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Background: Affective temperaments are documented predictors of psychopathology, but cumulating data suggest their relationship with coronary artery disease (CAD). We aimed to evaluate their role in relation to surrogate semiquantitative markers of coronary plaque burden, as assessed by coronary CT angiography (CCTA)., Methods: We included 351 patients who were referred for CCTA due to suspected CAD. All patients completed the Temperament Evaluation of Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A). The severity and extent of CAD was evaluated by CCTA, applying semiquantitative plaque burden scores, notably Segment Involvement Score (SIS) and Segment Stenosis Score (SSS). Logistic regression analyses were performed to define the predictors of CAD severity and extent., Results: Regarding the scores evaluated by TEMPS-A that consists of 110 questions, in men, significant inverse association was found between hyperthymic temperament score and SSS (β = -0.143, (95%CI: -0.091 to -0.004), p = 0.034). Compared to the TEMPS-A form, applying the abbreviated version - containing 40 questions - significant relationship between affective temperaments and SSS or SIS was found in case of both sexes. Concerning men, hyperthymic temperament was demonstrated to be independent predictor of both SSS (β = -0.193, (95%CI: -0.224 to -0.048), p = 0.004) and SIS (β = -0.194, (95%CI: -0.202 to -0.038), p = 0.004). Additionally, we proved, that significant positive association between irritable temperament and SSS (β = 0.152, (95%CI: 0.002 to 0.269), p = 0.047) and SIS (β = 0.155, (95%CI: 0.004 to 0.221), p = 0.042) exists among women., Limitations: Cross-sectional analysis of a single center study with self-reported questionnaires., Conclusions: Assessment of affective temperaments could offer added value in stratifying cardiovascular risk for patients beyond traditional risk factors., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Background: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization., Objectives: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA)., Methods: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort., Results: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA., Conclusions: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328)., Competing Interests: Funding Support and Author Disclosures This study received funding from HeartFlow Inc. The company performed the computational fluid dynamics, and artificial intelligence quantitative coronary plaque analysis but was not involved in the study design, collection, analysis, and interpretation of data; the writing of this paper; or the decision to submit it for publication. Dr Koo has received institutional research grants from Abbott, Philips, and HeartFlow Inc. Dr Nam has received institutional research grants from Abbott and Genoss. Dr Merkely has received direct personal payments for speaker fees or studies from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Medtronic, and Novartis and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, DUKE Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr de Bruyne has received institutional unrestricted research grants from Abbott, Boston Scientific, and Biotronik; has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE, Bayer, Philips, HeartFlow Inc, Edwards Life Sciences, Sanofi, and Omega Pharma. Dr Ko has equity in Artrya and has received honoraria from Medtronic, Abbott Vascular, and Canon Medical. Dr Leipsic is a consultant for and holds stock options in HeartFlow Inc and modest personal core lab fees from Arineta. Dr Shah has received honoraria as a speaker for HeartFlow Inc. Dr Bax has received unrestricted research grants from Abbott and Edwards Lifesciences to the Department of Cardiology, Leiden University Medical Center, the Netherlands. Dr Shaw has received honoraria from HeartFlow Inc and Elucid Imaging. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate if the effect of cardiac computed tomography (CT) vs. invasive coronary angiography (ICA) on cardiovascular events differs based on smoking status., Materials and Methods: This pre-specified subgroup analysis of the pragmatic, prospective, multicentre, randomised DISCHARGE trial (NCT02400229) involved 3561 patients with suspected coronary artery disease (CAD). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, or stroke). Secondary endpoints included an expanded MACE composite (MACE, transient ischaemic attack, or major procedure-related complications)., Results: Of 3445 randomised patients with smoking data (mean age 59.1 years + / - 9.7, 1151 men), at 3.5-year follow-up, the effect of CT vs. ICA on MACE was consistent across smoking groups (p for interaction = 0.98). The percutaneous coronary intervention rate was significantly lower with a CT-first strategy in smokers and former smokers (p = 0.01 for both). A CT-first strategy reduced the hazard of major procedure-related complications (HR: 0.21, 95% CI: 0.03, 0.81; p = 0.045) across smoking groups. In current smokers, the expanded MACE composite was lower in the CT- compared to the ICA-first strategy (2.3% (8) vs 6.0% (18), HR: 0.38; 95% CI: 0.17, 0.88). The rate of non-obstructive CAD was significantly higher in all three smoking groups in the CT-first strategy., Conclusion: For patients with stable chest pain referred for ICA, the clinical outcomes of CT were consistent across smoking status. The CT-first approach led to a higher detection rate of non-obstructive CAD and fewer major procedure-related complications in smokers., Clinical Relevance Statement: This pre-specified sub-analysis of the DISCHARGE trial confirms that a CT-first strategy in patients with stable chest pain referred for invasive coronary angiography with an intermediate pre-test probability of coronary artery disease is as effective as and safer than invasive coronary angiography, irrespective of smoking status., Trial Registration: ClinicalTrials.gov NCT02400229., Key Points: • No randomised studies have assessed smoking status on CT effectiveness in symptomatic patients referred for invasive coronary angiography. • A CT-first strategy results in comparable adverse events, fewer complications, and increased coronary artery disease detection, irrespective of smoking status. • A CT-first strategy is safe and effective for stable chest pain patients with intermediate pre-test probability for CAD, including never smokers., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Importance: The effectiveness and safety of computed tomography (CT) and invasive coronary angiography (ICA) in different age groups is unknown., Objective: To determine the association of age with outcomes of CT and ICA in patients with stable chest pain., Design, Setting, and Participants: The assessor-blinded Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) randomized clinical trial was conducted between October 2015 and April 2019 in 26 European centers. Patients referred for ICA with stable chest pain and an intermediate probability of obstructive coronary artery disease were analyzed in an intention-to-treat analysis. Data were analyzed from July 2022 to January 2023., Interventions: Patients were randomly assigned to a CT-first strategy or a direct-to-ICA strategy., Main Outcomes and Measures: MACE (ie, cardiovascular death, nonfatal myocardial infarction, or stroke) and major procedure-related complications. The primary prespecified outcome of this secondary analysis of age was major adverse cardiovascular events (MACE) at a median follow-up of 3.5 years., Results: Among 3561 patients (mean [SD] age, 60.1 [10.1] years; 2002 female [56.2%]), 2360 (66.3%) were younger than 65 years, 982 (27.6%) were between ages 65 to 75 years, and 219 (6.1%) were older than 75 years. The primary outcome was MACE at a median (IQR) follow-up of 3.5 (2.9-4.2) years for 3523 patients (99%). Modeling age as a continuous variable, age, and randomization group were not associated with MACE (hazard ratio, 1.02; 95% CI, 0.98-1.07; P for interaction = .31). Age and randomization group were associated with major procedure-related complications (odds ratio, 1.15; 95% CI, 1.05-1.27; P for interaction = .005), which were lower in younger patients., Conclusions and Relevance: Age did not modify the effect of randomization group on the primary outcome of MACE but did modify the effect on major procedure-related complications. Results suggest that CT was associated with a lower risk of major procedure-related complications in younger patients., Trial Registration: ClinicalTrials.gov Identifier: NCT02400229.

Background Coronary artery calcium (CAC) has prognostic value for major adverse cardiovascular events (MACE) in asymptomatic individuals, whereas its role in symptomatic patients is less clear. Purpose To assess the prognostic value of CAC scoring for MACE in participants with stable chest pain initially referred for invasive coronary angiography (ICA). Materials and Methods This prespecified subgroup analysis from the Diagnostic Imaging Strategies for Patients With Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial, conducted between October 2015 and April 2019 across 26 centers in 16 countries, focused on adult patients with stable chest pain referred for ICA. Participants were randomly assigned to undergo either ICA or coronary CT. CAC scores from noncontrast CT scans were categorized into low, intermediate, and high groups based on scores of 0, 1-399, and 400 or higher, respectively. The end point of the study was the occurrence of MACE (myocardial infarction, stroke, and cardiovascular death) over a median 3.5-year follow-up, analyzed using Cox proportional hazard regression tests. Results The study involved 1749 participants (mean age, 60 years ± 10 [SD]; 992 female). The prevalence of obstructive coronary artery disease (CAD) at CT angiography rose from 4.1% (95% CI: 2.8, 5.8) in the CAC score 0 group to 76.1% (95% CI: 70.3, 81.2) in the CAC score 400 or higher group. Revascularization rates increased from 1.7% to 46.2% across the same groups ( P < .001). The CAC score 0 group had a lower MACE risk (0.5%; HR, 0.08 [95% CI: 0.02, 0.30]; P < .001), as did the 1-399 CAC score group (1.9%; HR, 0.27 [95% CI: 0.13, 0.59]; P = .001), compared with the 400 or higher CAC score group (6.8%). No significant difference in MACE between sexes was observed ( P = .68). Conclusion In participants with stable chest pain initially referred for ICA, a CAC score of 0 showed very low risk of MACE, and higher CAC scores showed increasing risk of obstructive CAD, revascularization, and MACE at follow-up. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Hanneman and Gulsin in this issue.

Background Recent trials support the role of cardiac CT in the evaluation of symptomatic patients suspected of having coronary artery disease (CAD); however, body mass index (BMI) has been reported to negatively impact CT image quality. Purpose To compare initial use of CT versus invasive coronary angiography (ICA) on clinical outcomes in patients with stable chest pain stratified by BMI category. Materials and Methods This prospective study represents a prespecified BMI subgroup analysis of the multicenter Diagnostic Imaging Strategies for Patients with Stable Chest Pain and Intermediate Risk of Coronary Artery Disease (DISCHARGE) trial conducted between October 2015 and April 2019. Adult patients with stable chest pain and a CAD pretest probability of 10%-60% were randomly assigned to undergo initial CT or ICA. The primary end point was major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal myocardial infarction, or stroke. The secondary end point was an expanded MACE composite, including transient ischemic attack, and major procedure-related complications. Competing risk analyses were performed using the Fine and Gray subdistribution Cox proportional hazard model to assess the impact of the relationship between BMI and initial management with CT or ICA on the study outcomes, whereas noncardiovascular death and unknown causes of death were considered competing risk events. Results Among the 3457 participants included, 831 (24.0%), 1358 (39.3%), and 1268 (36.7%) had a BMI of less than 25, between 25 and 30, and greater than 30 kg/m 2 , respectively. No interaction was found between CT or ICA and BMI for MACE ( P = .29), the expanded MACE composite ( P = .38), or major procedure-related complications ( P = .49). Across all BMI subgroups, expanded MACE composite events (CT, 10 of 409 [2.4%] to 23 of 697 [3.3%]; ICA, 26 of 661 [3.9%] to 21 of 422 [5.1%]) and major procedure-related complications during initial management (CT, one of 638 [0.2%] to five of 697 [0.7%]; ICA, nine of 630 [1.4%] to 12 of 422 [2.9%]) were less frequent in the CT versus ICA group. Participants with a BMI exceeding 30 kg/m² exhibited a higher nondiagnostic CT rate (7.1%, P = .044) compared to participants with lower BMI. Conclusion There was no evidence of a difference in outcomes between CT and ICA across the three BMI subgroups. Clinical trial registration no. NCT02400229 © RSNA, 2024 Supplemental material is available for this article.

Background: Coronary low-attenuation plaque (LAP) burden is a strong predictor of myocardial infarction in patients with stable chest pain. We aimed to assess the relationship between LAP burden and circulating levels of high-sensitivity cardiac troponin T (hs-cTnT), and to explore the potential underlying etiology in patients undergoing clinically indicated coronary CT angiography (CCTA)., Methods: A comprehensive metabolic and lipid panel, as well as C-reactive protein (CRP) and hs-cTnT tests were obtained from consecutive patients with stable chest pain at the time of CCTA. Qualitative and quantitative coronary plaque analysis, CT-derived fractional flow reserve (FFR) calculation, and pericoronary adipose tissue (PCAT) attenuation measurement around the right coronary artery were performed on CCTA images. Linear regression analyses were performed to identify independent associations with hs-cTnT concentration and mediation analysis was used to assess whether ischemia or markers of inflammation mediate hs-cTnT elevation., Results: In total, 114 patients (56.3 ​± ​10.6 years, 44.7 ​% female) were enrolled. In multivariable analysis, age (β ​= ​0.04 [95%CI: 0.02; 0.06], p ​< ​0.001), female sex (β ​= ​-0.77 [95%CI: -1.20; 0.33], p ​< ​0.001), and LAP burden (β ​= ​0.03 [95%CI: 0.001; 0.06], p ​= ​0.04) were independently associated with hs-cTnT levels. Mediation analysis, on the other hand, did not identify a significant mediating effect of lesion-specific ischemia based on CT-FFR, circulating CRP levels, or PCAT values between LAP burden and hs-cTnT levels (all p ​> ​0.05)., Conclusion: Although ischemia and inflammation have previously been proposed to mediate the association between LAP burden and hs-cTnT levels, our results did not confirm the role of these pathophysiological pathways in patients with stable chest pain., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: The diagnosis of acute myocardial infarction is based on ECG abnormalities besides to chest pain and dyspnea. It is caused by myocardial hypoperfusion, in most patients due to severe coronary artery narrowing or occlusion, but it can also occur without visible coronary artery changes. The non-ST-elevation form (NSTEMI) is usually associated with less complaints compared to the ST-elevation form (STEMI), the ECG changes are not so typical, so its recognition is more difficult in the early stage. Possibility of myocardial cell damage reduction is the restoration of perfusion with coronary intervention., Objective: To investigate how much time elapses in acute NSTEMI from the onset of the complaint to the opening of the coronary vasodilator balloon., Method: From 3733 acute coronary interventions performed in NSTEMI between 01. 01. 2016 and 12. 31. 2020, in 1376 patients who underwent percutaneous intervention for the first time, the onset of the complaints, the date of the first medical contact and opening of the balloon, as well as the 30-day or 1-year mortality were known. The median values of the time differences and the mortality data were compared with the similar data of 1718 STEMI patients of this period. The median times were given in hours:minutes, incidence in percent, a two-sample t-test was calculated for the comparison of mortality data., Results: In NSTEMI, the median time between the first medical contact (5:35 vs. 2:05 h:min) and PTCA balloon opening (18:12 vs. 4:05 h:min) was longer compared to the onset of the complaint as in STEMI. Within 2 hours, 21.3% of NSTEMI patients reached the first medical contact and 1.2% had the PTCA balloon opened, in STEMI this ratios were 48.7% and 11.7%. Within 4 hours, these were in NSTEMI 36.3% and 6.1%, in STEMI 64.1% and 46.8%. The 30-day mortality rate in NSTEMI was lower than in STEMI (5.9% vs. 7.9%, p = 0.03), the 1-year rate was higher (16.1% vs. 12.5%, p = 0.004). In 554 primarily admitted patients who met the study criteria, the median P-B time intervals were shorter (10:55 h:min), the mortality data showed a mild but statistically insignificant difference (5.6% at 30 days, 13.9% at 1 year)., Conclusion: Based on the 1-year mortality data, NSTEMI cannot be considered less harmful compared to STEMI. After the onset of hypoperfusion, myocardium necrosis proportional to the elapsed time increases the likelihood of subsequent heart failure. For this reason, it seems advisable for patients to reach the intervention center earlier than at present due to the invasive diagnostic and therapeutic options. Orv Hetil. 2023; 164(47): 1865-1870.

Objective: To compare cardiac computed tomography (CT) with invasive coronary angiography (ICA) as the initial strategy in patients with diabetes and stable chest pain., Research Design and Methods: This prespecified analysis of the multicenter DISCHARGE trial in 16 European countries was performed in patients with stable chest pain and intermediate pretest probability of coronary artery disease. The primary end point was a major adverse cardiac event (MACE) (cardiovascular death, nonfatal myocardial infarction, or stroke), and the secondary end point was expanded MACE (including transient ischemic attacks and major procedure-related complications)., Results: Follow-up at a median of 3.5 years was available in 3,541 patients of whom 557 (CT group n = 263 vs. ICA group n = 294) had diabetes and 2,984 (CT group n = 1,536 vs. ICA group n = 1,448) did not. No statistically significant diabetes interaction was found for MACE (P = 0.45), expanded MACE (P = 0.35), or major procedure-related complications (P = 0.49). In both patients with and without diabetes, the rate of MACE did not differ between CT and ICA groups. In patients with diabetes, the expanded MACE end point occurred less frequently in the CT group than in the ICA group (3.8% [10 of 263] vs. 8.2% [24 of 294], hazard ratio [HR] 0.45 [95% CI 0.22-0.95]), as did the major procedure-related complication rate (0.4% [1 of 263] vs. 2.7% [8 of 294], HR 0.30 [95% CI 0.13 - 0.63])., Conclusions: In patients with diabetes referred for ICA for the investigation of stable chest pain, a CT-first strategy compared with an ICA-first strategy showed no difference in MACE and may potentially be associated with a lower rate of expanded MACE and major procedure-related complications., (© 2023 by the American Diabetes Association.)

Background: Limited information is available on the comparative efficacy and safety of different stent platforms in patients at high bleeding risk undergoing an abbreviated dual antiplatelet therapy duration after percutaneous coronary intervention (PCI). The aim of this study was to compare the safety and effectiveness of the biodegradable-polymer sirolimus-eluting stent with the durable-polymer zotarolimus-eluting stent in patients at high bleeding risk receiving 1 month of dual antiplatelet therapy after PCI., Methods: The Bioflow-DAPT Study is an international, randomized, open-label trial conducted at 52 interventional cardiology hospitals in 18 countries from February 24, 2020, through September 20, 2021. Patients with a clinical indication to PCI because of acute or chronic coronary syndrome who fulfilled 1 or more criteria for high bleeding risk were eligible for enrollment. Patients were randomized to receive either biodegradable-polymer sirolimus-eluting stents or durable-polymer, slow-release zotarolimus-eluting stents after successful lesion preparation, followed by 1 month of dual antiplatelet therapy and thereafter single antiplatelet therapy. The primary outcome was the composite of death from cardiac causes, myocardial infarction, or stent thrombosis at 1 year, and was powered for noninferiority, with an absolute margin of 4.1% at 1-sided 5% alpha., Results: A total of 1948 patients at high bleeding risk were randomly assigned (1:1) to receive biodegradable-polymer sirolimus-eluting stents (969 patients) or durable-polymer zotarolimus-eluting stents (979 patients). At 1 year, the primary outcome was observed in 33 of 969 patients (3.6%) in the biodegradable-polymer sirolimus-eluting stent group and in 32 of 979 patients (3.4%) in the durable-polymer zotarolimus-eluting stent group (risk difference, 0.2 percentage points; upper boundary of the 1-sided 95% CI, 1.8; upper boundary of the 1-sided 97.5% CI, 2.1; P <0.0001 for noninferiority for both tests)., Conclusions: Among patients at high risk for bleeding who received 1 month of dual antiplatelet therapy after PCI, the use of biodegradable-polymer sirolimus-eluting stents was noninferior to the use of durable-polymer zotarolimus-eluting stents with regard to the composite of death from cardiac causes, myocardial infarction, or stent thrombosis., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04137510., Competing Interests: Disclosures Dr Valgimigli reports grants and personal fees from Terumo and personal fees from AstraZeneca, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, IDORSIA Pharmaceuticals Ltd, Universität Basel, Department Klinische Forschung, Vifor, Bristol Myers Squibb SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio. Dr Wlodarczak has no conflicts of interest to report. Dr Tölg reports personal fees for lectures from Biotronik. Dr Merkely reports personal fees from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, CSL Behring, Daiichi Sankyo, Duke Clinical Research Institute, Medtronic, and Novartis, and institutional grants from Abbott, AstraZeneca, Biotronik, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, CSL Behring, Daiichi Sankyo, Duke Clinical Institute, Eli Lilly, Medtronic, Novartis, Terumo, and VIFOR Pharma. Dr Kelbæk has no conflicts of interest to report. Dr Legutko reports lecture fees from Abiomed, AstraZeneca, Berlin Chemie-Menarini, Abbott, Bayer AG, Ely Lilly, Medtronic, MSD, Philips-Volcano, Procardia, Sanofi, and Novartis; meeting or travel fees from Abbott, Boston, Medtronic, and Abiomed; and data safety monitoring board or advisory board fees from AstraZeneca, Berlin Chemie-Menarini, Abbott, Sanofi, Gedeon Richte, Hemolens Diagnostics, Novartis, and Ferrer. Dr Galli reports consulting fees from BIOACADEMY and lecture fees from PCR. Dr Godin reports lecture fees from B. Braun, Medtronic, and Edwards, and data safety monitoring board or advisory board fees from Terumo and Microport. Dr Toth reports grants and personal fees from Terumo, Abbott Vascular, Biotronik, and Medtronic. Dr Lhermusier reports consulting fees from Abbott and meeting or travel fees from Medtronic. Dr Honton reports consulting fees from Medtronic, Shockwave, Terumo, and Microport; lecture fees from Shockwave, Medtronic, and Boston; and data safety monitoring board or advisory board fees from Microport, Terumo, and Medtronic. Dr Dietrich reports educational event fees to his institution from Cordis. Drs. Stammen and Ferdinande have no conflicts of interest to report. Dr Silvain reports consulting fees from AstraZeneca, Bayer Health Care SAS, CSL Behring SA, Sanofi-Aventis France, and Zoll, and stock options without payment at 4P-Pharma. Dr Capodanno reports honoraria fees from Biotronik and honoraria fees to his institution from Medtronic. Dr Cayla reports personal consulting fees from Edwards, Medtronic, and Microport CRM, and personal honoraria fees from Amgen, AstraZeneca, Abbott, Bayer, Biotronik, Bristol-Myers Squibb, Edwards, Microport, Medtronic, Pfizer, and Sanofi-Aventis.

Introduction: Obtaining accurate coronary artery calcium (CAC) score measurements from CCTA datasets with virtual non-iodine (VNI) algorithms would reduce acquisition time and radiation dose. We aimed to assess the agreement of VNI-derived and conventional true non-contrast (TNC)-based CAC scores and to identify the predictors of accuracy., Methods: CCTA datasets were acquired with either 120 or 140 ​kVp. CAC scores and volumes were calculated from TNC and VNI images in 197 consecutive patients undergoing CCTA. CAC density score, mean volume/lesion, aortic Hounsfield units and standard deviations were then measured. Finally, percentage deviation (VNI - TNC/TNC∗100) of CTA-derived CAC scores from non-enhanced scans was calculated for each patient. Predictors (including anthropometric and acquisition parameters, as well as CAC characteristics) of the degree of discrepancy were evaluated using linear regression analysis., Results: While the agreement between TNC and VNI was substantial (mean bias, 6.6; limits of agreement, 178.5/145.3), a non-negligible proportion of patients (36/197, 18.3%) were falsely reclassified as CAC score ​= ​0 on VNI. The use of higher tube voltage significantly decreased the percentage deviation relative to TNC-based values (β ​= ​-0.21 [95%CI: 0.38 to -0.03], p ​= ​0.020) and a higher CAC density score also proved to be an independent predictor of a smaller difference (β ​= ​-0.22 [95%CI: 0.37 to -0.07], p ​= ​0.006)., Conclusion: The performance of VNI-based calcium scoring may be improved by increased tube voltage protocols, while the accuracy may be compromised for calcified lesions of lower density. The implementation of VNI in clinical routine, however, needs to be preceded by a solution for detecting smaller lesions as well., Competing Interests: Declaration of conflicting interest M. V–N.: None; A. V–S. received research grant from Siemens and consulting fees from Bayer and Elucid Bioimaging.; T. E. received travel support and speaker fee from Siemens Healthineers and institutional research support from Siemens Healthineers; E. Zs.: None; N. F.: None; B. Sch. is an employee of Siemens Healthineers, Forchheim, Germany; T. N. is an employee of Siemens Healthineers, Forchheim, Germany; M. K.: is an employee of Siemens Healthineers, Forchheim, Germany; B.V.: None; M.B.: None; M.K.: None; A.K.: None; B.M.: None; P. M-H.: None; B. Sz.: None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to evaluate whether invasive fractional flow reserve (FFRi) of non-infarction related (non-IRA) lesions changes over time in ST-elevation myocardial infarction (STEMI) patients. Moreover, we assessed the diagnostic performance of coronary CT angiography-derived FFR(FFR CT ) following the index event in predicting follow-up FFRi., Methods: We prospectively enrolled 38 STEMI patients (mean age 61.6 ​± ​9 years, 23.1% female) who underwent non-IRA baseline and follow-up FFRi measurements and a baseline FFR CT (within ≤10 days after STEMI). Follow-up FFRi was performed at 45-60 days (FFRi and FFR CT value of ≤0.8 was considered positive)., Results: FFRi values showed significant difference between baseline and follow-up (median and interquartile range (IQR) 0.85 [0.78-0.92] vs. 0.81 [0.73-0.90] p ​= ​0.04, respectively). Median FFR CT was 0.81 [0.68-0.93]. In total, 20 lesions were positive on FFR CT . A stronger correlation and smaller bias were found between FFR CT and follow-up FFRi (ρ ​= ​0.86,p ​< ​0.001,bias:0.01) as compared with baseline FFRi (ρ ​= ​0.68, p ​< ​0.001,bias:0.04). Comparing follow-up FFRi and FFR CT, no false negatives but two false positive cases were found. The overall accuracy was 94.7%, with sensitivity and specificity of 100.0% and 90.0% for identifying lesions ≤0.8 on FFRi. Accuracy, sensitivity, and specificity were 81.5%, 93.3%, and 73.9%, respectively, for identifying significant lesions on baseline FFRi using index FFR CT ., Conclusion: FFR CT in STEMI patients close to the index event could identify hemodynamically relevant non-IRA lesions with higher accuracy than FFRi measured at the index PCI, using follow-up FFRi as the reference standard. Early FFR CT in STEMI patients might represent a new application for cardiac CT to improve the identification of patients who benefit most from staged non-IRA revascularization., Competing Interests: Declaration of competing interest Campbell Rogers and Amy Collinsworth are HeartFlow employees, Dr. Leipsic serves as a consultant at HeartFlow., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Several inflammatory biomarkers were found to be associated with an increased risk of cardiovascular disease. Neutrophil-to-lymphocyte ratio (NLR) is a marker of subclinical inflammation that increases with the stress response. Visceral adiposity index (VAI) calculated as a combination of anthropometric and metabolic parameters reflects both the extent and function of visceral adipose tissue. Given the association of subclinical inflammation with both obesity and cardiovascular diseases, it is plausible that the inflammation-CVD association is modulated by the amount and function of adipose tissue. Thus, our aim was to examine the association between NLR and coronary artery calcium score (CACS), an intermediate marker of coronary artery disease in asymptomatic patients across VAI tertiles. Methods: Data from 280 asymptomatic participants of a cardiovascular screening program were analysed. In addition to the collection of lifestyle and medical history, a non-contrast cardiac CT scan and laboratory tests were performed on all participants. Multivariate logistic regression was conducted with CACS > 100 as the outcome and with conventional cardiovascular risk factors and NLR, VAI, and NLR by VAI tertile as predictors. Results: We found an interaction between VAI tertiles and NLR; NLR values were similar in the lower VAI tertiles, while they were higher in the CACS > 100 in the 3rd VAI tertile (CACS ≤ 100: 1.94 ± 0.58 vs. CACS > 100: 2.48 ± 1.1, p = 0.008). According to multivariable logistic regression, the interaction between NLR and VAI tertiles remained: NLR was associated with CACS > 100 in the 3rd VAI tertile (OR = 1.67, 95% CI 1.06-2.62, p = 0.03) but not in the lower tertiles even after adjustment for age, sex, smoking, history of hypertension, hyperlipidaemia, and diabetes mellitus, as well as high-sensitivity C-reactive protein. Our findings draw attention to the independent association between subclinical, chronic, systemic inflammation and subclinical coronary disease in obesity.

Background: Coronary CT angiography (CCTA) pericoronary adipose tissue (PCAT) markers are promising indicators of inflammation., Objective: To determine the effect of patient and imaging parameters on the associations between non-calcified plaque (NCP) and PCAT attenuation and gradient., Methods: This was a single-center, retrospective analysis of consecutive patients with stable chest pain who underwent CCTA and had zero calcium scores. CCTA images were evaluated for the presence of NCP, obstructive stenosis, segment stenosis and involvement score (SSS, SIS), and high-risk plaque (HRP). PCAT markers were assessed using semi-automated software. Uni- and multivariable regression models correcting for patient and imaging characteristics between plaque and PCAT markers were evaluated., Results: Overall, 1652 patients had zero calcium score (mean age: 51 years ​± ​11 [SD], 871 women); PCAT attenuation values ranged between -123 HU and -51 HU, and 649 patients had plaque. In univariable analysis, the presence of NCP, SSS, SIS, and HRP were associated with PCAT attenuation (2, 1, 1, 6 HU; respectively; p ​< ​.001 all); while obstructive stenosis was not (1 HU, p ​= ​.58). In multivariable analysis, none of the plaque markers were associated with PCAT attenuation (0 HU p ​= ​.93, 0 HU p ​= ​.39, 1 HU p ​= ​.18, 2 HU p ​= ​.10, 1 HU p ​= ​.71, respectively), while patient and imaging characteristics showed significant associations, such as: male sex (1 HU, p ​= ​.003), heart rate [1/min] (-0.2 HU, p ​< ​.001), 120 ​kVp (8 HU, p ​< ​.001) and pixel spacing [mm 3 ] (32 HU, p ​< ​.001). Similar results were observed for PCAT gradient., Conclusion: PCAT markers were significantly associated with NCP, however the associations did not persist following correction for patient and imaging characteristics., Competing Interests: Conflicts of interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac computed tomography (CT) is often performed before catheter ablation of atrial fibrillation to map atrial and pulmonary anatomy. Incident coronary artery disease (CAD) may also be diagnosed during cardiac CT angiography (CTA). Our aim was to assess whether coronary CTA might be able to identify a significant proportion of patients with obstructive CAD prior to their catheter ablation procedure event, even in asymptomatic patients., Methods: Consecutive patients undergoing pre-ablation coronary CTA for atrial fibrillation between 2013 and 2020 were retrospectively selected. Patients with previously diagnosed CAD were excluded. Obstructive CAD was defined as ≥50% luminal stenosis. We analyzed the relationship between obstructive CAD, any chest pain, and traditional risk factors., Results: Overall, 2321 patients [median age 63.0 (54.4-69.2), 1052/2321 (45.3%) female] underwent coronary CTA and 488/2321 (21.0%) were diagnosed with obstructive CAD. There was no difference regarding the rate of obstructive CAD in patients with any chest pain compared to patients without any chest pain [91/404 (22.5%) vs. 397/1917 (20.7%), P = 0.416, respectively). The following parameters were associated with obstructive CAD: age > 65 years [odds ratio (OR) = 2.51; 95% confidence interval (CI), 2.02-3.13; P < 0.001), male sex (OR = 1.59; 95% CI, 1.28-1.98; P < 0.001), hypertension (OR = 1.40; 95% CI, 1.08-1.81; P = 0.012), diabetes (OR = 1.50; 95% CI, 1.13-1.99; P = 0.006), dyslipidaemia (OR = 1.33; 95% CI, 1.07-1.66; P = 0.011) and history of smoking (OR = 1.34; 95% CI, 1.07-1.68; P = 0.011)., Conclusions: The high prevalence of obstructive CAD even in patients without chest pain highlights the importance of additional coronary artery diagnostics in patients undergoing left atrial CTA awaiting catheter ablation for atrial fibrillation. These patients regardless of chest pain thus may require further risk modification to decrease their potential ischemic and thromboembolic risk., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: We wished to assess whether different clinical definitions of coronary artery disease (CAD) [segment stenosis and involvement score (SSS, SIS), Coronary Artery Disease-Reporting and Data System (CAD-RADS)] affect which patients are considered to progress and which risk factors affect progression., Methods and Results: We enrolled 115 subsequent patients (60.1 ± 9.6 years, 27% female) who underwent serial coronary computed tomography angiography (CTA) imaging with &gt;1year between the two examinations. CAD was described using SSS, SIS, and CAD-RADS. Linear mixed models were used to investigate the effects of risk factors on the overall amount of CAD and the effect on annual progression rate of different definitions. Coronary plaque burdens were SSS 4.63 ± 4.06 vs. 5.67 ± 5.10, P &lt; 0.001; SIS 3.43 ± 2.53 vs. 3.89 ± 2.65, P &lt; 0.001; CAD-RADS 0:8.7% vs. 0.0% 1:44.3% vs. 40.9%, 2:34.8% vs. 40.9%, 3:7.0% vs. 9.6% 4:3.5% vs. 6.1% 5:1.7% vs. 2.6%, P &lt; 0.001, at baseline and follow-up, respectively. Overall, 53.0%, 29.6%, and 28.7% of patients progressed over time based on SSS, SIS, and CAD-RADS, respectively. Of the patients who progressed based on SSS, only 54% showed changes in CAD-RADS. Smoking and diabetes increased the annual progression rate of SSS by 0.37/year and 0.38/year, respectively (both P &lt; 0.05). Furthermore, each year increase in age raised SSS by 0.12 [confidence interval (CI) 0.05-0.20, P = 0.001] and SIS 0.10 (CI 0.06-0.15, P &lt; 0.001), while female sex was associated with 2.86 lower SSS (CI -4.52 to -1.20, P &lt; 0.001) and 1.68 SIS values (CI -2.65 to -0.77, P = 0.001)., Conclusion: CAD-RADS could not capture the progression of CAD in almost half of patients with serial CTA. Differences in CAD definitions may lead to significant differences in patients who are considered to progress, and which risk factors are considered to influence progression., Competing Interests: Conflict of interest: B.S., M.K., and P.M.-H. were supported by the KH-17 Programme of the National Research, Development and Innovation Office of the Ministry of Innovation and Technology in Hungary (NKFIH). B.S. was supported by the ÚNKP-20-4-II New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation fund. B.V. and M.B. were supported by the ‘NTP-NFTÖ’ (Nemzeti Tehetség Program, Nemzet Fiatal Tehetségeiért Ösztöndíj) program of the Ministry of Human Capacities in Hungary (EMMI)., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: In the diagnosis of obstructive coronary artery disease (CAD), computed tomography (CT) is an accurate, noninvasive alternative to invasive coronary angiography (ICA). However, the comparative effectiveness of CT and ICA in the management of CAD to reduce the frequency of major adverse cardiovascular events is uncertain., Methods: We conducted a pragmatic, randomized trial comparing CT with ICA as initial diagnostic imaging strategies for guiding the treatment of patients with stable chest pain who had an intermediate pretest probability of obstructive CAD and were referred for ICA at one of 26 European centers. The primary outcome was major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) over 3.5 years. Key secondary outcomes were procedure-related complications and angina pectoris., Results: Among 3561 patients (56.2% of whom were women), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 38 of 1808 patients (2.1%) in the CT group and in 52 of 1753 (3.0%) in the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P = 0.10). Major procedure-related complications occurred in 9 patients (0.5%) in the CT group and in 33 (1.9%) in the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final 4 weeks of follow-up was reported in 8.8% of the patients in the CT group and in 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48)., Conclusions: Among patients referred for ICA because of stable chest pain and intermediate pretest probability of CAD, the risk of major adverse cardiovascular events was similar in the CT group and the ICA group. The frequency of major procedure-related complications was lower with an initial CT strategy. (Funded by the European Union Seventh Framework Program and others; DISCHARGE ClinicalTrials.gov number, NCT02400229.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease., Methods: In the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use., Results: We included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% [95% CI, 56%-67%], unique environment, 37% [95% CI, 33%-44%]), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% [95% CI, 50%-66%]; unique environmental, 42% [95% CI, 34%-50%] and additive genetic, 78% [95% CI, 73%-80%]; unique environmental, 22% [95% CI, 20%-27%]), respectively., Conclusions: Noncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT01738828.

Background: Affective temperaments are regarded as subclinical manifestations of major mood disorders and cumulating evidence suggest their role in cardiovascular (CV) pathology. We wished to analyze associations between affective temperaments and severe coronary artery disease (CAD), as assessed by coronary computed tomography angiography (CCTA)., Methods: 225 consecutive patients referred to CCTA due to suspected CAD were included. Medical history and demographic parameters were recorded and all patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). The severity and extent of CAD was evaluated by CCTA. Logistic regression analysis was used to identify predictors of severe CAD (≥70% luminal stenosis in ≥1 major coronary artery)., Results: According to multivariate logistic regression analysis, elevated hyperthymic affective temperament scores significantly decreased the odds of severe CAD (OR=0.92 CI: 0.84-1.00, p = 0.04), while independent positive associations were observed in case of dyslipidemia (OR=4.23 CI: 1.81-9.88, p = 0.001) and cyclothymic affective temperament scores (OR=1.12 CI: 1.02-1.23, p = 0.02). Furthermore, receiver operating curve (ROC) analysis was used to define ideal cutoff values. Hyperthymic temperament scores >11 (OR=0.41 CI: 0.19-0.90, p = 0.03), cyclothymic scores >7 (OR=3.23 CI: 1.35-7.76, p = 0.01) and irritable scores >6 (OR=2.79 CI: 1.17-6.69, p = 0.02) were also independently associated with severe CAD., Limitations: Our study was limited by the cross-sectional design and the self-report nature of the questionnaires., Conclusions: Evaluation of affective temperaments might help to identify patients with elevated risk for severe CAD and subsequent need for coronary intervention., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The clinical significance of myocardial bridging (MB) on the left anterior descending artery (LAD) is debated. We aimed to assess the association between MB and LAD plaque volumes/compositions in a case-control set up., Methods: In our retrospective analysis we investigated 50 cases with incidentally recognized LAD MB and 50 matched controls without LAD MB on coronary computed tomography angiography. We quantified plaque volumes proximal to the MB and beneath it in patients with MB and in the corresponding coronary segments in patients without MB., Results: In total, we have included 100 patients (mean age 60.6 ± 10.8 years, males: 80%). Plaque volume was similar in the LAD segments proximal to the MB in cases vs. controls (150.0 mm 3 [IQR: 90.7-194.5 mm 3 ] vs. 132.8 mm 3 [IQR: 94.2-184.3 mm 3 ], respectively; p = 0.95) while the plaque volume was smaller beneath LAD MB vs. control segment (16.2 mm 3 [IQR: 12.6-25.8 mm 3 ] vs. 21.1 mm 3 [IQR: 14.0-42.4 mm 3 ], respectively; p = 0.002). No significant differences were found regarding different plaque components in segments proximal to the MB while fatty plaque and necrotic core volumes were smaller or negligible in coronary segment beneath MB than in controls (0.07 mm 3 [IQR: 0.005-0.27 mm 3 ] vs. 12.7 mm 3 [IQR: 7.4-24.4 mm 3 ] and 0.00 mm 3 [IQR: 0.00-0.04 mm 3 ] vs. 0.06 mm 3 [IQR: 0.03-2.8 mm 3 ], respectively (p < 0.001)., Conclusion: Comparing patients with MB vs. matched controls without it, MB was not associated with increased plaque volumes in LAD segment proximal to MB and plaque quantity was smaller in the MB segment. Our data are supportive of benign nature of incidentally recognized LAD MB., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries' atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet., Materials and Methods: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries., Results: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S&#95;hyper) were moderately heritable (0.67 [95% CI: 0.37-1] and 0.69 [95% CI: 0.38-1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0-0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm&#95;hyper was 0.48 [95% CI: 0.30-0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42-1]., Conclusions: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.

Background: Quantitative coronary plaque parameters are increasingly being utilized as surrogate endpoints of pharmaceutical trials. However, little is known whether differences in segmentation significantly alter parameter values., Methods: Overall, 100 coronary plaques with adverse imaging characteristics were segmented automatically, by two experts (R 1 -R 2 ) and three nonexperts (R 3 -R 5 ). Low attenuation noncalcified (LANCP), noncalcified and calcified plaque volume were calculated and 4310 radiomic features were extracted. Intraclass correlation coefficient (ICC) values were calculated between the segmentations., Results: ICC values between expert readers were 0.84 [CI: 0.77-0.89] for total; 0.83 [CI: 0.76-0.88] for noncalcified; 0.96 [CI: 0.94-0.98] for calcified and 0.65 [CI: 0.51-0.75] for LANCP volumes. Comparing nonexperts' and experts' results, ICC ranged between 0.64 and 0.90 for total; 0.63-0.91 for noncalcified; 0.86-0.96 for calcified and 0.34-0.84 for LANCP volume. All readers (R 1 -R 5 ) showed poor agreement with automatic segmentation (range: 0.00-0.27), except for calcified plaque volumes (range: 0.73-0.88). Regarding radiomic features, expert readers (R 1 -R 2 ) achieved good reproducibility (ICC>0.80) in 88.6% (39/44) of first-order, 62.0% (424/684) of gray level co-occurrence matrix (GLCM), 75.8% (50/66) of gray level run length matrix (GLRLM) and 19.8% (696/3516) of geometrical parameters. Between experts and nonexperts, ICC ranged between: 70.5%-86.4% for first-order, 31.0%-58.3% for GLCM, 24.2%-78.8% for GLRLM and 6.2%-21.1% for geometrical features, while between all readers and automatic segmentation ICC ranged between: 25.0%-38.6%; 0.0%-0.0%; 0.0%-3.0% and 1.1%-1.4%, respectively., Conclusions: Even among experts there is a considerable amount of disagreement in LANCP volumes. Nevertheless, expert readers have the best agreement which currently cannot be replaced with nonexperts' or automatic segmentation., Competing Interests: Declaration of competing interest Márton Kolossváry is the creator and developer of the Radiomics Imaging Analysis software (RIA) which was used for radiomic feature calculation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess whether anthropometrics, clinical risk factors, and coronary artery calcium score (CACS) can predict the need of further testing after coronary CT angiography (CTA) due to non-diagnostic image quality and/or the presence of significant stenosis., Methods: Consecutive patients who underwent coronary CTA due to suspected coronary artery disease (CAD) were included in our retrospective analysis. We used multivariate logistic regression and receiver operating characteristics analysis containing anthropometric factors: body mass index, heart rate, and rhythm irregularity (model 1); and parameters used for pre-test likelihood estimation: age, sex, and type of angina (model 2); and also added total calcium score (model 3) to predict downstream testing., Results: We analyzed 4120 (45.7% female, 57.9 ± 12.1 years) patients. Model 3 significantly outperformed models 1 and 2 (area under the curve, 0.84 [95% CI 0.83-0.86] vs. 0.56 [95% CI 0.54-0.58] and 0.72 [95% CI 0.70-0.74], p < 0.001). For patients with sinus rhythm of 50 bpm, in case of non-specific angina, CACS above 435, 756, and 944; in atypical angina CACS above 381, 702, and 890; and in typical angina CACS above 316, 636, and 824 correspond to 50%, 80%, and 90% probability of further testing, respectively. However, higher heart rates and arrhythmias significantly decrease these cutoffs (p < 0.001)., Conclusion: CACS significantly increases the ability to identify patients in whom deferral from coronary CTA may be advised as CTA does not lead to a final decision regarding CAD management. Our results provide individualized cutoff values for given probabilities of the need of additional testing, which may facilitate personalized decision-making to perform or defer coronary CTA., Key Points: • Anthropometric parameters on their own are insufficient predictors of downstream testing. Adding parameters of the Diamond and Forrester pre-test likelihood test significantly increases the power of prediction. • Total CACS is the most important independent predictor to identify patients in whom coronary CTA may not be recommended as CTA does not lead to a final decision regarding CAD management. • We determined specific CACS cutoff values based on the probability of downstream testing by angina-, arrhythmia-, and heart rate-based groups of patients to help individualize patient management.

Cigarette smoking is a well-known risk factor for coronary artery disease (CAD). However, the impact of smoking on outcomes after coronary revascularization, especially in patients with left main CAD (LMCAD) is less well understood. The EXCEL trial randomized 1,905 patients with LMCAD and visually assessed low or intermediate anatomical complexity (SYNTAX score ≤32) to PCI with everolimus-eluting stents or CABG. Patients were categorized according to smoking status (current, former, or never), and their outcomes at 5 years were compared by logistic regression with follow-up time included as a log-transformed offset variable. The primary endpoint was a composite of death, myocardial infarction, or stroke. Among 1893 patients with known smoking status at baseline, 416 (22%) were current smokers and 774 (41%) were former smokers. The crude rates of the primary endpoint were 19.5% for never smokers, 20.5% for former smokers (p = 0.61 vs never smokers), and 23.1% for smokers (p = 0.15 vs never smokers). Compared with never smokers, the adjusted risk of the primary endpoint was higher for current smokers (adjOR 1.82, 95% confidence interval [CI] 1.126 to 2.63; p = 0.001), but not for former smokers (adjOR 1.00, 95% CI 0.75 to 1.33, p = 0.10). The relative efficacy of PCI versus CABG for the 5-year primary endpoint was similar irrespective of smoking status (P interaction  = 0.22). In conclusion, current smokers in the EXCEL trial had a higher adjusted 5-year risk of the primary composite endpoint of death, myocardial infarction, or stroke than never smokers, whereas former smokers were not at increased risk. Active smoking was a risk factor after LMCAD revascularization irrespective of revascularization method., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We assessed the diagnostic and prognostic implications of early cardiac magnetic resonance (CMR), CMR-based deformation imaging and conventional risk factors in patients with troponin-positive acute chest pain and non-obstructed coronary arteries., Methods: In total, 255 patients presenting between 2009 and 2019 with troponin-positive acute chest pain and non-obstructed coronary arteries who underwent CMR in ≤7 days were followed for a clinical endpoint of all-cause mortality. Cine movies, T2-weighted and late gadolinium-enhanced images were evaluated to establish a diagnosis of the underlying heart disease. Further CMR analysis, including left ventricular strain, was carried out., Results: CMR (performed at a mean of 2.7 days) provided the diagnosis in 86% of patients (54% myocarditis, 22% myocardial infarction (MI) and 10% Takotsubo syndrome and myocardial contusion (n=1)). The 4-year mortality for a diagnosis of MI, myocarditis, Takotsubo and normal CMR patients was 10.2%, 1.6%, 27.3% and 0%, respectively. We found a strong association between CMR diagnosis and mortality (log-rank: 24, p<0.0001). Takotsubo and MI as the diagnosis, age, hypertension, diabetes, female sex, ejection fraction, stroke volume index and most of the investigated strain parameters were univariate predictors of mortality; however, in the multivariate analysis, only hypertension and circumferential mechanical dispersion measured by strain analysis were independent predictors of mortality., Conclusions: CMR performed in the early phase establishes the proper diagnosis in patients with troponin-positive acute chest pain and non-obstructed coronary arteries and provides additional prognostic factors. This may indicate that CMR could play an additional role in risk stratification in this patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health-related quality of life (HRQoL) is impaired in patients with stable angina but patients often present with other forms of chest pain. The aim of this study was to compare the pre-diagnostic HRQoL in patients with suspected coronary artery disease (CAD) according to angina type, gender, and presence of obstructive CAD., Methods: From the pilot study for the European DISCHARGE trial, we analysed data from 24 sites including 1263 patients (45.9% women, 61.1 ± 11.3 years) who were clinically referred for invasive coronary angiography (ICA; 617 patients) or coronary computed tomography angiography (CTA; 646 patients). Prior to the procedures, patients completed HRQoL questionnaires: the Short Form (SF)-12v2, the EuroQoL (EQ-5D-3 L) and the Hospital Anxiety and Depression Scale., Results: Fifty-five percent of ICA and 35% of CTA patients had typical angina, 23 and 33% had atypical angina, 18 and 28% had non-anginal chest discomfort and 5 and 5% had other chest discomfort, respectively. Patients with typical angina had the poorest physical functioning compared to the other angina groups (SF-12 physical component score; 41.2 ± 8.8, 43.3 ± 9.1, 46.2 ± 9.0, 46.4 ± 11.4, respectively, all age and gender-adjusted p < 0.01), and highest anxiety levels (8.3 ± 4.1, 7.5 ± 4.1, 6.5 ± 4.0, 4.7 ± 4.5, respectively, all adjusted p < 0.01). On all other measures, patients with typical or atypical angina had lower HRQoL compared to the two other groups (all adjusted p < 0.05). HRQoL did not differ between patients with and without obstructive CAD while women had worse HRQoL compared with men, irrespective of age and angina type., Conclusions: Prior to a diagnostic procedure for stable chest pain, HRQoL is associated with chest pain characteristics, but not with obstructive CAD, and is significantly lower in women., Trial Registration: Clinicaltrials.gov, NCT02400229.

Background and Aims: Visceral obesity is a marker of dysfunctional adipose tissue and ectopic fat infiltration. Many studies have shown that visceral fat dysfunction has a close relationship with cardiovascular disease. For a better identification of visceral adiposity dysfunction, the visceral adiposity index (VAI) is used. Coronary artery calcium score (CACS) is known to have a strong correlation with the total plaque burden therefore provides information about the severity of the coronary atherosclerosis. CACS is a strong predictor of cardiac events and it refines cardiovascular risk assessment beyond conventional risk factors. Our aim was to evaluate the association between VAI and CACS in an asymptomatic Caucasian population., Methods and Results: Computed tomography scans of 460 participants were analyzed in a cross-sectional, voluntary screening program. A health questionnaire, physical examination and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. Mean VAI was 1.41 ± 0.07 in men and 2.00 ± 0.15 in women. VAI showed a positive correlation with total coronary calcium score (r = 0.242) in males but not in females. VAI was stratified into tertiles by gender. In males, third VAI tertile was independently associated with CACS>100 (OR: 3.21, p = 0.02) but not with CACS>0 after the effects of conventional risk factors were eliminated., Conclusion: VAI tertiles were associated with calcium scores and the highest VAI tertile was an independent predictor for the presence of CACS>100 in males but not in females., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict interests., (Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Long-term outcomes after percutaneous coronary intervention (PCI) with contemporary drug-eluting stents, as compared with coronary-artery bypass grafting (CABG), in patients with left main coronary artery disease are not clearly established., Methods: We randomly assigned 1905 patients with left main coronary artery disease of low or intermediate anatomical complexity (according to assessment at the participating centers) to undergo either PCI with fluoropolymer-based cobalt-chromium everolimus-eluting stents (PCI group, 948 patients) or CABG (CABG group, 957 patients). The primary outcome was a composite of death, stroke, or myocardial infarction., Results: At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], -0.9 to 6.5; P = 0.13). Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1). In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, -1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, -1.3 to 4.2) were not significantly different. All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, -1.9 percentage points; 95% CI, -3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, -0.8 percentage points; 95% CI, -2.4 to 0.9). Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0)., Conclusions: In patients with left main coronary artery disease of low or intermediate anatomical complexity, there was no significant difference between PCI and CABG with respect to the rate of the composite outcome of death, stroke, or myocardial infarction at 5 years. (Funded by Abbott Vascular; EXCEL ClinicalTrials.gov number, NCT01205776.)., (Copyright © 2019 Massachusetts Medical Society.)

Aims: Identification of invasive and radionuclide imaging markers of coronary plaque vulnerability by a single, widely available non-invasive technique may provide the opportunity to identify vulnerable plaques and vulnerable patients in broad populations. Our aim was to assess whether radiomic analysis outperforms conventional assessment of coronary computed tomography angiography (CTA) images to identify invasive and radionuclide imaging markers of plaque vulnerability., Methods and Results: We prospectively included patients who underwent coronary CTA, sodium-fluoride positron emission tomography (NaF18-PET), intravascular ultrasound (IVUS), and optical coherence tomography (OCT). We assessed seven conventional plaque features and calculated 935 radiomic parameters from CTA images. In total, 44 plaques of 25 patients were analysed. The best radiomic parameters significantly outperformed the best conventional CT parameters to identify attenuated plaque by IVUS [fractal box counting dimension of high attenuation voxels vs. non-calcified plaque volume, area under the curve (AUC): 0.72, confidence interval (CI): 0.65-0.78 vs. 0.59, CI: 0.57-0.62; P < 0.001], thin-cap fibroatheroma by OCT (fractal box counting dimension of high attenuation voxels vs. presence of low attenuation voxels, AUC: 0.80, CI: 0.72-0.88 vs. 0.66, CI: 0.58-0.73; P < 0.001), and NaF18-positivity (surface of high attenuation voxels vs. presence of two high-risk features, AUC: 0.87, CI: 0.82-0.91 vs. 0.65, CI: 0.64-0.66; P < 0.001)., Conclusion: Coronary CTA radiomics identified invasive and radionuclide imaging markers of plaque vulnerability with good to excellent diagnostic accuracy, significantly outperforming conventional quantitative and qualitative high-risk plaque features. Coronary CTA radiomics may provide a more accurate tool to identify vulnerable plaques compared with conventional methods. Further larger population studies are warranted., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Volumetric and radiomic analysis of atherosclerotic plaques on coronary CT angiography have been shown to predict high-risk plaque morphology and to predict patient outcomes. However, there is limited information whether image reconstruction algorithms and preprocessing steps (type of binning, number of bins used for discretization) may influence parameter values., Methods: We retrospectively identified 60 coronary lesions on coronary CT angiography (CTA). All images were reconstructed using filtered back projection (FBP), hybrid (HIR) and model-based (MIR) iterative reconstruction. Plaques were segmented manually on HIR images and copied to FBP and MIR images to ensure identical voxels were analyzed. Overall, 4 volumetric and 169 radiomic parameters were calculated. Intra-class correlation coefficient (ICC) was used to assess reproducibility between image reconstructions, while linear regression analysis was used to assess the effect of preprocessing steps done before calculating radiomic metrics., Results: All volumetric and radiomic metrics had ICC>0.90 except for first-order statistics: mode, harmonic mean, minimum (0.45, 0.76, 0.84; respectively) and gray level co-occurrence (GLCM) parameters: inverse difference sum and sum variance (0.01, 0.04; respectively). Among GLCM parameters 90% were significantly affected by the type of binning and 100% by the number of bins. In case of gray level run length matrix parameters 100% of metrics were affected by both preprocessing steps., Conclusions: Volumetric and radiomic statistics are robust to image reconstruction algorithms. However, all radiomic variables were affected by preprocessing steps therefore, showing the need for standardization before being implemented into everyday clinical practice., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background Visual and histogram-based assessments of coronary CT angiography have limited accuracy in the identification of advanced lesions. Radiomics-based machine learning (ML) could provide a more accurate tool. Purpose To compare the diagnostic performance of radiomics-based ML with that of visual and histogram-based assessment of ex vivo coronary CT angiography cross sections to identify advanced atherosclerotic lesions defined with histologic examination. Materials and Methods In this prospective study, 21 coronary arteries from seven hearts obtained from male donors (mean age, 52.3 years ± 5.3) were imaged ex vivo with coronary CT angiography between February 23, 2009, and July 31, 2010. From 95 coronary plaques, 611 histologic cross sections were coregistered with coronary CT cross sections. Lesions were considered advanced if early fibroatheroma, late fibroatheroma, or thin-cap atheroma was present. CT cross sections were classified as showing homogeneous, heterogeneous, or napkin-ring sign plaques on the basis of visual assessment. The area of low attenuation (<30 HU) and the average Hounsfield unit were quantified. Radiomic parameters were extracted and used as inputs to ML algorithms. Eight radiomics-based ML models were trained on randomly selected cross sections (training set, 75% of the cross sections) to identify advanced lesions. Visual assessment, histogram-based assessment, and the best ML model were compared on the remaining 25% of the data (validation set) by using the area under the receiver operating characteristic curve (AUC) to identify advanced lesions. Results After excluding sections with no visible plaque ( n = 134) and with heavy calcium ( n = 32), 445 cross sections were analyzed. Of those 445 cross sections, 134 (30.1%) were advanced lesions. Visual assessment of the 445 cross sections indicated that 207 (46.5%) were homogeneous, 200 (44.9%) were heterogeneous, and 38 (8.5%) demonstrated the napkin-ring sign. A radiomics-based ML model incorporating 13 parameters outperformed visual assessment (AUC = 0.73 with 95% confidence interval [CI] of 0.63, 0.84 vs 0.65 with 95% CI of 0.56, 0.73, respectively; P = .04), area of low attenuation (AUC = 0.55 with 95% CI of 0.42, 0.68; P = .01), and average Hounsfield unit (AUC = 0.53 with 95% CI of 0.42, 0.65; P = .004) in the identification of advanced atheromatous lesions. Conclusion Radiomics-based machine learning analysis improves the discriminatory power of coronary CT angiography in the identification of advanced atherosclerotic lesions. Published under a CC BY 4.0 license.

Objectives: This meta-analysis determined the diagnostic performance of coronary computed tomography (CT) angiography (CTA), CT myocardial perfusion (CTP), fractional flow reserve CT (FFR CT ), the transluminal attenuation gradient (TAG), and their combined use with CTA versus FFR as a reference standard for detection of hemodynamically significant coronary artery disease (CAD)., Background: CTA provides excellent anatomic, albeit limited functional information for the evaluation of CAD. Recently, various functional CT techniques emerged to assess the hemodynamic consequences of CAD., Methods: This meta-analysis was performed in adherence to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. PubMed, EMBASE, and Web of Science were searched from inception until September 7, 2017. Bayesian random effects analysis was used to compute pooled sensitivity, specificity, and the summary receiver-operating characteristic curve of the index tests and compare them with the FFR as a reference standard. Analyses were performed on vessel and patient levels. Because CTA has excellent sensitivity, specificity was considered most relevant. Individual FFR CT values were collected., Results: Overall, 54 articles and 5,330 patients were included. At vessel level, pooled specificity of CTP (0.86; 95% confidence interval [CI]: 0.76 to 0.93), FFR CT (0.78; 95% CI: 0.72 to 0.83) and TAG (0.77; 95% CI: 0.61 to 0.89) were substantially higher than that of CTA (0.61; 95% CI: 0.54 to 0.68). The addition of FFR CT, CTP, and TAG to CTA resulted in high to excellent specificities (0.80 to 0.92). The summary receiver-operating characteristic curve at vessel level yielded superior diagnostic accuracy for CTP, FFR CT , and combined CTA and CTP, compared with CTA. A subanalysis of on-site versus off-site FFR CT revealed no substantial differences between the sensitivity (0.84 vs. 0.85) and specificity (0.80 vs. 0.73) of the 2 techniques. In a second subanalysis, dynamic CTP showed higher sensitivity (0.85 vs. 0.72), but had a lower specificity (0.81 vs. 0.90) than static CTP., Conclusions: CTP and FFR CT demonstrated a substantial improvement in the identification of hemodynamically significant CAD compared with CTA; therefore, their integration to clinical workflow before revascularization is recommended., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: ACEF score has been shown to have predictive ability in the patients undergoing percutaneous coronary intervention (PCI). The ACEF II score has recently been developed to predict short-term mortality after cardiac surgery. We compared the predictive ability of the ACEF and ACEF II scores to predict mortality after PCI in the all-comers population., Methods: The ACEF and ACEF II scores were calculated in 15,968 patients enrolled in the GLOBAL LEADERS study. Discrimination and calibration were assessed for outcomes after PCI. Recalibration of the regression model by updating the intercept and slope were performed to adjust the original ACEF model to the PCI setting. In a stratified approach, patients were divided into quintiles according to the score. Outcomes were compared between quintiles., Results: The ACEF and ACEF II score were available in 14,941 and 14,355 patients respectively. Discrimination for 30-day all-cause mortality was acceptable for both scores (C-statistic ACEF 0.75 and ACEF II 0.77). For 2-year all-cause mortality, the discrimination of ACEF score was acceptable (C-statistic 0.72) while the discrimination of ACEF II score was moderate (C-statistic 0.69). Both scores identified patients at high risk of mortality but overestimated all-cause mortality at 30 days in all quintiles. After recalibration, agreement between predicted and observed 30-day all-cause mortality in both scores are close to the identity line., Conclusions: The ACEF II model did not improve the predictive ability of the ACEF score. Recalibrated ACEF model can be used to estimated all-cause mortality rate at 30 days after PCI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Percutaneous coronary intervention (PCI) is often favoured over coronary artery bypass grafting (CABG) surgery for revascularization in patients with chronic obstructive pulmonary disease (COPD). We studied whether COPD affected clinical outcomes according to revascularization in the Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) trial, in which PCI with everolimus-eluting stents was non-inferior to CABG for the treatment of patients with left main coronary artery disease and low or intermediate SYNTAX scores., Methods: Patients with a history of COPD were propensity score matched to those without COPD. Outcomes at 30 days and 3 years in both groups were compared in patients randomized to PCI versus CABG., Results: COPD status was available for 1901 of 1905 randomized patients (99.8%), 148 of whom had COPD (7.8%). Propensity score matching yielded 135 patients with COPD and 675 patients without COPD. Patients with COPD had higher 3-year rates of the primary composite end point of death, myocardial infarction or stroke (31.7% vs 14.5%, P < 0.0001), death (17.1% vs 7.5%, P = 0.0005) and myocardial infarction (18.3% vs 7.3%, P < 0.0001), but not stroke (3.3% vs 2.9%, P = 0.84). There were no statistically significant interactions in the relative risks of PCI versus CABG for the primary composite end point in patients with and without COPD at 30 days [hazard ratio (HR) 0.39, 95% confidence interval (CI) 0.12-1.21 vs HR 0.55, 95% CI 0.29-1.06; Pinteraction = 0.61] or at 3 years (HR 0.85, 95% CI 0.46-1.56 vs HR 1.28, 95% CI 0.84-1.94; Pinteraction = 0.27)., Conclusions: In the EXCEL trial, COPD was independently associated with poor prognosis after left main coronary artery disease revascularization. The relative risks of PCI versus CABG at 30 days and 3 years were consistent in patients with and without COPD., Clinical Trial Registration Number: http://www.clinicaltrials.gov; NCT01205776., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Detecting early-stage atherosclerosis is an important step towards cardiovascular disease prevention. Coronary artery calcium (CAC) score is a sensitive and non-invasive tool for detecting coronary atherosclerosis. Higher serum uric acid (SUA) levels are known to be associated with cardiovascular diseases. However, there is inconsistency regarding the independence of the association. The aim of our study was to assess the association of CAC and SUA in an asymptomatic population. CAC scans of 281 participants were analyzed in a voluntary screening program. A health questionnaire, physical examination, and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. 36.3% (n = 102) of the participants had no detectable CAC and 13.9% (n = 39) had a CAC score of > 300. SUA showed positive correlation with CAC score (0.175, p < 0.01). SUA was independently associated with Ca score > 300 (OR 5.17, p = 0.01) after the effects of conventional risk factors were eliminated.

Aims: The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain., Methods and Results: We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009-2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84-1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79-1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91-1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50-0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37-0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52-0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality., Conclusion: In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We sought to compare quantitative coronary CT angiography (CTA) assessment versus standard clinical reading to identify heart transplanted (HTX) patients with progressive coronary wall thickening., Methods: 35 patients (23 males, age 58 [IQR: 50;61] years) underwent 256-slice coronary CTA at one year and two years after HTX to rule out cardiac allograft vasculopathy (CAV). In addition to the standard clinical read, we quantified total vessel wall volume in all coronaries up to 2-mm luminal diameter. Fixed threshold settings were used to assess calcified (>350 HU) and non-calcified vessel wall components with high- (131-350 HU), intermediate- (75-130 HU) and low-attenuation (<75 HU)., Results: Total lumen volume did not change between baseline and follow-up studies (p = 0.59). Total vessel wall volume showed significant increase (464 [IQR: 338; 570] vs. 563 [IQR: 345; 717] mm 3 , p < 0.001). The volume of high-, intermediate and low-attenuation non-calcified wall components showed progression (332 [IQR: 217;425] vs. 385 [IQR: 238;489], 40 [IQR: 12;48] vs. 59 [IQR: 16;83] and 18 [IQR: 4;21] vs. 46 [IQR: 6;41] mm 3 , respectively, p < 0.05 all), while calcified volume did not change between baseline and follow-up CTAs (72 [IQR: 16;127] vs. 72 [IQR: 29;102] mm 3 , p = 0.73). Quantitative analysis identified more patients with progressive coronary wall thickening (≥10% cut-off) than standard clinical read (11 vs. 22, p = 0.01)., Conclusion: Quantitative coronary wall assessment is feasible with coronary CTA in HTX patients. Coronary wall thickening within the first two years after HTX is mainly attributable to non-calcified lesion components and might be an early sign of CAV., (Copyright © 2019 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: We sought to compare clinical outcomes and procedural characteristics with transradial access (TRA) versus transfemoral access (TFA) in patients who were treated with PCI for left main (LM) coronary artery disease., Methods and Results: The EXCEL trial was a prospective, international, open-label, multicentre trial that randomised 1,905 patients with LM disease and SYNTAX scores ≤32 to PCI with everolimus-eluting stents versus coronary artery bypass grafting. The present analysis cohort consisted of 931 patients undergoing PCI with TRA or TFA, but not both. The primary endpoint was a composite of death, myocardial infarction (MI), or stroke at three years. Multivariable Cox proportional hazards regression was used to adjust for differences in baseline covariates. PCI in EXCEL was performed exclusively with TRA in 248 (26.6%) patients and with TFA in 683 (73.4%) patients. TRA patients were younger and less likely to have hypertension and chronic kidney disease. The mean number of vessels and lesions treated was higher in TFA patients, although the SYNTAX score was similar in both groups. Patients undergoing TRA and TFA had similar 30-day rates of TIMI major or minor bleeding (2.4% versus 3.8%, respectively, p=0.30). At three years, TRA and TFA patients had similar rates of the primary endpoint (15.7% versus 14.8%, adjusted HR 1.11, 95% CI: 0.73-1.69, p=0.64), as well as the individual rates of death, MI, stroke, ischaemia-driven revascularisation and stent thrombosis., Conclusions: In the EXCEL trial, PCI of LM disease with TRA was associated with comparable early and late clinical outcomes to TFA.

Background: Distal left main (LM) coronary artery bifurcation disease increases percutaneous coronary intervention (PCI) procedural complexity and is associated with worse outcomes than isolated ostial/shaft disease. The optimal treatment strategy for distal LM disease is undetermined. We sought to determine whether outcomes after PCI of LM distal bifurcation lesions are influenced by treatment with a provisional 1-stent versus planned 2-stent technique, and if so, whether such differences are conditioned by the complexity of the LM bifurcation lesion., Methods and Results: The clinical and angiographic characteristics, procedural methods and outcomes, and clinical events through 3-year follow-up were compared in patients undergoing distal LM PCI with a 1-stent provisional versus planned 2-stent technique in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). Among 529 patients undergoing planned distal LM PCI, 344 (65.0%) and 185 (35.0%) were treated with intended 1-stent provisional and planned 2-stent techniques, respectively. The primary composite end point rate of death, myocardial infarction, or stroke at 3 years was significantly lower in patients treated with the provisional 1-stent versus planned 2-stent method (14.1% versus 20.7%; adjusted hazard ratio, 0.55; 95% CI, 0.35-0.88; P=0.01), driven by differences in cardiovascular death (3.3% versus 8.3%, P=0.01) and myocardial infarction (7.7% versus 12.8%, P=0.06). The 3-year rate of ischemia-driven revascularization of the LM complex was also lower in the provisional group (7.2% versus 16.3%, P=0.001). In 342 patients with distal LM bifurcation disease that did not involve both major side branch vessels, the 3-year primary end point was lower with a provisional 1-stent versus planned 2-stent technique (13.8% versus 23.3%, P=0.04), whereas no significant difference was present in 182 patients with distal LM bifurcation disease that did involve both side branch vessels (14.3% versus 19.2%, P=0.36)., Conclusions: Among patients with distal LM bifurcation disease in the EXCEL trial randomized to PCI, 3-year adverse outcomes were worse with planned 2-stent treatment compared with a provisional 1-stent approach, a difference that was confined to patients without major involvement of both LM side branch vessels., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01205776.

Importance: CER-001 is a negatively charged, engineered pre-β high-density lipoprotein (HDL) mimetic containing apolipoprotein A-I and sphingomyelin. Preliminary studies demonstrated favorable effects of CER-001 on cholesterol efflux and vascular inflammation. A post hoc reanalysis of a previously completed study of intravenous infusion of CER-001, 3 mg/k, showed that the intravenous infusion in patients with a high coronary plaque burden promoted regression as assessed by intravascular ultrasonography., Objective: To determine the effect of infusing CER-001 on coronary atherosclerosis progression in statin-treated patients., Design, Setting, and Participants: A double-blind, randomized, multicenter trial evaluating the effect of 10 weekly intravenous infusions of CER-001, 3 mg/kg, (n = 135) or placebo (n = 137) in patients with an acute coronary syndrome (ACS) and baseline percent atheroma volume (PAV) greater than 30% in the proximal segment of an epicardial artery by intravascular ultrasonography. The study included 34 academic and community hospitals in Australia, Hungary, the Netherlands, and the United States in patients with ACS presenting for coronary angiography. Patients were enrolled from August 15, 2015, to November 19, 2016., Interventions: Participants were randomized to receive weekly CER-001, 3 mg/kg, or placebo for 10 weeks in addition to statins., Main Outcomes and Measures: The primary efficacy measure was the nominal change in PAV from baseline to day 78 measured by serial intravascular ultrasonography imaging. The secondary efficacy measures were nominal change in normalized total atheroma volume and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated., Results: Among 293 patients (mean [SD] age, 59.8 [9.4] years; 217 men [79.8%] and 261 white race/ethnicity [96.0%]), 86 (29%) had statin prior use prior to the index ACS and 272 (92.8%) had evaluable imaging at follow-up. The placebo and CER-001 groups had similar posttreatment median levels of low-density lipoprotein cholesterol (74 mg/dL vs 79 mg/dL; P = .15) and high-density lipoprotein cholesterol (43 mg/dL vs 44 mg/dL; P = .66). The primary efficacy measure, PAV, decreased 0.41% with placebo (P = .005 compared with baseline), but not with CER-001 (-0.09%; P = .67 compared with baseline; between group differences, 0.32%; P = .15). Similar percentages of patients in the placebo and CER-001 groups demonstrated regression of PAV (57.7% vs 53.3%; P = .49). Infusions were well tolerated, with no differences in clinical and laboratory adverse events observed between treatment groups., Conclusions and Relevance: Infusion of CER-001 did not promote regression of coronary atherosclerosis in statin-treated patients with ACS and high plaque burden., Trial Registration: ClinicalTrials.gov Identifier: NCT2484378.

Objectives: The authors sought to determine the extent to which the site of the left main coronary artery (LM) lesion (distal bifurcation versus ostial/shaft) influences the outcomes of revascularization with percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG)., Background: Among 1,905 patients with LM disease and site-assessed SYNTAX scores of <32 randomized in the EXCEL (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, revascularization with PCI and CABG resulted in similar rates of the composite primary endpoint of death, myocardial infarction (MI), or stroke at 3 years., Methods: Outcomes from the randomized EXCEL trial were analyzed according to the presence of angiographic core laboratory-determined diameter stenosis ≥50% involving the distal LM bifurcation (n = 1,559; 84.2%) versus disease isolated to the LM ostium or shaft (n = 293; 15.8%)., Results: At 3 years, there were no significant differences between PCI and CABG for the primary composite endpoint of death, MI, or stroke for treatment of both distal LM bifurcation disease (15.6% vs. 14.9%, odds ratio [OR]: 1.08, 95% confidence interval [CI]: 0.81 to 1.42; p = 0.61) and isolated LM ostial/shaft disease (12.4% vs. 13.5%, OR: 0.90, 95% CI: 0.45 to 1.81; p = 0.77) (p interaction  = 0.65). However, at 3 years, ischemia-driven revascularization occurred more frequently after PCI than CABG in patients with LM distal bifurcation disease (13.0% vs. 7.2%, OR: 2.00, 95% CI: 1.41 to 2.85; p = 0.0001), but were not significantly different in patients with disease only at the LM ostium or shaft (9.7% vs. 8.4%, OR: 1.18, 95% CI: 0.52 to 2.69; p = 0.68) (p interaction  = 0.25)., Conclusions: In the EXCEL trial, PCI and CABG resulted in comparable rates of death, MI, or stroke at 3 years for treatment of LM disease, including those with distal LM bifurcation disease. Repeat revascularization rates during follow-up after PCI compared with CABG were greater for lesions in the distal LM bifurcation but were similar for disease isolated to the LM ostium or shaft., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Cardiac allograft vasculopathy (CAV) is among the top causes of death 1 year after heart transplantation (HTx). Coronary CT angiography (CTA) is a potential alternative to invasive imaging in the diagnosis of CAV. However, the higher heart rate (HR) of HTx recipients prompts the use of retrospective ECG-gating, which is associated with higher radiation dose, a major concern in this patient population. Therefore, we sought to evaluate the feasibility and image quality of low-radiation-dose prospectively ECG-triggered coronary CTA in HTx recipients., Materials and Methods: In total, 1270 coronary segments were evaluated in 50 HTx recipients and 50 matched control subjects who did not undergo HTx. The control subjects were selected from our clinical database and were matched for age, sex, body mass index, HR, and coronary dominance. Scans were performed using 256-MDCT with prospective ECG-triggering. The degree of motion artifacts was evaluated on a per-segment basis on a 4-point Likert-type scale., Results: The median HR was 74.0 beats/min (interquartile range [IQR], 67.8-79.3 beats/min) in the HTx group and 73.0 beats/min (IQR, 68.5-80.0 beats/min) in the matched control group (p = 0.58). In the HTx group, more segments had diagnostic image quality compared with the control group (624/662 [94.3%] vs 504/608 [82.9%]; p < 0.001). The mean effective radiation dose was low in both groups (3.7 mSv [IQR, 2.4-4.3 mSv] in the HTx group vs 4.3 mSv [IQR, 2.6-4.3 mSv] in the control group; p = 0.24)., Conclusion: Prospectively ECG-triggered coronary CTA examinations of HTx recipients yielded diagnostic image quality with low radiation dose. Coronary CTA is a promising noninvasive alternative to routine catheterization during follow-up of HTx recipients to diagnose CAV.

Objective: A bidirectional relationship exists between psychiatric disorders and cardiovascular diseases, however less is known with regards to personality traits. Accumulating data suggest that affective temperaments are both associated with psychiatric and somatic diseases. The aim of our study was to evaluate the associations between different affective temperaments and the presence of coronary atherosclerosis., Methods: 200 consecutive patients referred to coronary computed tomography angiography (CCTA) due to suspected coronary artery disease (CAD) were included in our study. Medical history and demographic parameters were recorded and all patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) and the Beck Depression Inventory (BDI). The presence of coronary artery disease was evaluated based on the CCTA images., Results: 39 patients were free of any coronary atherosclerosis (CCTA-) and 161 had coronary atherosclerosis (CCTA+). Hyperthymic affective temperament score was higher in CCTA- subjects as compared to CCTA+ (13.1±3.0 vs 11.5±4.6, p=0.010, respectively). Hyperthymic affective temperament score showed a significant independent, inverse relationship with coronary atherosclerosis (OR: 0.91 CI: 0.82-0.99, p=0.04)., Conclusion: Our results suggest that hyperthymic affective temperament is independently associated with the absence of CAD. It requires further research to delineate the mechanism mediating the effect of hyperthymia on better coronary artery health and establishing potential biochemical or behavioral factors, both of which could be exploited for prevention and treatment purposes. But it is plausible, that the evaluation of affective temperaments have importance both in relation with psychiatric and cardiovascular disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Napkin-ring sign (NRS) is an independent prognostic imaging marker of major adverse cardiac events. However, identification of NRS is challenging because of its qualitative nature. Radiomics is the process of extracting thousands of quantitative parameters from medical images to create big-data data sets that can identify distinct patterns in radiological images. Therefore, we sought to determine whether radiomic analysis improves the identification of NRS plaques., Methods and Results: From 2674 patients referred to coronary computed tomographic angiography caused by stable chest pain, expert readers identified 30 patients with NRS plaques and matched these with 30 non-NRS plaques with similar degree of calcification, luminal obstruction, localization, and imaging parameters. All plaques were segmented manually, and image data information was analyzed using Radiomics Image Analysis package for the presence of 8 conventional and 4440 radiomic parameters. We used the permutation test of symmetry to assess differences between NRS and non-NRS plaques, whereas we calculated receiver-operating characteristics' area under the curve values to evaluate diagnostic accuracy. Bonferroni-corrected P <0.0012 was considered significant. None of the conventional quantitative parameters but 20.6% (916/4440) of radiomic features were significantly different between NRS and non-NRS plaques. Almost half of these (418/916) reached an area under the curve value >0.80. Short- and long-run low gray-level emphasis and surface ratio of high attenuation voxels to total surface had the highest area under the curve values (0.918; 0.894 and 0.890, respectively)., Conclusions: A large number of radiomic features are different between NRS and non-NRS plaques and exhibit excellent discriminatory value., (© 2017 The Authors.)

Objectives: Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA., Methods: Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol., Results: 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034)., Conclusions: Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA., Key Points: • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

Background: Structured reporting in cardiac imaging is strongly encouraged to improve quality through consistency. The Coronary Artery Disease - Reporting and Data System (CAD-RADS) was recently introduced to facilitate interdisciplinary communication of coronary CT angiography (CTA) results. We aimed to assess the agreement between manual and automated CAD-RADS classification using a structured reporting platform., Methods: Five readers prospectively interpreted 500 coronary CT angiographies using a structured reporting platform that automatically calculates the CAD-RADS score based on stenosis and plaque parameters manually entered by the reader. In addition, all readers manually assessed CAD-RADS blinded to the automatically derived results, which was used as the reference standard. We evaluated factors influencing reader performance including CAD-RADS training, clinical load, time of the day and level of expertise., Results: Total agreement between manual and automated classification was 80.2%. Agreement in stenosis categories was 86.7%, whereas the agreement in modifiers was 95.8% for "N", 96.8% for "S", 95.6% for "V" and 99.4% for "G". Agreement for V improved after CAD-RADS training (p = 0.047). Time of the day and clinical load did not influence reader performance (p > 0.05 both). Less experienced readers had a higher total agreement as compared to more experienced readers (87.0% vs 78.0%, respectively; p = 0.011)., Conclusions: Even though automated CAD-RADS classification uses data filled in by the readers, it outperforms manual classification by preventing human errors. Structured reporting platforms with automated calculation of the CAD-RADS score might improve data quality and support standardization of clinical decision making., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: More than 3.5 million invasive coronary angiographies (ICA) are performed in Europe annually. Approximately 2 million of these invasive procedures might be reduced by noninvasive tests because no coronary intervention is performed. Computed tomography (CT) is the most accurate noninvasive test for detection and exclusion of coronary artery disease (CAD). To investigate the comparative effectiveness of CT and ICA, we designed the European pragmatic multicentre DISCHARGE trial funded by the 7th Framework Programme of the European Union (EC-GA 603266)., Methods: In this trial, patients with a low-to-intermediate pretest probability (10-60 %) of suspected CAD and a clinical indication for ICA because of stable chest pain will be randomised in a 1-to-1 ratio to CT or ICA. CT and ICA findings guide subsequent management decisions by the local heart teams according to current evidence and European guidelines., Results: Major adverse cardiovascular events (MACE) defined as cardiovascular death, myocardial infarction and stroke as a composite endpoint will be the primary outcome measure. Secondary and other outcomes include cost-effectiveness, radiation exposure, health-related quality of life (HRQoL), socioeconomic status, lifestyle, adverse events related to CT/ICA, and gender differences., Conclusions: The DISCHARGE trial will assess the comparative effectiveness of CT and ICA., Key Points: • Coronary artery disease (CAD) is a major cause of morbidity and mortality. • Invasive coronary angiography (ICA) is the reference standard for detection of CAD. • Noninvasive computed tomography angiography excludes CAD with high sensitivity. • CT may effectively reduce the approximately 2 million negative ICAs in Europe. • DISCHARGE addresses this hypothesis in patients with low-to-intermediate pretest probability for CAD.

A 69-year-old woman presented with symptoms of presumed cardiac involvement of idiopathic retroperitoneal fibrosis, otherwise known as Ormond disease. Distinct pericoronary tissue proliferations were depicted at cardiac magnetic resonance (MR) imaging and coronary computed tomographic (CT) angiography. On images, the coronary manifestation was termed the "mistletoe sign." The presence of the mistletoe sign on cardiac MR and coronary CT angiographic images is probably rare, but it might be a characteristic manifestation of retroperitoneal fibrosis. With the increasing number of noninvasive cardiac imaging tests performed worldwide, the recognition of the mistletoe sign could be helpful in diagnosing retroperitoneal fibrosis. © RSNA, 2016 Online supplemental material is available for this article.