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Objective: Data describing the prevalence, characteristics and management of coronary chronic total occlusions (CTOs) in patients undergoing coronary CT angiography (CCTA) have not been reported. The purpose of this study was to determine the prevalence, characteristics and treatment strategies of CTO identified by CCTA. Methods: We identified 23 745 patients who underwent CCTA for suspected coronary artery disease (CAD) from the prospective international CCTA registry. Baseline clinical data were collected, and allocation to early coronary revascularisation performed within 90 days of CCTA was determined. Multivariable hierarchical mixed-effects logistic regression reporting OR with 95% CI was performed. Results: The prevalence of CTO was 1.4% (342/23 745) in all patients and 6.2% in patients with obstructive CAD (≥50% stenosis). The presence of CTO was independently associated with male sex (OR 3.12, 95% CI 2.39 to 4.08, p

ObjectiveTo investigate the impact of probiotic Bifidobacterium longum ssp. infantis on the fecal microbiota and plasma cytokines in neonates with congenital heart disease.Study designSixteen infants with congenital heart disease were randomly assigned to receive either B. infantis (4.2 × 10(9) colony-forming units two times daily) or placebo for 8 weeks. Stool specimens from enrolled infants and from six term infants without heart disease were analyzed for microbial composition. Plasma cytokines were analyzed weekly in the infants with heart disease.ResultsHealthy control infants had increased total bacteria, total Bacteroidetes and total bifidobacteria compared to the infants with heart disease, but there were no significant differences between the placebo and probiotic groups. Plasma interleukin (IL)10, interferon (IFN)γ and IL1β levels were transiently higher in the probiotic group.ConclusionCongenital heart disease in infants is associated with dysbiosis. Probiotic B. infantis did not significantly alter the fecal microbiota. Alterations in plasma cytokines were found to be inconsistent.

Background: In our model of a congenital heart defect (CHD) with increased pulmonary blood flow (PBF; shunt), we have recently shown a disruption in carnitine homeostasis, associated with mitochondrial dysfunction and decreased endothelial nitric oxide syn

Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect.Methods:An aorta-to-pulmonary-artery shunt was placed in 11 f

Objective: Carnitine homeostasis is disrupted in lambs with endothelial dysfunction secondary to increased pulmonary blood flow (Shunt). Our recent studies have also indicated that the disruption in carnitine homeostasis correlates with a decrease in PPAR-

Changes in left ventricular systolic and diastolic function and outflow gradient were evaluated in patients with obstructive hypertrophic cardiomyopathy after intravenous acute treatment with verapamil (15 patients) and after six months of oral chronic treatment (11 patients). All patients had severe symptoms despite beta blockade, and the condition of all but two improved appreciably after chronic treatment with verapamil. Resting left ventricular outflow tract gradient decreased in six of 15 patients after intravenous verapamil, and in five of 11 patients after long term treatment, but there was no change in provocable gradients nor any correlation between changes in gradient and improvement in symptoms. Left ventricular ejection rate did not change after intravenous or oral treatment. End systolic pressure/end systolic volume index remained unchanged after oral verapamil treatment. Whereas left ventricular total stroke volume index and end diastolic volume index increased without any significant change in left ventricular end diastolic pressure, indicating improved left ventricular diastolic function. In some patients the left ventricular diastolic pressure-volume curve shifted downwards or to the right or both. These findings suggest that improvement in symptoms with verapamil in patients with obstructive hypertrophic cardiomyopathy is unlikely to be related to changes in left ventricular outflow gradient or in systolic function and may be related to improved diastolic function. [ABSTRACT FROM PUBLISHER]

Objectives: The purpose of the study was to determine the effectiveness of a collaborative educational, continuous quality improvement (CQI) initiative to increase appropriate use of coronary computed tomography angiography (CCTA). Background: Potential overuse of CCTA has prompted multisociety appropriate use criteria (AUC) publications. Methods: This prospective, observational study was conducted with pre-intervention (July 2007 to June 2008), intervention (July 2008 to June 2010), and follow-up (July 2010 to December 2010) periods during which patients were enrolled in the Advanced Cardiovascular Imaging Consortium (ACIC) at 47 Michigan hospitals. Continuous education was provided to referring physicians. The possibility of losing third-party payer coverage in the absence of a measurable change in AUC was emphasized. AUC was compared between the 3 periods. Results: The study group included 25,387 patients. Compared with the pre-intervention period, there was a 23.4% increase in appropriate (61.3% to 80%, p < 0.0001), 60.3% decrease in inappropriate (14.6% to 5.8%, p < 0.0001), 40.8% decrease in uncertain (10.3% to 6.1%, p < 0.0001), and 41.7% decrease in unclassifiable (13.9% to 8.1%, p < 0.0001) scans during follow-up. Between pre-intervention and follow-up, change in CCTA referrals by provider specialty were cardiology (appropriate: 60.4% to 79.5%; inappropriate: 13% to 5.2%; p < 0.0001), internal medicine/family practice (appropriate: 51.1% to 70.4%; inappropriate: 20.2% to 12.5%; p < 0.0001), emergency medicine (appropriate: 83.6% to 91.6%; inappropriate: 9.1% to 0.6%; p < 0.0001), and other (appropriate: 61.1% to 83.2%; inappropriate: 18.6% to 5.9%; p < 0.0001). Conclusions: Application of a systematic CQI and emphasis on possible loss of coverage were associated with a significant improvement in the proportion of CCTA examinations meeting AUC across referring physician specialties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease., Background: Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy., Methods: This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques)., Results: CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0.146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis., Conclusions: Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)., Competing Interests: Author Disclosures This study was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (grant 2012027176) and funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. This work was supported by a grant from Research year of Inje University in 20170038. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning (grant 2012027176). Dr. Min has received funding from the National Institutes of Health (grants R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907), the Qatar National Priorities Research Program (grant 09-370-3-089), and GE Healthcare; has served as a consultant to HeartFlow; serves on the scientific advisory board of Arineta; and has an equity interest in MDDX. Dr. Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Chun has received funding from a National Research Foundation grant funded by the South Korea government (MEST) (NRF-2015R1D1A1A01059717). Dr. Leipsic serves as a consultant and has stock options in HeartFlow and Circle Cardiovascular Imaging; and receives speaking fees from GE Healthcare. Dr. Budoff has received grant support from the National Institutes of Health and GE Healthcare. Dr. Samady has received grant support from Phillips/Volcano and St. Jude Abbott/Medtronic/Gilead. Dr. Andreini is on the Speakers Bureau for GE Healthcare; and receives grant support from GE Healthcare and Bracco. Dr. Pontone has received institutional research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Berman has received software royalties from Cedars-Sinai. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, CeloNova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) according to sex., Background: Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR CT improves sex-based patient management decisions compared to CCTA alone is unknown., Methods: Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates., Results: A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR CT . Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm 3 /g vs. 24.76 ± 7.22 mm 3 /g; p < 0.0001) that is associated with higher FFR CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284)., Conclusions: FFR CT differs between the sexes, as women have a higher FFR CT for the same degree of stenosis. In FFR CT -positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)., Competing Interests: Author Disclosures This study was supported by HeartFlow, Inc., Redwood City, California, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events. Dr. Fairbairn is on the Speakers Bureau for Heartflow. Dr. Hurwitz-Koweek is on the Speakers Bureau for Heartflow; and has unrestricted grant funding from Siemens and Heartflow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Nieman has received unrestricted institutional research grants from Siemens, Bayer, GE, and HeartFlow. Dr. Bax has received unrestricted research grants from Edwards Lifescience, Medtronic, Boston Scientific, Biotronik, and GE Healthcare; and is on the Speakers Bureau with Abbott. Dr. Pontone is a consultant for GE Healthcare; and has research grants from GE Healthcare and Heartflow. Dr. Raff has received institutional grants from HeartFlow. Dr. Chinnaiyan has received institutional grants from HeartFlow. Dr. Rabbat has received institutional grants from HeartFlow. Dr. Binukrishnan is on the Speakers Bureau for Heartflow. Dr. Rogers is an employee of and has equity in Heartflow. Dr. Berman has received unrestricted research support from Heartflow. Dr. Patel has received grants from HeartFlow, Jansen, Bayer, AstraZeneca, and NHLBI; and has served as a consultant for Jansen, Bayer, AstraZeneca, Genzyme, and Merck. Dr. Douglas has received institutional grants from HeartFlow. Dr. Leipsic is a consultant for and has stock options in Circle CVI and Heartflow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Noninvasive fractional flow reserve derived from coronary CT angiography (FFR CT ) is increasingly used in patients with coronary artery disease as a gatekeeper to the catheterization laboratory. While there is emerging evidence of the clinical benefit of FFR CT in patients with moderate coronary disease as determined with coronary CT angiography, there has been less focus on interpretation, reporting, and integration of FFR CT results into routine clinical practice. Because FFR CT analysis provides a plethora of information regarding pressure and flow across the entire coronary tree, standardized criteria on interpretation and reporting of the FFR CT analysis result are of crucial importance both in context of the clinical adoption and in future research. This report represents expert opinion and recommendation on a standardized FFR CT interpretation and reporting approach. Published under a CC BY 4.0 license., Competing Interests: Disclosures of Conflicts of Interest: B.L.N. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has received unrestricted institutional research grants from Siemens and HeartFlow; travel expenses covered at TCT 2017 by HeartFlow (no personal payment). Other relationships: disclosed no relevant relationships. T.A.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has been an invited speaker sponsored by HeartFlow. Other relationships: disclosed no relevant relationships. R.D.S. disclosed no relevant relationships. M.G.R. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author is consultant for HeartFlow. Other relationships: disclosed no relevant relationships. B.K. Activities related to the present article: has been an invited speaker at symposiums sponsored by Canon Medical, Medtronic, and St Jude, and has received research funding from Canon Medical. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. J.M.J. disclosed no relevant relationships. K.N. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: unrestricted institutional research support from HeartFlow, Siemens, GE, and Bayer; coverage of travel expenses to the present study results at the TCT in 2018 by HeartFlow; Steering committee ADVANCE registry for HeartFlow (unpaid). Other relationships: disclosed no relevant relationships. K.M.C. Activities related to the present article: institution receives grant from HeartFlow. Activities not related to the present article: Medical Advisory Board for HeartFlow (no personal compensation); institution receives grants from HeartFlow. Other relationships: disclosed no relevant relationships. N.P.S. disclosed no relevant relationships. H.M. disclosed no relevant relationships. J.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has received speaker honoraria from GE Healthcare, served as a consultant for Edwards Lifesciences, and served as a consultant and has stock options in Circle CVI and HeartFlow; has core laboratory contracts with Edwards Lifesciences, Medtronic, Abbott, Noevasc; research support from Edwards. Other relationships: disclosed no relevant relationships. G.R. disclosed no relevant relationships., (2019 by the Radiological Society of North America, Inc.)

Aims: Coronary artery calcium score (CACS) is a strong predictor of major adverse cardiac events (MACE). Conversely, statins, which markedly reduce MACE risk, increase CACS. We explored whether CACS progression represents compositional plaque volume (PV) progression differently according to statin use., Methods and Results: From a prospective multinational registry of consecutive patients (n = 2252) who underwent serial coronary computed tomography angiography (CCTA) at a ≥ 2-year interval, 654 patients (61 ± 10 years, 56% men, inter-scan interval 3.9 ± 1.5 years) with information regarding the use of statins and having a serial CACS were included. Patients were divided into non-statin (n = 246) and statin-taking (n = 408) groups. Coronary PVs (total, calcified, and non-calcified; sum of fibrous, fibro-fatty, and lipid-rich) were quantitatively analysed, and CACS was measured from both CCTAs. Multivariate linear regression models were constructed for both statin-taking and non-statin group to assess the association between compositional PV change and change in CACS. In multivariate linear regression analysis, in the non-statin group, CACS increase was positively associated with both non-calcified (β = 0.369, P = 0.004) and calcified PV increase (β = 1.579, P < 0.001). However, in the statin-taking group, CACS increase was positively associated with calcified PV change (β = 0.756, P < 0.001) but was negatively associated with non-calcified PV change (β = -0.194, P = 0.026)., Conclusion: In the non-statin group, CACS progression indicates the progression of both non-calcified and calcified PV progression. However, under the effect of statins, CACS progression indicates only calcified PV progression, but not non-calcified PV progression. Thus, the result of serial CACS should be differently interpreted according to the use of statins., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

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

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

Aims: Non-invasive assessment of stable chest pain patients is a critical determinant of resource utilization and clinical outcomes. Increasingly coronary computed tomography angiography (CCTA) with selective CCTA-derived fractional flow reserve (FFRCT) is being used. The ADVANCE Registry, is a large prospective examination of using a CCTA and FFRCT diagnostic pathway in real-world settings, with the aim of determining the impact of this pathway on decision-making, downstream invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular events (MACE)., Methods and Results: A total of 5083 patients with symptoms concerning for coronary artery disease (CAD) and atherosclerosis on CCTA were enrolled at 38 international sites from 15 July 2015 to 20 October 2017. Demographics, symptom status, CCTA and FFRCT findings, treatment plans, and 90 days outcomes were recorded. The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management plans occurred in 66.9% [confidence interval (CI): 64.8-67.6] of patients. Non-obstructive coronary disease was significantly lower in ICA patients with FFRCT ≤0.80 (14.4%) compared to patients with FFRCT >0.80 (43.8%, odds ratio 0.19, CI: 0.15-0.25, P < 0.001). In total, 72.3% of subjects undergoing ICA with FFRCT ≤0.80 were revascularized. No death/myocardial infarction (MI) occurred within 90 days in patients with FFRCT >0.80 (n = 1529), whereas 19 (0.6%) MACE [hazard ratio (HR) 19.75, CI: 1.19-326, P = 0.0008] and 14 (0.3%) death/MI (HR 14.68, CI 0.88-246, P = 0.039) occurred in subjects with an FFRCT ≤0.80., Conclusions: In a large international multicentre population, FFRCT modified treatment recommendation in two-thirds of subjects as compared to CCTA alone, was associated with less negative ICA, predicted revascularization, and identified subjects at low risk of adverse events through 90 days.

Objectives: This study sought to describe the impact of statins on individual coronary atherosclerotic plaques., Background: Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear., Methods: We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications., Results: Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features were lower in lesions in statin-taking patients (0.49 ± 2.39% per year vs. 1.06 ± 2.42% per year and 0.9% per year vs. 1.6% per year, respectively; all p < 0.001). The rates of progression to >50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development., Conclusions: Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Diagnosis of coronary artery disease and management strategies have relied solely on the presence of diameter stenosis ≥50%. We assessed whether direct quantification of plaque burden (PB) and plaque characteristics assessed by coronary computed tomography angiography could provide additional value in terms of predicting rapid plaque progression., Methods and Results: From a 13-center, 7-country prospective observational registry, 1345 patients (60.4±9.4 years old; 57.1% male) who underwent repeated coronary computed tomography angiography >2 years apart were enrolled. For conventional angiographic analysis, the presence of stenosis ≥50%, number of vessel involved, segment involvement score, and the presence of high-risk plaque feature were determined. For quantitative analyses, PB and annual change in PB (△PB/y) in the entire coronary tree were assessed. Clinical outcomes (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were recorded. Rapid progressors, defined as a patient with ≥median value of △PB/y (0.33%/y), were older, more frequently male, and had more clinical risk factors than nonrapid progressors (all P <0.05). After risk adjustment, addition of baseline PB improved prediction of rapid progression to each angiographic assessment of coronary artery disease, and the presence of high-risk plaque further improved the predictive performance (all P <0.001). For prediction of adverse outcomes, adding both baseline PB and △PB/y showed best predictive performance (C statistics, 0.763; P <0.001)., Conclusions: Direct quantification of atherosclerotic PB in addition to conventional angiographic assessment of coronary artery disease might be beneficial for improving risk stratification of coronary artery disease., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02803411., (© 2018 American Heart Association, Inc.)

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

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

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.

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