined as segment involvement score of >4. During a median follow-up of 5.2 years (interquartile range 4.1-6.0), 340 (7.3%) MACE occurred. Within the non-obstructive CAD group (n = 2065), proximal involvement was observed in 1767 (85.6%) cases. When compared to non-obstructive CAD patients without proximal involvement, those with proximal involvement had an increased MACE risk (log-rank P = 0.033). Multivariate Cox analysis showed when compared to patients with no CAD, proximal non-obstructive CAD was associated with increased MACE risk [hazard ratio (HR) 1.90, 95% confidence interval (CI) 1.47-2.45, P < 0.001] after adjusting for extensive CAD and conventional cardiovascular risk factors; however, non-proximal non-obstructive CAD did not increase MACE risk (HR 1.26, 95% CI 0.79-2.01, P = 0.339).ConclusionsIndependent of plaque extent, proximal coronary involvement was associated with increased MACE risk in patients with non-obstructive CAD. The plaque location information by coronary computed tomography angiography may provide additional risk prediction over CAD extent in patients with non-obstructive CAD.

AimsAlthough there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS).Methods and resultsWithin the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (

ObjectivesThis study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.BackgroundCoronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.MethodsUtilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.ResultsCL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p

AimsIn patients without obstructive coronary artery disease (CAD), we examined the prognostic value of risk factors and atherosclerotic extent.Methods and resultsPatients from the long-term CONFIRM registry without prior CAD and without obstructive (≥50%) stenosis were included. Within the groups of normal coronary computed tomography angiography (CCTA) (N = 1849) and non-obstructive CAD (N = 1698), the prognostic value of traditional clinical risk factors and atherosclerotic extent (segment involvement score, SIS) was assessed with Cox models. Major adverse cardiac events (MACE) were defined as all-cause mortality, non-fatal myocardial infarction, or late revascularization. In total, 3547 patients were included (age 57.9 ± 12.1 years, 57.8% male), experiencing 460 MACE during 5.4 years of follow-up. Age, body mass index, hypertension, and diabetes were the clinical variables associated with increased MACE risk, but the magnitude of risk was higher for CCTA defined atherosclerotic extent; adjusted hazard ratio (HR) for SIS >5 was 3.4 (95% confidence interval [CI] 2.3-4.9) while HR for diabetes and hypertension were 1.7 (95% CI 1.3-2.2) and 1.4 (95% CI 1.1-1.7), respectively. Exclusion of revascularization as endpoint did not modify the results. In normal CCTA, presence of ≥1 traditional risk factors did not worsen prognosis (log-rank P = 0.248), while it did in non-obstructive CAD (log-rank P = 0.025). Adjusted for SIS, hypertension and diabetes predicted MACE risk in non-obstructive CAD, while diabetes did not increase risk in absence of CAD (P-interaction = 0.004).ConclusionAmong patients without obstructive CAD, the extent of CAD provides more prognostic information for MACE than traditional cardiovascular risk factors. An interaction was observed between risk factors and CAD burden, suggesting synergistic effects of both.