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ObjectivesThis study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).BackgroundCoronary CTA can noninvasively assess coronary plaques quantitatively.MethodsPatients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.ResultsThree distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a closed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm3 [interquartile range (IQR): 0.0 to 39.6 mm3]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm3 [IQR: 0.0 to 127.4 mm3]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm3 [IQR: 96.7 to 306.4 mm3]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p

ObjectivesThe aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.BackgroundCoronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.MethodsThis analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) × 100 at a per-plaque and per-patient level (summation of all individual plaques).ResultsCPV was strongly correlated with plaque volume (r = 0.780; p

ObjectivesThis study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.BackgroundCoronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.MethodsUtilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested case-control study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of this model was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.ResultsCL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p

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

ObjectivesThis study aimed to determine the rate and extent of plaque progression (PP), changes in plaque features, and clinical predictors of PP in patients with diabetes mellitus (DM).BackgroundThe natural history of coronary PP in patients with DM is not well established.MethodsA total of 1,602 patients (age 61.3 ± 9.0 years; 60.3% men; median scan interval 3.8 years) who underwent serial coronary computed tomography angiography over a period of at least 24 months were enrolled and analyzed from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) trial. Study endpoints were changes in plaque features in diabetics with PP and risk factors for PP by serial coronary computed tomography angiography between patients with and without DM. PP was defined if plaque volume at follow-up minus plaque volume at baseline was >0.ResultsDM was an independent risk factor for PP (84.6%; 276 of 326 patients with PP) in multivariate analysis (odds ratio [OR]: 1.526; 95% confidence interval [CI]: 1.100 to 2.118; p = 0.011). Independent risk factors for PP in patients with DM were male sex (OR: 1.485; 95% CI: 1.003 to 2.199; p = 0.048) and mean plaque burden at baseline ≥75% (OR: 3.121; 95% CI: 1.701 to 5.725; p ≤0.001). After propensity matching, percent changes in overall plaque volume (30.3 ± 36.9% in patients without DM and 36.0 ± 29.7% in those with DM; p = 0.032) and necrotic core volume (-7.0 ± 35.8% in patients without DM and 21.5 ± 90.5% in those with DM; p = 0.007) were significantly greater in those with DM. The frequency of spotty calcification, positive remodeling, and burden of low-attenuation plaque were significantly greater in patients with DM.ConclusionsPeople with DM experience greater PP, particularly significantly greater progression in adverse plaque, than those without DM. Male sex and mean plaque burden >75% at baseline were identified as independent risk factors for PP.

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

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

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

ObjectivesThe purpose of this study was to examine sex-specific associations, if any, between per-vessel coronary artery disease (CAD) extent and the risk of major adverse cardiovascular events (MACE) over a 5-year study duration.BackgroundThe presence and extent of CAD diagnosed by coronary computed tomography angiography (CTA) is associated with increased short-term mortality and MACE. Nevertheless, some uncertainty remains regarding the influence of sex on these findings.Methods5,632 patients (mean age 60.2 ± 11.8 years, 36.5% women) from the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry were followed for 5 years. Obstructive CAD was defined as ≥50% luminal stenosis in a coronary vessel. Using Cox proportional hazards models, we calculated the hazard ratio (HR) for incident MACE among women and men, defined as death or myocardial infarction.ResultsObstructive CAD was more prevalent in men (42% vs. 26%; p < 0.001), whereas women were more likely to have normal coronary arteries (43% vs. 27%; p < 0.001). There were a total of 798 incident MACE events. After adjustment, there was a strong association between increased MACE risk and nonobstructive CAD (HR: 2.16 for women, 2.56 for men; p < 0.001 for both), obstructive 1-vessel CAD (HR: 3.69 and 2.66; p < 0.001), 2-vessel CAD (HR: 3.92 and 3.55; p < 0.001), and 3-vessel/left main CAD (HR: 5.94 and 4.44; p < 0.001). Further exploratory analyses of atherosclerotic burden did not identify sex-specific patterns predictive of MACE.ConclusionsIn a large prospective coronary CTA cohort followed long-term, we did not observe an interaction of sex for the association between MACE risk and increased per-vessel extent of obstructive CAD. These findings highlight the persistent prognostic significance of anatomic CAD subsets as detected by coronary CTA for the risk of MACE in both women and men.

Background: Vulnerable plaque presents prognostic implications in addition to functional significance., Objectives: The aim of this study was to identify relevant features of vulnerable plaque in functionally significant lesions., Methods: In this multicenter, prospective study conducted across 5 countries, including patients who had invasive fractional flow reserve (FFR) ≤0.80, a total of 95 patients with available pullback pressure gradient (PPG) and plaque analysis on coronary computed tomographic angiography and optical coherence tomography were analyzed. Vulnerable plaque was defined as the presence of plaque rupture or thin-cap fibroatheroma on optical coherence tomography. Among the 25 clinical characteristics, invasive angiographic findings, physiological indexes, and coronary computed tomographic angiographic findings, significant predictors of vulnerable plaque were identified., Results: Mean percentage diameter stenosis, FFR, and PPG were 77.8% ± 14.6%, 0.66 ± 0.13, and 0.65 ± 0.13, respectively. Vulnerable plaque was present in 53 lesions (55.8%). PPG and FFR were identified as significant predictors of vulnerable plaque (P < 0.05 for all). PPG >0.65 and FFR ≤0.70 were significantly related to a higher probability of vulnerable plaque after adjustment for each other (OR: 6.75 [95% CI: 2.39-19.1]; P < 0.001] for PPG >0.65; OR: 4.61 [95% CI: 1.66-12.8]; P = 0.003 for FFR ≤0.70). When categorizing lesions according to combined PPG >0.65 and FFR ≤0.70, the prevalence of vulnerable plaque was 20.0%, 57.1%, 66.7%, and 88.2% in the order of PPG ≤0.65 and FFR >0.70, PPG ≤0.65 and FFR ≤0.70, PPG >0.65 and FFR >0.70, and PPG >0.65 and FFR ≤0.70 (P for trend < 0.001), respectively., Conclusions: Among low-FFR lesions, the presence of vulnerable plaque can be predicted by PPG combined with FFR without additional anatomical or plaque characteristics. (Precise Percutaneous Coronary Intervention Plan [P3] Study; NCT03782688)., Competing Interests: Funding Support and Author Disclosures This study received funding from HeartFlow and was also supported by grants from the Patient-Centered Clinical Research Coordinating Center (HI19C0481 and HC19C0305) funded by the Ministry of Health and Welfare and from the Ministry of Food and Drug Safety (RS-2023-00215667), Republic of Korea. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow; and has received speaker fees from Abbott Vascular. Dr Leipsic is a consultant for and holds stock options in Circle CVI and HeartFlow; has received a research grant from GE; and has received modest speaker fees from GE and Philips. Drs Sonck and Munhoz have received research grants provided by the Cardiopath PhD program. Dr Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr Otake has received research grants from Abbott Vascular; and has received speaker fees from HeartFlow and Abbott Vascular. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Koo has received institutional research grants from HeartFlow. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordics; and has received institutional research grants from Bayer, Philips Healthcare, and Novo Nordisk. Dr Jensen has received unrestricted institutional research grants from Siemens and HeartFlow. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Shinke has received research grants from Boston Scientific and Abbott Vascular. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr De Bruyne has received consulting fees from Boston Scientific and Abbott Vascular; has received research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow, Edwards Lifesciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and has received consulting fees from HeartFlow, OpSens, Abbott Vascular, and Philips Volcano. 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.)

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.)

Background: Noninvasive stress testing is commonly used for detection of coronary ischemia but possesses variable accuracy and may result in excessive health care costs., Objectives: This study aimed to derive and validate an artificial intelligence-guided quantitative coronary computed tomography angiography (AI-QCT) model for the diagnosis of coronary ischemia that integrates atherosclerosis and vascular morphology measures (AI-QCT ISCHEMIA ) and to evaluate its prognostic utility for major adverse cardiovascular events (MACE)., Methods: A post hoc analysis of the CREDENCE (Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia) and PACIFIC-1 (Comparison of Coronary Computed Tomography Angiography, Single Photon Emission Computed Tomography [SPECT], Positron Emission Tomography [PET], and Hybrid Imaging for Diagnosis of Ischemic Heart Disease Determined by Fractional Flow Reserve) studies was performed. In both studies, symptomatic patients with suspected stable coronary artery disease had prospectively undergone coronary computed tomography angiography (CTA), myocardial perfusion imaging (MPI), SPECT, or PET, fractional flow reserve by CT (FFR CT ), and invasive coronary angiography in conjunction with invasive FFR measurements. The AI-QCT ISCHEMIA model was developed in the derivation cohort of the CREDENCE study, and its diagnostic performance for coronary ischemia (FFR ≤0.80) was evaluated in the CREDENCE validation cohort and PACIFIC-1. Its prognostic value was investigated in PACIFIC-1., Results: In CREDENCE validation (n = 305, age 64.4 ± 9.8 years, 210 [69%] male), the diagnostic performance by area under the receiver-operating characteristics curve (AUC) on per-patient level was 0.80 (95% CI: 0.75-0.85) for AI-QCT ISCHEMIA , 0.69 (95% CI: 0.63-0.74; P < 0.001) for FFR CT , and 0.65 (95% CI: 0.59-0.71; P < 0.001) for MPI. In PACIFIC-1 (n = 208, age 58.1 ± 8.7 years, 132 [63%] male), the AUCs were 0.85 (95% CI: 0.79-0.91) for AI-QCT ISCHEMIA , 0.78 (95% CI: 0.72-0.84; P = 0.037) for FFR CT , 0.89 (95% CI: 0.84-0.93; P = 0.262) for PET, and 0.72 (95% CI: 0.67-0.78; P < 0.001) for SPECT. Adjusted for clinical risk factors and coronary CTA-determined obstructive stenosis, a positive AI-QCT ISCHEMIA test was associated with aHR: 7.6 (95% CI: 1.2-47.0; P = 0.030) for MACE., Conclusions: This newly developed coronary CTA-based ischemia model using coronary atherosclerosis and vascular morphology characteristics accurately diagnoses coronary ischemia by invasive FFR and provides robust prognostic utility for MACE beyond presence of stenosis., Competing Interests: Funding Support and Author Disclosures This project has been supported by the Foundation “De Drie Lichten” in the Netherlands. Dr Nurmohamed has received grants from the Dutch Heart Foundation (Dekker 03-007-2023-0068) and grants from the European Atherosclerosis Society (2023); and is co-founder of Lipid Tools. Mr Wang, Dr Chan, Ms Crabtree, Ms Aquino, Dr Min, and Dr Earls are employees of Cleerly Inc. Dr Choi has received grant support from GW Heart and Vascular Institute; equity in Cleerly, Inc; and has received consulting fees from Siemens Healthineers. Dr Knaapen has received research grants from HeartFlow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The interplay between coronary hemodynamics and plaque characteristics remains poorly understood., Objectives: The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics., Methods: This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value., Results: A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87)., Conclusions: Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688)., Competing Interests: Funding and Author Disclosures The study was sponsored by the Cardiac Research Institute Aalst with unrestricted grants from HeartFlow Inc. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow Inc; and speaker fees from Abbott Vascular. Dr Leipsic is a consultant and has holding stock options in Circle CVI and HeartFlow Inc; has received a research grant from GE; and modest speaker fees from GE and Philips. Drs Sonck and Munhoz have received research grants provided by the Cardiopath Ph.D. program. Dr Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow Inc. Dr Otake has received research grants from Abbott Vascular; and speaker fees from HeartFlow Inc and Abbott Vascular. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Koo has received institutional research grants from HeartFlow Inc. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordisk; and research grants from Bayer and Philips Healthcare. Dr Jensen has received unrestricted institutional research grants from Siemens and HeartFlow Inc. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Shinke has received research grants from Boston Scientific and Abbott Vascular. CT is an employee of HeartFlow Inc. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; significant institutional research support from St. Jude Medical (CONTRAST [Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?]; NCT02184117) and Philips/Volcano Corporation (DEFINE-FLOW [Combined Pressure and Flow Measurements to Guide Treatment of Coronary Stenoses]; NCT02328820) for studies using intracoronary pressure and flow sensors; has an institutional licensing agreement with Boston Scientific for the smart-minimum FFR algorithm commercialized under 510(k) K191008; and has pending patents on diagnostic methods for quantifying aortic stenosis and transcatheter aortic valve replacement physiology, as well as algorithms to correct pressure tracings from fluid-filled catheters. Dr De Bruyne has received 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 owns equity in Siemens, GE, Philips, HeartFlow Inc, Edwards Life Sciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow Inc, and Abbott Vascular; and consultancy fees from HeartFlow Inc, OpSens, Abbott Vascular, and Philips Volcano. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Statins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse., Objectives: This study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins., Methods: The multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque., Results: The authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively)., Conclusions: In patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction., Competing Interests: Funding Support and Author Disclosures This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) (grant no. 2012027176). The study was also funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging (New York, New York, USA) and the Michael Wolk Foundation (New York, New York, USA). Dr Min is an employee of Cleerly Inc. Dr Leipsic is a consultant to and holds stock options in Circle CVI and HeartFlow; and has received modest speaking fees from Philips and GE Healthcare. Dr Chinnaiyan is a noncompensated medical advisory board member of Heartflow Inc. Dr Samady serves on the scientific advisory board of Philips; has equity interest in Covanos Inc; and has a research grant from Medtronic, Abbott Vascular, and Philips. Dr Virmani is a consultant of Abbott Vascular, Boston Scientific, Celonova, OrbusNeich Medical, Terumo Corporation, W.L. Gore, Edwards Lifesciences, Cook Medical, CSI, ReCor Medical, SinoMedical Sciences Technology, Surmodics, and Bard BD; and is a scientific Advisory Board Member of Medtronic and Xeltis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. All rights reserved.)

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is common in current clinical practice. Cardiac magnetic resonance (CMR) plays an important role in its management and is increasingly recommended by all the current guidelines. However, the prognostic value of CMR in patients with MINOCA is still undetermined., Objectives: The purpose of this study was to determine the diagnostic and prognostic value of CMR in the management of patients with MINOCA., Methods: A systematic review was performed to identify studies reporting the results of CMR findings in patients with MINOCA. Random effects models were used to determine the prevalence of different disease entities: myocarditis, myocardial infarction (MI), or takotsubo syndrome. Pooled odds ratios (ORs) and 95% CIs were calculated to evaluate the prognostic value of CMR diagnosis in the subgroup of studies that reported clinical outcomes., Results: A total of 26 studies comprising 3,624 patients were included. The mean age was 54.2 ± 5.3 years, and 56% were men. MINOCA was confirmed in only 22% (95% CI: 0.17-0.26) of the cases and 68% of patients with initial MINOCA were reclassified after the CMR assessment. The pooled prevalence of myocarditis was 31% (95% CI: 0.25-0.39), and takotsubo syndrome 10% (95% CI: 0.06-0.12). In a subgroup analysis of 5 studies (770 patients) that reported clinical outcomes, CMR diagnosis of confirmed MI was associated with an increased risk of major adverse cardiovascular events (pooled OR: 2.40; 95% CI: 1.60-3.59)., Conclusions: In patients with MINOCA, CMR has been demonstrated to add an important diagnostic and prognostic value, proving to be crucial for the diagnosis of this condition. Sixty-eight percent of patients with initial MINOCA were reclassified after the CMR evaluation. CMR-confirmed diagnosis of MINOCA was associated with an increased risk of major adverse cardiovascular events at follow-up., Competing Interests: Funding Support and Author Disclosures Dr Mileva has received speaker fees from Abbott. Drs Paolisso, Fabbricatore, and Munhoz have received research grants provided by the Cardiopath PhD program. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Marta Belmonte has received a research grant from the Cardiopath PhD program. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Clinical reads of coronary computed tomography angiography (CTA), especially by less experienced readers, may result in overestimation of coronary artery disease stenosis severity compared with expert interpretation. Artificial intelligence (AI)-based solutions applied to coronary CTA may overcome these limitations., Objectives: This study compared the performance for detection and grading of coronary stenoses using artificial intelligence-enabled quantitative coronary computed tomography (AI-QCT) angiography analyses to core lab-interpreted coronary CTA, core lab quantitative coronary angiography (QCA), and invasive fractional flow reserve (FFR)., Methods: Coronary CTA, FFR, and QCA data from 303 stable patients (64 ± 10 years of age, 71% male) from the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia) trial were retrospectively analyzed using an Food and Drug Administration-cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination., Results: Disease prevalence was high, with 32.0%, 35.0%, 21.0%, and 13.0% demonstrating ≥50% stenosis in 0, 1, 2, and 3 coronary vessel territories, respectively. Average AI-QCT analysis time was 10.3 ± 2.7 minutes. AI-QCT evaluation demonstrated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94%, 68%, 81%, 90%, and 84%, respectively, for ≥50% stenosis, and of 94%, 82%, 69%, 97%, and 86%, respectively, for detection of ≥70% stenosis. There was high correlation between stenosis detected on AI-QCT evaluation vs QCA on a per-vessel and per-patient basis (intraclass correlation coefficient = 0.73 and 0.73, respectively; P < 0.001 for both). False positive AI-QCT findings were noted in in 62 of 848 (7.3%) vessels (stenosis of ≥70% by AI-QCT and QCA of <70%); however, 41 (66.1%) of these had an FFR of <0.8., Conclusions: A novel AI-based evaluation of coronary CTA enables rapid and accurate identification and exclusion of high-grade stenosis and with close agreement to blinded, core lab-interpreted quantitative coronary angiography. (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia [CREDENCE]; NCT02173275)., Competing Interests: Funding Support and Author Disclosures Drs Choi and Marques have equity interest in Cleerly Inc. Dr Earls has equity interest in and as of April 1, 2021, is an employee of Cleerly Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although cardiac magnetic resonance (CMR) is considered the gold standard for myocardial fibrosis detection, cardiac computed tomography (CCT) is emerging as a promising alternative., Objectives: The purpose of this study was to assess feasibility and diagnostic accuracy of a comprehensive functional and anatomical evaluation with CCT as compared with CMR in patients with newly diagnosed left ventricular dysfunction (LVD)., Methods: A total of 128 consecutive patients with newly diagnosed LVD were screened. Based on the exclusion criteria, 28 cases were excluded. CCT was performed within 10 days from CMR. Biventricular volumes and ejection fraction, and presence and pattern of delayed enhancement (DE), were determined, along with evaluation of coronary arteries among patients undergoing invasive angiography in the 6 months after CCT., Results: Six cases were excluded because of claustrophobia at CMR. Among the 94 patients who formed the study population, the concordance between CCT and CMR in suggesting the cause of the LVD was high (94.7%, 89/94 patients) in the overall population and was 100% for identifying ischemic cardiomyopathy. The CCT diagnostic rate for DE assessment was also high (96.7%, 1,544/1,598 territories) and similar to that of CMR (97.4%; P = 0.345, CCT vs CMR). Moreover, CCT showed high diagnostic accuracy in the detection of DE (94.8%, 95% CI: 93.6%-95.8%) in a territory-based analysis. Biventricular volumes and function parameters as measured by CCT and CMR were similar, without significant differences with the exception of a modest difference in RV volume. CCT was confirmed to be accurate for assessing arterial coronary circulation. The mean radiation exposure of the whole CCT was 7.78 ± 2.53 mSv (0.84 ± 0.24 mSv for DE)., Conclusions: CCT performed with low-dose whole-heart coverage scanner and high-concentration contrast agent appears an effective noninvasive tool for a comprehensive assessment of patients with newly diagnosed LVD., Competing Interests: Funding Support and Author Disclosures This study has received a grant from Bracco, Man, Italy; study registration number R584-CCM 615. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined., Objectives: The purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV)., Methods: Patients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with ≥2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed., Results: A total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 ± 9.3 years; 65.0% men). The mean PVAT density was -74.1 ± 11.5 HU, and total PV was 48.1 ± 83.5 mm 3 (19.2 ± 44.8 mm 3 of calcified PV and 28.9 ± 51.0 mm 3 of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050)., Conclusions: Increase in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: 202016B02). The study was also funded in part by a grant from the Dalio Foundation. Dr Leipsic has served as a consultant for and holds stock options in HeartFlow and Circle CVI. Drs Kitslaar and Reiber are employees of Medis Medical Imaging. Dr Samady has served on the scientific advisory board of Philips; has equity interest in Covanos Inc; and has received a research grant from Medtronic. Dr Lin has received grant support from GE Healthcare. Dr Min has received funding from GE Healthcare; has served on the scientific advisory board of Arineta and GE Healthcare; and has an equity interest in and is an employee of Cleerly, Inc. Dr Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science and ICT (MSIT) (Grant No. 2012027176). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Low fractional flow reserve (FFR) values after percutaneous coronary intervention (PCI) carry a worse prognosis than high post-PCI FFR values. Therefore, the ability to predict post-PCI FFR might play an important role in procedural planning. Post-PCI FFR values can now be computed from pre-PCI coronary computed tomography angiography (CTA) using the fractional flow reserve derived from coronary computed tomography angiography revascularization planner (FFR CT Planner)., Objectives: The aim of this study was to validate the accuracy of the FFR CT Planner., Methods: In this multicenter, investigator-initiated, prospective study, patients with chronic coronary syndromes and significant lesions based on invasive FFR ≤0.80 were recruited. The FFR CT Planner was applied to the fractional flow reserve derived from coronary computed tomography angiography (FFR CT ) model, simulating PCI. The primary objective was the agreement between the predicted post-PCI FFR by the FFR CT Planner and measured post-PCI FFR. Accuracy of the FFR CT Planner's luminal dimensions was assessed by using post-PCI optical coherence tomography as the reference., Results: Overall, 259 patients were screened, with 120 patients (123 vessels) included in the final analysis. The mean patient age was 64 ± 9 years, and 24% had diabetes. Measured FFR post-PCI was 0.88 ± 0.06, and the FFR CT Planner FFR was 0.86 ± 0.06 (mean difference: 0.02 ± 0.07 FFR unit; limits of agreement: -0.12 to 0.15). Optical coherence tomography minimal stent area was 5.60 ± 2.01 mm 2 , and FFR CT Planner minimal stent area was 5.0 ± 2.2 mm 2 (mean difference: 0.66 ± 1.21 mm 2 ; limits of agreement: -1.7 to 3.0). The accuracy and precision of the FFR CT Planner remained high in cases with focal and diffuse disease and with low and high calcium burden., Conclusions: The FFR CT -based technology was accurate and precise for predicting FFR after PCI. (Precise Percutaneous Coronary Intervention Plan Study [P3]; NCT03782688)., Competing Interests: Funding Support and Author Disclosures The study was sponsored by the Cardiac Research Institute Aalst with unrestricted grants from HeartFlow and Cardiopath. Drs Sonck and Munhoz have received research grants provided by the Cardiopath PhD program. Dr De Bruyne has received consultancy fees from Boston Scientific and Abbott Vascular; research grants from Coroventis Research, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and owns equity in Siemens, GE, Philips, HeartFlow, Edwards LifeSciences, Bayer, Sanofi, and Celyad. Dr Collet has received research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, Siemens, HeartFlow, and Abbott Vascular; and consultancy fees from HeartFlow, OpSens, Abbott Vascular, and Philips Volcano. Dr Ko has received consulting fees from Canon Medical, Abbott, and Medtronic. Dr Mizukami has received consulting fees from Zeon Medical and HeartFlow; and speaker fees from Abbott Vascular. Dr Heggermont reports that Cardiac Research Institute Aalst receives consultancy fees on his behalf from Boston Scientific, Abbott Vascular, MicroPort, Medtronic, Biotronik, and AstraZeneca. Dr Updegrove and Ms Collinsworth are employees of HeartFlow. Dr Leipsic is a consultant and reports holding stock options in Circle CVI and HeartFlow; and has received a research grant from GE and modest speaker fees from GE and Philips. Drs Norgaard and Møller Jensen have received unrestricted institutional research grants from Siemens and HeartFlow. Dr Otake has received research grants from Abbott Vascular; and speaker fees from HeartFlow and Abbott Vascular. Dr Ihdayhid has received consulting fees from Canon, Artrya Medical, and Boston Scientific. Dr Koo has received institutional research grants from HeartFlow. Dr Andreini has received research grants from GE Healthcare and Bracco. Dr Barbato has received speaker fees from Boston Scientific, Abbott Vascular, and GE. Dr Maeng has received advisory board and lecture fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Boston Scientific, and Novo Nordics; and research grants from Bayer and Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Among symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque., Objectives: Among patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume., Methods: A total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as ≥50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up)., Results: Across baseline CAC scores from 0 to ≥400, total plaque volume ranged from 30.4 to 522.4 mm 3 (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC ≥100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm 3 increase in calcified plaque, there was a 5.5 mm 3 increase in noncalcified plaque volume. By comparison, patients with CAC scores of ≥400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC ≥400 (P < 0.001)., Conclusions: CAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk., Competing Interests: Funding Support and Author Disclosures Partial funding was provided by a gift from the Dalio Foundation (New York, New York) and supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation funded by the Ministry of Science and Information and Communications Technology of Korea (Grant number 2012027176). Dr Chinnaiyan is a medical advisor (unpaid) for Heartflow, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA)., Background: The impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain., Methods: A total of 1,236 consecutive patients (age: 60 ± 9 years; 41% female) who underwent serial CCTA at an interval of ≥2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta., Results: With increasing luminal HU (<350, 350-500, and >500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P < 0.001), and fibrofatty plaque (26%, 13%, and 4%; P < 0.001) and necrotic core (1.6%, 0.3%, and 0.0%; P < 0.001) were decreased. Higher tube voltage scanning (80, 100, and 120 kV) resulted in decreasing luminal attenuation (689 ± 135, 497 ± 89, and 391 ± 73 HU; P < 0.001) and calcified plaque volume (59%, 34%, and 23%; P < 0.001) and increased fibrofatty plaque (3%, 9%, and 18%; P < 0.001) and necrotic core (0.2%, 0.1%, and 0.6%; P < 0.001). Mediation analysis showed that the impact of 100 kV on plaque composition, compared with 120 kV, was primarily caused by an indirect effect through blood pool attenuation. Tube voltage scanning of 80 kV maintained a direct effect on fibrofatty plaque and necrotic core in addition to an indirect effect through the luminal attenuation., Conclusions: Low tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)., Competing Interests: Funding Support and Author Disclosures This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (MSIT) (grant number 2012027176). The study was also funded in part by a grant from the Dalio Foundation (New York, New York). Dr Leipsic receives institutional grants to provide core lab services to Edwards Life Sciences, Abbott, Boston Scientific, and Medtronic and is a consultant to and has stock options in Circle CVI and HeartFlow. Dr Andreini is on the Speakers Bureau for GE Healthcare and receives grant support from GE Healthcare and Bracco. Dr Budoff has received grant support from the National Institutes of Health and GE Healthcare. Dr Chun has received funding from a National Research Foundation grant funded by the South Korea government (MEST) (NRF- 2015R1D1A1A01059717). Dr Pontone has received institutional research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, ART, BioSensors International, Biotronik, Boston Scientific, CeloNova, Claret Medical, Cook Medical, Cordis, Edwards Lifesciences, Medtronic, MicroVention, OrbusNeich, ReCord, SINO Medical Technology, Spectranetics, Surmodics, Terumo Corporation, W.L. Gore, and Xeltis; has received honoraria from 480 Biomedical, Abbott Vascular, Boston Scientific, Cook Medical, Lutonix, Medtronic, Terumo Corporation, and W.L. Gore; and is a consultant for 480 Biomedical, Abbott Vascular, Medtronic, and W.L. Gore. Dr Samady has received grant support from Phillips/Volcano and St. Jude Abbott/Medtronic/Gilead. Dr Berman has received software royalties from Cedars-Sinai. Dr Bax has received unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr Chang has received funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT, and Future Planning (grant 2012027176). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Coronary computed tomography angiography (CCTA) is now an established tool in the diagnostic work-up of patients suspected to have coronary artery disease. Yet, its usefulness beyond this phase has not been fully explored. The current review focuses on the implementation of CCTA as a tool to plan and guide coronary interventions in the catheterization laboratory. Specifically, we explore the potential of CCTA to improve patient selection for percutaneous revascularization, provide the rationale for better resource use, and present a novel approach to incorporate 3-dimensional CT guidance for percutaneous coronary interventions., Competing Interests: Funding Support and Author Disclosures Dr. Collet has received research grants from Biosensors, Heart Flow Inc., and Abbott Vascular; and consultancy fees from Opsens, Boston Scientific, HeartFlow Inc., and Philips Volcano. Dr. Sonck has received research grants provided by the Cardiopath PhD program. Dr. Kitslaar is an employee of Medis Medical Imaging Systems. Dr. De Bruyne has received institutional consultancy fees and/or research grants from Abbott, Boston Scientific, and Biotronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression., Background: It is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD)., Methods: The study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at ≥2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed., Results: Of the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 ± 9 years of age vs. 59 ± 9 years of age; p < 0.001) and had higher total cholesterol levels (195 ± 41 mg/dl vs. 187 ± 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm 3 [interquartile range (IQR): 0 to 121.8 mm 3 ] vs. 56.7 mm 3 [IQR: 6.8 to 152.1 mm 3 ] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (β = 2.83; p = 0.004) but slower noncalcified PV progression (β = -3.39; p = 0.008) and less development of high-risk plaques (β = -0.18; p = 0.049) than in men., Conclusions: The compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (NCT02803411)., Competing Interests: Author Relationship With Industry This work was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176) (to Dr. Chang). The study was also funded in part by a generous gift from the Dalio Institute of Cardiovascular Imaging and the Michael Wolk Foundation. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Dr. Min has received funding from the Dalio Foundation, National Institutes of Health, and GE Healthcare; has served on the scientific advisory board of Arineta and GE Healthcare; and owns equity interest in Cleerly. Dr. Samady has served on the scientific advisory board of Philips; owns equity interest in Covanos Inc.; and has received research grant support from Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess whether coronary atherosclerosis analysis by coronary computed tomography angiography (CTA) may improve prognostic stratification among patients with diffuse coronary artery disease (CAD) BACKGROUND: Coronary CTA has recently emerged as a promising noninvasive tool for advanced analysis of coronary atherosclerosis., Methods: The multicenter CAPIRE (Coronary Atherosclerosis in outlier subjects: Protective and novel Individual Risk factors Evaluation) study is part of the GISSI Outlier Project. A prospective cohort of subjects who underwent coronary CTA for suspected CAD was enrolled. Based on risk factor (RF) burden, patients were defined as having a low clinical risk (0 to 1 RF with the exclusion of patients with diabetes mellitus as single RF) or at high clinical risk (3 or more RFs). Patients with 2 RFs were not enrolled in the study. Coronary CTA advanced plaque assessment was performed. Outcome measures were 3 combined endpoints: acute coronary syndrome (ACS), cardiac death + ACS, and cardiac death + ACS + late revascularization., Results: Among the 544 patients enrolled in the CAPIRE study, in 522 patients, a mean follow-up of 37 ± 10 months was obtained (16 patients were excluded due to 1 < segment involvement score <5 at core lab coronary CTA analysis and 6 patients were lost at follow-up). Higher atherosclerotic burden was found in patients with higher clinical risk, but prevalence of elevated noncalcified plaque volume did not significantly differ between low- versus high-risk patients. Quantitative plaque parameters by coronary CTA were associated with composite endpoints at multivariable analysis when corrected for univariate predictors. Elevated noncalcified plaque volume, expressed as dichotomic variable, was associated with all combined endpoints. Even if the low absolute number of events represents a limitation to the present study, patients with low noncalcified plaque volume had similar risk of cardiac events independently from the presence of multivessel disease, while patients with high noncalcified plaque volume had higher rates of cardiac events., Conclusions: The CAPIRE study confirmed the prognostic value of atherosclerosis assessment by coronary CTA, demonstrating high noncalcified plaque volume as the most ACS-predictive parameter in patients with extensive CAD. (GISSE Outliers CAPIRE [CAPIRE]; NCT02157662)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP)., Background: It is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP., Methods: Patients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) <50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. HRP was defined as lesions with ≥2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions., Results: A total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 ± 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05)., Conclusions: The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to assess the diagnostic performance of coronary computed tomography angiography (CTA) alone, adenosine-stress myocardial perfusion assessed by computed tomography (CTP) alone, and coronary CTA + CTP by using a 16-cm Z-axis coverage scanner versus invasive coronary angiography (ICA) and fractional flow reserve (FFR) as the clinical standard., Background: Diagnostic performance of coronary CTA for in-stent restenosis detection is still challenging. Recently, CTP showed additional diagnostic power over coronary CTA in patients with suspected coronary artery disease. However, few data are available on CTP performance in patients with previous stent implantation., Methods: Consecutive stable patients with previous coronary stenting referred for ICA were enrolled. All patients underwent stress myocardial CTP and rest CTP + coronary CTA. Invasive FFR was performed during ICA when clinically indicated. The diagnostic rate and diagnostic accuracy of coronary CTA, CTP, and coronary CTA + CTP were evaluated in stent-, territory-, and patient-based analyses., Results: In the 150 enrolled patients (132 men; mean age 65.1 ± 9.1 years), the CTP diagnostic rate was significantly higher than that of coronary CTA in all analyses (territory based [96.7% vs. 91.1%; p < 0.0001] and patient based [96% vs. 68%; p < 0.0001]). When ICA was used as gold standard, CTP diagnostic accuracy was significantly higher than that of coronary CTA in all analyses (territory based [92.1% vs. 85.5%, p < 0.03] and patient based [86.7% vs. 76.7%, p < 0.03]). The concordant coronary CTA + CTP assessment exhibited the highest diagnostic accuracy values versus ICA (95.8% in the territory-based analysis). The diagnostic accuracy of CTP was significantly higher than that of coronary CTA (75% vs. 30.5%; p < 0.001). The radiation exposure of coronary CTA + CTP was 4.15 ± 1.5 mSv., Conclusions: In patients with coronary stents, CTP significantly improved the diagnostic rate and accuracy of coronary CTA alone compared with both ICA and invasive FFR as gold standard., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to determine whether cardiac magnetic resonance (CMR) may identify structural heart disease (SHD) in patients with ventricular arrhythmia who had echocardiography ruled out pathological findings., Background: Approximately one-half of sudden cardiac deaths are attributable to malignant VA. Echocardiography is commonly used to identify SHD that is the most frequent substrate of VA., Methods: A single-center prospective study was conducted in consecutive patients with significant VA, categorized as >1,000 but <10,000 ventricular ectopic beats [VEBs]/24 h; ≥10,000 VEBs/24 h; nonsustained ventricular tachycardia, sustained ventricular tachycardia, or a history of resuscitated cardiac arrest, and no pathological findings at echocardiography, requiring a clinically indicated CMR. Primary endpoint was CMR detection of SHD. Secondary endpoints were a composite of CMR detection of SHD and abnormal findings not specific for a definite SHD diagnosis., Results: A total of 946 patients were enrolled (mean 41 ± 16 years of age; 64% men). CMR studies were used to diagnose SHD in 241 patients (25.5%) and abnormal findings not specific for a definite SHD diagnosis in 187 patients (19.7%). Myocarditis (n = 91) was the more frequent disease, followed by arrhythmogenic cardiomyopathy (n = 55), dilated cardiomyopathy (n = 39), ischemic heart disease (n = 22), hypertrophic cardiomyopathy (n = 13), congenital cardiac disease (n = 10), left ventricle noncompaction (n = 5), and pericarditis (n = 5). The strongest univariate and multivariate predictors of SHD on CMR images were chest pain (odds ratios [OR]: 2.52 and 2.38, respectively) and sustained ventricular tachycardia (ORs: 2.67 and 2.23, respectively)., Conclusions: SHD was able to be identified on CMR imaging in a sizable number of patients with significant VA and completely normal echocardiography. Chest pain and sustained ventricular tachycardia were the strongest predictors of positive CMR imaging results., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of the study were to test the diagnostic accuracy of integrated evaluation of dynamic myocardial computed tomography perfusion (CTP) on top of coronary computed tomography angiography (cCTA) plus fractional flow reserve computed tomography derived (FFR CT ) by using a whole-heart coverage computed tomography (CT) scanner as compared with clinically indicated invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR)., Background: Recently, new techniques such as dynamic stress computed tomography perfusion (stress-CTP) emerged as potential strategies to combine anatomical and functional evaluation in a one-shot scan. However, previous experiences with this technique were associated with high radiation exposure., Methods: Eighty-five consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest cCTA followed by stress dynamic CTP with a whole-heart coverage CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). FFR CT was also measured by using the rest cCTA dataset. The diagnostic accuracy to detect functionally significant coronary artery disease (CAD) in a vessel-based model of cCTA alone, cCTA+FFR CT , cCTA+CTP, or cCTA+FFR CT +CTP were assessed and compared by using ICA and invasive FFR as reference. The overall effective dose of dynamic CTP was also measured., Results: The prevalence of obstructive CAD and functionally significant CAD was 77% and 57%, respectively. The sensitivity and specificity of cCTA alone, cCTA+FFR CT , and cCTA+CTP were 83% and 66%, 86% and 75%, and 73% and 86%, respectively. Both the addition of FFR CT and CTP improves the area under the curve (AUC: 0.876 and 0.878, respectively) as compared with cCTA alone (0.826; p < 0.05). The sequential strategy of cCTA+FFR CT +CTP showed the highest AUC (0.919; p < 0.05) as compared with all other strategies. The mean effective radiation dose (ED) for cCTA and stress CTP was 2.8 ± 1.2 mSv and 5.3 ± 0.7 mSv, respectively., Conclusions: The addition of dynamic stress CTP on top of cCTA and FFR CT provides additional diagnostic accuracy with acceptable radiation exposure., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The objective of this meta-analysis was to assess the predictive value of late gadolinium enhancement (LGE) and global systolic impairment for future major adverse cardiovascular events in left ventricular noncompaction (LVNC)., Background: The prognosis of patients with LVNC, with and without left ventricular dysfunction and LGE, is still unclear., Methods: A systematic review of published research and a meta-analysis reporting a combined endpoint of hard (cardiac death, sudden cardiac death, appropriate defibrillator firing, resuscitated cardiac arrest, cardiac transplantation, assist device implantation) and minor (heart failure hospitalization and thromboembolic events) events was performed., Results: Four studies with 574 patients with LVNC and 677 with no LVNC and an average follow-up duration of 5.2 years were analyzed. In patients with LVNC, LGE was associated with the combined endpoint (pooled odds ratio: 4.9; 95% confidence interval: 1.63 to 14.6; p = 0.005) and cardiac death (pooled odds ratio: 9.8; 95% confidence interval: 2.44 to 39.5; p < 0.001). Preserved left ventricular systolic function was found in 183 patients with LVNC: 25 with positive LGE and 158 with negative LGE. In LVNC with preserved ejection fraction, positive LGE was associated with hard cardiac events (odds ratio: 6.1; 95% confidence interval: 2.1 to 17.5; p < 0.001). No hard cardiac events were recorded in patients with LVNC, preserved ejection fraction, and negative LGE., Conclusions: Patients with LVNC but without LGE have a better prognosis than those with LGE. When LGE is negative and global systolic function is preserved, no hard cardiac events are to be expected. Currently available criteria allow diagnosis of LVNC, but to further define the presence and prognostic significance of the disease, LGE and/or global systolic impairment must be considered for better risk stratification., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to compare the diagnostic accuracy of coronary computed tomography angiography (cCTA) with that of cCTA+fractional flow reserve derived from cCTA datasets (FFR CT ) and that of cCTA+static stress-computed tomography perfusion (stress-CTP) in detecting functionally significant coronary artery lesions using invasive coronary angiography (ICA) plus invasive FFR as the reference standard., Background: FFR CT and static stress-CTP are new techniques that combine anatomy and functional evaluation to improve assessment of coronary artery disease (CAD) using cCTA., Methods: A total of 147 consecutive symptomatic patients scheduled for clinically indicated ICA+invasive FFR were evaluated with cCTA, FFR CT , and stress-CTP., Results: Vessel-based and patient-based sensitivity, specificity, and negative predictive values, and positive predictive values, and accuracy rates of cCTA were 99%, 76%, 100%, 61%, 82%, and 95%, 54%, 94%, 63%, 73%, respectively. cCTA+FFR CT showed vessel-based and patient-based sensitivity, specificity, and negative predictive values, and positive predictive values and accuracy rates of 88%, 94%, 95%, 84%, 92%, and 90%, 85%, 92%, 83%, 87%, respectively. Finally, cCTA+stress-CTP showed vessel-based and patient-based sensitivity, specificity, and negative predictive values, and positive predictive values and accuracy rates of 92%, 95%, 97%, 87%, 94% and 98%, 87%, 99%, 86%, 92%, respectively. Both FFR CT and stress-CTP significantly improved specificity and positive predictive values compared to those of cCTA alone. The area under the curve to detect flow-limiting stenoses of cCTA, cCTA+FFR CT , and cCTA+CTP were 0.89, 0.93, 0.92, and 0.90, 0.94, and 0.93 in a vessel-based and patient-based model, respectively, with significant additional values for both cCTA+FFR CT and cCTA+CTP versus cCTA alone (p < 0.001) but no differences between cCTA+FFR CT versus cCTA+CTP., Conclusions: FFR CT and stress-CTP in addition to cCTA are valid and comparable tools to evaluate the functional relevance of CAD., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study compared the safety and diagnostic yield of a selective referral strategy using coronary computed tomographic angiography (CCTA) compared with a direct referral strategy using invasive coronary angiography (ICA) as the index procedure., Background: Among patients presenting with signs and symptoms suggestive of coronary artery disease (CAD), a sizeable proportion who are referred to ICA do not have a significant, obstructive stenosis., Methods: In a multinational, randomized clinical trial of patients referred to ICA for nonemergent indications, a selective referral strategy was compared with a direct referral strategy. The primary endpoint was noninferiority with a multiplicative margin of 1.33 of composite major adverse cardiovascular events (blindly adjudicated death, myocardial infarction, unstable angina, stroke, urgent and/or emergent coronary revascularization or cardiac hospitalization) at a median follow-up of 1-year., Results: At 22 sites, 823 subjects were randomized to a selective referral and 808 to a direct referral strategy. At 1 year, selective referral met the noninferiority margin of 1.33 (p = 0.026) with a similar event rate between the randomized arms of the trial (4.6% vs. 4.6%; hazard ratio: 0.99; 95% confidence interval: 0.66 to 1.47). Following CCTA, only 23% of the selective referral arm went on to ICA, which was a rate lower than that of the direct referral strategy. Coronary revascularization occurred less often in the selective referral group compared with the direct referral to ICA (13% vs. 18%; p < 0.001). Rates of normal ICA were 24.6% in the selective referral arm compared with 61.1% in the direct referral arm of the trial (p < 0.001)., Conclusions: In stable patients with suspected CAD who are eligible for ICA, the comparable 1-year major adverse cardiovascular events rates following a selective referral and direct referral strategy suggests that both diagnostic approaches are similarly effective. In the selective referral strategy, the reduced use of ICA was associated with a greater diagnostic yield, which supported the usefulness of CCTA as an efficient and accurate method to guide decisions of ICA performance. (Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization [CONSERVE]; NCT01810198)., (Published by Elsevier Inc.)

Objectives: This study aimed to evaluate the correlation between different haptoglobin (Hp) phenotypes and myocardial infarction characteristics as detected by cardiac magnetic resonance (CMR) in consecutive patients after ST-segment elevation myocardial infarction (STEMI)., Background: Hp is a plasma protein that prevents iron-mediated oxidative tissue damage. CMR has emerged as the gold standard technique to detect left ventricular ejection fraction (LVEF), extent of scar with late gadolinium enhancement (LGE) technique, microvascular obstruction (MVO), and myocardial hemorrhage (MH) in patients with STEMI treated by primary percutaneous coronary intervention (pPCI)., Methods: A total of 145 consecutive STEMI patients (mean age 62.2 ± 10.3 years; 78% men) were prospectively enrolled and underwent Hp phenotyping and CMR assessment within 1 week after STEMI., Results: CMR showed an area at risk (AAR) involving 26.6 ± 19.1% of left ventricular (LV) mass with a late LGE extent of 15.2 ± 13.1% of LV mass. MVO and MH occurred in 38 (26%) and 12 (8%) patients, respectively. Hp phenotypes 1-1, 2-1, 2-2 were observed in 15 (10%), 62 (43%), and 68 (47%), respectively. Multivariable analysis demonstrated that body mass index, Hp2-2, diabetes, and peak troponin I were independent predictors of MVO with Hp2-2 associated with the highest odds ratio (OR) (OR: 5.5 [95% confidence interval [CI]: 2.1 to 14.3; p < 0.001]). Hp2-2 significantly predicted both the presence (area under the curve [AUC]: 0.63 [95% CI: 0.53 to 0.72; p = 0.008]) and extent of MVO (AUC: 0.63 [95% CI: 0.54 to 0.72; p = 0.007])., Conclusions: Hp phenotype is an independent predictor of MVO. Therefore, Hp phenotyping could be used for risk stratification and may be useful in assessing new therapies to reduce myocardial reperfusion injury in patients with STEMI., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to evaluate the diagnostic accuracy of stress computed tomography myocardial perfusion (CTP) for the detection of functionally significant coronary artery disease (CAD) by using invasive coronary angiography (ICA) plus invasive fractional flow reserve (FFR) as the reference standard in consecutive intermediate- to high-risk symptomatic patients., Background: Stress CTP recently emerged as a potential strategy to combine the anatomic and functional evaluation of CAD in a single scan., Methods: A total of 100 consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest coronary computed tomography angiography (CTA) followed by stress static CTP with a whole-heart coverage CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). Diagnostic accuracy and overall effective dose were assessed and compared versus those of ICA and invasive FFR., Results: The prevalence of obstructive CAD and functionally significant CAD were 69% and 44%, respectively. Coronary CTA alone demonstrated a per-vessel and per-patient sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of 98%, 76%, 99%, 63%, and 83% and of 98%, 54%, 96%, 68%, and 76%, respectively. Combining coronary CTA with stress CTP, per-vessel and per-patient sensitivity, specificity, negative predictive value, positive predictive value, and accuracy were 91%, 94%, 96%, 86%, and 93% and 98%, 83%, 98%, 86%, and 91%, with a significant improvement in specificity, positive predictive value, and accuracy in both models. The mean effective dose for coronary CTA and stress CTP were 2.8 ± 1.4 mSv and 2.5 ± 1.1 mSv., Conclusions: The inclusion of stress CTP for the evaluation of patients with an intermediate to high risk for CAD is feasible and improved the diagnostic performance of coronary CTA for detecting functionally significant CAD., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to investigate whether early post-infarction cardiac magnetic resonance (CMR) parameters provide additional long-term prognostic value beyond traditional outcome predictors in ST-segment elevation myocardial infarction (STEMI) patients., Background: Long-term prognostic significance of CMR in STEMI patients has not been assessed yet., Methods: This was a longitudinal study from a multicenter registry that prospectively included STEMI patients undergoing CMR after infarction. Between May 2003 and August 2015, 810 revascularized STEMI patients were included. CMR was performed at a median of 4 days after STEMI. Infarct size, microvascular obstruction (MVO), and left ventricular (LV) volumes and function were measured. Primary endpoint was a composite of all death and decompensated heart failure (HF)., Results: During median follow-up of 5.5 years (range 1.0 to 13.1 years), primary endpoint occurred in 99 patients (39 deaths and 60 HF hospitalization). MVO was a strong predictor of the composite endpoint after correction for important clinical, CMR, and angiographic parameters, including age, LV systolic function, and infarct size. The independent prognostic value of MVO was confirmed in all multivariate models irrespective of whether it was included as a dichotomous (presence of MVO, hazard ratio [HR]: 1.985 to 1.995), continuous (MVO extent as % LV, HR: 1.095 to 1.097), or optimal cutoff value (MVO extent ≥2.6% of LV; HR: 3.185 to 3.199; p < 0.05 for all). MVO extent ≥2.6% of LV was a strong independent predictor of all death (HR: 2.055; 95% confidence interval: 1.076 to 3.925; p = 0.029) and HF hospitalization (HR: 5.999; 95% confidence interval: 3.251 to 11.069; p < 0.001). Finally, MVO extent ≥2.6% of LV provided incremental prognostic value over traditional outcome predictors (net reclassification improvement index: 0.16 to 0.30; p < 0.05 for all models)., Conclusions: Early post-infarction CMR-based MVO is a strong independent prognosticator in revascularized STEMI patients. Remarkably, MVO extent ≥2.6% of LV improved long-term risk stratification over traditional outcome predictors., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to determine the long-term prognostic value of coronary computed tomography angiography (CTA) in a large coronary artery bypass graft (CABG) population., Background: Coronary CTA has shown prognostic utility in patients without previous revascularization. However, prognostication with coronary CTA in CABG patients has not been fully assessed., Methods: Between March 2005 and April 2009, 887 consecutive CABG patients (mean age 66.8 ± 8.4 years) were considered for the inclusion in the study. Patients were classified by the number of unprotected coronary territories (UCTs) and a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS). A primary endpoint (cardiovascular [CV] death, nonfatal myocardial infarction [MI]) and a secondary combined adverse events endpoint (CV death, MI, unstable angina, and late revascularizations) were recorded., Results: Among the 887 evaluated, 166 did not meet the inclusion criteria. The final study population consisted of 721 subjects. Ten patients were excluded for unevaluable coronary CTA images. Of the remaining 711 patients, follow-up (mean 73.5 ± 14 months) was obtained in 698. Three hundred forty-seven events were recorded. By univariable analysis, the strongest coronary CTA predictors of events were UCT 2 and 3 (hazard ratio [HR] for CV death/MI: 7.5 and 10.19, p < 0.0001 and p < 0.0003, respectively) and CAPS 4 (HR for CV death/MI: 24.1, p < 0.0001). A high number of UCTs was also a strong multivariable independent predictor of CV death/MI (HR: 7.78 and 10.18 for UCT 2 and 3, p < 0.0001 and p < 0.0007, respectively). Cumulative survival rates for CV death/MI and composite adverse CV events were 86% and 73% with UCT 0, 84% and 49% with UCT 1, 53% and 3% with UCT 2, and 29% and 0% with UCT 3, respectively., Conclusions: Coronary CTA appears to be a promising tool for long-term risk stratification of CABG patients. The UCT score has significant prognostic value to predict CV deaths/MI., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of the study was to perform a comparison of the prognostic performance of computed tomography coronary angiography (CTA) and exercise electrocardiography (ex-ECG) in patients with suspected coronary artery disease (CAD)., Background: CAD is a major cause of mortality and morbidity, and its management consumes a large proportion of the health care budget. Therefore, identification of patients at high risk of adverse events is crucial. Despite its limited accuracy, ex-ECG is the most commonly used noninvasive test in CAD evaluation. CTA was recently introduced as alternative test., Methods: We enrolled 681 patients (age 61.3 ± 10.4 years, 461 men) with atypical or typical angina and no history of CAD. All patients underwent ex-ECG and CTA and were followed for 44 ±12 months. The endpoints were all cardiac events, defined as nonfatal myocardial infarction, cardiac death, and revascularization, and hard cardiac events, defined as all cardiac events excluding revascularization., Results: ex-ECG and CTA were rated as positive in 419 (61%) and 274 (40%) of 681 patients, respectively. In univariate analysis, both ex-ECG and CTA were predictors of all cardiac events (hazard ratio [HR]: 2.09, 95% confidence interval [CI]: 1.5 to 2.8; p < 0.0001 and HR: 21.1, 95% CI: 14.6 to 30.5; p < 0.0001, respectively) and hard cardiac events (HR: 1.9, 95% CI: 1.1 to 3.2; p = 0.02 and HR: 6.8, 95% CI: 3.9 to 11.0; p < 0.0001, respectively), whereas in a multivariate analysis, CAD with ≥50% stenoses detected by CTA was the only independent predictor of hard cardiac events. Stratifying our population by ex-ECG and CTA findings, Kaplan-Meier curves showed that ex-ECG provides only a further risk stratification in the subset of patients with positive findings on CTA and a low to intermediate likelihood of CAD. Moreover, positive findings on CTA identify a shorter event-free period, regardless the ex-ECG findings for both all cardiac events and hard cardiac events, respectively., Conclusions: CTA may have a higher prognostic value compared with ex-ECG in patients with suspected CAD, mainly in those with a low to intermediate pre-test likelihood of CAD., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to assess the long-term prognostic role of multidetector computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD)., Background: Use of CTA is increasing in patients with suspected CAD. Although there is a large body of data supporting the prognostic role of CTA for major adverse cardiac events in the intermediate term, its long-term prognostic role in patients with suspected CAD is not well studied., Methods: Between February 2005 and March 2008, 1,304 consecutive patients were prospectively studied with CTA for detecting the presence and assessing extent of CAD (disease extension and coronary plaque scores). Patients were classified according to the presence of normal coronaries and nonobstructive (<50%) and obstructive (>50%) coronary lesions. The composite rates of hard cardiac events (cardiac deaths and nonfatal myocardial infarctions) and all cardiac events (including late revascularization) were the endpoints of the study., Results: Seventy patients were excluded because their CTA data were uninterpretable. Of the remaining 1,234 patients, clinical follow-up (mean 52 ± 22 months) was obtained for 1,196 (97%). A total of 475 events were recorded, with 136 hard events (18 cardiac deaths and 118 nonfatal myocardial infarctions) and 123 late revascularizations. A total of 216 patients with early elective revascularizations were excluded from the survival analysis. Significant independent predictors of events in multivariate analysis were multivessel disease and left main CAD. Cumulative event-free survival was 100% for hard and all events in patients with normal coronary arteries, 88% for hard events and 72% for all events in patients with nonobstructive CAD, and 54% for hard events and 31% for all events in patients with obstructive CAD. Multivessel CAD was associated with a higher rate of hard cardiac events., Conclusions: CTA provides prognostic information in patients with suspected CAD and unknown cardiac disease, showing excellent long-term prognosis when there is no evidence of atherosclerosis and allowing risk stratification when CAD is present., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aims of this study were to analyze in a large series of patients undergoing transcatheter aortic valve implantation (TAVI): 1) the accuracy of 3-dimensional transesophageal echocardiographic (3DTEE) measurement of left coronary cusp (LCC) length and of the distances from left main coronary ostium (LM) to the aortic annulus (AA) pre-operatively and to the aortic prosthesis post-operatively; and 2) the role of the 3DTEE measurements in predicting the prosthetic deployment and the association between prosthesis position and aortic regurgitation (AR) and/or prosthesis-patient mismatch (PPM)., Background: Coronary ostia occlusion is a possible complication in TAVI; therefore, the careful pre-operative evaluation of AA-LM and LCC length, and the post-operative analysis of the relationship between the prosthesis and LM, may influence the procedural outcomes. Even though multidetector computed tomography (MDCT) is the gold standard pre-operatively, sometimes it cannot be performed and it is rarely repeated post-operatively., Methods: In 122 patients undergoing TAVI, pre-operative AA-LM and LCC measurements obtained by 3DTEE and MDCT were compared. Post-operatively, the feasibility of 3DTEE evaluation of the prosthesis-LM distance was performed. The relationship between 3DTEE overlap of the prosthesis with the anterior mitral leaflet and AR/PPM was assessed., Results: Pre-operatively, 3DTEE AA-LM (r = 0.83) and LCC (r = 0.69) significantly correlated with MDCT. Post-operatively, 3DTEE prosthesis-LM distance was 2.1 ± 1.9 mm. The prosthesis reached or exceeded LM in 6 and 10 cases, respectively. Prosthesis overlap with mitral leaflet was 4.7 ± 1.8 mm. Significant correlation between the 3DTEE computed and nominal length of the prosthesis was found (r = 0.61). No correlations were found between prosthesis-mitral leaflet overlap and aortic regurgitation or PPM., Conclusions: AA-LM distance and LCC length may be accurately estimated by 3DTEE, which may represent a valid alternative to MDCT. Pre- and post-3DTEE data concerning the aortic root, such as LM, aortic valve, and prosthetic morphology, give new insights into TAVI and its complications., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)