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

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.

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.)

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.)

Aims: To identify the effect of early revascularization on 5-year survival in patients with CAD diagnosed by coronary-computed tomographic angiography (CCTA)., Methods and Results: We examined 5544 stable patients with suspected CAD undergoing CCTA who were followed a median of 5.5 years in a large international registry. Patients were categorized as having low-, intermediate-, or high-risk CAD based on CCTA findings. Two treatment groups were defined: early revascularization within 90 days of CCTA (n = 1171) and medical therapy (n = 4373). To account for the non-randomized referral to revascularization, we developed a propensity score by logistic regression. This score was incorporated into Cox proportional hazard models to calculate the effect of revascularization on all-cause mortality. Death occurred in 363 (6.6%) patients and was more frequent in medical therapy. In multivariable models, when compared with medical therapy, the mortality benefit of revascularization varied significantly over time and by CAD risk (P for interaction 0.04). In high-risk CAD, revascularization was significantly associated with lower mortality at 1 year (hazard ratio [HR] 0.22, 95% confidence interval [CI] 0.11-0.47) and 5 years (HR 0.31, 95% CI 0.18-0.54). For intermediate-risk CAD, revascularization was associated with reduced mortality at 1 year (HR 0.45, 95% CI 0.22-0.93) but not 5 years (HR 0.63, 95% CI 0.33-1.20). For low-risk CAD, there was no survival benefit at either time point., Conclusions: Early revascularization was associated with reduced 1-year mortality in intermediate- and high-risk CAD detected by CCTA, but this association only persisted for 5-year mortality in high-risk CAD., (© The Author 2017 Published on behalf of the European Society of Cardiology.)

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.)

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.)

Aims: Coronary computed tomographic angiography (CCTA) has become an important tool for non-invasive diagnosis of coronary artery disease (CAD). Coronary dominance can be assessed by CCTA; however, the predictive value of coronary dominance is controversially discussed. The aim of this study was to evaluate the prevalence and prognosis of coronary dominance in a large prospective, international multicentre cohort of patients undergoing CCTA., Methods and Results: The study population consisted of 6382 patients with or without CAD (47% females, 53% males, mean age 56.9 ± 12.3 years) who underwent CCTA and were followed over a period of 60 months. Right or left coronary dominance was determined. Right dominance was present in 91% (n = 5817) and left in 9% (n = 565) of the study population. At the end of follow-up, outcome in patients with obstructive CAD (>50% luminal stenosis) and right dominance was similar compared with patients with left dominance [hazard ratio (HR) 0.46, 95% CI 0.16-1.32, P = 0.15]. Furthermore, no differences were observed for the type of coronary dominance in patients with non-obstructive CAD (HR 0.95, 95% CI 0.41-2.21, P = 0.8962) or normal coronary arteries (HR 1.04, 95% CI 0.68-1.59, P = 0.9). Subgroup analysis in patients with left main disease revealed an elevated hazard of the combined endpoint for left dominance (HR 6.45, 95% CI 1.66-25.0, P = 0.007), but not for right dominance., Conclusion: In our study population, survival after 5 years of follow-up did not differ significantly between patients with left or right coronary dominance. Thus, assessment of coronary vessel dominance by CCTA may not enhance risk stratification in patients with normal coronary arteries or obstructive CAD, but may add prognostic information for specific subpopulations., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Prior studies examining coronary atherosclerosis in the young have been limited by retrospective analyses in small cohorts. We examined the relationship between cardiovascular risk factors (RFs) and prevalence and severity of coronary atherosclerosis in a large, prospective, multinational registry of consecutive young individuals undergoing coronary computerized tomographic angiography (CCTA)., Method and Results: Of 27 125 patients undergoing CCTA, 1635 young (<45 years) individuals without known coronary artery disease (CAD) or coronary anomalies were identified. Coronary plaque was assessed for any CAD, obstructive CAD (≥50% stenosis), and presence of calcified plaque (CP) and non-calcified plaque (NCP). Among 1635 subjects (70% men, age 38 ± 6 years), any CAD, obstructive CAD, CP, and NCP were observed in 19, 4, 5, and 8%, respectively. Compared with women, men demonstrated higher rates of any CAD (21 vs. 12%, P < 0.001), CP (6 vs. 3%, P = 0.01), and NCP (9 vs. 5%, P = 0.008), although no difference was observed for rates of obstructive CAD (5 vs. 4%, P = 0.46). Any CAD, obstructive CAD, and NCP were higher for young individuals with diabetes, hypertension, dyslipidaemia, current smoking, or family history of CAD; while only diabetes and dyslipidaemia were associated with CP. Increasing cardiovascular RFs was associated with a greater prevalence and extent and severity of CAD, with individuals with 0, 1, 2, ≥3 RFs manifesting a dose-response increase in any CAD (P < 0.001, for trend), obstructive CAD (P < 0.001, for trend), NCP (P < 0.001, for trend), and CP (P < 0.001, for trend). In multivariable analysis adjusting for sex and cardiovascular RFs, male sex was the strongest predictor for any CAD (odds ratio [OR] = 1.95, 95% confidence interval [CI] = 1.43-2.66, P < 0.001), CP (OR = 1.46, 95% CI = 1.08-1.98, P = 0.01), and NCP (OR = 1.33, 95% CI = 1.06-1.67, P = 0.01); family history of CAD was the strongest predictor for obstructive CAD (OR = 2.71, 95% CI = 1.65-4.45, P < 0.001)., Conclusion: Any and obstructive CAD is present in 1 in 5 and 1 in 20 young individuals, respectively, with family history associated with the greatest risk of obstructive CAD., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Objectives: This study sought to develop a clinical model that identifies patients with and without high-risk coronary artery disease (CAD)., Background: Although current clinical models help to estimate a patient's pre-test probability of obstructive CAD, they do not accurately identify those patients with and without high-risk coronary anatomy., Methods: Retrospective analysis of a prospectively collected multinational coronary computed tomographic angiography (CTA) cohort was conducted. High-risk anatomy was defined as left main diameter stenosis ≥50%, 3-vessel disease with diameter stenosis ≥70%, or 2-vessel disease involving the proximal left anterior descending artery. Using a cohort of 27,125, patients with a history of CAD, cardiac transplantation, and congenital heart disease were excluded. The model was derived from 24,251 consecutive patients in the derivation cohort and an additional 7,333 nonoverlapping patients in the validation cohort., Results: The risk score consisted of 9 variables: age, sex, diabetes, hypertension, current smoking, hyperlipidemia, family history of CAD, history of peripheral vascular disease, and chest pain symptoms. Patients were divided into 3 risk categories: low (≤7 points), intermediate (8 to 17 points) and high (≥18 points). The model was statistically robust with area under the curve of 0.76 (95% confidence interval [CI]: 0.75 to 0.78) in the derivation cohort and 0.71 (95% CI: 0.69 to 0.74) in the validation cohort. Patients who scored ≤7 points had a low negative likelihood ratio (<0.1), whereas patients who scored ≥18 points had a high specificity of 99.3% and a positive likelihood ratio (8.48). In the validation group, the prevalence of high-risk CAD was 1% in patients with ≤7 points and 16.7% in those with ≥18 points., Conclusions: We propose a scoring system, based on clinical variables, that can be used to identify patients at high and low pre-test probability of having high-risk CAD. Identification of these populations may detect those who may benefit from a trial of medical therapy and those who may benefit most from an invasive strategy., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to examine the risk of mortality associated with nonobstructive coronary artery disease (CAD) and to determine the impact of baseline statin and aspirin use on mortality., Approach and Results: Coronary computed tomographic angiography permits direct visualization of nonobstructive CAD. To date, the prognostic implications of nonobstructive CAD and the potential benefit of directing therapy based on nonobstructive CAD have not been carefully examined. A total of 27 125 consecutive patients who underwent computed tomographic angiography (12 enrolling centers and 6 countries) were prospectively entered into the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry. Patients, without history of previous CAD or obstructive CAD, for whom baseline statin and aspirin use was available were analyzed. Each coronary segment was classified as normal or nonobstructive CAD (1%-49% stenosis). Patients were followed up for a median of 27.2 months for all-cause mortality. The study comprised 10 418 patients (5712 normal and 4706 with nonobstructive CAD). In multivariable analyses, patients with nonobstructive CAD had a 6% (95% confidence interval, 1%-12%) higher risk of mortality for each additional segment with nonobstructive plaque (P=0.021). Baseline statin use was associated with a reduced risk of mortality (hazard ratio, 0.44; 95% confidence interval, 0.28-0.68; P=0.0003), a benefit that was present for individuals with nonobstructive CAD (hazard ratio, 0.32; 95% confidence interval, 0.19-0.55; P<0.001) but not for those without plaque (hazard ratio, 0.66; 95% confidence interval, 0.30-1.43; P=0.287). When stratified by National Cholesterol Education Program/Adult Treatment Program III, no mortality benefit was observed in individuals without plaque. Aspirin use was not associated with mortality benefit, irrespective of the status of plaque., Conclusions: The presence and extent of nonobstructive CAD predicted mortality. Baseline statin therapy was associated with a significant reduction in mortality for individuals with nonobstructive CAD but not for individuals without CAD., Clinical Trial Registration: URL: http://clinicaltrials.gov/. Unique identifier NCT01443637., (© 2015 American Heart Association, Inc.)

Objective: This study sought to determine the correlation between baseline cardiac medications and cardiovascular outcomes in patients with obstructive coronary artery disease (CAD) diagnosed by coronary computed tomographic angiography (CCTA)., Methods: 1637 patients (mean age 64.8 ± 10.2 years, 69.6% male) with obstructive CAD from the CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry were followed over the course of three years. Obstructive CAD was defined as a ≥50% stenosis in an epicardial vessel. Medications analyzed included statins, aspirin, beta-blockers, angiotensin converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). Using Cox proportional-hazards models, we calculated the hazard ratio (HR) with 95% confidence intervals (95% CIs) for incident major adverse cardiovascular events (MACE), defined as death, acute coronary syndrome, or myocardial infarction., Results: At the time of CCTA, 59%, 54%, 40%, and 46% of patients were using statins, aspirin, beta-blockers, and ACE inhibitors or ARBs, respectively. Statins were associated with a 43% (95% CI = 0.38-0.87, p = 0.008) lower adjusted risk of MACE. Following adjustment, aspirin, beta-blockers, ACE inhibitors and ARBs did not attenuate the risk of MACE. When restricted to patients with multivessel obstructive CAD, only statins were associated with lower risk of MACE., Conclusion: In patients with obstructive CAD by CCTA, the baseline use of statins was associated with improved clinical outcomes. Other cardiac medications-including aspirin, beta-blockers, ACE inhibitors, and ARBs-were not associated with reduced risk of MACE., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To determine the clinical outcomes of women and men with nonobstructive coronary artery disease ( CAD coronary artery disease ) with coronary computed tomographic (CT) angiography data in patients who were similar in terms of CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution., Materials and Methods: Institutional review board approval was obtained for all participating sites, with either informed consent or waiver of informed consent. In a prospective international multicenter cohort study of 27 125 patients undergoing coronary CT angiography at 12 centers, 18 158 patients with no CAD coronary artery disease or nonobstructive (<50% stenosis) CAD coronary artery disease were examined. Men and women were propensity matched for age, CAD coronary artery disease risk factors, angina typicality, and CAD coronary artery disease extent and distribution, which resulted in a final cohort of 11 462 subjects. Nonobstructive CAD coronary artery disease presence and extent were related to incident major adverse cardiovascular events ( MACE major adverse cardiovascular events ), which were inclusive of death and myocardial infarction and were estimated by using multivariable Cox proportional hazards models., Results: At a mean follow-up ± standard deviation of 2.3 years ± 1.1, MACE major adverse cardiovascular events occurred in 164 patients (0.6% annual event rate). After matching, women and men experienced identical annualized rates of myocardial infarction (0.2% vs 0.2%, P = .72), death (0.5% vs 0.5%, P = .98), and MACE major adverse cardiovascular events (0.6% vs 0.6%, P = .94). In multivariable analysis, nonobstructive CAD coronary artery disease was associated with similarly increased MACE major adverse cardiovascular events for both women (hazard ratio: 1.96 [95% confidence interval { CI confidence interval }: 1.17, 3.28], P = .01) and men (hazard ratio: 1.77 [95% CI confidence interval : 1.07, 2.93], P = .03)., Conclusion: When matched for age, CAD coronary artery disease risk factors, angina typicality, and nonobstructive CAD coronary artery disease extent, women and men experience comparable rates of incident mortality and myocardial infarction.

Purpose: To assess whether gradations of left ventricular (LV) ejection fraction (LVEF) and volumes measured with coronary computed tomography (CT) would augment risk stratification and discrimination for incident mortality., Materials and Methods: This study was approved by the institutional review board, and informed consent was obtained when required. Subjects without known coronary artery disease (CAD) who underwent cardiac CT angiography with quantitative LV measurements were categorized according to LVEF (≥ 55%, 45%-54.9%, 35%-44.9%, or <35%). LV end-systolic volume (LVESV) and LV end-diastolic volume (LVEDV) were classified as normal (≥ 90 mL) or abnormal (≥ 200 mL). CAD extent and severity was categorized as none, nonobstructive, obstructive (≥ 50%), one-vessel, two-vessel, and three-vessel or left main disease. LVEF and volumes were assessed for risk prediction and discrimination of future mortality by using Cox hazards model and receiver operating characteristic curve analysis, respectively., Results: During a follow-up of 2.0 years ± 0.9, 7758 patients (mean age, 58.5 years ± 13.0; 4220 male patients [54.4%]) were studied. At multivariable analysis, worsening LVEF was independently associated with mortality for moderately (hazard ratio = 3.14, P < .001) and severely (hazard ratio = 5.19, P < .001) abnormal ejection fraction. LVEF demonstrated improved discrimination for mortality (Az = 0.816) when compared with CAD risk factors alone (Az = 0.781) or CAD risk factors plus extent and severity. At multivariable analysis of a subgroup of 3706 individuals, abnormal LVEDV (hazard ratio = 4.02) and LVESV (hazard ratio = 6.46) helped predict mortality (P < .001). Similarly, LVESV and LVEDV demonstrated improved discrimination when compared with CAD risk factors or CAD extent and severity (P < .05)., Conclusion: LV dysfunction and volumes measured with cardiac CT angiography augment risk prediction and discrimination for future mortality., (© RSNA, 2014.)

Aims: Prior studies evaluating the prognostic utility of cardiac CT angiography (CCTA) have been largely constrained to an all-cause mortality endpoint, with other cardiac endpoints generally not reported. To this end, we sought to determine the relationship of extent and severity of coronary artery disease (CAD) by CCTA to risk of incident major adverse cardiac events (MACEs) (defined as death, myocardial infarction, and late revascularization)., Methods and Results: We identified subjects without prior known CAD who underwent CCTA and were followed for MACE. CAD by CCTA was defined as none (0% luminal stenosis), mild (1-49% luminal stenosis), moderate (50-69% luminal stenosis), or severe (≥70% luminal stenosis), and ≥50% luminal stenosis was considered as obstructive. CAD severity was judged on per-patient, per-vessel, and per-segment basis. Time to MACE was estimated using univariable and multivariable Cox proportional hazards models. Among 15 187 patients (57 ± 12 years, 55% male), 595 MACE events (3.9%) occurred at a 2.4 ± 1.2 year follow-up. In multivariable analyses, an increased risk of MACE was observed for both non-obstructive [hazard ratio (HR) 2.43, P < 0.001] and obstructive CAD (HR: 11.21, P < 0.001) when compared with patients with normal CCTA. Risk-adjusted MACE increased in a dose-response relationship based on the number of vessels with obstructive CAD ≥50%, with increasing hazards observed for non-obstructive (HR: 2.54, P < 0.001), obstructive one-vessel (HR: 9.15, P < 0.001), two-vessel (HR: 15.00, P < 0.001), or three-vessel or left main (HR: 24.53, P < 0.001) CAD. Among patients stratified by age <65 vs. ≥65 years, older individuals experienced higher risk-adjusted hazards for MACE for non-obstructive, one-, and two-vessel, with similar event rates for three-vessel or left main (P < 0.001 for all) compared with normal individuals age <65. Finally, there was a dose relationship of CAD findings by CCTA and MACE event rates with each advancing decade of life., Conclusion: Among individuals without known CAD, non-obstructive, and obstructive CAD are associated with higher MACE rates, with different risk profiles based on age.

Aims: The prognostic value of coronary artery calcium (CAC) scoring is well established and has been suggested for use to exclude significant coronary artery disease (CAD) for symptomatic individuals with CAD. Contrast-enhanced coronary computed tomographic angiography (CCTA) is an alternative modality that enables direct visualization of coronary stenosis severity, extent, and distribution. Whether CCTA findings of CAD add an incremental prognostic value over CAC in symptomatic individuals has not been extensively studied., Methods and Results: We prospectively identified symptomatic patients with suspected but without known CAD who underwent both CAC and CCTA. Symptoms were defined by the presence of chest pain or dyspnoea, and pre-test likelihood of obstructive CAD was assessed by the method of Diamond and Forrester (D-F). CAC was measured by the method of Agatston. CCTAs were graded for obstructive CAD (>70% stenosis); and CAD plaque burden, distribution, and location. Plaque burden was determined by a segment stenosis score (SSS), which reflects the number of coronary segments with plaque, weighted for stenosis severity. Plaque distribution was established by a segment-involvement score (SIS), which reflects the number of segments with plaque irrespective of stenosis severity. Finally, a modified Duke prognostic index-accounting for stenosis severity, plaque distribution, and plaque location-was calculated. Nested Cox proportional hazard models for a composite endpoint of all-cause mortality and non-fatal myocardial infarction (D/MI) were employed to assess the incremental prognostic value of CCTA over CAC. A total of 8627 symptomatic patients (50% men, age 56 ± 12 years) followed for 25 months (interquartile range 17-40 months) comprised the study cohort. By CAC, 4860 (56%) and 713 (8.3%) patients had no evident calcium or a score of >400, respectively. By CCTA, 4294 (49.8%) and 749 (8.7%) had normal coronary arteries or obstructive CAD, respectively. At follow-up, 150 patients experienced D/MI. CAC improved discrimination beyond D-F and clinical variables (area under the receiver-operator characteristic curve 0.781 vs. 0.788, P = 0.004). When added sequentially to D-F, clinical variables, and CAC, all CCTA measures of CAD improved discrimination of patients at risk for D/MI: obstructive CAD (0.82, P < 0.001), SSS (0.81, P < 0.001), SIS (0.81, P = 0.003), and Duke CAD prognostic index (0.82, P < 0.0001)., Conclusion: In symptomatic patients with suspected CAD, CCTA adds incremental discriminatory power over CAC for discrimination of individuals at risk of death or MI.

Background: Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored., Methods: From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1-49%, 50-69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) - inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) - and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification., Results: Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61-3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75-3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09-1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18-2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29-2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05-1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06)., Conclusion: For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Fractional flow reserve derived from computed tomography angiography (FFRCT) is a noninvasive method for diagnosis of ischemic coronary lesions. To date, the diagnostic performance of FFRCT for lesions of intermediate stenosis severity remains unexamined., Methods and Results: Among 407 vessels from 252 patients at 17 centers who underwent CT, FFRCT, invasive coronary angiography, and invasive FFR, we identified 150 vessels of intermediate stenosis by CT, defined as 30% to 69% stenosis. FFRCT, FFR, and CT were interpreted in blinded fashion by independent core laboratories. FFRCT and FFR ≤0.80 were considered hemodynamically significant, whereas CT stenosis ≥50% was considered obstructive. Diagnostic performance of FFRCT versus CT was assessed for accuracy, sensitivity, specificity, positive predictive values, and negative predictive values. Area under the receiver operating characteristic curve and net reclassification improvement were evaluated. For lesions of intermediate stenosis severity, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFRCT were 71%, 74%, 67%, 41%, and 90%, whereas accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of CT stenosis were 63%, 34%, 72%, 27%, and 78%. FFRCT demonstrated superior discrimination compared with CT stenosis on per-patient (area under the receiver operating characteristic curve, 0.81 versus 0.50; P=0.0001) and per-vessel basis (area under the receiver operating characteristic curve, 0.79 versus 0.53; P<0.0001). FFRCT demonstrated significant reclassification of CT stenosis for lesion-specific ischemia (net reclassification improvement, 0.45; 95% confidence interval, 0.25-0.65; P=0.01)., Conclusions: FFRCT possesses high diagnostic performance for diagnosis of ischemic for lesions of intermediate stenosis severity. Notably, the high sensitivity and negative predictive value suggest the ability of FFRCT to effectively rule out intermediate lesions that cause ischemia.

Background: Patients with flow-limiting coronary stenoses exhibit elevated left ventricular end-diastolic pressure (LVEDP) and abnormal left ventricular (LV) relaxation., Objective: We investigated the relationship of extent and severity of coronary artery disease (CAD) by coronary CT angiography (CTA) to LVEDP and measures of LV diastolic dysfunction., Methods: We identified consecutive patients undergoing coronary CTA and transthoracic echocardiography who were assessed for diastolic function. CAD was evaluated on a per-patient, per-vessel, and per-segment basis for intraluminal diameter stenosis by using an 18-segment model (0 = none, 1 = 1%-49%, 2 = 50%-69%, and 3 = 70%-100%) and summed over segments to obtain overall coronary plaque burden (segment stenosis score [SSS]; maximum = 54). Transthoracic echocardiography evaluated mitral inflow E wave-to-A wave ratio, tissue Doppler early mitral annual tissue velocity axial excursion, stage of diastolic dysfunction, and LV dimensions and estimated LVEDP from the ratio of mitral inflow velocity to early mitral annular (medial) tissue velocity., Results: Four hundred seventy-eight patients (57% women; mean age, 57.9 ± 14.6 years; 24.9% prior CAD) comprised the study population. Increasing per-patient maximal coronary stenosis, number of vessels with obstructive stenosis, and SSS were associated with increased LVEDP. The prevalence of advanced diastolic dysfunction increased with greater number of obstructive vessels. In multivariable analyses, SSS was associated with increased LVEDP (0.8 mm Hg per tertile increase in SSS, 0.5-1.1; P < .001); reduced E' axial excursion (-0.3; 95% confidence interval [CI], -0.5 to -0.1; P = .001), increased LV mass index (1.6 g/m(2) per tertile increase in SSS; P = .04), and increased relative wall thickness (0.005; 95% CI, 0.004-0.009; P = .03), with consistent relationships persisting even among persons with per-patient maximal stenosis <50% and LV ejection fraction ≥ 55%., Conclusions: Extent and severity of obstructive as well as nonobstructive CAD by coronary CTA are associated with increased LVEDP and measures of diastolic dysfunction., (Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to analyze the predictive value of coronary computed tomography angiography (CCTA) and to model and validate an optimized score for prognosis of 2-year survival on the basis of a patient population with suspected coronary artery disease (CAD)., Background: Coronary computed tomography angiography carries important prognostic information in addition to the detection of obstructive CAD. But it is still unclear how the results of CCTA should be interpreted in the context of clinical risk predictors., Methods: The analysis is based on a test sample of 17,793 patients and a validation sample of 2,506 patients, all with suspected CAD, from the international CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry. On the basis of CCTA data and clinical risk scores, an optimized score was modeled. The endpoint was all-cause mortality., Results: During a median follow-up of 2.3 years, 347 patients died. The best CCTA parameter for prediction of mortality was the number of proximal segments with mixed or calcified plaques (C-index 0.64, p < 0.0001) and the number of proximal segments with a stenosis >50% (C-index 0.56, p = 0.002). In an optimized score including both parameters, CCTA significantly improved overall risk prediction beyond National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) score as best clinical score. According to this score, a proximal segment with either a mixed or calcified plaque or a stenosis >50% is equivalent to a 5-year increase in age or the risk of smoking., Conclusions: In CCTA, both plaque burden and stenosis, particularly in proximal segments, carry incremental prognostic value. A prognostic score on the basis of this data can improve risk prediction beyond clinical risk scores., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Patients with chronic kidney disease have a worse cardiovascular prognosis than those without. The aim of this study was to determine the incremental prognostic value of coronary computed tomographic angiography in predicting mortality across the entire spectrum of renal function in patients with known or suspected coronary artery disease (CAD). A large international multicenter registry was queried, and patients with left ventricular ejection fraction (LVEF) and creatinine data were screened. National Cholesterol Education Program Adult Treatment Panel III risk was calculated. Coronary computed tomographic angiographic results were evaluated for CAD severity (normal, nonobstructive, or obstructive) and an LVEF <50%. Patients were followed for the end point of all-cause mortality. Among 5,655 patients meeting the study criteria, follow-up was available for 5,572 (98.9%; median follow-up duration 18.6 months). All-cause mortality (66 deaths) significantly increased with every 10-unit decrease in renal function (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.07 to 1.41). All-cause mortality occurred in 0.33% of patients without coronary atherosclerosis, 1.82% of patients with nonobstructive CAD, and 2.43% of patients with obstructive CAD. Multivariate Cox proportional-hazards models revealed that impaired renal function (HR 2.29, 95% CI 1.65 to 3.18), CAD severity (HR 1.81, 95% CI 1.31 to 2.51), and an abnormal LVEF (HR 4.16, 95% CI 2.45 to 7.08) were independent predictors of all-cause mortality. In conclusion, coronary computed tomographic angiographic measures of CAD severity and the LVEF provide effective risk stratification across a wide spectrum of renal function. Furthermore, renal dysfunction, CAD severity, and the LVEF have additive value for predicting all-cause death in patients with suspected obstructive CAD., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The association between lipoprotein levels and coronary plaque composition is not well understood., Objective: The aim of this prospective international multicenter study of statin-naive individuals was to evaluate the association of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC) to coronary plaque composition by coronary computed tomographic angiography (CTA)., Methods: We studied 4575 individuals without known coronary artery disease not taking statin medications who underwent coronary CTA. Comparisons were made between those with high versus low LDL, HDL, TC, and non-HDL. We assessed the relationship of lipoproteins and plaques of specific composition (noncalcified [NCP], partially calcified [PCP], or calcified [CP] plaque)., Results: Mean age was 57 ± 11 years (55% men). In univariable analyses, high LDL, low HDL, high TC, and high non-HDL were each associated with increased prevalence of NCPs, PCPs, and CPs (P < 0.05 for all). In multivariable analyses, high non-HDL was associated with the presence of NCP (odds ratio, 1.47; 95% CI, 1.22-1.78: P < 0.001). In the further subanalysis, a weak relationship between the highest group of non HDL (≥190 mg/dL) and the presence of CP was also noted (odds ratio, 1.33; 95% CI, 1.01-1.76; P = 0.04). Further, high non-HDL was associated with increasing numbers of segments with NCP (β coefficient, 0.043; 95% CI, 0.021-0.065; P < 0.001) but not segments with PCP or CP., Conclusion: NCP presence and extent are associated with high non-HDL. These results suggest a relationship between lipid profile and plaque composition., (Copyright © 2013 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Studies examining coronary computed tomographic angiography (CCTA) have demonstrated increased mortality related to coronary artery disease (CAD) severity but are limited to relatively nondiverse ethnic populations. The aim of this study was to evaluate the prognostic significance of CAD on CCTA according to ethnicity for patients without previous CAD in a prospective international CCTA registry of 11 sites (7 countries) who underwent 64-slice CCTA from 2005 to 2010. CAD was defined as any coronary artery atherosclerosis and obstructive CAD as ≥50% stenosis. All-cause mortality and nonfatal myocardial infarction (MI) were assessed by ethnicity using Kaplan-Meier and Cox proportional hazards, controlling for baseline risk factors, medications, and revascularization. A total of 16,451 patients of mean age 58 years (55% men) were followed over a median of 2.0 years (interquartile range 1.4 to 3.2). Patients were 60.1% Caucasian, 34.4% East Asian, and 5.5% African. Death or MI occurred in 0.5% (38 of 7,109) among patients with no CAD, 1.6% (91 of 5,600) among those with nonobstructive CAD, and 3.8% (142 of 3,742) among those with ≥50% stenosis (p <0.001 among all groups). The annualized incidence of death or MI comparing obstructive to no obstructive CAD among Caucasians was 2.2% versus 0.7% (adjusted hazard ratio [aHR] 2.77, 95% confidence interval [CI] 1.73 to 4.43, p <0.001), among Africans 4.8% versus 1.1% (aHR 6.25, 95% CI 1.12 to 34.97, p = 0.037), and among East Asians 0.8% versus 0.1% (aHR 4.84, 95% CI 2.24 to 10.9, p <0.001). Compared to other ethnicities, East Asians had fewer than expected events (aHR 0.25, 95% CI 0.16 to 0.38, p <0.001). In conclusion, the presence and severity of CAD visualized by CCTA predict death or MI across 3 large ethnicities, whereas normal results on CCTA identify patients at very low risk., (Published by Elsevier Inc.)

Objectives: This study sought to examine patterns of follow-up invasive coronary angiography (ICA) and revascularization (REV) after coronary computed tomography angiography (CCTA)., Background: CCTA is a noninvasive test that permits direct visualization of the extent and severity of coronary artery disease (CAD). Post-CCTA patterns of follow-up ICA and REV are incompletely defined., Methods: We examined 15,207 intermediate likelihood patients from 8 sites in 6 countries; these patients were without known CAD, underwent CCTA, and were followed up for 2.3 ± 1.2 years for all-cause mortality. Coronary artery stenosis was judged as obstructive when ≥50% stenosis was present. A multivariable logistic regression was used to estimate ICA use. A Cox proportional hazards model was used to estimate all-cause mortality., Results: During follow-up, ICA rates for patients with no CAD to mild CAD according to CCTA were low (2.5% and 8.3%), with similarly low rates of REV (0.3% and 2.5%). Most ICA procedures (79%) occurred ≤3 months of CCTA. Obstructive CAD was associated with higher rates of ICA and REV for 1-vessel (44.3% and 28.0%), 2-vessel (53.3% and 43.6%), and 3-vessel (69.4% and 66.8%) CAD, respectively. For patients with <50% stenosis, early ICA rates were elevated; over the entirety of follow-up, predictors of ICA were mild left main, mild proximal CAD, respectively, or higher coronary calcium scores. In patients with <50% stenosis, the relative hazard for death was 2.2 (p = 0.011) for ICA versus no ICA. Conversely, for patients with CAD, the relative hazard for death was 0.61 for ICA versus no ICA (p = 0.047)., Conclusions: These findings support the concept that CCTA may be used effectively as a gatekeeper to ICA., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary lesions of intermediate severity often cause ischemia, and fractional flow reserve (FFR)-guided revascularization for these coronary lesions is safe and effective. FFR derived from coronary computed tomography (FFR(CT)) is a noninvasive method for diagnosis of lesion-specific ischemia, but its performance for intermediate stenoses has not been examined to date. We examined the performance of FFR(CT) versus FFR at the time of invasive angiography in 66 vessels of 60 patients who were identified as having an intermediate stenosis, defined by quantitative coronary angiographic percent diameter stenosis 40% to 69%. Ischemia for FFR(CT) and FFR was defined as ≤0.80. Diagnostic performance of FFR(CT) was determined compared to an invasive FFR standard. Mean age of the study group was 63.5 ± 8.1 years (81% men). Thirty-one patients (47%) demonstrated ischemia with an FFR ≤0.80, with 2 of 16 (12.5%), 21 of 37 (56.8%), and 8 of 13 (61.5%) lesions of 40% to 49%, 50% to 59%, and 60% to 69% stenosis causal of ischemia, respectively. At an FFR ≤0.80 cutoff for lesion-specific ischemia, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR(CT) were 86.4%, 90.3%, 82.9%, 82.4%, and 90.6%, respectively, with an area under the receiver operator characteristics curve of 0.95 (p <0.001) and good correlation to FFR (0.60, p <0.0001). No biases between FFR(CT) and FFR were noted by Bland-Altman analysis (0.03 ± 0.12, p = 0.054). In conclusion, FFR(CT) is a novel noninvasive method for diagnosis of lesion-specific ischemia of coronary lesions of intermediate stenosis severity., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Coronary computed tomographic angiography (CCTA) employing CT scanners of 64-detector rows or greater represents a novel non-invasive method for detection of coronary artery disease (CAD), providing excellent diagnostic information when compared to invasive angiography. In addition to its high diagnostic performance, prior studies have shown that CCTA can provide important prognostic information, although these prior studies have been generally limited to small cohorts at single centers. The Coronary CT Angiography EVALUATION FOR CLINICAL OUTCOMES: An International Multicenter registry, or CONFIRM, is a large, prospective, multinational, dynamic observational cohort study of patients undergoing CCTA. This registry currently represents more than 32,000 consecutive adults suspected of having CAD who underwent ≥ 64-detector row CCTA at 12 centers in 6 countries between 2005 and 2009. Based on its large sample size and adequate statistical power, the data derived from CONFIRM registry have and will continue to provide key answers to many important topics regarding CCTA. Based on its multisite international national design, the results derived from CONFIRM should be considered as more generalizable than prior smaller single-center studies. This article summarizes the current status of several studies from CONFIRM registry.

Objective: We examined the prevalence, extent, severity, and prognosis of coronary artery disease (CAD) in individuals with and without diabetes (DM) who are similar in CAD risk factors., Research Design and Methods: We identified 23,643 consecutive individuals without known CAD undergoing coronary computed tomography angiography. A total of 3,370 DM individuals were propensity matched in a 1-to-2 fashion to 6,740 unique non-DM individuals. CAD was defined as none, nonobstructive (1-49% stenosis), or obstructive (≥ 50% stenosis). All-cause mortality was assessed by risk-adjusted Cox proportional hazards models., Results: At a 2.2-year follow-up, 108 (3.2%) and 115 (1.7%) deaths occurred among DM and non-DM individuals, respectively. Compared with non-DM individuals, DM individuals possessed higher rates of obstructive CAD (37 vs. 27%) and lower rates of having normal arteries (28 vs. 36%) (P < 0.0001). CAD extent was higher for DM versus non-DM individuals for obstructive one-vessel disease (19 vs. 14%), two-vessel disease (9 vs. 7%), and three-vessel disease (9 vs. 5%) (P < 0.0001 for comparison), with higher per-segment stenosis in the proximal and mid-segments of every coronary artery (P < 0.001 for all). Compared with non-DM individuals with no CAD, risk of mortality for DM individuals was higher for those with no CAD (hazard ratio 3.63 [95% CI 1.67-7.91]; P = 0.001), nonobstructive CAD (5.25 [2.56-10.8]; P < 0.001), one-vessel disease (6.39 [2.98-13.7]; P < 0.0001), two-vessel disease (12.33 [5.622-27.1]; P < 0.0001), and three-vessel disease (13.25 [6.15-28.6]; P < 0.0001)., Conclusions: Compared with matched non-DM individuals, DM individuals possess higher prevalence, extent, and severity of CAD. At comparable levels of CAD, DM individuals experience higher risk of mortality compared with non-DM individuals.

Background: The predictive value of coronary computed tomographic angiography (cCTA) in subjects without chest pain syndrome (CPS) has not been established. We investigated the prognostic value of coronary artery disease detection by cCTA and determined the incremental risk stratification benefit of cCTA findings compared with clinical risk factor scoring and coronary artery calcium scoring (CACS) for individuals without CPS., Methods and Results: An open-label, 12-center, 6-country observational registry of 27 125 consecutive patients undergoing cCTA and CACS was queried, and 7590 individuals without CPS or history of coronary artery disease met the inclusion criteria. All-cause mortality and the composite of all-cause mortality and nonfatal myocardial infarction were measured. During a median follow-up of 24 months (interquartile range, 18-35 months), all-cause mortality occurred in 136 individuals. After risk adjustment, compared with individuals without evidence of coronary artery disease by cCTA, individuals with obstructive 2- and 3-vessel disease or left main coronary artery disease experienced higher rates of death and composite outcome (P<0.05 for both). Both CACS and cCTA significantly improved the performance of standard risk factor prediction models for all-cause mortality and the composite outcome (likelihood ratio P<0.05 for all), but the incremental discriminatory value associated with their inclusion was more pronounced for the composite outcome and for CACS (C statistic for model with risk factors only was 0.71; for risk factors plus CACS, 0.75; for risk factors plus CACS plus cCTA, 0.77). The net reclassification improvement resulting from the addition of cCTA to a model based on standard risk factors and CACS was negligible., Conclusions: Although the prognosis for individuals without CPS is stratified by cCTA, the additional risk-predictive advantage by cCTA is not clinically meaningful compared with a risk model based on CACS. Therefore, at present, the application of cCTA for risk assessment of individuals without CPS should not be justified.

Background: Clinical outcomes and resource utilization after coronary computed tomography angiography (CTA) versus myocardial perfusion single-photon emission CT (MPS) in patients with stable angina and suspected coronary artery disease (CAD) has not been examined., Objective: We determined the near-term clinical effect and resource utilization after cardiac CTA compared with MPS., Methods: We randomly assigned 180 patients (age, 57.3 ± 9.8 years; 50.6% men) presenting with stable chest pain and suspected CAD at 2 sites to initial diagnostic evaluation by coronary CTA (n = 91) or MPS (n = 89). The primary outcome was near-term angina-specific health status; the secondary outcomes were incident medical and invasive treatments for CAD, CAD health care costs, and estimated radiation dose., Results: No patients experienced myocardial infarction or death with 98.3% follow-up at 55 ± 34 days. Both arms experienced comparable improvements in angina-specific health status. Patients who received coronary CTA had increased incident aspirin (22% vs 8%; P = 0.04) and statin (7% vs -3.5%; P = 0.03) use, similar rates of CAD-related hospitalization, invasive coronary angiography, noninvasive cardiac imaging tests, and increased revascularization (8% vs 1%; P = 0.03). Coronary CTA had significantly lower total costs ($781.08 [interquartile range (IQR), $367.80-$4349.48] vs $1214.58 [IQR, $978.02-$1569.40]; P < 0.001) with no difference in induced costs. Coronary CTA had a significantly lower total estimated effective radiation dose (7.4 mSv [IQR, 5.0-14.0 mSv] vs 13.3 mSv [IQR, 13.1-38.0 mSv]; P < 0.0001) with no difference in induced radiation., Conclusion: In a pilot randomized controlled trial, patients with stable CAD undergoing coronary CTA and MPS experience comparable improvements in near-term angina-related quality of life. Compared with MPS, coronary CTA evaluation is associated with more aggressive medical therapy, increased coronary revascularization, lower total costs, and lower effective radiation dose., (Copyright © 2012. Published by Elsevier Inc.)

Background: Fractional flow reserve calculated from coronary CT (FFR(CT)) is a novel method for determining lesion-specific ischemia., Objective: To assess the effect of CT quality on accuracy of FFR(CT), we compared performance of FFR(CT) with severe stenosis by CT in relation to image quality; heart rate; signal-to-noise ratio (SNR); and common CT artifacts, including calcification, motion, and poor contrast enhancement., Methods: FFR(CT) was performed on 159 vessels in 103 patients undergoing CT, FFR(CT), and FFR. Ischemia was defined as FFR(CT) and FFR ≤ 0.80, and severe stenosis by CT was defined by ≥50% reduction in luminal diameter. FFR(CT) and CT stenosis were compared with FFR, which served as the reference., Results: On a vessel basis, accuracy of FFR(CT) was higher than CT stenosis for satisfactory or poor quality CTs (87.5% vs 64.6%), for heart rates > 65 beats/min (100% vs 52.9%), and for SNR less than the median (26.3) (84.4% vs 64.1%). Accuracy of FFR(CT) was superior to CT stenosis in the presence of calcification (85.7% vs 66.7%), motion (90.5% vs 57.1%), and poor contrast opacification (100.0% vs 71.4%). Similar relations were observed for exploratory analyses of FFR(CT) and CT stenosis on a patient basis. In 42 subjects who underwent coronary calcium scanning, accuracy of FFR(CT) was 77.8% (n = 18), 100% (n = 11), and 100% (n = 13) for coronary calcium scores of 0-100, 101-400, and >400, respectively., Conclusions: Accuracy of FFR(CT) is superior to CT stenosis for determining lesion-specific ischemia. The performance of FFR(CT) remains robust across an array of factors known to adversely affect CT quality., (Copyright © 2012. Published by Elsevier Inc.)

Objectives: The purpose of this study was to describe the prevalence and severity of coronary artery disease (CAD) in relation to prognosis in symptomatic patients without coronary artery calcification (CAC) undergoing coronary computed tomography angiography (CCTA)., Background: The frequency and clinical relevance of CAD in patients without CAC are unclear., Methods: We identified 10,037 symptomatic patients without CAD who underwent concomitant CCTA and CAC scoring. CAD was assessed as <50%, ≥50%, and ≥70% stenosis. All-cause mortality and the composite endpoint of mortality, myocardial infarction, or late coronary revascularization (≥90 days after CCTA) were assessed., Results: Mean age was 57 years, 56% were men, and 51% had a CAC score of 0. Among patients with a CAC score of 0, 84% had no CAD, 13% had nonobstructive stenosis, and 3.5% had ≥50% stenosis (1.4% had ≥70% stenosis) on CCTA. A CAC score >0 had a sensitivity, specificity, and negative and positive predictive values for stenosis ≥50% of 89%, 59%, 96%, and 29%, respectively. During a median of 2.1 years, there was no difference in mortality among patients with a CAC score of 0 irrespective of obstructive CAD. Among 8,907 patients with follow-up for the composite endpoint, 3.9% with a CAC score of 0 and ≥50% stenosis experienced an event (hazard ratio: 5.7; 95% confidence interval: 2.5 to 13.1; p < 0.001) compared with 0.8% of patients with a CAC score of 0 and no obstructive CAD. Receiver-operator characteristic curve analysis demonstrated that the CAC score did not add incremental prognostic information compared with CAD extent on CCTA for the composite endpoint (CCTA area under the curve = 0.825; CAC + CCTA area under the curve = 0.826; p = 0.84)., Conclusions: In symptomatic patients with a CAC score of 0, obstructive CAD is possible and is associated with increased cardiovascular events. CAC scoring did not add incremental prognostic information to CCTA., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Guidelines for the management of patients with suspected coronary artery disease (CAD) rely on the age, sex, and angina typicality-based pretest probabilities of angiographically significant CAD derived from invasive coronary angiography (guideline probabilities). Reliability of guideline probabilities has not been investigated in patients referred to noninvasive CAD testing., Methods and Results: We identified 14048 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography. Angina typicality was recorded with the use of accepted criteria. Pretest likelihoods of CAD with ≥ 50 diameter stenosis (CAD50) and ≥ 70 diameter stenosis (CAD70) were calculated from guideline probabilities. Computed tomographic angiography images were evaluated by ≥ 1 expert reader to determine the presence of CAD50 and CAD70. Typical angina was associated with the highest prevalence of CAD50 (40 in men, 19 in women) and CAD70 (27 men, 11 women) compared with other symptom categories (P<0.001 for all). Observed CAD50 and CAD70 prevalences were substantially lower than those predicted by guideline probabilities in the overall population (18 versus 51 for CAD50, 10 versus 42 for CAD70; P<0.001), driven by pronounced differences in patients with atypical angina (15 versus 47 for CAD50, 7 versus 37 for CAD70) and typical angina (29 versus 86 for CAD50, 19 versus 71 for CAD70). Marked overestimation of disease prevalence by guideline probabilities was found at all participating centers and across all sex and age subgroups., Conclusion: In this multinational study of patients referred for coronary computed tomographic angiography, determination of pretest likelihood of angiographically significant CAD by the invasive angiography-based guideline probabilities greatly overestimates the actual prevalence of disease.

Objectives: We sought to determine the incremental prognostic value of 64 multi-slice coronary computed tomography angiography (CCTA) in coronary artery bypass graft (CABG) patients., Background: Prognostication in CABG patients can be difficult. Anatomical assessment of native coronary artery disease and graft patency might provide useful information, but the utility of CCTA in the assessment of CABG patients is unknown., Methods: Six hundred fifty-seven CABG patients with all-cause mortality follow-up were identified from a multicenter CCTA registry, of 10,628 patients from 5 CCTA centers. Clinical risk was profiled with modified logistic and additive EuroSCOREs (European Systems for Cardiac Operative Risk Evaluations). The CCTA defined coronary anatomy. Patients were classified by unprotected coronary territory (UCT) or a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS)., Results: Forty-four deaths occurred during a mean follow-up of 20 months. Left ventricular ejection fraction, creatinine, age, severity of native vessel disease, UCT, CAPS, and EuroSCOREs were univariate predictors of mortality (p < 0.001). In multivariate analysis with additive EuroSCORE, UCT (p = 0.004) and CAPS were predictive of events (p < 0.001). In comparison with additive EuroSCORE, CAPS score was associated with a 27% net reclassification index., Conclusions: Coronary computed tomography angiography provides incremental anatomical data to clinical risk assessment to help determine the prognosis of patients after CABG. The CAPS evaluation with CCTA might help identify those patients at highest risk., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to determine the diagnostic performance of a new method for quantifying fractional flow reserve (FFR) with computational fluid dynamics (CFD) applied to coronary computed tomography angiography (CCTA) data in patients with suspected or known coronary artery disease (CAD)., Background: Measurement of FFR during invasive coronary angiography is the gold standard for identifying coronary artery lesions that cause ischemia and improves clinical decision-making for revascularization. Computation of FFR from CCTA data (FFR(CT)) provides a noninvasive method for identifying ischemia-causing stenosis; however, the diagnostic performance of this new method is unknown., Methods: Computation of FFR from CCTA data was performed on 159 vessels in 103 patients undergoing CCTA, invasive coronary angiography, and FFR. Independent core laboratories determined FFR(CT) and CAD stenosis severity by CCTA. Ischemia was defined by an FFR(CT) and FFR ≤0.80, and anatomically obstructive CAD was defined as a CCTA with stenosis ≥50%. Diagnostic performance of FFR(CT) and CCTA stenosis was assessed with invasive FFR as the reference standard., Results: Fifty-six percent of patients had ≥1 vessel with FFR ≤0.80. On a per-vessel basis, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 84.3%, 87.9%, 82.2%, 73.9%, 92.2%, respectively, for FFR(CT) and were 58.5%, 91.4%, 39.6%, 46.5%, 88.9%, respectively, for CCTA stenosis. The area under the receiver-operator characteristics curve was 0.90 for FFR(CT) and 0.75 for CCTA (p = 0.001). The FFR(CT) and FFR were well correlated (r = 0.717, p < 0.001) with a slight underestimation by FFR(CT) (0.022 ± 0.116, p = 0.016)., Conclusions: Noninvasive FFR derived from CCTA is a novel method with high diagnostic performance for the detection and exclusion of coronary lesions that cause ischemia., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: We determined the effect of reduced 80-kVp tube voltage on the radiation dose and image quality of coronary CT angiography (CTA) in patients with a normal body mass index (BMI)., Subjects and Methods: A prospective, multicenter, multivendor trial was performed of 208 consecutive patients with a normal BMI (< 25 kg/m(2)) who had been referred for coronary CTA and did not have a history of coronary revascularization. Patients were randomized to 80-kVp imaging (n = 103) or 100-kVp imaging (n = 105). Three blinded readers graded interpretability and image quality. Study signal, noise, and contrast were also compared., Results: Imaging with 80 kVp instead of 100 kVp was associated with 47% lower median radiation dose (median dose-length product, 62.0 mGy · cm [interquartile range, 54.0-123.3 mGy · cm] vs 117.0 mGy · cm [110.0-225.9 mGy · cm], respectively; 0.9 mSv [0.8-1.7 mSv] vs 1.6 mSv [1.4-3.2 mSv]; p < 0.001 for each) with no significant difference in interpretability (99% vs 99%; p = 0.99) or image quality (median score, 4.0 [interquartile range, 3.6-4.0] vs 4.0 [interquartile range, 3.8-4.0]; p = 0.20). Studies obtained using 80 kVp were associated with 27% increased signal (mean ± SD, 756 ± 157 vs 594 ± 105 HU; p < 0.001), 25% higher contrast (890 ± 156 vs 709 ± 108 HU; p < 0.001), and 50% greater noise (55 ± 15 vs 37 ± 12 HU; p < 0.001) with resultant 15% and 16% decreases in signal-to-noise (mean ± SD, 15 ± 5 vs 17 ± 5; p < 0.001) and contrast-to-noise (mean ± SD, 17 ± 6 vs 21 ± 5; p < 0.001) ratios, respectively., Conclusion: Coronary CTA using 80 kVp instead of 100 kVp was associated with a nearly 50% reduction in radiation dose with no significant difference in interpretability and noninferior image quality despite lower signal-to-noise and contrast-to-noise ratios. The use of 80-kVp tube voltage should be considered in dose-reduction strategies for coronary CTA of individuals with a normal BMI.

Background: Large multicenter studies validating the prognostic value of coronary computed tomographic angiography (CCTA) and left ventricular ejection fraction (LVEF) are lacking. We sought to confirm the independent and incremental prognostic value of coronary artery disease (CAD) severity measured using 64-slice CCTA over LVEF and clinical variables., Methods and Results: A large international multicenter registry (CONFIRM Registry) was queried, and CCTA patients with LVEF data on CCTA were screened. Patients with a history of myocardial infarction, coronary revascularization, or cardiac transplantation were excluded. The National Cholesterol Education Program-Adult Treatment Panel III risk was calculated for each patient, and CCTA was evaluated for CAD severity (normal, nonobstructive, non-high-risk, or high-risk CAD) and LVEF <50%. Patients were followed for an end point of all-cause mortality; 27 125 patients underwent CCTA at 12 participating centers, with a total of 14 064 patients meeting the analysis criteria. Follow-up was available for 13 966 (99.3%) patients (mean follow-up of 22.5 months; 95% confidence interval, 22.3 to 22.7 months). All-cause mortality (271 deaths) occurred in 0.65% of patients without coronary atherosclerosis, 1.99% of patients with nonobstructive CAD, 2.90% of patients with non-high-risk CAD, and 4.95% for patients with high-risk CAD. Multivariable analysis confirmed that LVEF <50% (hazard ratio, 2.74; 95% confidence interval, 2.12 to 3.51) and CAD severity (hazard ratio,1.58; 95% confidence interval, 1.42 to 1.76) were predictors of all-cause mortality, and CAD severity had incremental value over LVEF and clinical variables., Conclusions: Our results demonstrate that CCTA measures of CAD severity and LVEF have independent prognostic value. Incorporation of CAD severity provides incremental value for predicting all-cause death over routine clinical predictors and LVEF in patients with suspected obstructive CAD.

Objectives: We examined mortality in relation to coronary artery disease (CAD) as assessed by ≥64-detector row coronary computed tomography angiography (CCTA)., Background: Although CCTA has demonstrated high diagnostic performance for detection and exclusion of obstructive CAD, the prognostic findings of CAD by CCTA have not, to date, been examined for age- and sex-specific outcomes., Methods: We evaluated a consecutive cohort of 24,775 patients undergoing ≥64-detector row CCTA between 2005 and 2009 without known CAD who met inclusion criteria. In these patients, CAD by CCTA was defined as none (0% stenosis), mild (1% to 49% stenosis), moderate (50% to 69% stenosis), or severe (≥70% stenosis). CAD severity was judged on a per-patient, per-vessel, and per-segment basis. Time to mortality was estimated using multivariable Cox proportional hazards models., Results: At a 2.3 ± 1.1-year follow-up, 404 deaths had occurred. In risk-adjusted analysis, both per-patient obstructive (hazard ratio [HR]: 2.60; 95% confidence interval [CI]: 1.94 to 3.49; p < 0.0001) and nonobstructive (HR: 1.60; 95% CI: 1.18 to 2.16; p = 0.002) CAD conferred increased risk of mortality compared with patients without evident CAD. Incident mortality was associated with a dose-response relationship to the number of coronary vessels exhibiting obstructive CAD, with increasing risk observed for nonobstructive (HR: 1.62; 95% CI: 1.20 to 2.19; p = 0.002), obstructive 1-vessel (HR: 2.00; 95% CI: 1.43 to 2.82; p < 0.0001), 2-vessel (HR: 2.92; 95% CI: 2.00 to 4.25; p < 0.0001), or 3-vessel or left main (HR: 3.70; 95% CI: 2.58 to 5.29; p < 0.0001) CAD. Importantly, the absence of CAD by CCTA was associated with a low rate of incident death (annualized death rate: 0.28%). When stratified by age <65 years versus ≥65 years, younger patients experienced higher hazards for death for 2-vessel (HR: 4.00; 95% CI: 2.16 to 7.40; p < 0.0001 vs. HR: 2.46; 95% CI: 1.51 to 4.02; p = 0.0003) and 3-vessel (HR: 6.19; 95% CI: 3.43 to 11.2; p < 0.0001 vs. HR: 3.10; 95% CI: 1.95 to 4.92; p < 0.0001) CAD. The relative hazard for 3-vessel CAD (HR: 4.21; 95% CI: 2.47 to 7.18; p < 0.0001 vs. HR: 3.27; 95% CI: 1.96 to 5.45; p < 0.0001) was higher for women as compared with men., Conclusions: Among individuals without known CAD, nonobstructive and obstructive CAD by CCTA are associated with higher rates of mortality, with risk profiles differing for age and sex. Importantly, absence of CAD is associated with a very favorable prognosis., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: We examined mortality risk in relation to extent and composition of nonobstructive plaques by 64-detector row coronary computed tomographic angiography (CCTA)., Background: The prognostic significance of nonobstructive coronary artery plaques by CCTA is poorly understood., Methods: We prospectively evaluated consecutive adults from 2 centers undergoing 64-detector row CCTA without prior documented coronary artery disease (CAD) and without obstructive (≥50%) CAD by CCTA. Luminal diameter stenosis severity was classified for each segment as none (0%) or mild (1% to 49%), and plaque composition was classified as noncalcified, calcified, or mixed., Results: During 3.1 ± 0.5 years, 54 intermediate-term (≥90 days) deaths occurred among 2,583 patients (2.09%), with 4 early (<90 days) deaths. Adjusted for CAD risk factors, the presence of any nonobstructive plaque was associated with higher mortality (hazard ratio [HR]: 1.98, 95% confidence Interval [CI]: 1.06 to 3.69, p = 0.03), with the highest risk among those exhibiting nonobstructive CAD in 3 epicardial vessels (HR: 4.75, 95% CI: 2.10 to 10.75, p = 0.0002) or ≥5 segments (HR: 5.12, 95% CI: 2.16 to 12.10, p = 0.0002). Higher mortality for nonobstructive CAD was observed even among patients with low 10-year Framingham risk (3.4%, p < 0.0001) as well as those with no traditional, medically treatable CAD risk factors, including diabetes mellitus, hypertension, and dyslipidemia (6.7%, p < 0.0001). No independent relationship between plaque composition and incident mortality was observed. Importantly, patients without evident plaque experienced a low rate of incident death during follow-up (0.34%/year)., Conclusions: The presence and extent of nonobstructive plaques augment prediction of incident mortality beyond conventional clinical risk assessment., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac computed tomographic angiography (CCTA) permits simultaneous assessment of coronary artery disease (CAD) and left ventricular mass (LVM). While increased LVM predicts mortality and is associated with obstructive CAD, the relationship of LVM with non-obstructive CAD is unknown., Methods: We evaluated 212 consecutive patients undergoing 64-detector row CCTA at 2 sites without evident cardiovascular disease or obstructive (≥70%) CAD by CCTA. LVM was measured by CCTA using Simpson's method of disks and indexed to body surface area (LVMI) and height to the allometric power of 2.7(LVM/ht2.7). CCTAs were evaluated by scoring a modified AHA 16-segment coronary artery model for none = 0 (0% stenosis), mild = 1 (1-49% stenosis) or moderate = 2 (50-69% stenosis). Overall CAD plaque burden was estimated by summing scores across all segments for a segment stenosis score (SSS, max = 32)., Results: The mean age was 53.3 ± 12.8 with 52% female, 48% hypertensive, and 7.4% diabetic. The mean LVM was 109 ± 32.5 g; 58.5% had any coronary artery plaque. In multivariable linear regression, SSS was significantly associated with increased LVM, LVMI and LVM/ht2.7. LVM increased by 2.0 g for every 1-point increase in SSS (95% CI 0.06-3.4, p = 0.006). Agatston scores provided no additional predictive value for increased LVM above and beyond SSS., Conclusion: Non-obstructive CAD visualized by CCTA is associated with increased LVM independent of effects of clinical risk factors and calcium scoring. Whether addition of LVM to stenosis assessment in patients undergoing CCTA enhances risk prediction of future CAD events warrants investigation., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary computed tomographic angiography (CCTA) of 64-detector rows or greater represents a novel noninvasive anatomic method for evaluation of patients with suspected coronary artery disease (CAD). Early studies suggest a potential for prognostic risk assessment by CCTA findings but were limited by small patient cohorts or single centers. The CONFIRM (COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter) registry is a large, prospective, multinational dynamic observational study of patients undergoing CCTA. The primary aim of CONFIRM is to determine the prognostic value of CCTA findings for the prediction of future adverse CAD events., Methods: The CONFIRM registry currently represents 27,125 consecutive patients at 12 cluster sites in 6 countries in North America, Europe, and Asia. CONFIRM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, and local demographic characteristics and medical facilities to ensure a broad-based sample of patients. Patients comprising the present CONFIRM cohort include those with suspected but without known CAD, with known CAD, or asymptomatic persons undergoing CAD evaluation. A data dictionary comprising a wide array of demographic, clinical, and CCTA findings was developed by the CONFIRM investigators and is uniformly used for all patients. Patients are followed up after CCTA performance to identify adverse CAD events, including death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization., Conclusions: From a number of countries worldwide, the information collected from the CONFIRM registry will add incremental and important insights into CCTA findings that confer prognostic value beyond demographic and clinical characteristics. The results of the CONFIRM registry will provide valuable information about the optimal methods for using CCTA findings., (Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Coronary computed tomographic angiography (CCTA) is associated with ionizing radiation, prompting concerns of future cancer risk. Recent studies have reported reduced radiation doses and similar image quality by the selective use of dose reduction techniques, although the clinical penetration of these methods has been limited. In a quality improvement initiative, a comprehensive, standardized radiation dose reduction protocol was implemented, and its effect on radiation dose and image quality was assessed. A total of 449 patients who underwent 64-detector CCTA at 3 centers were prospectively evaluated, and patients were compared before (n = 247) and after (n = 202) the implementation of a standardized body mass index-based and heart rate-based protocol that simultaneously incorporated multiple dose reduction strategies. Median radiation dose decreased from 2.6 mSv (interquartile range 2.0 to 4.2) to 1.3 mSv (interquartile range 0.8 to 1.9) after the implementation of the standardized protocol (p < 0.001). On multivariate analysis, reduction in overall radiation dose was observed by numerous dose reduction techniques, with varying efficacy of dose lowering: prospective (vs retrospective) electrocardiographic gating (-82%), reduced tube voltage (-41% for 100 vs 120 kV), lower tube current (-25% per -100 mA), and reduced overall scan length (-6% per -1 cm) (p < 0.001 for each). No differences were observed between patients before and after the initiation of the protocol for study interpretability (96% vs 96%, p = 0.66). There was an increase in signal-to-noise ratio after implementing the standardized protocol (11 ± 3 vs 12 ± 4, p < 0.01). In conclusion, a quality improvement protocol for CCTA incorporating multiple dose reduction techniques permits significant radiation dose reduction and may improve the safety profile of CCTA., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: Coronary computed tomographic angiography (CCTA) requires iodinated contrast and often atrioventricular nodal blocking agents and nitroglycerin for heart rate lowering and coronary vasodilation, respectively. To date, the periprocedural safety of CCTA is unknown., Objectives: The purpose of this study was to evaluate the periprocedural safety of CCTA., Methods: We prospectively evaluated 232 patients with symptomatic chest pain without preexisting renal insufficiency at 16 sites who underwent CCTA as part of the Assessment by Coronary Computed Tomographic Angiography of Individuals Undergoing Invasive Coronary Angiography (ACCURACY) trial. Patients received iodinated contrast, β-blockers, and nitroglycerin as part of a predefined CCTA protocol. We assessed the rates of adverse events (AEs) related to these agents., Results: As measured by serum creatinine and creatinine clearance, no significant change was observed in renal function from baseline (1.00 ± 0.19 mg/dL; modification of diet in renal disease [MDRD]: 76.91 ± 17.96 mL/min/1.73 m(2)) to 48 hours (1.0 ± 0.2 mg/dL; P = 1.00; MDRD change: 0.2 ± 12.4 mL/min/1.73 m(2); P = 0.83) or at 30 days (1.0 ± 0.2 mg/dL; P = 0.52; MDRD change: -0.9 ± 16.9 mL/min/1.73 m(2); P = 0.77). Mean systolic blood pressure decreased from baseline (133 ± 19 mm Hg) at 1 hour (125 ± 17 mm Hg; P < 0.001) and rebounded at 48 hours (133 ± 17 mm Hg). Mean heart rate decreased from baseline (65 ± 10 beats/min) at 1 hour (60 ± 7 beats/min) but rose at 48 hours (69 ± 11 beats/min; P < 0.001. All patients were asymptomatic from baseline to follow-up., Conclusions: The performance of CCTA is safe with low rates of AEs., (© 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary computed tomographic angiography (CCTA) possesses high accuracy to detect coronary artery disease (CAD), although studies have reported differences in diagnostic performance. Prior trials used different numbers of interpreters, and the optimal number to detect CAD is unknown., Objective: We compared the diagnostic performance of 1, 2, 3, and 5 randomly selected interpreters for CCTA., Methods: We evaluated 50 patients randomly selected from 2 multicenter studies with both 64-detector CCTA and invasive quantitative coronary angiography (QCA). Five blinded, experienced readers independently interpreted CCTA and assessed for obstructive CAD (≥ 50% stenosis) and high-risk CAD (left main, proximal left anterior descending, or 3-vessel stenoses). A core laboratory performed QCA. For each patient, different random combinations of readers were selected; the accuracy of 1, 2, and 5 readers was compared with 3 readers., Results: Obstructive and high-risk CAD were observed in 20 of 50 (40%) and 6 of 50 (12%) patients, respectively. With combinations of 1, 2, 3, or 5 readers, there was a range of per-patient diagnostic performance (sensitivity, 100% each; specificity, 67%-90%; accuracy, 80%-94%; P = NS), per-segment diagnostic performance (sensitivity, 67%-83%; specificity, 87%-93%; accuracy, 87%-92%; P < .001 for 1 vs 3 and 2 vs 3 readers), and detection of high-risk CAD (sensitivity, 83%-100%; specificity, 73%-80%; accuracy, 76%-82%; P = NS). The highest diagnostic accuracy was observed with 3 readers for each comparison., Conclusion: The diagnostic performance of CCTA to detect obstructive or high-risk CAD is generally high irrespective of the number of readers. Consensus interpretation by ≥ 3 readers provides the highest diagnostic accuracy., (© 2010 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of our study was to determine the effect of Adaptive Statistical Iterative Reconstruction (ASIR) on cardiac CT angiography (CTA) signal, noise, and image quality., Materials and Methods: We evaluated 62 consecutive patients at three sites who underwent clinically indicated cardiac CTA using an ASIR-capable 64-MDCT scanner and a low-dose cardiac CTA technique. Studies were reconstructed using filtered back projection (FBP), ASIR-FBP composites using 20-80% ASIR, and 100% ASIR. The signal and noise were measured in the aortic root and each of the four coronary arteries. Two blinded readers graded image quality on a 5-point Likert scale and determined the proportion of interpretable segments. All segments were included for analysis regardless of size., Results: In comparison with FBP (0% ASIR), the use of 20%, 40%, 60%, 80%, and 100% ASIR resulted in reduced image noise between groups (-7%, -17%, -26%, -35%, and -43%, respectively; p < 0.001) without difference in signal (p = 0.60). There were significant differences between groups (0%, 20%, 40%, 60%, 80%, and 100% ASIR) in the Likert scores (1.5, 2.1, 3.7, 3.8, 2.0, and 1.1, respectively; p < 0.001) and proportion of interpretable segments (88.7%, 89.3%, 90.5%, 90.4%, 88.0%, and 87.3%, respectively; p < 0.001). Reconstruction using 40% and 60% ASIR had the highest Likert scores and largest proportion of interpretable segments. In comparison with FBP, each was associated with higher Likert scores and increased interpretable segments (p < 0.001 for all)., Conclusion: ASIR resulted in noise reduction and significantly impacted image quality. When using a low tube current technique, cardiac CTA reconstruction using 40% or 60% ASIR significantly improved image quality and the proportion of interpretable segments compared with FBP reconstruction.

Objective: The objective of our study was to assess the impact of Adaptive Statistical Iterative Reconstruction (ASIR) on radiation dose and study quality for coronary CT angiography (CTA)., Subjects and Methods: We prospectively evaluated 574 consecutive patients undergoing coronary CTA at three centers. Comparisons were performed between consecutive groups initially using filtered back projection (FBP) (n = 331) and subsequently ASIR (n = 243) with regard to patient and scan characteristics, radiation dose, and diagnostic study quality., Results: There was no difference between groups in the use of prospective gating, tube voltage, or scan length. The examinations performed using ASIR had a lower median tube current than those obtained using FBP (median [interquartile range], 450 mA [350-600] vs 650 mA [531-750], respectively; p < 0.001). There was a 44% reduction in the median radiation dose between the FBP and ASIR cohorts (4.1 mSv [2.3-5.2] vs 2.3 mSv [1.9-3.5]; p < 0.001). After adjustment for scan settings, ASIR was associated with a 27% reduction in radiation dose compared with FBP (95% CI, 21-32%; p < 0.001). Despite the reduced current, ASIR was not associated with a difference in adjusted signal, noise, or signal-to-noise ratio (p = not significant). No differences existed between FBP and ASIR for interpretability per coronary artery (98.5% vs 99.3%, respectively; p = 0.12) or per patient (96.1% vs 97.1%, p = 0.65). CONCLUSION. ASIR enabled reduced tube current and lower radiation dose in comparison with FBP, with preserved signal, noise, and study interpretability, in a large multicenter cohort. ASIR represents a new technique to reduce radiation dose in coronary CTA studies.

Although numerous strategies for radiation dose decrease in coronary computed tomographic angiography are effective, their combined impact on diagnostic performance is not known. We therefore assessed the effect of a standardized coronary computed tomographic angiographic protocol on diagnostic accuracy. We evaluated 80 consecutive patients from 3 sites with coronary computed tomographic angiography and quantitative coronary angiography. All sites initially used nonstandardized protocols; 2 sites then initiated a standardized protocol, and 1 site continued its nonstandardized protocol as a time-overlapping control. Two blinded readers interpreted coronary computed tomographic angiographic studies; a third obtained consensus. A blinded core laboratory performed quantitative coronary angiography. Each segment was graded as <50% or > or =50% diameter stenosis. Compared to those using nonstandardized protocols (n = 35), studies using standardized protocols (n = 45) had a trend to increased use of prospective gating (p = 0.09), lower voltage (p <0.01), decreased current (p <0.01), and shorter scan length (p <0.01). Median (interquartile range) radiation dose decreased from 5.7 mSv (4.0 to 10.8) to 2.0 mSv (1.3 to 3.4, p <0.001). There were no significant differences in sensitivity (100%, 20 of 20, vs 100%, 18 of 18, p = 1.0), specificity (93%, 14 of 15, vs 85%, 23 of 27, p = 0.61), or accuracy (97%, 34 of 35, vs 91%, 41 of 45, p = 0.27) by patient; sensitivity (83%, 33 of 40, vs 83%, 25 of 30, p = 0.93), specificity (92%, 86 of 93, vs 92%, 134 of 146, p = 0.85), or accuracy (89%, 119 of 133, vs 90%, 159 of 176, p = 0.80) by artery; or sensitivity (80%, 44 of 55, vs 72%, 26 of 36, p = 0.74), specificity (94%, 332 of 353, vs 94%, 499 of 531, p = 0.96), or accuracy (92%, 376 of 408, vs 93%, 525 of 567, p = 0.80) by segment. In conclusion, a standardized dose-decrease protocol for coronary computed tomographic angiography decreases radiation dose without affecting diagnostic performance., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

AimsCoronary 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 resultsOf 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