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We aimed to compare semiquantitative coronary computed tomography angiography (CCTA) risk scores – which score presence, extent, composition, stenosis and/or location of coronary artery disease (CAD) – and their prognostic value between patients with and without diabetes mellitus (DM). Risk scores derived from general chest-pain populations are often challenging to apply in DM patients, because of numerous confounders. Out of a combined cohort from the Leiden University Medical Center and the CONFIRM registry with 5-year follow-up data, we performed a secondary analysis in diabetic patients with suspected CAD who were clinically referred for CCTA. A total of 732 DM patients was 1:1 propensity-matched with 732 non-DM patients by age, sex and cardiovascular risk factors. A subset of 7 semiquantitative CCTA risk scores was compared between groups: 1) any stenosis ≥50%, 2) any stenosis ≥70%, 3) stenosis-severity component of the coronary artery disease-reporting and data system (CAD-RADS), 4) segment involvement score (SIS), 5) segment stenosis score (SSS), 6) CT-adapted Leaman score (CT-LeSc), and 7) Leiden CCTA risk score. Cox-regression analysis was performed to assess the association between the scores and the primary endpoint of all-cause death and non-fatal myocardial infarction. Also, area under the receiver-operating characteristics curves were compared to evaluate discriminatory ability. A total of 1,464 DM and non-DM patients (mean age 58 ± 12 years, 40% women) underwent CCTA and 155 (11%) events were documented after median follow-up of 5.1 years. In DM patients, the 7 semiquantitative CCTA risk scores were significantly more prevalent or higher as compared to non-DM patients (p ≤ 0.022). All scores were independently associated with the primary endpoint in both patients with and without DM (p ≤ 0.020), with non-significant interaction between the scores and diabetes (interaction p ≥ 0.109). Discriminatory ability of the Leiden CCTA risk score in DM patients was significantly better than any stenosis ≥50% and ≥70% (p = 0.003 and p = 0.007, respectively), but comparable to the CAD-RADS, SIS, SSS and CT-LeSc that also focus on the extent of CAD (p ≥ 0.265). Coronary atherosclerosis scoring with semiquantitative CCTA risk scores incorporating the total extent of CAD discriminate major adverse cardiac events well, and might be useful for risk stratification of patients with DM beyond the binary evaluation of obstructive stenosis alone. [ABSTRACT FROM AUTHOR]

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). 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. 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). 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. 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/) [ABSTRACT FROM AUTHOR]

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

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

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

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

Background Coronary computed tomography angiography (coronary CTA) can prognosticate outcomes in patients without modifiable risk factors over medium term follow-up. This ability was driven by major adverse cardiovascular events (MACE). Objective Determine if coronary CTA could discriminate risk of mortality with longer term follow-up. In addition we sought to determine the long-term relationship to MACE. Methods From 12 centers, 1884 patients undergoing coronary CTA without prior coronary artery disease (CAD) or any modifiable CAD risk factors were identified. The presence of CAD was classified as none (0% stenosis), mild (1% to 49% stenosis) and obstructive (≥50% stenosis severity). The primary endpoint was all-cause mortality and the secondary endpoint was MACE. MACE was defined as the combination of death, nonfatal myocardial infarction, unstable angina, and late target vessel revascularization (>90 days). Results Mean age was 55.6 ± 14.5 years. At mean 5.6 ± 1.3 years follow-up, 145(7.7%) deaths occurred. All-cause mortality demonstrated a dose-response relationship to the severity and number of coronary vessels exhibiting CAD. Increased mortality was observed for >1 segment non-obstructive CAD (hazard ratio [HR]:1.73; 95% confidence interval [CI]: 1.07–2.79; p = 0.025), obstructive 1&2 vessel CAD (HR: 1.70; 95% CI: 1.08–2.71; p = 0.023) and 3-vessel or left main CAD (HR: 2.87; 95% CI: 1.57–5.23; p = 0.001). Both obstructive CAD (HR: 6.63; 95% CI: 3.91–11.26; p < 0.001) and non-obstructive CAD (HR: 2.20; 95% CI: 1.31–3.67; p = 0.003) predicted MACE with increased hazard associated with increasing CAD severity; 5.60% in no CAD, 13.24% in non-obstructive and 36.28% in obstructive CAD, p < 0.001 for trend. Conclusions In individuals being assessed for CAD with no modifiable risk factors, all-cause mortality in the long term (>5 years) was predicted by the presence of more than 1 segment of non-obstructive plaque, obstructive 1- or 2-vessel CAD and 3 vessel/left main CAD. Any CAD, whether non-obstructive or obstructive, predicted MACE over the same time period. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to examine the long-term prognosis in asymptomatic individuals with a coronary artery calcium (CAC) score of 0 and its associated warranty period. Background Emerging evidence supports a CAC score of 0 as a favorable cardiovascular short-to intermediate-term prognostic factor. Methods A total of 9,715 individuals undergoing CAC imaging were stratified by age, Framingham risk score (FRS), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) categories and followed for a mean of 14.6 years (range 12.9 to 16.8 years). Cox regression, area under the receiver-operating characteristic curve, and net reclassification information were used to assess all-cause mortality, discrimination, and reclassification of a CAC score of 0 compared with the FRS and NCEP ATP III, respectively. A warranty period was pre-defined as <1% annual mortality rate. Vascular age was estimated by linear regression. Results In 4,864 individuals with a baseline CAC score of 0 (mean age, 52.1 ± 10.8 years; 57.9% male), 229 deaths occurred. The warranty period of a CAC score of 0 was almost 15 years for individuals at low and intermediate risk with no significant differences regarding age and sex. A CAC score of 0 was associated with a vascular age of 1, 10, 20, and 30 years less than the chronological age of individuals between 50 and 59, 60 and 69, 70 and 79, and 80 years of age and older, respectively. The CAC score was the strongest predictor of death (hazard ratio: 2.67, 95% confidence interval: 2.29 to 3.11) that enabled discrimination and consistent reclassification beyond the FRS (area under the receiver-operating characteristic curve: 0.71 vs. 0.64, p < 0.001) and NCEP ATP III (area under the receiver-operating characteristic curve: 0.72 vs. 0.64, p < 0.001). Conclusions A CAC score of 0 confers a 15-year warranty period against mortality in individuals at low to intermediate risk that is unaffected by age or sex. Furthermore, in individuals considered at high risk by clinical risk scores, a CAC score of 0 confers better survival than in individuals at low to intermediate risk but with any CAC score. [ABSTRACT FROM AUTHOR]

Background: Coronary artery calcium (CAC) is a well-established predictor of clinical outcomes for population screening. Limited evidence is available as to its predictive value in symptomatic patients without obstructive coronary artery disease (CAD). The aim of the current study was to assess the prognostic value of CAC scores among symptomatic patients with nonobstructive CAD. Methods: From the COronary Computed Tomographic Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) registry, 7,200 symptomatic patients with nonobstructive CAD (<50% coronary stenosis) on coronary-computed tomographic angiography were prospectively enrolled and followed for a median of 2.1 years. Patients were categorized as without (0% stenosis) or with (>0% but <50% coronary stenosis) a luminal stenosis. CAC scores were calculated using the Agatston method. Univariable and multivariable Cox proportional hazard models were employed to estimate all-cause mortality and/or myocardial infarction (MI). Four-year death and death or MI rates were 1.9% and 3.3%. Results: Of the 4,380 patients with no luminal stenosis, 86% had CAC scores of <10 while those with a luminal stenosis had more prevalent and extensive CAC with 31.9% having a CAC score of ≥100. Among patients with no luminal stenosis, CAC was not predictive of all-cause mortality ( P = .44). However, among patients with a luminal stenosis, 4-year mortality rates ranged from 0.8% to 9.8% for CAC scores of 0 to ≥400 ( P < .0001). The mortality hazard was 6.0 ( P = .004) and 13.3 ( P < .0001) for patients with a CAC score of 100-399 and ≥400. In patients with a luminal stenosis, CAC remained independently predictive in all-cause mortality ( P < .0001) and death or MI ( P < .0001) in multivariable models containing CAD risk factors and presenting symptoms. Conclusions: CAC allows for the identification of those at an increased hazard for death or MI in symptomatic patients with nonobstructive disease. From the CONFIRM registry, the extent of CAC was an independent estimator of long-term prognosis among symptomatic patients with luminal stenosis and may further define risk and guide preventive strategies in patients with nonobstructive CAD. [ABSTRACT FROM AUTHOR]

Background: Short-term risk scores, such as the Framingham risk score (FRS), frequently classify younger patients as low risk despite the presence of uncontrolled cardiovascular risk factors. Among patients with low FRS, estimation of lifetime risk is associated with significant differences in coronary arterial calcium scores (CACS); however, the relationship of lifetime risk to coronary atherosclerosis on coronary CT angiography (CCTA) and prognosis has not been studied. Methods and Results: We evaluated asymptomatic 20-60-year-old patients without diabetes or known coronary artery disease (CAD) within an international CT registry who underwent ≥64-slice CCTA. Patients with low FRS (<10%) were stratified as low (<39%) or high (≥39%) lifetime CAD risk, and compared for the presence and severity of CAD and prognosis for death, myocardial infarction, and late coronary revascularization (>90 days post CCTA). 1,863 patients of mean age of 47 years were included, with 48% of the low FRS patients at high lifetime risk. Median follow-up was 2.0 years. Comparing low-to-high lifetime risk, respectively, the prevalence of any CAD was 32% vs 41% ( P < .001) and ≥50% stenosis was 7.4% vs 9.6% ( P = .09). For those with CAD, subjects at low vs high lifetime risk had lower CACS (median 12 [IQR 0-94] vs 38 [IQR 0.05-144], P = .02) and less purely calcified plaque, 35% vs 45% ( P < .001). Prognosis did not differ due to low number of events. Conclusion: Assessment of lifetime risk among patients at low FRS identified those with the increase in CAD prevalence and severity and a higher proportion of calcified plaque. [ABSTRACT FROM AUTHOR]

Abstract: Background: Risk assessment in the extensive calcified plaque phenotype has been limited by small sample size. Objective: We studied all-cause mortality rates among asymptomatic patients with markedly elevated Agatston scores > 1000. Methods: We studied a clinical cohort of 44,052 asymptomatic patients referred for coronary calcium scans. Mean follow-up was 5.6 years (range, 1–13 years). All-cause mortality rates were calculated after stratifying by Agatston score (0, 1–1000, 1001–1500, 1500–2000, and >2000). A multivariable Cox regression model adjusting for self-reported traditional risk factors was created to assess the relative mortality hazard of Agatston scores 1001 to 1500, 1501 to 2000, and >2000. With the use of post-estimation modeling, we assessed for the presence of an upper threshold of risk with high Agatston scores. Results: A total of 1593 patients (4% of total population) had Agatston score > 1000. There was a continuous graded decrease in estimated 10-year survival across increasing Agatston score, continuing when Agatston score > 1000 (Agatston score 1001–1500, 78%; Agatston score 1501–2000, 74%; Agatston score > 2000, 51%). After multivariable adjustment, Agatston scores 1001 to 1500, 1501 to 2000, and >2000 were associated with an 8.05-, 7.45-, and 13.26-fold greater mortality risk, respectively, than for Agatston score of 0. Compared with Agatston score 1001 to 1500, Agatston score 1501 to 2000 had a similar all-cause mortality risk, whereas Agatston score > 2000 had an increased relative risk (Agatston score 1501–2000: hazard ratio [HR], 1.01 [95% CI, 0.67–1.51]; Agatston score > 2000: HR, 1.79 [95% CI, 1.30–2.46]). Graphical assessment of the predicted survival model suggests no upper threshold for risk associated with calcified plaque in coronary arteries. Conclusion: Increasing calcified plaque in coronary arteries continues to predict a graded decrease in survival among patients with extensive Agatston score > 1000 with no apparent upper threshold. [Copyright &y& Elsevier]

Abstract: 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 &y& Elsevier]

Objectives: The aim of this study was to further explore the interplay between smoking status, coronary artery calcium (CAC), and all-cause mortality. Background: Prior studies have not directly compared the relative prognostic impact of CAC in smokers versus nonsmokers. In particular, although a calcium score of zero (CAC = 0) is a known favorable prognostic marker, whether smokers with CAC = 0 have as good a prognosis as nonsmokers with CAC = 0 is unknown. Given that computed tomography (CT) screening for lung cancer appears effective in smokers, the relative prognostic implications of visualizing any CAC versus no CAC on such screening also deserve study. Methods: Our study cohort consisted of 44,042 asymptomatic individuals referred for noncontrast cardiac CT (age 54 ± 11 years, 54% men). Subjects were followed for a mean of 5.6 years. The primary endpoint was all-cause mortality. Results: Approximately 14% (n = 6,020) of subjects were active smokers at enrollment. There were 901 deaths (2.05%) overall, with increased mortality in smokers versus nonsmokers (4.3% vs. 1.7%, p < 0.0001). Smoking remained a risk factor for mortality across increasing strata of CAC scores (1 to 100, 101 to 400, and >400). At each stratum of elevated CAC score, mortality in smokers was consistently higher than mortality in nonsmokers from the CAC stratum above. In multivariable analysis within these strata, we found mortality hazard ratios of 3.8 (95% confidence interval [CI]: 2.8 to 5.2), 3.5 (95% CI: 2.6 to 4.9), and 2.7 (95% CI: 2.1 to 3.5), respectively, in smokers compared with nonsmokers. However, among the 19,898 individuals with CAC = 0, the mortality hazard ratio for smokers without CAC was 3.6 (95% CI: 2.3 to 5.7), compared with nonsmokers without CAC. Conclusions: Smoking is a risk factor for death across the entire spectrum of subclinical coronary atherosclerosis. Smokers with any CAC had significantly higher mortality than smokers without CAC, a finding with implications for smokers undergoing lung cancer CT-based screening. However, the absence of CAC might not be as useful a “negative risk factor” in active smokers, because this group has mortality rates similar to nonsmokers with mild-to-moderate atherosclerosis. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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 &y& Elsevier]

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 &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: We sought to derive normative reference values for the thoracic great vessels using multidetector computed tomography (MDCT) in a healthy normotensive non-obese population free of cardiovascular disease. Materials and Methods: Non-gated axial computed tomography (CT) of the chest has traditionally been used to evaluate normal great vessel anatomy for prognosis and management. However, non-gated axial chest CT cannot account for the obliquity, systolic expansion, and non-axial motion of the great vessels during the cardiac cycle and may misclassify patients as normal or abnormal for prognostic and management purposes. To date, normative reference values for double-oblique, short-axis great vessel diameters have not been established using current generation electrocardiogram (ECG)-gated 64-detector row MDCT. A total of 103 (43% women, age 51 ± 14 years) consecutive normotensive, non-obese adults free of cardiopulmonary or great vessel structural disease, arrhythmias, or significant coronary artery disease were studied by MDCT. Individuals underwent examination for determination of end-diastolic (ED) pulmonary artery (PA) and superior vena cava (SVC) dimensions in double-oblique short axes for comparison with the ascending aorta and the right-sided cardiac chambers. Results: For right sided great vessels, the 5th to 95th interval was 1.89–3.03 cm for ED PA diameter and 1.08–4.42 cm2 for SVC cross-sectional area. The pulmonary artery to ascending aortic (PA-to-Ao) ratio was 0.66–1.13. In multivariate analysis, the PA was significantly associated with weight, whereas the PA-to-Ao ratio was inversely associated with age. Axial PA measurements were significantly higher and PA-to-Ao measurements significantly lower than corresponding short axis measurements (P = .04 and P < .001, respectively). Conclusions: This study establishes ECG-gated MDCT reference values for right-sided great vessel dimensions derived from a healthy population of individuals free of cardiovascular disease, hypertension, and obesity. The traditional axial PA-to-Ao discriminant value of 1 for pulmonary hypertension is a poor diagnostic tool because it encompasses normal patients and is negatively affected by age. Thoracic great vessels should be measured by CT in ECG-gated double-oblique short-axis for accurate quantitation. These data may serve as a reference to identify right-sided great vessel pathology in individuals being referred for ECG-gated MDCT imaging. [Copyright &y& Elsevier]

Objectives: We sought to quantify the mortality rates associated with absent and low positive (CAC 1 to 10) coronary artery calcium (CAC). Background: There is increasing interest in the absence of CAC as a “negative” cardiovascular risk factor. However, published event rates for individuals with no CAC vary, likely owing to differences in baseline risk, follow-up period, and outcome ascertainment. The prognostic significance of low CAC (CAC 1 to 10) is not well described. Methods: Annualized all-cause mortality rates were assessed in 44,052 consecutive asymptomatic patients referred for CAC testing. Mean follow-up of the cohort was 5.6 ± 2.6 years (range 1 to 13 years). Results: A total of 19,898 patients (45%) had no CAC on screening electron beam tomography, whereas 5,388 (12%) had low levels of CAC (CAC 1 to 10), and 18,766 (43%) had CAC >10. There were 104 deaths in those with no CAC (0.52%), 58 deaths in those with CAC 1 to 10 (1.06%), and 739 deaths in those with CAC >10 (3.96%). Annualized all-cause mortality rates for CAC = 0, CAC 1 to 10, and CAC >10 were 0.87, 1.92, and 7.48 deaths/1,000 person-years, respectively. The hazard ratio (HR) for all-cause mortality among CAC 1 to 10 versus CAC = 0 after adjustment for traditional risk factors was 1.99 (95% confidence interval [CI]: 1.44 to 2.75). Smoking (HR: 3.97, 95% CI: 2.75 to 5.41) and diabetes mellitus (HR: 3.36, 95% CI: 2.09 to 5.41) were associated with few events observed in CAC = 0 group. Conclusions: In appropriately selected asymptomatic patients, the absence of CAC predicts excellent survival with 10-year event rates of approximately 1%. A finding of 0 CAC might be used as a rationale to emphasize lifestyle therapies rather than pharmacotherapy and to forgo repeated imaging studies. Individuals with low CAC score (CAC 1 to 10) are at increased risk above individuals with a 0 score and could be considered a distinct risk group by physicians and investigators. [Copyright &y& Elsevier]

Objectives: We derived mean values for cardiac dimensions, volumes, function, and mass in a normotensive nonobese population free of cardiovascular disease. Background: Multidetector computed tomography (MDCT) permits study of cardiac chamber size, function, and mass. Age- and gender-specific mean values are not available. Methods: A total of 103 normotensive, nonobese adults (43% women, age 51 ± 14 years) who presented consecutively to 2 medical centers for clinically indicated MDCTs with neither history of nor MDCT evidence of significant cardiovascular disease were studied for left ventricular (LV) and right ventricular (RV) end-systolic (ES) and end-diastolic (ED) linear dimensions and volumes; LV and RV ejection fraction (EF), and LV mass (LVM); and left atrial (LA) and right atrial (RA) end-systolic volumes (LAESV and RAESV, respectively) by 1-dimensional (1D), 2-dimensional (2D), and 3-dimensional (3D) measurements. Results: The LV volumes using 3D techniques were lower than 2D techniques (LVEDV mean 144 ± 71 ml vs. 150 ± 70 ml), with higher LVEF (63 ± 15% vs. 57 ± 13%) (p < 0.001 for both). Mean LVM/height2.7 was 24.3 ± 11.0 g/m2.7 and mean relative wall thickness was 0.16 to 0.44. Evaluation by 20 versus 10 cardiac phases resulted in higher LVEF (mean difference: 3.4 ± 9.0%, p < 0.001). For LVEDV, interobserver (r = 0.99, p < 0.001) and intraobserver (r2 = 0.97, p < 0.001) correlations were high. Mean RVEDV was 82 ± 57 ml and RVEF was 58 ± 16. The LAESV determined by 3D techniques was higher than by that determined by 2D methods (102 ± 48 ml vs. 87 ± 57 ml, p = 0.0003). The RAESV determined by 3D techniques was 111.9 ± 29.1 ml. The LV size and LVM were greater in men than in women (p < 0.01). The LV size declined with age (p < 0.01), but LVM did not. Conclusions: This study establishes age- and gender-specific values for LV, RV, LA, and RA size, function, and mass in adults free of cardiovascular disease, hypertension, and obesity using 1D, 2D, and 3D methods. These data can be used as a reference for future MDCT studies. [Copyright &y& Elsevier]

Background: Dilatation of the aortic root and other segments of the thoracic aorta is important in the pathogenesis of aortic regurgitation and of aortic dissection. Although echocardiographic criteria exist to detect aortic root dilation, comparably standardized methods have not been developed to detect enlargement of the remainder of the thoracic aorta. Nongated axial chest computed tomography (CT), traditionally used to evaluate aortic size, does not account for the obliquity, systolic expansion, and nonaxial motion of the aorta during the cardiac cycle. Reference values for aortic diameters in anatomically correct double-oblique short axis images have not been established with the use of electrocardiogram (ECG)-gated 64-detector row multidetector CT (MDCT). Objectives: To establish reference values for thoracic aortic diameters MDCT in healthy normotensive nonobese adults without evident cardiovascular disease. Methods: A total of 103 (43% women, age 51 ± 14 years) consecutive normotensive, nonobese adults free of cardiac or aortic structural disease or arrhythmia underwent MDCT examination to determine aortic dimensions. Results: End-diastolic diameter 95% confidence intervals were 2.5–3.7 cm for the aortic root, 2.1–3.5 cm for the ascending aorta, and 1.7–2.6 cm for the descending thoracic aorta. Aortic diameters were significantly greater at end systole than end diastole (mean difference 1.9 ± 1.2 mm for ascending and 1.3 ± 1.8 for descending thoracic aorta, P < 0.001). Aortic root and ascending aortic diameter increased significantly with age and body surface area. Conclusions: This study establishes age- and sex-specific ECG-gated MDCT reference values for thoracic aortic diameters in healthy, normotensive, nonobese adults to identify aortic pathology by MDCT. MDCT measurements of the thoracic aorta should use ECG-gated double-oblique short-axis images for accurate quantification. [Copyright &y& Elsevier]

Background: The diagnostic accuracy of coronary computed tomographic angiography (CTA) is high with few reports noting its ability to stratify risk. The quantity and quality of prognostic evidence with myocardial perfusion single-photon emission computed tomography (SPECT) (MPS) is diverse, with little comparative evidence between methods. The aim of this report was to compare all-cause death rates for 7 CTA subsets, using the Duke prognostic index, compared with percentage of ischemic myocardium by MPS. Methods: We performed a matched cohort comparison of patients with suspected coronary artery disease (CAD) referred for evaluation of new onset chest pain with 693 and 3067 patients undergoing CTA and MPS. The primary endpoint was time to all-cause death estimated with univariable and multivariable (controlling for pretest CAD likelihood and cardiac risk factors) Cox proportional hazards models. Patients undergoing MPS were matched, using a propensity scoring technique, to the CTA cohort, yielding 16%, 60%, and 24% of the patients with low, intermediate, and high pretest CAD likelihood (P = 0.39). Results: Two-year mortality was similar for CTA and MPS at 3.2% (P = 0.71). For CTA, the Duke prognostic index was independently predictive of death in risk-adjusted models controlling for risk factors and pretest likelihood of CAD (P < 0.0001). Patients with <50% stenosis had the highest survival at 99.7%. Survival worsened from 96% for patients with 2 moderate stenoses or 1 ≥70% stenosis (P = 0.013) to 85% survival for patients with ≥50% left main stenosis (P < 0.0001). For MPS, the percentage of ischemic myocardium was independently predictive of death (P < 0.0001). For patients with no MPS ischemia, 100% survival was observed. Survival worsened from 94.0% to 83.0% for patients with 5% to ≥20% ischemic myocardium (P < 0.0001). In the comparative analysis of CTA to MPS, annual mortality rates were similar with the Duke CAD index compared with the percentage of ischemic myocardium (P = 0.53). Annual mortality rates ranged from 0.1% to 11.7% by the extent and severity of abnormalities noted on CTA and MPS (P = 0.53). Conclusion: A directly proportional relation was observed between the extent and severity of MPS ischemia and angiographic CAD. High-risk ischemia is more often associated with extensive CAD and high mortality risk. The results from this matched, observational study require additional validation for longer-term predictive models that include major adverse cardiovascular events and diverse patient subsets. [Copyright &y& Elsevier]

Tests the hypothesis that electron beam computed tomography (EBCT) might be an effective and cost-beneficial technique for the identification of coronary artery disease (CAD) in patients with low to intermediate pretest probability of the disease. Conclusion that in a pathway based on EBCT as the initial test for CAD provides a substantial cost benefit.

The epidemic of coronary artery disease continues to affect a large number of individuals who often experience sudden and unexpected events. This underscores the need to develop more effective programs to detect silent atherosclerosis, with the ultimate goal of preventing coronary events. The use of conventional risk factors is helpful in assessing the median risk of a population, but it is often unsatisfactory in estimating the actual risk of an individual patient. As a consequence, newer imaging modalities are being developed to detect atherosclerosis in its early developmental phases. Technologies such as electron-beam computed tomography (EBCT) may render risk stratification more accurate if used in the appropriate patient populations and with the right diagnostic approach. Several studies have already demonstrated the power of coronary calcification as a strong predictor of future cardiovascular events. Nonetheless, the medical literature is currently pervaded by an animated debate, as some investigators still have concerns about the effectiveness of a preventive approach driven by technology. The use of Bayesian models to interpret data acquired with EBCT screening may provide practitioners with valuable evidence to aid in their decision making. [ABSTRACT FROM AUTHOR]

Introduction Prior studies have demonstrated a decline in the predictive ability of conventional risk factors (RF) with advancing age, emphasizing the need for novel tools to improve risk stratification in the elderly. Coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events, but its long-term prognostic utility beyond RFs in elderly persons is unknown. Methods A consecutive series of 9715 individuals underwent CAC scoring and were followed for a mean of 14.6 ± 1.1 years. Multivariable Cox proportional hazards regression (HR) with 95% confidence intervals (95% CI) was employed to assess the independent relationship of CAC and RFs with all-cause death. The incremental value of CAC, stratified by age, was examined by using an area under the receiver operator characteristic curve (AUC) and category-free net reclassification improvement (NRI). Results Of the overall study sample, 728 (7.5%) adults (mean age 74.2 ± 4.2 years; 55.6% female) were 70 years or older, of which 157 (21.6%) died. The presence of any CAC was associated with a >4-fold (95% CI = 2.84–6.59) adjusted risk of death for those over the age of 70, which was higher compared with younger study counterparts, or other measured RFs. For individuals 70 years or older, the discriminatory ability of CAC improved upon that of RFs alone (C statistics 0.764 vs. 0.675, P < 0.001). CAC also enabled improved reclassification (category-free NRI = 84%, P < 0.001) when added to RFs. Conclusion In a large-scale observational cohort registry, CAC improves prediction, discrimination, and reclassification of elderly individuals at risk for future death. [ABSTRACT FROM AUTHOR]

Background To examine the performance of coronary artery calcification (CAC) for stratifying long-term risk of death in asymptomatic hypertensive patients. Methods and results 8905 consecutive asymptomatic individuals without cardiovascular disease or diabetes who underwent CAC testing (mean age 53.3 ± 10.5, 59.3% male) were followed for a mean of 14 years and categorized on the background of hypertension as well as age above or below 60 years (in accordance with the 2014 Guidelines from the Joint National Committee 8). The prevalence and severity of CAC were higher for those with hypertension versus without hypertension (P < 0.001), and the extent increased proportionally with advancing age (P < 0.001). Following adjustment, the presence of CAC in hypertensive with respect to normotensive, was associated with worse prognosis for individuals above the age of 60 years (HR 7.74 [95% CI: 5.15-11.63] vs. HR 4.83 [95% CI: 3.18-7.33]) than individuals below the age of 60 (HR 3.18 [95% CI: 2.42-4.19] vs. HR 2.14 [95% CI: 1.61-2.85]), respectively. A zero CAC score in hypertensive over the age of 60 years was associated with a lower but persisting risk of mortality for (HR 2.48 [95% CI: 1.50-4.08]) that was attenuated non-significant for those below the age of 60 years (P = 0.09). In a "low risk" hypertensive population, the presence any CAC was associated with an almost five-fold (HR 4.68 [95% CI: 2.22-9.87]) increased risk of death. Conclusion The presence and extent of CAC effectively may help the clinicians to further discriminate the long-term risk of mortality among asymptomatic hypertensive individuals, beyond conventional cardiovascular risk and current guidelines. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 &y& Elsevier]

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 &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Although family history (FH) of coronary artery disease (CAD) is considered a risk factor for future cardiovascular events, the prevalence, extent, severity, and prognosis of young patients with FH of CAD have been inadequately studied. From 27,125 consecutive patients who underwent coronary computed tomographic angiography, 6,308 young patients (men aged <55 years and women aged <65 years) without known CAD were identified. Obstructive CAD was defined as >50% stenosis in a coronary artery >2 mm diameter. Risk-adjusted logistic regression, Kaplan-Meier, and Cox proportional-hazards models were used to compare patients with and without FH of CAD. Compared with subjects without FH of CAD, those with FH of CAD (FH + ) had higher prevalences of any CAD (40% vs 30%, p <0.001) and obstructive CAD (11% vs 7%, p <0.001), with multivariate odds of FH-I- increasing the likelihood of obstructive CAD by 71% (p <0.001). After a mean follow-up period of 2 ± 1 years (42 myocardial infarctions and 39 all-cause deaths), FH + patients experienced higher annual rates of myocardial infarction (0.5% vs 0.2%, log-rank p = 0.001), with a positive FH the strongest predictor of myocardial infarction (hazard ratio 2.6, 95% confidence interval 1.4 to 4.8, p = 0.002). In conclusion, young FH+ patients have higher presence, extent, and severity of CAD, which are associated with increased risk for myocardial infarction. Compared with other clinical CAD risk factors, positive FH in young patients is the strongest clinical predictor of future unheralded myocardial infarction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Coronary artery calcium (CAC) has emerged as an important prognostic indicator for coronary heart disease risk. The purpose of this study was to assess the impact of increasing CAC burden among those with and without hypertension (HTN). Methods: The study cohort consisted of 44,052 consecutive asymptomatic individuals free of known coronary heart disease referred for electron beam computed tomography (EBT) for the assessment of subclinical atherosclerosis. Patients were followed for a mean of 5.6 ± 2.6 years (range 1–13 years). The primary endpoint for the study cohort was mortality from any cause. Results: About one third (34%) of the subjects were affected by hypertension. There were 901 deaths (2.05%) in the total study population over a mean follow-up of 5.6 ± 2.6 years (range 1–13 years). The lowest event rate was observed in those with no CAC among those without hypertension (1.6 events per 1000 person years), whereas those with CAC ≥400 and hypertension had the highest all fatality rate (9.8 per 1000 person years). Compared to a CAC score of 0, increasing CAC scores (1–99, 100–399, and ≥400) were associated with increases in all-cause mortality. The hazard ratio was 2.19–7.74-fold among those without HTN and 3.00–5.83 fold among those with HTN. Overall likelihood ratio chi square statistics demonstrated that the addition of CAC scores increased mortality prediction beyond traditional risk among those with hypertension. Conclusion: Addition of CAC scores contributed significantly in predicting mortality in addition to just traditional risk factors alone among those with and without hypertension. [Copyright &y& Elsevier]

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 &y& Elsevier]

Abstract: Objective: The effect of statins on coronary artery plaque features beyond stenosis severity is not known. Coronary CT angiography (CCTA) is a novel non-invasive method that permits direct visualization of coronary atherosclerotic features, including plaque composition. We evaluated the association of statin use to coronary plaque composition type in patients without known coronary artery disease (CAD) undergoing CCTA. Methods: From consecutive individuals, we identified 6673 individuals (2413 on statin therapy and 4260 not on statin therapy) with no known CAD and available statin use status. We studied the relationship between statin use and the presence and extent of specific plaque composition types, which was graded as non-calcified (NCP), mixed (MP), or calcified (CP) plaque. Results: The mean age was 59 ± 11 (55% male). Compared to the individuals not taking statins, those taking statins had higher prevalence of risk factors and obstructive CAD. In multivariable analyses, statin use was associated with increased the presence of MP [odds ratio (OR) 1.46, 95% confidence interval (CI) 1.27–1.68), p < 0.001] and CP (OR 1.54, 95% CI 1.36–1.74, p < 0.001), but not NCP (OR 1.11, 95% CI 0.96–1.29, p = 0.1). Further, in multivariable analyses, statin use was associated with increasing numbers of coronary segments possessing MP (OR 1.52, 95% CI 1.34–1.73, p < 0.001) and CP (OR 1.52, 95% CI 1.36–1.70, p < 0.001), but not coronary segments with NCP (OR 1.09, 95% CI 0.94–1.25, p = 0.2). Conclusion: Statin use is associated with an increased prevalence and extent of coronary plaques possessing calcium. The longitudinal effect of statins on coronary plaque composition warrants further investigation. [Copyright &y& Elsevier]

Abstract: Two patients with prosthetic aortic valves – one bioprosthetic and one mechanical – presented with bacteremia and underwent evaluation for infective prosthetic valve endocarditis. Multidetector computed tomography (MDCT) imaging demonstrated vegetations on both prosthetic valves confirmed by transesophageal echocardiography. Based on the MDCT coronary artery assessment, neither patient underwent pre-operative invasive coronary angiography. Both patients underwent surgical treatment without complication. In conclusion, this report demonstrates that MDCT can, in some cases, accurately image vegetations on prosthetic aortic valves in infective endocarditis. [Copyright &y& Elsevier]

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 &y& Elsevier]

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 &y& Elsevier]

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 &y& Elsevier]