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Background: Coronary CT angiography (CCTA) is well-established for diagnosis and stratification of coronary artery disease (CAD). Its usefulness in guiding percutaneous coronary interventions (PCI) and stent sizing is unknown., Methods: This is a sub-analysis of the Precise Percutaneous Coronary Intervention Plan (P3) study (NCT03782688). We analyzed 65 vessels with matched CCTA and pre-PCI optical coherence tomography (OCT) assessment. The CCTA-guided stent size was defined by the mean distal reference lumen diameter rounded up to the nearest stent diameter. The OCT lumen-guided stent size was the mean distal reference lumen diameter rounded to the closest stent diameter. The agreement on stent diameters was determined with Kappa statistics, Passing-Bablok regression analysis, and the Bland-Altman method., Results: The distal reference lumen diameter by CCTA and OCT were 2.75 ​± ​0.53 ​mm and 2.72 ​± ​0.55 ​mm (mean difference 0.06, limits of agreement -0.7 to 0.82). There were no proportional or systematic differences (coefficient A 1.06, 95% CI 0.84 to 1.3 and coefficient B -0.22, 95% CI -0.83 to 0.36) between methods. The agreement between the CCTA and OCT stent size was substantial (Cohen's weighted Kappa 0.74, 95% CI 0.64 to 0.85). Compared to OCT stent diameter, CCTA stent size was concordant in 52.3% of the cases; CCTA overestimated stent size in 20.0% and underestimated in 27.7%., Conclusion: CCTA accurately assessed the reference vessel diameter used for stent sizing. CCTA-based stent sizing showed a substantial agreement with OCT. CCTA allows for PCI planning and may aid in selecting stent diameter., Competing Interests: Declaration of competing interest TM reports receiving consulting fees from Zeon Medical and HeartFlow Inc, and speaker fees from Abbott Vascular. BLN has received an unrestricted institutional research grant from HeartFlow Inc. MM is supported by a grant from the Novo Nordisk Foundation (grant NNF22OC0074083). BKK received an Institutional Research Grant from Abbott Vascular, Boston Scientific Corporation, and Philips. BDB reports receiving consultancy fees from Boston Scientific and Abbott Vascular, research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular, and owning equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, Celyad. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, Abbott Vascular, and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. The other authors have no further disclosures., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The association between coronary computed tomography angiography (CTA) derived fractional flow reserve (FFR CT ) and risk of recurrent angina in patients with new onset stable angina pectoris (SAP) and stenosis by CTA is uncertain., Methods: Multicenter 3-year follow-up study of patients presenting with symptoms suggestive of new onset SAP who underwent first-line CTA evaluation and subsequent standard-of-care treatment. All patients had at least one ≥30 ​% coronary stenosis. A per-patient lowest FFR CT -value ≤0.80 represented an abnormal test result. Patients with FFR CT ≤0.80 who underwent revascularization were categorized according to completeness of revascularization: 1) Completely revascularized (CR-FFR CT ), all vessels with FFR CT ≤0.80 revascularized; or 2) incompletely revascularized (IR-FFR CT ) ≥1 vessels with FFR CT ≤0.80 non-revascularized. Recurrent angina was evaluated using the Seattle Angina Questionnaire., Results: Amongst 769 patients (619 [80 ​%] stenosis ≥50 ​%, 510 [66 ​%] FFR CT ≤0.80), 174 (23 ​%) reported recurrent angina at follow-up. An FFR CT ≤0.80 vs ​> ​0.80 associated to increased risk of recurrent angina, relative risk (RR): 1.82; 95 ​% CI: 1.31-2.52, p ​< ​0.001. Risk of recurrent angina in CR-FFR CT (n ​= ​135) was similar to patients with FFR CT >0.80, 13 ​% vs 15 ​%, RR: 0.93; 95 ​% CI: 0.62-1.40, p ​= ​0.72, while IR-FFR CT (n ​= ​90) and non-revascularized patients with FFR CT ≤0.80 (n ​= ​285) had increased risk, 37 ​% vs 15 ​% RR: 2.50; 95 ​% CI: 1.68-3.73, p ​< ​0.001 and 30 ​% vs 15 ​%, RR: 2.03; 95 ​% CI: 1.44-2.87, p ​< ​0.001, respectively. Use of antianginal medication was similar across study groups., Conclusion: In patients with SAP and coronary stenosis by CTA undergoing standard-of-care guided treatment, FFR CT provides information regarding risk of recurrent angina., Competing Interests: Declaration of competing interest CR is a full-time employee of HeartFlow, and receives salary and stock options from HeartFlow. ELG has no conflicts related to this manuscript but has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, MSD, Lundbeck Pharma and Organon. He is investigator in clinical studies sponsored by AstraZeneca or Bayer and has received unrestricted research grants from Boehringer Ingelheim. JL is a consultant and holds stock options in Circle CVI and HeartFlow. KN acknowledges support from the NIH and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc and Novartis. MP has received research grants from Janssen, Bayer, Heartflow and NIH and is part of the following advisory boards: Janssen, Bayer, Heartflow, Phillips. SM is a full-time employee of HeartFlow, and shareholder of HeartFlow. TF is associated with the HeartFlow speakers bureau. All other authors had no disclosures to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: The diagnostic value is unclear of a 0 coronary artery calcium (CAC) score to rule out obstructive coronary artery disease (CAD) and near-term clinical events across different age groups., Objective: To assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD and to assess the implications of such a CAC score and obstructive CAD across different age groups., Design, Setting, and Participants: This cohort study obtained data from the Western Denmark Heart Registry and had a median follow-up time of 4.3 years. Included patients were aged 18 years or older who underwent computed tomography angiography (CTA) between January 1, 2008, and December 31, 2017, because of symptoms that were suggestive of CAD. Data analysis was performed from April 5 to July 7, 2021., Exposures: Obstructive CAD, which was defined as 50% or more luminal stenosis., Main Outcomes and Measures: Proportion of individuals with obstructive CAD who had a CAC score of 0. Risk-adjusted diagnostic likelihood ratios were used to assess the diagnostic value of a CAC score of 0 for reducing the likelihood of obstructive CAD beyond clinical variables. Risk factors associated with myocardial infarction and death were estimated., Results: A total of 23 759 symptomatic patients, of whom 12 771 (54%) had a CAC score of 0, were included. This cohort had a median (IQR) age of 58 (49-65) years and was primarily composed of women (13 160 [55%]). Overall, the prevalence of obstructive CAD was relatively low across all age groups, ranging from 3% (39 of 1278 patients) in those who were younger than 40 years to 8% (52 of 619) among those who were 70 years or older. In patients with obstructive CAD, 14% (725 of 5043) had a CAC score of 0, and the prevalence varied across age groups from 58% (39 of 68) among those who were younger than 40 years, 34% (192 of 562) among those aged 40 to 49 years, 18% (268 of 1486) among those aged 50 to 59 years, 9% (174 of 1963) among those aged 60 to 69 years, to 5% (52 of 964) among those who were 70 years or older. The added diagnostic value of a CAC score of 0 decreased at a younger age, with a risk factor-adjusted diagnostic likelihood ratio of a CAC score of 0 ranging from 0.68 (approximately 32% lower likelihood of obstructive CAD than expected) in those who were younger than 40 years to 0.18 (approximately 82% lower likelihood than expected) in those who were 70 years or older. The presence of obstructive vs nonobstructive CAD among those with a CAC score of 0 was associated with a multivariable adjusted hazard ratio of 1.51 (95% CI, 0.98-2.33) for myocardial infarction and all-cause death; however, this hazard ratio varied from 1.80 (95% CI, 1.02-3.19) in those who were younger than 60 years to 1.24 (95% CI, 0.64-2.39) in those who were 60 years or older., Conclusions and Relevance: This cohort study found that the diagnostic value of a CAC score of 0 to rule out obstructive CAD beyond clinical variables was dependent on age, with the added diagnostic value being smaller for younger patients. In symptomatic patients who were younger than 60 years, a sizable proportion of obstructive CAD occurred among those without CAC and was associated with an increased risk of myocardial infarction and all-cause death.

Objective: This study aimed to investigate the outcome of computed tomography (CT) angiography with optional CT-derived fractional flow reserve (FFRCT) of intermediate-range coronary artery disease in non-emergent patients referred on a suspicion of chronic coronary syndrome., Methods: Patients were classified as high risk and low-intermediate risk according to the presence of typical angina or either atypical or nonangina chest pain. Outcome was assessed as the cumulative incidence proportion of a composite end point of unstable angina pectoris, unplanned revascularization, nonfatal myocardial infarction, and all-cause mortality., Results: The study included 743 patients. Mean follow-up was 2.2 (range, 0.1-2.5) years. Low-intermediate-risk and high-risk patients who had invasive coronary angiography deferred had comparable proportions of adverse events (1.4% vs 2.6% [P = 0.27]). Adverse events in high-risk patients with FFRCT >0.80 was 3.3% versus 1.4% in patients where no additional testing was performed (P = 0.79)., Conclusions: Computed tomography-derived fractional flow reserve >0.8 conveys an excellent prognosis. Computed tomography angiography with optional FFRCT allows for the safe cancellation of invasive coronary angiography in high-risk patients., Competing Interests: The authors have no conflicts of interest related to the present article but report the following general conflicts. T.V.K., O.N.M., E.P., and J.M.J. have no conflicts of interest to declare. B.L.N. has received unrestricted institutional research grants from Siemens and Hearthflow. H.E.B. has received an unrestricted institutional research grant from Hearthflow. E.L.G. has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, MSD, MundiPharma, Portola Pharmaceuticals, and Roche. He is an investigator in the SATELLITE and FLAVOUR studies (AstraZeneca) and has received unrestricted research grants from Boehringer Ingelheim., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFR CT ) is a safe alternative to invasive coronary angiography. A negative FFR CT has been shown to have low cardiac event rates compared to those with a positive FFR CT . However, the clinical utility of FFR CT according to age is not known., Methods: Patients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or <65 years of age. The impact of FFR CT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFR CT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFR CT was deemed to be ​≤ ​0.8., Results: FFR CT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) ​≥ ​65 years of age. Subjects ≥65 years were more likely to have anatomic obstructive disease on CTA (≥50% stenosis), compared to those aged <65 (69.7% and 73.2% respectively, p ​= ​0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFR CT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those ​≥ ​or <65, regardless of FFR CT positivity or stenosis severity <50% or ≥50%. With a negative FFR CT result, and anatomical stenosis ≥50%, those ​≥ ​and <65 years of age, had similar rates of MACE (0.2% for both, p ​= ​0.1) and revascularisation (8.7% and 10.4% respectively p ​= ​0.4). Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFR CT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006-1.08, p ​= ​0.02). Amongst patients with a FFR CT > 0.80, there was no effect of age on the odds of revascularisation., Conclusion: The findings of this study point to a low risk of MACE events or need for revascularisation in those aged ​≥ ​or <65 with a FFR CT >0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFR CT are largely constant regardless of age., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: The ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFR CT ). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFR CT within the ADVANCE registry., Methods: 5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFR CT findings, and clinical outcomes through 1-year follow-up, were recorded and compared between tertiles., Results: The number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1-3). The rate of positive FFR CT ≤0.80 was higher for cohorts 2 (67.3%) and 3 (74.6%) than for cohort 1 (57.1%, p < 0.001). Invasive FFR rates decreased from 25.8% to 22.4% between cohort 1 and 3 (p = 0.023). Moreover, patients with a FFR CT ≤0.80 were less frequently referred for invasive coronary angiography (ICA) (from 62.9% to 52.9%, p < 0.001), and underwent fewer revascularizations between cohort 1 and 3 (from 41.9% to 32.0%, p < 0.001). The prevalence of major events was low (1.2%) and similar between cohorts., Conclusions: Growing experience with FFR CT improved the likelihood of identifying hemodynamically significant CAD and safely reduced the need for ICA and revascularization in patients with anatomically significant disease even in the instance of an abnormal FFR CT., Competing Interests: Declaration of competing interest Dr. Nous has received travel sponsorship from HeartFlow. Dr. Fairbairn has served on the Speakers Bureau for HeartFlow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Hurwitz-Koweek has received research support and fee as speaker from HeartFlow and Siemens. Dr. Pontone has received research grant and/or fee as speaker from GE Healthcare, Bracco, and HeartFlow. Dr. Budde has institutional research support from HeartFlow and Siemens Healthineers. Dr. Sonck has received research grant support from the Cardiopath PhD program. Dr. Rabbat has served as a consultant for HeartFlow. Dr. Mullen is an employee of and owns equity in HeartFlow. Dr. De Bruyne has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE Healthcare, Bayer, Philips, HeartFlow, Edwards Lifesciences, and Sanofi. Dr. Rogers is employee of and owns equity in HeartFlow. Dr. Leipsic has served as a consultant for and owns stock options in Circle CVI and HeartFlow. Dr. Patel has received research grants from HeartFlow, Bayer, Janssen, and the National Heart, Lung, and Blood Institute; and has served on the advisory board for HeartFlow, Bayer, and Janssen. Dr. Nieman has received institutional research support from Siemens Healthineers, HeartFlow, GE Healthcare, and Bayer Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Turner syndrome (TS) is associated with coronary artery disease (CAD), an important cause of premature death in TS. However, the determinants of CAD in women with TS remain unknown. In a cross-sectional study design, 168 women without clinical evidence of CAD (115 with TS and 53 without TS) were assessed for the presence and volume of subclinical CAD using coronary CT angiography. Karyotype, the presence of congenital heart defects and conventional cardiovascular risk factors were also registered. Comparative analyses were performed (1) between women with and without TS and (2) in the TS group, between women with and without subclinical CAD. The prevalence of CAD, in crude and adjusted analyses, was not increased for women with TS (crude prevalence: 40 [35%] in TS vs. 25 [47%] in controls, p = 0.12). The volume of atherosclerosis was not higher in women with TS compared with controls (median and interquartile range 0 [0-92] in TS vs. 0 [0-81]mm 3 in controls, p = 0.29). Among women with TS, women with subclinical CAD were older (46 ± 13 vs. 37 ± 11 years, p < 0.001), had higher blood pressure (systolic blood pressure 129 ± 16 vs. 121 ± 16 mmHg, p < 0.05) and were more frequently diagnosed with type 2 diabetes (5 [13%] vs. 2 [3%], p < 0.05). Karyotype or congenital heart defects were not associated with subclinical CAD. Some women with TS show early signs of CAD, however overall, not more than women without TS. Conventional cardiovascular risk factors were the principal determinants of CAD also in TS, and CAD prevention strategies should be observed.ClinicalTrial.gov Identifier: NCT01678261 ( https://clinicaltrials.gov/ct2/show/NCT01678261 ).

Objectives: The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFR CT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFR CT ) with downstream care and clinical outcomes., Background: Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes., Methods: Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFR CT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured., Results: At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFR CT  ≤0.80 and in 89 (5.60%) with an FFR CT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFR CT  ≤0.80 and 12 occurred in those with an FFR CT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFR CT  ≤0.80 compared with 10 (0.60%) patients with an FFR CT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFR CT  ≤0.80 compared with patients with an FFR CT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01)., Conclusions: The 1-year outcomes from the ADVANCE FFR CT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFR CT compared with patients with abnormal FFR CT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679)., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: We examined whether severity of coronary artery disease (CAD) measured by coronary computed tomography angiography can be used to predict rates of myocardial infarction (MI) and death in patients with and without diabetes., Methods and Results: A cohort study of consecutive patients (n = 48 731) registered in the Western Denmark Cardiac Computed Tomography Registry from 2008 to 2016. Patients were stratified by diabetes status and CAD severity (no, non-obstructive, or obstructive). Endpoints were MI and death. Event rates per 1000 person-years, unadjusted and adjusted incidence rate ratios were computed. Median follow-up was 3.6 years. Among non-diabetes patients, MI event rates per 1000 person-years were 1.4 for no CAD, 4.1 for non-obstructive CAD, and 9.1 for obstructive CAD. Among diabetes patients, the corresponding rates were 2.1 for no CAD, 4.8 for non-obstructive CAD, and 12.6 for obstructive CAD. Non-diabetes and diabetes patients without CAD had similar low rates of MI [adjusted incidence rate ratio 1.40, 95% confidence interval (CI): 0.71-2.78]. Among diabetes patients, the adjusted risk of MI increased with severity of CAD (no CAD: reference; non-obstructive CAD: adjusted incidence rate ratio 1.71, 95% CI: 0.79-3.68; obstructive CAD: adjusted incidence rate ratio 4.42, 95% CI: 2.14-9.17). Diabetes patients had higher death rates than non-diabetes patients, irrespective of CAD severity., Conclusion: In patients without CAD, diabetes patients have a low risk of MI similar to non-diabetes patients. Further, MI rates increase with CAD severity in both diabetes and non-diabetes patients; with diabetes patients with obstructive CAD having the highest risk of MI., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background Coronary CT angiography with noninvasive fractional flow reserve (FFR) predicts lesion-specific ischemia when compared with invasive FFR. The longer term prognostic value of CT-derived FFR (FFR CT ) is unknown. Purpose To determine the prognostic value of FFR CT when compared with coronary CT angiography and describe the relationship of the numeric value of FFR CT with outcomes. Materials and Methods This prospective subanalysis of the NXT study (Clinicaltrials.gov: NCT01757678) evaluated participants suspected of having stable coronary artery disease who were referred for invasive angiography and who underwent FFR, coronary CT angiography, and FFR CT . The incidence of the composite primary end point of death, myocardial infarction, and any revascularization and the composite secondary end point of major adverse cardiac events (MACE: cardiac death, myocardial infarction, unplanned revascularization) were compared for an FFR CT of 0.8 or less versus stenosis of 50% or greater on coronary CT angiograms, with treating physicians blinded to the FFR CT result. Results Long-term outcomes were obtained in 206 individuals (age, 64 years ± 9.5), including 64% men. At median follow-up of 4.7 years, there were no cardiac deaths or myocardial infarctions in participants with normal FFR CT . The incidence of the primary end point was more frequent in participants with positive FFR CT compared with clinically significant stenosis at coronary CT angiography (73.4% [80 of 109] vs 48.7% [91 of 187], respectively; P < .001), with the majority of outcomes being planned revascularization. Corresponding hazard ratios (HRs) were 9.2 (95% confidence interval [CI]: 5.1, 17; P < .001) for FFR CT and 5.9 (95% CI: 1.5, 24; P = .01) for coronary CT angiography. FFR CT was a superior predictor compared with coronary CT angiography for primary end point (C-index FFR CT , 0.76 vs coronary CT angiography, 0.54; P < .001) and MACE (FFR CT , 0.71 vs coronary CT angiography, 0.52; P = .001). Frequency of MACE was higher in participants with positive FFR CT compared with coronary CT angiography (15.6% [17 of 109] vs 10.2% [19 of 187], respectively; P = .02), driven by unplanned revascularization. MACE HR was 5.5 (95% CI: 1.6, 19; P = .006) for FFR CT and 2.0 ( 95% CI: 0.3, 14; P = .46) for coronary CT angiography. Each 0.05-unit FFR CT reduction was independently associated with greater incidence of primary end point (HR, 1.7; 95% CI: 1.4, 1.9; P < .001) and MACE (HR, 1.4; 95% CI: 1.1, 1.8; P < .001). Conclusion In stable patients referred for invasive angiography, a CT-derived fractional flow reserve (FFR CT ) value of 0.8 or less was a predictor of long-term outcomes driven by planned and unplanned revascularization and was superior to clinically significant stenosis on coronary CT angiograms. Additionally, the numeric value of FFR CT was an independent predictor of outcomes. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Dennie and Rubens in this issue.

Background: The aim of this study was to compare changes in health service utilization, preventive medical management, and cholesterol levels in patients without coronary artery disease (CAD) or with non-obstructive CAD as determined by coronary computed tomography angiography (CTA)., Methods: Single-center five-year observational registry-based cohort study of consecutive patients with chest pain undergoing coronary CTA with subsequent 12 months follow-up in general practice., Results: We included 3032 patients with a normal test result (n = 2179) or a diagnosis of non-obstructive CAD (n = 853) by coronary CTA. Median age was 55 (interquartile range: 47-63) years and 44% were males. After coronary CTA, the probability of a decrease in consultations with general practitioner was higher in patients with no CAD compared to patients with non-obstructive CAD (adjusted OR = 0.81 [95% CI: 0.68-0.96], P = 0.016). Accordingly, patients with non-obstructive CAD more frequently received prescriptions on lipid-lowering medical therapy (adjusted OR = 4.50 [95% CI: 3.31-6.12], P < 0.001) than patients with no CAD after coronary CTA. In patients with non-obstructive CAD, mean total-cholesterol reduction was 0.51 (P < 0.001) compared to 0.13 mmol/L (P < 0.001) in patients without non-obstructive CAD. The relative reduction in low-density lipoprotein was 14% higher (P < 0.001) in patients with compared to patients without non-obstructive CAD after coronary CTA., Conclusions: Coronary CTA with subsequent follow-up in general practice has the potential to align health service utilization that prioritizes high-risk patients and facilitate optimized preventive management., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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

Background: Clinical outcomes following coronary computed tomography-derived fractional flow reserve (FFR CT ) testing in clinical practice are unknown., Objectives: This study sought to assess real-world clinical outcomes following a diagnostic strategy including first-line coronary computed tomography angiography (CTA) with selective FFR CT testing., Methods: The study reviewed the results of 3,674 consecutive patients with stable chest pain evaluated with CTA and FFR CT testing to guide downstream management in patients with intermediate stenosis (30% to 70%). The composite endpoint (all-cause death, myocardial infarction, hospitalization for unstable angina, and unplanned revascularization) was determined in 4 patient groups: 1) CTA stenosis <30%, optimal medical treatment (OMT), and no additional testing; 2) FFR CT >0.80, OMT, no additional testing; 3) FFR CT  ≤0.80, OMT, no additional testing; and 4) FFR CT  ≤0.80, OMT, and referral to invasive coronary angiography. Patients were followed for a median of 24 (range 8 to 41) months., Results: FFR CT was available in 677 patients, and the test result was negative (>0.80) in 410 (61%) patients. In 75% of the patients with FFR CT >0.80, maximum coronary stenosis was ≥50%. The cumulative incidence proportion (95% confidence interval [CI]) of the composite endpoint at the end of follow-up was comparable in groups 1 (2.8%; 95% CI: 1.4% to 4.9%) and 2 (3.9%; 95% CI: 2.0% to 6.9%) (p = 0.58) but was higher (when compared with group 1) in groups 3 (9.4%; p = 0.04) and 4 (6.6%; p = 0.08). Risk of myocardial infarction was lower in group 4 (1.3%) than in group 3 (8%; p < 0.001)., Conclusions: In patients with intermediate-range coronary stenosis, FFR CT is effective in differentiating patients who do not require further diagnostic testing or intervention (FFR CT >0.80) from higher-risk patients (FFR CT  ≤0.80) in whom further testing with invasive coronary angiography and possibly intervention may be needed. Further studies assessing the risk and optimal management strategy in patients undergoing first-line CTA with selective FFR CT testing are needed., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Coronary stenosis and plaque evaluation by coronary computed tomography angiography (CTA) may contribute to identify hemodynamically relevant lesions. We evaluated the most stenotic lesion including plaques proximal to it versus a total vessel analyses combined with stenosis for ischemia., Methods: Patients scheduled for clinically indicated invasive coronary angiography (ICA) for suspected coronary artery disease underwent coronary CTA and ICA including fractional flow reserve (FFR) as part of the NXT trial (clinicaltrials.govNCT01757678). Stenoses were visually graded ≤50%, 51-70%, and >70% on coronary CTA. Semi-automated plaque analyses were performed using a proximal to the FFR pressure sensor location (including the most severe lesion to the coronary ostium) versus a total vessel (vessel diameter ≥2 mm) approach. Coronary stenosis and plaque parameters were evaluated for discrimination of ischemia by logistic regressions and combined models analyzed using receiver operating characteristics (ROC) with invasive FFR≤ 0.80 as reference standard., Results: In 254 patients, mean (±SD) age 64 (±10) years, 64% male, a coronary CTA stenosis >50% was present in 239 (49%) vessels. Invasive FFR was ≤0.80 in 100 (21%) vessels. Coronary stenosis severity and low-density non-calcified plaque (LD-NCP) volume were independent predictors of ischemia in the "proximal" and "total-vessel" analyses. Stenosis severity + total vessel LD-NCP assessment performed better than stenosis severity + proximal LD-NCP evaluation (Area under curve [AUC] (95%CI): 0.83 (0.78-0.87) vs 0.81 (0.76-0.86), p-value = 0.009), whereas stenosis severity + proximal LD-NCP performed better than stenosis alone (AUC (95%CI): 0.81 (0.76-0.86) vs 0.78 (0.73-0.83), p-value = 0.019)., Conclusion: Adding total vessel high-risk plaque volume to stenosis severity improves discrimination of ischemia in coronary CTA performed in patients with stable angina pectoris., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Aims: To assess the use of downstream coronary angiography (ICA) and short-term safety of frontline coronary CT angiography (CTA) with selective CT-derived fractional flow reserve (FFRCT) testing in stable patients with typical angina pectoris., Methods and Results: Between 1 January 2016 and 30 June 2016 all patients (N = 774) referred to non-emergent ICA or coronary CTA at Aarhus University Hospital on a suspicion of CAD had frontline CTA performed. Downstream testing and treatment within 3 months and adverse events ≥90 days were registered. Patients were divided into two groups according to the presence of typical angina pectoris, which according to local practice would have resulted in referral to ICA, (low-intermediate-risk, n = 593 [76%]; high-risk, n = 181 [24%]) with mean pre-test probability of CAD of 31 ± 16% and 67 ± 16%, respectively. Coronary CTA was performed in 745 (96%) patients in whom FFRCT was prescribed in 212 (28%) patients. In the high- vs. low-intermediate-risk group, ICA was cancelled in 75% vs. 91%. Coronary revascularization was performed more frequently in high-risk than in low-intermediate-risk patients, 76% vs. 52% (P = 0.03). Mean follow-up time was 157 ± 50 days. Serious clinical events occurred in four patients, but not in any patients with cancelled ICA by coronary CTA with selective FFRCT testing., Conclusion: Frontline coronary CTA with selective FFRCT testing in stable patients with typical angina pectoris in real-world practice is associated with a high rate of safe cancellation of planned ICAs.

Objectives: The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR., Background: In patients with stable ischemic heart disease, FFR-guided revascularization, as compared with medical therapy alone, is reported to improve outcomes. Because morphological characteristics are the basis of plaque rupture and acute coronary events, a relationship between FFR and lesion characteristics may exist., Methods: This is a subanalysis of NXT (HeartFlowNXT: HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography), a prospective, multicenter study of 254 patients (age 64 ± 10 years, 64% male) with suspected stable ischemic heart disease; coronary computed tomography angiography including plaque morphology assessment, invasive angiography, and FFR were obtained for 383 lesions. Ischemia was defined by invasive FFR ≤0.80. Computed tomography angiography-defined morphological characteristics of plaques and their vascular location were used in univariate and multivariate analyses to examine their predictive value for invasive FFR. The distribution of various combinations of plaque morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR were examined., Results: The percentage of luminal stenosis, low-attenuation plaque (LAP) or necrotic core volume, left anterior descending coronary artery territory, and the presence of multiple lesions per vessel were the predictors of FFR. When grouped on the basis of degree of luminal stenosis, FFR-negative lesions had consistently smaller LAP volumes compared with FFR-positive lesions. The distribution of plaque characteristics in lesions with normal and abnormal FFR demonstrated that whereas FFR-negative lesions excluded likelihood of stenotic plaques with moderate to high LAP volumes, only one-third of FFR-positive lesions demonstrated obstructive plaques with moderate to high LAP volumes., Conclusions: In addition to the severity of luminal stenosis, necrotic core volume is an independent predictor of FFR. The distribution of plaque characteristics among lesions with varying luminal stenosis and normal and abnormal FFR may explain the outcomes associated with FFR-guided therapy., (Copyright © 2018. Published by Elsevier Inc.)

Aims: Fractional flow reserve (FFR) derived from coronary computed tomography (FFRCT) has high diagnostic performance in stable coronary artery disease (CAD). The diagnostic performance of FFRCT in patients with hypertension (HTN) and diabetes (DM), who are at risk of microvascular impairment, is not known., Methods and Results: We analysed the diagnostic performance of FFRCT, in patients (vessels) with DM (n = 16), HTN (n = 186), DM + HTN (n = 58) vs. controls (n = 107) with or with suspected CAD. Patients (vessels) were further divided according to left ventricular mass index (LVMI) tertiles. Reference standard was invasively measured FFR ≤0.80. Per-patient diagnostic accuracy (95% CI) in control patients was 71.7% (61.6-81.8) vs. 79.3 (74.0-85.0) (P = 0.12), 75.0% (47.6-92.7) (P = 0.52), and 75.9% (62.8-86.1) (P = 0.39) in patients with HTN, DM, and HTM + DM, respectively. There was no difference in discrimination of ischaemia by FFRCT between groups. On a per-vessel level, there was no significant difference in diagnostic performance or discrimination of ischaemia by FFRCT between groups. There was a decline in both per-patient and -vessel diagnostic specificity of FFRCT in the upper LVMI tertile when compared with lower tertiles; however, discrimination of ischaemia by FFRCT was unaltered across LVMI tertiles., Conclusion: The diagnostic performance of FFRCT is independent of the presence of HTN and DM. FFRCT is a robust method in a broad stable CAD population, including patients at high risk for microvascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Background: We hypothesize that in patients with suspected coronary artery disease (CAD), lower values of the ratio of total epicardial coronary arterial lumen volume to left ventricular myocardial mass (V/M) result in lower fractional flow reserve (FFR)., Methods: V/M was computed in 238 patients from the NXT trial who underwent coronary computed tomography angiography (CTA), quantitative coronary angiography (QCA) and FFR measurement in 438 vessels. Nitroglycerin was administered prior to CT, QCA and FFR acquisition. The V/M ratio was quantified on a patient-level from CT image data by segmenting the epicardial coronary arterial lumen volume (V) and the left ventricular myocardial mass (M). Calcified and noncalcified plaque volumes were quantified using semi-automated software., Results: The median value of V/M (18.57 mm 3 /g) was used to define equal groups of low and high V/M patients. Patients with low V/M had greater diameter stenosis by QCA, more plaque and lower FFR (0.80 ± 0.12 vs. 0.87 ± 0.08; P < 0.0001) than those with high V/M. A total of 365 vessels in 202 patients had QCA stenosis ≤50% and measured FFR. In these patients, those with low V/M had higher percent diameter stenosis by QCA, greater total plaque volume and lower FFR (0.81 ± 0.12 vs. 0.88 ± 0.07; P < 0.0001) than those with high V/M. In multivariate logistic regression analysis, V/M was an independent predictor of FFR ≤0.80 (all p-values < 0.001)., Conclusions: Patients with a low V/M ratio have lower FFR overall and in non-obstructive CAD, independent of plaque measures., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study characterized and quantified subclinical atherosclerosis by coronary computed tomography angiography (CTA) in first-degree relatives of patients with early onset coronary artery disease (CAD)., Background: A strong family history of CAD is an important risk factor for adverse cardiovascular events. Whether predisposed individuals suffer an increased burden of coronary atherosclerosis and adverse plaque features is not known., Methods: We included 88 healthy middle-aged first-degree relatives from 59 families with early onset CAD. Participants were matched by age and sex with 88 control patients with atypical angina or nonanginal chest pain and no family history of CAD, referred for coronary CTA. A blinded analysis of plaque burden and composition was performed using semiautomated plaque quantification software. The relative differences between the median volumes or the odds ratios (OR) were compared between groups, using a mixed model., Results: First-degree relatives had significantly more affected coronary segments than controls (0 segments: 30% vs. 49%, respectively; 1 to 2 segments: 27% vs. 32%, respectively; 3 to 4 segments: 18% vs. 6%, respectively; and ≥5 segments: 25% vs. 14%, respectively; p = 0.001). In a multivariate model, the relative differences of total plaque, total calcified plaque (CP), total noncalcified plaque (NCP), and total low-density NCP (LD-NCP) were 5.8 (95% confidence interval [CI]: 2.8 to 11.9), 2.6 (95% CI: 1.5 to 4.5), 5.8 (95% CI: 2.9 to 12.0), and 3.6 (95% CI: 2.1 to 6.1), respectively. The adjusted OR of any positive remodeling plaque or any LD-NCP plaque was 4.2 (95% CI: 1.2 to 14) and 4.2 (95% CI: 1.9 to 9.5), respectively., Conclusions: Healthy first-degree relatives of patients with early onset CAD have an increased coronary plaque burden compared with symptomatic patients. The plaques display characteristics associated with myocardial ischemia and adverse coronary events., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To summarize the scientific basis of CT derived fractional flow reserve (FFR CT ) and present an updated review on the evidence from clinical trials and real-world observational data RECENT FINDINGS: In prospective multicenter studies of patients with stable coronary artery disease (CAD), FFR CT showed high diagnostic performance. More recently, FFR CT has advanced to the realm of clinical utility and real-world clinical practice with emerging data showing that FFR CT when compared to standard care is efficient in safely reducing downstream utilization of invasive coronary angiography (ICA), and costs, as well as improving the diagnostic yield of ICA. Moreover, FFR CT may broaden applicability of frontline coronary CTA testing to patients with high pre-test risk of CAD. Introducing FFR CT into clinical practice has the potential to significantly improve the management of patients with stable CAD. The optimal FFR CT testing interpretation strategy, as well as the relative cost-efficiency of FFR CT against standard noninvasive functional testing, need further investigation.

The application of computational fluid dynamics to coronary computed tomography angiography allows Fractional Flow Reserve (FFR) to be calculated non-invasively (FFR CT ), enabling computation of FFR from coronary computed tomography angiography acquired at rest both for individual lesions as well as along the entire course of a coronary artery. FFR CT , validated in a number of accuracy studies and a large clinical utility trial, is beginning to penetrate clinical practice. Importantly, while accuracy trials compared FFR CT to invasively measured FFR at a single point in the coronary tree, clinical reports of FFR CT provide information regarding a patient's entire coronary vasculature. Specifically, in distal coronary segments, calculated FFR CT values may be low and below 0.80 even in the absence of localized stenoses within the course of the artery. As a result, the reporting physician needs to understand how to interpret the findings in a clinically useful and thoughtful fashion. This review provides a brief overview of the background of both invasively measured and computationally derived FFR, explains changes in FFR along the course of normal coronary arteries and those affected by coronary atherosclerosis, and outlines the relevance of measurement location when interpreting and reporting FFR and FFR CT results., (Published by Elsevier Inc.)

Background: Data on the clinical utility of coronary computed tomography angiography-derived fractional flow reserve (FFR CT ) are sparse. In patients with intermediate (40-70%) coronary stenosis determined by coronary computed tomography angiography, we investigated the association of replacing standard myocardial perfusion imaging with FFR CT testing with downstream utilization of invasive coronary angiography (ICA) and the diagnostic yield of ICA (rate of no obstructive disease, and rate of revascularization)., Methods and Results: This was a single-center observational study of symptomatic patients with suspected coronary artery disease referred to coronary computed tomography angiography between 2013 and 2015. Patients were divided into 3 historical groups based on the adjunctive functional testing approach: myocardial perfusion imaging (n=1332) or FFR CT "implementation" (n=800) or "clinical use" (n=1391). Propensity score matching was used to estimate the average period effect on outcomes. Patients in the FFR CT clinical use group versus the myocardial perfusion imaging group were older and had higher pretest probability of obstructive disease. After adjusting for baseline risk characteristics, there was a reduction in downstream ICA utilization (absolute risk difference: -4.2; 95% CI, -6.9 to -1.6; P =0.002). In patients referred to ICA, findings of no obstructive coronary artery disease decreased (-12.8%; 95% CI, -22.2 to -3.4; P =0.008) and rate of coronary revascularization increased (14.1%; 95% CI, 3.3-24.9; P =0.01), as did availability of functional information for guidance of revascularization (27.8%; 95% CI, 11.3-44.4; P <0.001) after clinical adoption of FFR CT ., Conclusions: Replacing adjunctive myocardial perfusion imaging with FFR CT testing for functional assessment of intermediate stenosis determined by coronary computed tomography angiography in stable coronary artery disease was associated with less ICA utilization, and a higher ICA diagnostic yield. The findings in this observational study needs confirmation in prospective, randomized trials., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objectives: The goal of this study was to assess the real-world clinical utility of fractional flow reserve (FFR) derived from coronary computed tomography angiography (FFR CT ) for decision-making in patients with stable coronary artery disease (CAD)., Background: FFR CT has shown promising results in identifying lesion-specific ischemia. The real-world feasibility and influence on the diagnostic work-up of FFR CT testing in patients suspected of having CAD are unknown., Methods: We reviewed the complete diagnostic work-up of nonemergent patients referred for coronary computed tomography angiography over a 12-month period at Aarhus University Hospital, Denmark, including all patients with new-onset chest pain with no known CAD and with intermediate-range coronary lesions (lumen reduction, 30% to 70%) referred for FFR CT . The study evaluated the consequences on downstream diagnostic testing, the agreement between FFR CT and invasively measured FFR or instantaneous wave-free ratio (iFR), and the short-term clinical outcome after FFR CT testing., Results: Among 1,248 patients referred for computed tomography angiography, 189 patients (mean age 59 years; 59% male) were referred for FFR CT , with a conclusive FFR CT result obtained in 185 (98%). FFR CT was ≤0.80 in 31% of patients and 10% of vessels. After FFR CT testing, invasive angiography was performed in 29%, with FFR measured in 19% and iFR in 1% of patients (with a tendency toward declining FFR-iFR guidance during the study period). FFR CT  ≤0.80 correctly classified 73% (27 of 37) of patients and 70% (37 of 53) of vessels using FFR ≤0.80 or iFR ≤0.90 as the reference standard. In patients with FFR CT >0.80 being deferred from invasive coronary angiography, no adverse cardiac events occurred during a median follow-up period of 12 (range 6 to 18 months) months., Conclusions: FFR CT testing is feasible in real-world symptomatic patients with intermediate-range stenosis determined by coronary computed tomography angiography. Implementation of FFR CT for clinical decision-making may influence the downstream diagnostic workflow of patients. Patients with an FFR CT value >0.80 being deferred from invasive coronary angiography have a favorable short-term prognosis., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFR CT ) for the diagnosis of lesion-specific ischemia in nonculprit vessels of patients with recent in ST-segment elevation myocardial infarction (STEMI)., Background: In patients with stable angina, FFR CT has high diagnostic performance in identification of ischemia-causing lesions. The potential value of FFR CT for assessment of multivessel disease in patients with recent STEMI has not been evaluated., Methods: Coronary CTA with calculation of FFR CT and invasive coronary angiography with FFR were performed 1 month after STEMI in patients with multivessel disease. Coronary CTA and invasive coronary angiography stenosis >50% were considered obstructive. Lesion-specific ischemia was assumed if FFR CT was ≤0.80. FFR ≤0.80 was the reference standard. To evaluate the influence of vessel size, the total coronary vessel lumen volume relative to left ventricular mass (volume-to-mass ratio) was calculated and compared with that of patients with stable angina., Results: The study evaluated 124 nonculprit vessels from 60 patients. Accuracy, sensitivity, and specificity of FFR CT were 72%, 83%, and 66% versus 64% (p = 0.033), 93% (p = 0.15), and 49% (p < 0.001) for CTA and 72% (p = 1.00), 76% (p = 0.46), and 70% (p = 0.54) for invasive coronary angiography. Following STEMI, median volume-to-mass ratio was lower than in patients with stable angina, 53 versus 65 mm 3 /g (p = 0.009). In patients with volume-to-mass ratio ≥65 mm 3 /g (upper tertile) accuracy, sensitivity, and specificity of FFR CT were all 83% versus 56% (p = 0.009), 75% (p = 0.61), and 44% (p = 0.003) in patients with <49 mm 3 /g (lower tertile)., Conclusions: The diagnostic performance of FFR CT for staged detection of ischemia in STEMI patients with multivessel disease is moderate. STEMI patients have a smaller vessel volume than do patients with stable angina. The diagnostic performance of FFR CT is influenced by the volume-to-mass ratio. This study does not support routine use of FFR CT in the post-STEMI setting. (Assessment of Coronary Stenoses Using Coronary CT-Angiography and Noninvasive Fractional Flow Reserve; NCT01739075)., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Congenital heart disease, primarily involving the left-sided structures, is often seen in patients with Turner Syndrome. Moreover, a few case reports have indicated that coronary anomalies may be more prevalent in Turner Syndrome than in the normal population. We therefore set out to systematically investigate coronary arterial anatomy by computed tomographic coronary angiography (coronary CTA) in Turner Syndrome patients., Methods: Fifty consecutive women with Turner Syndrome (mean age 47 years [17-71]) underwent coronary CTA. Patients were compared with 25 gender-matched controls., Results: Coronary anomaly was more frequent in patients with Turner Syndrome than in healthy controls [20% vs. 4% (p = 0.043)]. Nine out of ten abnormal cases had an anomalous left coronary artery anatomy (absent left main trunk, n = 7; circumflex artery originating from the right aortic sinus, n = 2). One case had a tubular origin of the right coronary artery above the aortic sinus. There was no correlation between the presence of coronary arterial anomalies and karyotype, bicuspid aortic valve, or other congenital heart defects., Conclusion: Coronary anomalies are highly prevalent in Turner Syndrome. The left coronary artery is predominantly affected, with an absent left main coronary artery being the most common anomaly. No hemodynamically relevant coronary anomalies were found., (Copyright © 2016 Society of Cardiovascular Computed Tomography. All rights reserved.)

Background: Coronary computed tomographic angiography (CTA) plus estimation of fractional flow reserve using CTA (FFRCT) safely and effectively guides initial care over 90 days in patients with stable chest pain. Longer-term outcomes are unknown., Objectives: The study sought to determine the 1-year clinical, economic, and quality-of-life (QOL) outcomes of using FFRCT instead of usual care., Methods: Consecutive patients with stable, new onset chest pain were managed by either usual testing (n = 287) or CTA (n = 297) with selective FFRCT (submitted in 201, analyzed in 177); 581 of 584 (99.5%) completed 1-year follow-up. Endpoints were adjudicated major adverse cardiac events (MACE) (death, myocardial infarction, unplanned revascularization), total medical costs, and QOL., Results: Patients averaged 61 years of age with a mean 49% pre-test probability of coronary artery disease. At 1 year, MACE events were infrequent, with 2 in each arm of the planned invasive group and 1 in the planned noninvasive cohort (usual care strategy). In the planned invasive stratum, mean costs were 33% lower with CTA and selective FFRCT ($8,127 vs. $12,145 usual care; p < 0.0001); in the planned noninvasive stratum, mean costs did not differ when using an FFRCT cost weight of zero ($3,049 FFRCT vs. $2,579; p = 0.82), but were higher when using an FFRCT cost weight equal to CTA. QOL scores improved overall at 1 year (p < 0.001), with similar improvements in both groups, apart from the 5-item EuroQOL scale scores in the noninvasive stratum (mean change of 0.12 for FFRCT vs. 0.07 for usual care; p = 0.02)., Conclusions: In patients with stable chest pain and planned invasive coronary angiography, care guided by CTA and selective FFRCT was associated with equivalent clinical outcomes and QOL, and lower costs, compared with usual care over 1-year follow-up. (The PLATFORM Study: Prospective LongitudinAl Trial of FFRct: Outcome and Resource IMpacts [PLATFORM]; NCT01943903)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims  This study sought to investigate outcomes following a normal CT-derived fractional flow reserve (FFRCT) result in patients with moderate stenosis and coronary artery calcification, and to describe the relationship between the extent of calcification, stenosis, and FFRCT. Methods and results Data from 975 consecutive patients suspected of chronic coronary syndrome with stenosis (30–70%) determined by computed CT angiography and FFRCT to guide downstream management decisions were reviewed. Median (range) follow-up time was 2.2 (0.5–4.2) years. Coronary artery calcium (CAC) scores were ≥400 in 25%, stenosis ≥50% in 83%, and FFRCT >0.80 in 51% of the patients. There was a lower incidence of the composite endpoint (death, myocardial infarction, hospitalization for unstable angina, and unplanned coronary revascularization) at 4.2 years in patients with any CAC and FFRCT > 0.80 vs. FFRCT ≤ 0.80 (3.9% and 8.7%, P  = 0.04), however, in patients with CAC scores ≥400 the risk difference between groups did not reach statistical significance, 4.2% vs. 9.7% (P  = 0.24). A negative relationship between CAC scores and FFRCT irrespective of stenosis severity was demonstrated. Conclusion FFRCT shows promise in identifying patients with stenosis and calcification who can be managed without further downstream testing. Moreover, an inverse relationship between CAC levels and FFRCT was demonstrated. Studies are needed to further assess the clinical utility of FFRCT in patients with extensive coronary calcification. [ABSTRACT FROM AUTHOR]

The authors sought to assess the distribution of 5-year risk of cardiovascular disease (CVD) events (myocardial infarction, revascularizations, ischemic stroke) and death among symptomatic patients with varying degrees of coronary artery disease (CAD) ascertained from computed tomography angiography (CTA). CTA is used increasingly as the first-line test for evaluating patients with symptoms suggestive of CAD. This creates the daily clinical challenge of best using the information available from CTA to guide appropriate downstream allocation of preventive treatments. Among 21,275 patients from the Western Denmark Heart Registry, the authors developed a model predicting 5-year risk for CVD and death based on traditional risk factors and CAD severity. Only events occurring >90 days after CTA were included. During a median follow-up of 4.2 years, 1,295 CVD events and deaths occurred. The median 5-year risk for events was 4% (interquartile range: 3% to 8%), and ranged from <5% to >50% in individual patients. The degree of CAD severity was the strongest risk factor; however, traditional risk factors also contributed significantly to risk. Thus, risk distributions in patients with varying degree of CAD overlapped considerably, and patients with extensive nonobstructive CAD could have higher estimated risk than patients with obstructive CAD (stenosis >50%). Among patients with obstructive CAD, 12% had 5-year risk <10% whereas 24% had risk >20%. A similar large overlap in risk was found when revascularizations were excluded from the endpoint. The 5-year risk for CVD events and death varies substantially in symptomatic patients undergoing CTA, even in the presence of obstructive CAD. These results provide support for individual risk assessment to improve potential benefit when allocating preventive therapies following CTA. [ABSTRACT FROM AUTHOR]

Objectives: To obtain more powerful assessment of the prognostic value of fractional flow reserveCT testing we performed a systematic literature review and collaborative meta-analysis of studies that assessed clinical outcomes of CT-derived calculation of FFR (FFRCT) (HeartFlow) analysis in patients with stable coronary artery disease (CAD).Methods: We searched PubMed and Web of Science electronic databases for published studies that evaluated clinical outcomes following fractional flow reserveCT testing between 1 January 2010 and 31 December 2020. The primary endpoint was defined as 'all-cause mortality (ACM) or myocardial infarction (MI)' at 12-month follow-up. Exploratory analyses were performed using major adverse cardiovascular events (MACEs, ACM+MI+unplanned revascularisation), ACM, MI, spontaneous MI or unplanned (>3 months) revascularisation as the endpoint.Results: Five studies were identified including a total of 5460 patients eligible for meta-analyses. The primary endpoint occurred in 60 (1.1%) patients, 0.6% (13/2126) with FFRCT>0.80% and 1.4% (47/3334) with FFRCT ≤0.80 (relative risk (RR) 2.31 (95% CI 1.29 to 4.13), p=0.005). Likewise, MACE, MI, spontaneous MI or unplanned revascularisation occurred more frequently in patients with FFRCT ≤0.80 versus patients with FFRCT >0.80. Each 0.10-unit FFRCT reduction was associated with a greater risk of the primary endpoint (RR 1.67 (95% CI 1.47 to 1.87), p<0.001).Conclusions: The 12-month outcomes in patients with stable CAD show low rates of events in those with a negative FFRCT result, and lower risk of an unfavourable outcome in patients with a negative test result compared with patients with a positive test result. Moreover, the FFRCT numerical value was inversely associated with outcomes. [ABSTRACT FROM AUTHOR]

Aims Coronary plaque characteristics are associated with ischaemia. Differences in plaque volumes and composition may explain the discordance between coronary stenosis severity and ischaemia.We evaluated the association between coronary stenosis severity, plaque characteristics, coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT), and lesion-specific ischaemia identified by FFR in a substudy of the NXT trial (Analysis of Coronary Blood Flow Using CT Angiography: Next Steps). Methods and results Coronary CTA stenosis, plaque volumes, FFRCT, and FFR were assessed in 484 vessels from 254 patients. Stenosis >50% was considered obstructive. Plaque volumes (non-calcified plaque [NCP], low-density NCP [LD-NCP], and calcified plaque [CP]) were quantified using semi-automated software. Optimal thresholds of quantitative plaque variables were defined by area under the receiver-operating characteristics curve (AUC) analysis. Ischaemia was defined by FFR or FFRCT ≤0.80. Plaque volumes were inversely related to FFR irrespective of stenosis severity. Relative risk (95% confidence interval) for prediction of ischaemia for stenosis >50%, NCP ≥185 mm3, LD-NCP ≥30 mm3, CP ≥9 mm3, and FFRCT ≤0.80 were 5.0 (3.0-8.3), 3.7 (2.4-5.6), 4.6 (2.9-7.4), 1.4 (1.0-2.0), and 13.6 (8.4-21.9), respectively. Lowdensity NCP predicted ischaemia independent of other plaque characteristics. Low-density NCP and FFRCT yielded diagnostic improvement over stenosis assessment with AUCs increasing from 0.71 by stenosis >50% to 0.79 and 0.90 when adding LD-NCP ≥30 mm3 and LD-NCP ≥30 mm3 + FFRCT ≤0.80, respectively. Conclusion Stenosis severity, plaque characteristics, and FFRCT predict lesion-specific ischaemia. Plaque assessment and FFRCT provide improved discrimination of ischaemia compared with stenosis assessment alone. [ABSTRACT FROM AUTHOR]

Objectives The goal of this study was to examine the diagnostic performance of noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFR CT ) in relation to coronary calcification severity. Background FFR CT has shown promising results in identifying lesion-specific ischemia. The extent to which the severity of coronary calcification affects the diagnostic performance of FFR CT is not known. Methods Coronary calcification was assessed by using the Agatston score (AS) in 214 patients suspected of having coronary artery disease who underwent coronary CTA, FFR CT , and FFR (FFR examination was performed in 333 vessels). The diagnostic performance of FFR CT (≤0.80) in identifying vessel-specific ischemia (FFR ≤0.80) was investigated across AS quartiles (Q1 to Q4) and for discrimination of ischemia in patients and vessels with a low-mid AS (Q1 to Q3) versus a high AS (Q4). Coronary CTA stenosis was defined as lumen reduction >50%. Results Mean ± SD per-patient and per-vessel AS were 302 ± 468 (range 0 to 3,599) and 95 ± 172 (range 0 to 1,703), respectively. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of FFR CT across AS quartiles. Discrimination of ischemia by FFR CT was high in patients with a high AS (416 to 3,599) and a low-mid AS (0 to 415), with no difference in area under the receiver-operating characteristic curve (AUC) (0.86 [95% confidence interval (CI): 0.76 to 0.96] vs. 0.92 [95% CI: 0.88 to 0.96]) (p = 0.45). Similarly, discrimination of ischemia by FFR CT was high in vessels with a high AS (121 to 1,703) and a low-mid AS (0 to 120) (AUC: 0.91 [95% CI: 0.85 to 0.97] vs. 0.95 [95% CI: 0.91 to 0.98]; p = 0.65). Diagnostic accuracy and specificity of FFR CT were significantly higher than for stenosis assessment in each AS quartile at the per-patient (p < 0.001) and per-vessel (p < 0.05) level with similar sensitivity. In vessels with a high AS, FFR CT exhibited improved discrimination of ischemia compared with coronary CTA alone (AUC: 0.91 vs. 0.71; p = 0.004), whereas on a per-patient level, the difference did not reach statistical significance (AUC: 0.86 vs. 0.72; p = 0.09). Conclusions FFR CT provided high and superior diagnostic performance compared with coronary CTA interpretation alone in patients and vessels with a high AS. [ABSTRACT FROM AUTHOR]

Background Fractional flow reserve (FFR) is the standard of reference for assessing the hemodynamic significance of coronary stenoses in patients with stable coronary artery disease. Noninvasive FFR derived from coronary CT angiography (FFRCT) is a promising new noninvasive method for assessing the physiologic significance of epicardial stenoses. The reproducibility of FFRCT has not yet been established. Objective The aim of this study was to evaluate the variation of repeated analyses of FFRCT per se and in the context of the reproducibility of repeated FFR measurements. Methods Coronary CT angiography and invasive coronary angiography with repeated FFR measurements were performed in 28 patients (58 vessels) with suspected stable coronary artery disease. Based on the coronary CT angiography data set, FFRCT analyses were performed twice by 2 independent blinded analysts. Results In 12 of 58 (21%) vessels FFR was ≤ 0.80. The standard deviation for the difference between first and second FFRCT analyses was 0.034 vs 0.033 for FFR repeated measurements (P = .722). Limits of agreement were -0.06 to 0.08 for FFRCT and -0.07 to 0.06 for FFR. The coefficient of variation of FFRCT (CVFFRct) was 3.4% (95% confidence interval [CI], 1.4%-4.6%) vs 2.7% (95% CI, 1.8%-3.3%) for FFR. In vessels with mean FFR ranging between 0.70 and 0.90 (n = 25), the difference between the first and second FFRCT analyses was 0.035 and FFR repeated measurements was 0.043 (P = .357), whereas CVFFRct was 3.3% (95% CI, 1.5%-4.3%) and coefficient of variation for FFR was 3.6% (95% CI, 2.3%-4.6%). Conclusions The reproducibility of both repeated FFRCT analyses and repeated FFR measurements is high. [ABSTRACT FROM AUTHOR]

Background: Low-density lipoprotein cholesterol (LDL-C) is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD). However, a sizable proportion of middle-aged individuals with elevated LDL-C level have not developed coronary atherosclerosis as assessed by coronary artery calcification (CAC). Whether presence of CAC modifies the association of LDL-C with ASCVD risk is unknown. We evaluated the association of LDL-C with future ASCVD events in patients with and without CAC. Methods: The study included 23 132 consecutive symptomatic patients evaluated for coronary artery disease using coronary computed tomography angiography (CTA) from the Western Denmark Heart Registry, a seminational, multicenter-based registry with longitudinal registration of patient and procedure data. We assessed the association of LDL-C level obtained before CTA with ASCVD (myocardial infarction and ischemic stroke) events occurring during follow-up stratified by CAC>0 versus CAC=0 using Cox regression models adjusted for baseline characteristics. Outcomes were identified through linkage among national registries covering all hospitals in Denmark. We replicated our results in the National Heart, Lung, and Blood Institute –funded Multi-Ethnic Study of Atherosclerosis. Results: During a median follow-up of 4.3 years, 552 patients experienced a first ASCVD event. In the overall population, LDL-C (per 38.7 mg/dL increase) was associated with ASCVD events occurring during follow-up (adjusted hazard ratio [aHR], 1.14 [95% CI, 1.04–1.24]). When stratified by the presence or absence of baseline CAC, LDL-C was only associated with ASCVD in the 10 792/23 132 patients (47%) with CAC>0 (aHR, 1.18 [95% CI, 1.06–1.31]); no association was observed among the 12 340/23 132 patients (53%) with CAC=0 (aHR, 1.02 [95% CI, 0.87–1.18]). Similarly, a very high LDL-C level (> 193 mg/dL) versus LDL-C <116 mg/dL was associated with ASCVD in patients with CAC>0 (aHR, 2.42 [95% CI, 1.59–3.67]) but not in those without CAC (aHR, 0.92 [0.48–1.79]). In patients with CAC=0, diabetes, current smoking, and low high-density lipoprotein cholesterol levels were associated with future ASCVD events. The principal findings were replicated in the Multi-Ethnic Study of Atherosclerosis. Conclusions: LDL-C appears to be almost exclusively associated with ASCVD events over ≈5 years of follow-up in middle-aged individuals with versus without evidence of coronary atherosclerosis. This information is valuable for individualized risk assessment among middle-aged people with or without coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Background: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value.Objectives: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC).Methods: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease.Results: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD.Conclusions: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD. [ABSTRACT FROM AUTHOR]