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The purpose of this review is to summarize the work published by the Journal of Cardiovascular Computed Tomography (JCCT) for the year 2019, highlighting original research and new guidelines., Competing Interests: Declaration of competing interest CNC receives research support from and has received speaker fees from Siemens Healthineers. JAL serves as a consultant and holds stock options with Circle CVI and HeartFlow and receives research support from GE Healthcare. JKM receives funding from the Dalio Foundation, NIH, and GE Healthcare. JKM also serves on the scientific advisory board of Arineta and GE Healthcare, and has an equity interest in Cleerly., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aim: The long-term prognostic benefit of coronary computed tomographic angiography (CCTA) findings of coronary artery disease (CAD) in asymptomatic populations is unknown., Methods and Results: From the prospective multicentre international CONFIRM long-term study, we evaluated asymptomatic subjects without known CAD who underwent both coronary artery calcium scoring (CACS) and CCTA (n = 1226). Coronary computed tomographic angiography findings included the severity of coronary artery stenosis, plaque composition, and coronary segment location. Using the C-statistic and likelihood ratio tests, we evaluated the incremental prognostic utility of CCTA findings over a base model that included a panel of traditional risk factors (RFs) as well as CACS to predict long-term all-cause mortality. During a mean follow-up of 5.9 ± 1.2 years, 78 deaths occurred. Compared with the traditional RF alone (C-statistic 0.64), CCTA findings including coronary stenosis severity, plaque composition, and coronary segment location demonstrated improved incremental prognostic utility beyond traditional RF alone (C-statistics range 0.71-0.73, all P < 0.05; incremental χ2 range 20.7-25.5, all P < 0.001). However, no added prognostic benefit was offered by CCTA findings when added to a base model containing both traditional RF and CACS (C-statistics P > 0.05, for all)., Conclusions: Coronary computed tomographic angiography improved prognostication of 6-year all-cause mortality beyond a set of conventional RF alone, although, no further incremental value was offered by CCTA when CCTA findings were added to a model incorporating RF and CACS.

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.)

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.

Purpose: To assess the prevalence, extent, severity, and risk of coronary artery disease (CAD) in patients suspected of having CAD but with no medically modifiable risk factors., Materials and Methods: Institutional review board approval or waiver of consent was obtained at each center. This study was HIPAA compliant. From an international multicenter cohort study of 27 125 subjects undergoing coronary computed tomographic (CT) angiography from 12 centers, 5262 patients without known CAD and without modifiable risk factors were identified. CAD severity was defined as none (0%), mild (1%-49%), or obstructive (≥ 50%) on a per-patient, per-vessel, and per-segment basis. CAD presence, extent, and severity were related to incidence of major adverse cardiovascular event (MACE) by using Cox proportional hazards models., Results: At a mean follow-up of 2.3 years ± 1.2 (standard deviation), MACE occurred in 106 patients. CAD was common for nonobstructive (n = 1452, 27%) and obstructive (n = 629, 12%) CAD. In risk-adjusted analysis, per-patient obstructive CAD (hazard ratio [HR], 6.64; 95% confidence interval [CI]: 3.68, 12.00; P ≤ .001) was related to MACE. MACE was associated with a dose-response relationship to the number of vessels exhibiting obstructive CAD, increasing risk for obstructive one-vessel (HR, 6.11; 95% CI: 3.22, 11.6; P ≤ .001), two-vessel (HR, 5.86; 95% CI: 2.75, 12.5; P ≤ .0001), or three-vessel or left main (HR, 11.69; 95% CI: 5.38, 25.4; P ≤ .001) CAD. The increased hazard for MACE of obstructive disease holds true for symptomatic (HR, 11.9; 95% CI: 4.81, 29.6; P ≤ .001) and asymptomatic (HR, 6.3; 95% CI: 2.4, 16.7; P ≤ .001) patients. No CAD at coronary CT angiography was associated with a low annualized MACE rate: 0.31% versus 2.06% with obstructive disease., Conclusion: Among individuals suspected of having CAD but without modifiable risk factors, CAD is common, with significantly increased hazards for MACE and mortality.

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.)

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.

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.)

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.)

Atherosclerosis is present in about 50% of asymptomatic adults at middle age and in nearly all elderly individuals. The traditional diagnostic and treatment paradigm has addressed risk detection and reduction of binary events, including myocardial infarction (MI), stroke, and cardiovascular death. About 50% of all acute coronary syndromes occur in previously asymptomatic subjects, 90% of whom have modifiable risk factors; yet our current screening approaches fail to prevent the 1.2 million acute cardiovascular events that occur annually in the United States. In a patient with active disease, multiple treatment targets can be approached with a variety of lifestyle changes and medical therapy to render the disease quiescent in theory. A future approach may be interception of atherosclerosis before the identification of theoretical or actual risk of episodic events. This case review highlights use of advanced biomarkers and imaging to assess atherosclerotic disease activity in a 49-year-old asymptomatic woman who presents for evaluation after the death of her father from MI.