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Background: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease., Methods: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm 3 ) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization., Results: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P =0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P <0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P =0.018) together with family history, baseline percent atheroma volume, and rapid PP., Conclusions: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411., Competing Interests: Dr Chang receives funding from 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). Dr Min receives funding from GE Healthcare and serves on the scientific advisory board of Arineta and GE Healthcare. Dr Min also has an equity interest in and is an employee of Cleerly Inc. The other authors report no conflicts.

Background: Radiomics is expected to identify imaging features beyond the human eye. We investigated whether radiomics can identify coronary segments that will develop new atherosclerotic plaques on coronary computed tomography angiography (CCTA)., Methods: From a prospective multinational registry of patients with serial CCTA studies at ≥ 2-year intervals, segments without identifiable coronary plaque at baseline were selected and radiomic features were extracted. Cox models using clinical risk factors (Model 1), radiomic features (Model 2) and both clinical risk factors and radiomic features (Model 3) were constructed to predict the development of a coronary plaque, defined as total PV ​≥ ​1 ​mm 3 , at follow-up CCTA in each segment., Results: In total, 9583 normal coronary segments were identified from 1162 patients (60.3 ​± ​9.2 years, 55.7% male) and divided 8:2 into training and test sets. At follow-up CCTA, 9.8% of the segments developed new coronary plaque. The predictive power of Models 1 and 2 was not different in both the training and test sets (C-index [95% confidence interval (CI)] of Model 1 vs. Model 2: 0.701 [0.690-0.712] vs. 0.699 [0.0.688-0.710] and 0.696 [0.671-0.725] vs. 0.0.691 [0.667-0.715], respectively, all p ​> ​0.05). The addition of radiomic features to clinical risk factors improved the predictive power of the Cox model in both the training and test sets (C-index [95% CI] of Model 3: 0.772 [0.762-0.781] and 0.767 [0.751-0.787], respectively, all p ​< ​00.0001 compared to Models 1 and 2)., Conclusion: Radiomic features can improve the identification of segments that would develop new coronary atherosclerotic plaque., Clinical Trial Registration: ClinicalTrials.gov NCT0280341., Competing Interests: Declaration of competing interest Dr. Chang receives 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). Dr. James K. Min receives funding from GE Healthcare and serves on the scientific advisory board of Arineta and GE Healthcare. Dr. Min also has an equity interest in and is an employee of Cleerly, Inc. The remaining authors have no relevant disclosures., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Colchicine is an anti-inflammatory medication, classically used to treat a wide spectrum of autoimmune diseases. More recently, colchicine has proven itself a key pharmacotherapy in cardiovascular disease (CVD) management, atherosclerotic plaque modification, and coronary artery disease (CAD) treatment. Colchicine acts on many anti-inflammatory pathways, which translates to cardiovascular event reduction, plaque transformation, and plaque reduction. With the FDA's 2023 approval of colchicine for reducing cardiovascular events, a novel clinical pathway opens. This advancement paves the route for CVD management that synergistically merges lipid lowering approaches with inflammation inhibition modalities. This pioneering moment spurs the need for this manuscript's comprehensive review. Hence, this paper synthesizes and surveys colchicine's new role as an atherosclerotic plaque modifier, to provide a framework for physicians in the clinical setting. We aim to improve understanding (and thereby application) of colchicine alongside existing mechanisms for CVD event reduction. This paper examines colchicine's anti-inflammatory mechanism, and reviews large cohort studies that evidence colchicine's blossoming role within CAD management. This paper also outlines imaging modalities for atherosclerotic analysis, reviews colchicine's mechanistic effect upon plaque transformation itself, and synthesizes trials which assess colchicine's nuanced effect upon atherosclerotic transformation., Competing Interests: Declaration of competing interest Matthew J. Budoff discloses the following: received grants from the following companies: Novo Nordisk, Novartis, Astrazeneca, Heartflow, GE Healthcare, Amgen, and Boehringer Ingleheim, Department of Defense, Centers for Disease Control and the National Institutes of Health. Dr. Budoff received honoraria from Novo Nordisk, Esperion, Astrazeneca, Merck, Janssen, and Eli Lilly. Jonathon Leipsic is a consultant to and holds stock options in HeartFlow and Circle CVI and modest speaking fees from Philips and GE Healthcare. All the rest of authors have no conflicts to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background & Objectives: The long-term prognostic implications of CT angiography-derived fractional flow reserve (FFR CT ) remains unclear. We aimed to explore the long-term outcomes of FFR CT in the first-in-human study of it., Materials & Methods: A total of 156 vessels from 102 patients with stable coronary artery disease, who underwent coronary CT angiography (CCTA) and invasive FFR measurement, were followed. The primary endpoint was target vessel failure (TVF), including cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. Outcome analysis with FFR CT was performed on a per-vessel basis using a marginal Cox proportional hazard model., Results: During median 9.9 years of follow-up, TVF occurred in 20 (12.8%) vessels. FFR CT  ​≤0.80 discriminated TVF (hazard ratio [HR] 2.61, 95% confidence interval [CI] 1.06, 6.45). Among 94 vessels with deferral of percutaneous coronary intervention (PCI), TVF risk was inversely correlated with FFR CT  ​(HR 0.62 per 0.1 increase, 95% CI 0.44, 0.86), with the cumulative incidence of TVF being 2.6%, 15.2%, and 28.6% for vessels with FFR CT  ​>0.90, 0.81-0.90, and ≤0.80, respectively (p-for-trend 0.005). Predictive value for clinical outcomes of FFR CT was similar to that of invasive FFR (c-index 0.79 vs 0.71, P ​= ​0.28). The estimated TVF risk was higher in the deferral of PCI group than the PCI group for vessels with FFR CT ≤0.81., Conclusion: FFR CT showed improved long-term risk stratification and displayed a risk continuum similar to invasive FFR., Clinical Trial Registration: NCT01189331., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interest: BKK received research grants from Abbott, Philips, and HeartFlow, provided to the Seoul National University. JL holds stock options in and serves as a consultant to HeartFlow and Circle CVI, and has a research grant from GE Healthcare. GC, MS, CZ, and CAT are the employees and shareholders of HeartFlow, Inc., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Hyperpolarized 129 Xe gas MRI is an emerging technique to evaluate and measure regional lung function including pulmonary gas distribution and gas exchange. Chest computed tomography (CT) still remains the clinical gold standard for imaging of the lungs, though, in part due to the rapid CT protocols that acquire high-resolution images in seconds and the widespread availability of CT scanners. Quantitative approaches have enabled the extraction of structural lung parenchymal, airway and vascular measurements from chest CT that have been evaluated in many clinical research studies. Together, CT and 129 Xe MRI provide complementary information that can be used to evaluate regional lung structure and function, resulting in new insights into lung health and disease. 129 Xe MR-CT image registration can be performed to measure regional lung structure-function to better understand lung disease pathophysiology, and to perform image-guided pulmonary interventions. Here, a method for 129 Xe MRI-CT registration is outlined to support implementation in research or clinical settings. Registration methods and applications that have been employed to date in the literature are also summarized, and suggestions are provided for future directions that may further overcome technical challenges related to 129 Xe MR-CT image registration and facilitate broader implementation of regional lung structure-function evaluation.

Purpose To examine the relationship between smoking status and coronary volume-to-myocardial mass ratio (V/M) among individuals with coronary artery disease (CAD) undergoing CT fractional flow reserve (CT-FFR) analysis. Materials and Methods In this secondary analysis, participants from the ADVANCE registry evaluated for suspected CAD from July 15, 2015, to October 20, 2017, who were found to have coronary stenosis of 30% or greater at coronary CT angiography (CCTA) were included if they had known smoking status and underwent CT-FFR and V/M analysis. CCTA images were segmented to calculate coronary volume and myocardial mass. V/M was compared between smoking groups, and predictors of low V/M were determined. Results The sample for analysis included 503 current smokers, 1060 former smokers, and 1311 never-smokers (2874 participants; 1906 male participants). After adjustment for demographic and clinical factors, former smokers had greater coronary volume than never-smokers (former smokers, 3021.7 mm 3 ± 934.0 [SD]; never-smokers, 2967.6 mm 3 ± 978.0; P = .002), while current smokers had increased myocardial mass compared with never-smokers (current smokers, 127.8 g ± 32.9; never-smokers, 118.0 g ± 32.5; P = .02). However, both current and former smokers had lower V/M than never-smokers (current smokers, 24.1 mm 3 /g ± 7.9; former smokers, 24.9 mm 3 /g ± 7.1; never-smokers, 25.8 mm 3 /g ± 7.4; P < .001 [unadjusted] and P = .002 [unadjusted], respectively). Current smoking status (odds ratio [OR], 0.74 [95% CI: 0.59, 0.93]; P = .009), former smoking status (OR, 0.81 [95% CI: 0.68, 0.97]; P = .02), stenosis of 50% or greater (OR, 0.62 [95% CI: 0.52, 0.74]; P < .001), and diabetes (OR, 0.67 [95% CI: 0.56, 0.82]; P < .001) were independent predictors of low V/M. Conclusion Both current and former smoking status were independently associated with low V/M. Keywords: CT Angiography, Cardiac, Heart, Ischemia/Infarction Clinical trial registration no. NCT02499679 Supplemental material is available for this article . © RSNA, 2024.

Objectives: No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD., Methods: Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA., Results: In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3 years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively., Conclusions: The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD., Clinical Relevance Statement: The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies., Key Points: • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Competing Interests: Funding Support and Author Disclosures Dr Wood is a consultant for Edwards Lifesciences and Abbott; and has received research funding from Edwards Lifesciences and Abbott. Dr Leipsic is supported by a Canadian Research Chair in Advanced Cardiopulmonary Imaging; is a consultant for MVRX, Heartflow Inc, and Circle Cardiovascular Imaging; and provides CT core lab services for Edwards Lifesciences, Medtronic, Neovasc, Boston Scientific, and Tendyne Holdings for which no direct compensation is received. Dr Sathananthan has received speaker fees from Edwards Lifesciences; is a consultant for Edwards Lifesciences, Boston Scientific, NVT Medical, and Medtronic; and has received research support from Medtronic, Vivitro Labs, and Edwards Lifesciences. Dr Sellers is a consultant for Edwards Lifesciences, Anteris, Excision Medical, and Medtronic; and has received research support from Medtronic, Vivitro Labs, and Edwards Lifesciences. Dr Webb is a consultant for Edwards Lifesciences; and has received research funding from Edwards Lifesciences, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Long COVID impacts ∼10% of people diagnosed with COVID-19, yet the pathophysiology driving ongoing symptoms is poorly understood. We hypothesised that 129 Xe magnetic resonance imaging (MRI) could identify unique pulmonary phenotypic subgroups of long COVID, therefore we evaluated ventilation and gas exchange measurements with cluster analysis to generate imaging-based phenotypes., Methods: COVID-negative controls and participants who previously tested positive for COVID-19 underwent 129 XeMRI ∼14-months post-acute infection across three centres. Long COVID was defined as persistent dyspnea, chest tightness, cough, fatigue, nausea and/or loss of taste/smell at MRI; participants reporting no symptoms were considered fully-recovered. 129 XeMRI ventilation defect percent (VDP) and membrane (Mem)/Gas, red blood cell (RBC)/Mem and RBC/Gas ratios were used in k-means clustering for long COVID, and measurements were compared using ANOVA with post-hoc Bonferroni correction., Results: We evaluated 135 participants across three centres: 28 COVID-negative (40±16yrs), 34 fully-recovered (42±14yrs) and 73 long COVID (49±13yrs). RBC/Mem (p=0.03) and FEV 1 (p=0.04) were different between long- and COVID-negative; FEV 1 and all other pulmonary function tests (PFTs) were within normal ranges. Four unique long COVID clusters were identified compared with recovered and COVID-negative. Cluster1 was the youngest with normal MRI and mild gas-trapping; Cluster2 was the oldest, characterised by reduced RBC/Mem but normal PFTs; Cluster3 had mildly increased Mem/Gas with normal PFTs; and Cluster4 had markedly increased Mem/Gas with concomitant reduction in RBC/Mem and restrictive PFT pattern., Conclusion: We identified four 129 XeMRI long COVID phenotypes with distinct characteristics. 129 XeMRI can dissect pathophysiologic heterogeneity of long COVID to enable personalised patient care., Competing Interests: Conflicts of interest: Rachel Eddy reports grants from Michael Smith Health Research BC, Canadian Respiratory Research Network and Natural Sciences and Engineering Research Council Canada, consulting fees from VIDA Diagnostics Inc., payment or honoraria for lectures from Thorasys Thoracic Medical Systems Inc., support for attending meetings and/or travel from Canadian Institutes of Health Research – Institute of Circulatory and Respiratory Health, and a leadership or fiduciary role for the Xenon MRI Clinical Trials Consortium (Steering Committee Member). Conflicts of interest: David Mummy reports consultancy fees from Polarean Imaging plc. Conflicts of interest: Firoozeh Gerayeli reports grants from MITACS Accelerate. Conflicts of interest: Jonathon Leipsic reports grants from GE Healthcare, consultancy fees and support for attending meetings and/or travel from Heartflow, and owns stock/stock options in Heartflow. Conflicts of interest: Janice Leung reports grants from Canadian Institutes of Health Research and BC Lung Foundation, payment or honoraria for lectures, presentations, manuscript writing or educational events from BC Lung Foundation, participation on a data safety monitoring board or advisory board for Enhance Quality Safety, and Patient experience in Chronic Obstructive Pulmonary Disorder (EQuiP COPD), and leadership or fiduciary roles for Canadian Respiratory Research Network and CanCOLD Study. Conflicts of interest: Bastiaan Driehuys reports grants from Translating Duke Health (Duke Internal Award), royalties or licenses from Polarean Imaging, a leadership or fiduciary role with Polarean Imaging, and owns stock/stock options in Polarean Imaging. Conflicts of interest: Loretta G. Que reports grants from Translating Duke Health (Duke Internal Award), and a leadership or fiduciary role as member of XeMRI Consortium. Conflicts of interest: Mario Castro reports grants from NIH, ALA, PCORI, AstraZeneca, Gala Therapeutics, Genentech, GSK, Novartis, Pulmatrix, Sanofi-Aventis, Shionogi and Theravance, consulting fees from Genentech, Teva, Sanofi-Aventis, Merck, Novartis, Arrowhead Pharmaceuticals, Allakos, Amgen, OM Pharma, Pfizer, Pioneering Medicines and GSK, payment or honoraria for lectures, presentations, manuscript writing or educational events from Amgen, AstraZeneca, Genentech, Regeneron, Sanofi-Aventis and Teva, and owns stock/stock options in Aer Therapeutics. Conflicts of interest: Don D. Sin reports payment or honoraria for lectures, presentations, manuscript writing or educational events from GSK, AZ and BI, and participation on a data safety monitoring board or advisory board for NHLBI. Conflicts of interest: Peter Niedbalski reports grants from Scleroderma Foundation (new investigator grant) and American Heart Association (CDA 930177), and consultancy fees, payment or honoraria for lectures, and support for attending meetings and/or travel from Polarean Imaging Plc. Conflicts of interest: The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)

Murray law-based quantitative flow ratio (µQFR) assesses fractional flow reserve (FFR) in bifurcation lesions using a single angiographic view, enhancing the feasibility of analysis; however, accuracy may be compromised in suboptimal angiographic projections. FFR CT is a well-validated non-invasive method measuring FFR from coronary computed tomographic angiography (CCTA). We evaluated the feasibility of µQFR in left main (LM) bifurcations, the impact of the optimal/suboptimal fluoroscopic view with respect to CCTA, and its diagnostic concordance with FFR CT . In 300 patients with three-vessel disease, the values of FFR CT and µQFR were compared at distal LM, proximal left anterior descending artery (pLAD) and circumflex artery (pLCX). The optimal viewing angle of LM bifurcation was defined on CCTA by 3-dimensional coordinates and converted into a 2-dimensional fluoroscopic view. The best fluoroscopic projection was considered the closest angulation to the optimal viewing angle on CCTA. µQFR was successfully computed in 805 projections. In the best projections, µQFR sensitivity was 88.2% (95% CI 76.1-95.6) and 84.8% (71.1-93.7), and specificity was 96.8% (93.8-98.6) and 97.2% (94.4-98.9), in pLAD and pLCX, respectively, with regard to FFR CT . The AUC of µQFR for predicting FFR CT  ≤ 0.80 tended to be improved using the best versus suboptimal projections (0.94 vs. 0.89 [p = 0.048] in pLAD; 0.94 vs. 0.88 [p = 0.075] in pLCX). Computation of µQFR in LM bifurcations using a single angiographic view showed high feasibility from post-hoc analysis of coronary angiograms obtained for clinical purposes. The fluoroscopic viewing angle influences the diagnostic performance of physiological assessment using a single angiographic view., (© 2023. The Author(s).)

Background: A score combining the burden of stenosis severity on coronary computed tomography angiography (CCTA) and flow impairment by fractional flow reserve derived from computed tomography (FFR CT ) may be a better predictor of clinical events than either parameter alone., Methods: The Functional FFR CT Score (FFS) combines CCTA and FFR CT parameters in an allocated point-based system. The feasibility of the FFS was assessed in cohort of 72 stable chest pain patients with matched CCTA and FFR CT datasets. Validation was performed using 2 cohorts: (a) 4468 patients from the ADVANCE Registry to define its association with revascularization and major adverse cardiovascular events (MACE); (b) 212 patients from the FORECAST trial to determine predictors of MACE., Results: The median calculation time for the FFS was 10 (interquartile range 6-17) seconds, with strong intra-operator and inter-operator agreement (Cohen's Kappa 0.89 (±0.37, p ​< ​0.001) and 0.83 (±0.04, p ​< ​0.001, respectively). The FFS correlated strongly with both the CT-SYNTAX and the Functional CT-SYNTAX scores (rS ​= ​0.808 for both, p ​< ​0.001). In the ADVANCE cohort the FFS had good discriminatory abilities for revascularization with an area under the curve of 0.82, 95 ​% confidence interval (CI) 0.81-0.84, p ​< ​0.001. Patients in the highest FFS tertile had significantly higher rates of revascularization (61 ​% vs 5 ​%, p ​< ​0.001) and MACE (1.9 ​% vs 0.5 ​%, p ​= ​0.001) compared with the lowest FFS tertile. In the FORECAST cohort the FFS was an independent predictor of MACE at 9-month follow-up (hazard ratio 1.04, 95 ​% CI 1.01-1.08, p ​< ​0.01)., Conclusion: The FFS is a quick-to-calculate and reproducible score, associated with revascularization and MACE in two distinct populations of stable symptomatic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr Wood is a consultant to and has received research funding from Edwards Lifesciences and Abbott. Dr Webb is a consultant for Edwards Lifesciences; and has received research funding from Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Leipsic is supported by a Canadian Research Chair in Advanced Cardiopulmonary Imaging; is a consultant for MVRx, HeartFlow, and Circle Cardiovascular Imaging; and provides computed tomographic core lab services for Edwards Lifesciences, Medtronic, Neovasc, Boston Scientific, and Tendyne Holdings, for which no direct compensation is received. Dr Sathananthan has received speaking fees from Edwards Lifesciences; has received research support from Medtronic, Vivitro Labs, and Edwards Lifesciences; and is a consultant for Edwards Lifesciences, Boston Scientific, NVT, and Medtronic. Dr Sellers is a consultant to Edwards Lifesciences, Anteris Technologies, Excision Medical, and Medtronic; and has received research support from Medtronic, Vivitro Labs, and Edwards Lifesciences. Drs Moss and Boone are consultants for Edwards Lifesciences; and have received speaking fees from Edwards Lifesciences and Abbott Vascular. Dr Akodad is a consultant for Medtronic and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Favourable early outcomes have been reported following valve-in-valve transcatheter mitral valve replacement (TMVR). However, reports of long-term outcomes are lacking. We aimed to evaluate early and late outcomes in a large first-in-human valve-in-valve TMVR 13-year experience., Methods: All patients undergoing valve-in-valve TMVR in our centre from 2008 to 2021 were included. Clinical and echocardiographic outcomes, defined according to the Mitral Valve Academic Research Consortium, were reported., Results: A total of 119 patients were analysed: mean age 76.8 ± 10.2 years, mean Society of Thoracic Surgeons score 10.7 ± 6.8%, 55.4% female, 63.9% transapical access. Thirty-day mortality was 2.5% for the total population and 0.0% after transseptal TMVR. Maximum follow-up was 13.1 years. During a median follow-up of 3.4 years (interquartile range 1.8-5.3 years), 55 patients (46.2%) died, mainly from noncardiovascular causes. Valve hemodynamics were acceptable at 5 years, with 2.5% structural dysfunction. Patients treated from 2016 on (n = 68; 57.1%), following the advent of routine use of the Sapien 3 valve, CT screening, and transseptal access, were compared with those treated before 2016 (n = 51; 42.9%). Patients from 2016 on had a higher technical success rate (100.0% vs 94.1%; P = 0.04), shorter hospitalisation (P < 0.001), trending lower 30-day mortality (1.5% vs 3.9%; P = 0.4) and better 5-year survival (74.7% vs 41.1%; P = 0.03)., Conclusions: Valve-in-valve TMVR can be performed with little morbidity and low mortality. Mid- to long-term survival remains limited owing to advanced age and comorbidities. Structural bioprosthetic valve dysfunction was rare and redo TMVR feasible in selected patients. Outcomes continue to improve, but the role for valve-in-valve TMVR in lower surgical risk patients remains unclear., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Purpose To evaluate the performance of a new artificial intelligence (AI)-based tool by comparing the quantified stenosis severity at coronary CT angiography (CCTA) with a reference standard derived from invasive quantitative coronary angiography (QCA). Materials and Methods This secondary, post hoc analysis included 120 participants (mean age, 59.7 years ± 10.8 [SD]; 73 [60.8%] men, 47 [39.2%] women) from three large clinical trials (AFFECTS, P3, REFINE) who underwent CCTA and invasive coronary angiography with QCA. Quantitative analysis of coronary stenosis severity at CCTA was performed using an AI-based coronary stenosis quantification (AI-CSQ) software service. Blinded comparison between QCA and AI-CSQ was measured on a per-vessel and per-patient basis. Results The per-vessel AI-CSQ diagnostic sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 80%, 88%, 86%, 65%, and 94%, respectively, for diameter stenosis (DS) 50% or greater; and 78%, 92%, 91%, 47%, and 98%, respectively, for DS 70% or greater. The areas under the receiver operating characteristic curve (AUCs) to predict DS of 50% or greater and 70% or greater on a per-vessel basis were 0.92 (95% CI: 0.88, 0.95; P < .001) and 0.93 (95% CI: 0.89, 0.97; P < .001), respectively. The AUCs to predict DS of 50% or greater and 70% or greater on a per-patient basis were 0.93 (95% CI: 0.88, 0.97; P < .001) and 0.88 (95% CI: 0.81, 0.94; P < .001), respectively. Conclusion AI-CSQ at CCTA demonstrated a high diagnostic performance compared with QCA both on a per-patient and per-vessel basis, with high sensitivity for stenosis detection. Keywords: CT Angiography, Cardiac, Coronary Arteries Supplemental material is available for this article. Published under a CC BY 4.0 license.

Transcatheter aortic valve replacement (TAVR) generates significant debris, and strategies to mitigate cerebral embolization are needed. The novel Emboliner embolic protection catheter (Emboline, Inc., Santa Cruz, California) is designed to capture all particles generated during TAVR. This first-in-human study sought to assess the safety and feasibility of the device and to characterize the distribution and histopathology of the debris generated during TAVR. The SafePass 2 study was a prospective, nonrandomized, multicenter, single-arm investigation of the Emboliner device. Primary end points included 30-day major adverse cardiac and cerebrovascular events (MACCE) and technical performance. Computed tomography angiography was analyzed by an independent core laboratory, and filters were sent for histopathology of captured debris. Predictors of particle number were identified using >150 µm and >500 µm size thresholds. Of 31 subjects enrolled, technical success was 100%, and 30-day MACCE was 6.5% (2 cerebrovascular accidents, with 1 attributed to subtherapeutic dosing of rivaroxaban along with atrial fibrillation and the other to possible previous small ischemic strokes on magnetic resonance imaging; neither MACCE event had a causal relation to the Emboliner). All filters contained debris, with a median of 191.0 particles >150 µm and 14.0 particles >500 µm. Histopathology revealed mostly acute thrombus and valve or arterial tissue with lesser amounts of calcified tissue. A history of atrial fibrillation predicted a greater number of particles >500 µm (p = 0.0259) and its presence on admission was associated with 4.1 times more particles >150 µm (p = 0.0130) and 8.1 times more particles >500 µm (p = 0.0086). Self-expanding valves were associated with twice the number of particles >150 µm (p = 0.0281). TASK score was positively correlated with number of particles >500 µm (p = 0.0337). The Emboliner device was safe and feasible. Emboli after TAVR appear more numerous than previously documented. Atrial fibrillation, higher TASK score, and self-expanding valve use conferred higher embolic burden. Notably, none of the tested computed tomography angiography features were able to identify with higher embolic risk. Larger-scale studies are needed to identify high-risk patients for selective embolic protection device use., Competing Interests: Declaration of Competing Interest Dr. Ahmad is a consultant for Cardiovascular Systems Inc and Shockwave; and serves on the medical advisory board of Boston Scientific. Dr. Leipsic serves at Institutional Core Lab - Edwards, Medtronic, Boston Scientific, Abbott, and Pi-Cardia. Dr. Blanke is a consultant to Edwards Lifesciences and LARALAB; Institutional Core Lab – Edwards Lifesciences, Medtronic, Boston Scientific, Abbott, and Pi-Cardia. Dr. Webster receives institutional research funding – Emboline Inc. Dr. Nazif receives consulting fees or honoraria from Medtronic, Boston Scientific, and EnCompass Technologies. Dr. Parise receives consulting fees – Intact Vascular, Inc. (now Philips Image Guided Therapy), TriReme Medical LLC, and Veryan Medical Ltd. Dr. Lansky receives consulting fees from Med Alliance. The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Non-obstructing small coronary plaques may not be well recognized by expert readers during coronary computed tomography angiography (CCTA) evaluation. Recent developments in atherosclerosis imaging quantitative computed tomography (AI-QCT) enabled by machine learning allow for whole-heart coronary phenotyping of atherosclerosis, but its diagnostic role for detection of small plaques on CCTA is unknown., Methods: We performed AI-QCT in patients who underwent serial CCTA in the multinational PARADIGM study. AI-QCT results were verified by a level III experienced reader, who was blinded to baseline and follow-up status of CCTA. This retrospective analysis aimed to characterize small plaques on baseline CCTA and evaluate their serial changes on follow-up imaging. Small plaques were defined as a total plaque volume <50 ​mm 3 ., Results: A total of 99 patients with 502 small plaques were included. The median total plaque volume was 6.8 ​mm 3 (IQR 3.5-13.9 ​mm 3 ), most of which was non-calcified (median 6.2 ​mm 3 ; 2.9-12.3 ​mm 3 ). The median age at the time of baseline CCTA was 61 years old and 63% were male. The mean interscan period was 3.8 ​± ​1.6 years. On follow-up CCTA, 437 (87%) plaques were present at the same location as small plaques on baseline CCTA; 72% were larger and 15% decreased in volume. The median total plaque volume and non-calcified plaque volume increased to 18.9 ​mm 3 (IQR 8.3-45.2 ​mm 3 ) and 13.8 ​mm 3 (IQR 5.7-33.4 ​mm 3 ), respectively, among plaques that persisted on follow-up CCTA. Small plaques no longer visualized on follow-up CCTA were significantly more likely to be of lower volume, shorter in length, non-calcified, and more distal in the coronary artery, as compared with plaques that persisted at follow-up., Conclusion: In this retrospective analysis from the PARADIGM study, small plaques (<50 ​mm 3 ) identified by AI-QCT persisted at the same location and were often larger on follow-up CCTA., (Copyright © 2023 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: As TAVR is increasingly performed on younger patients with a longer life expectancy, the number of redo-TAVR procedures is likely to increase in the coming years. Limited data is currently available on this sometimes challenging procedure. We provide a summary of currently published literature on management of patients with a failed transcatheter aortic valve., Recent Findings: Recent registry data have increased the clinical knowledge on redo-TAVR. Additionally, numerous bench studies have provided valuable insights into the technical aspects of redo-TAVR with various combinations of valve types. Redo-TAVR can be performed safely in selected cases with a high procedural success and good short-term outcomes. However, at present, the procedure remains relatively infrequent and many patients are not eligible. Bench testing can be useful to understand important concepts such as valve expansion, neoskirt, leaflet overhang, and leaflet deflection as well as their potential clinical implications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Coronary accessibility following redo-transcatheter aortic valve replacement (redo-TAVR) is increasingly important, particularly in younger low-risk patients. This study aimed to predict coronary accessibility after simulated Sapien-3 balloon-expandable valve implantation within an Evolut supra-annular, self-expanding valve using pre-TAVR computed tomography (CT) imaging., Methods: A total of 219 pre-TAVR CT scans from the Evolut Low-Risk CT substudy were analyzed. Virtual Evolut and Sapien-3 valves were sized using CT-based diameters. Two initial Evolut implant depths were analyzed, 3 and 5 mm. Coronary accessibility was evaluated for 2 Sapien-3 in Evolut implant positions: Sapien-3 outflow at Evolut node 4 and Evolut node 5., Results: With a 3-mm initial Evolut implant depth, suitable coronary access was predicted in 84% of patients with the Sapien-3 outflow at Evolut node 4, and in 31% of cases with the Sapien-3 outflow at Evolut node 5 ( P <0.001). Coronary accessibility improved with a 5-mm Evolut implant depth: 97% at node 4 and 65% at node 5 ( P <0.001). When comparing 3- to 5-mm Evolut implant depth, sinus sequestration was the lowest with Sapien-3 outflow at Evolut node 4 (13% versus 2%; P <0.001), and the highest at Evolut node 5 (61% versus 32%; P <0.001)., Conclusions: Coronary accessibility after Sapien-3 in Evolut redo-TAVR relates to the initial Evolut implant depth, the Sapien-3 outflow position within the Evolut, and the native annular anatomy. This CT-based quantitative analysis may provide useful information to inform and refine individualized preprocedural CT planning of the initial TAVR and guide lifetime management for future coronary access after redo-TAVR., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02701283., Competing Interests: Disclosures Dr Tang is a physician proctor, consultant, and physician advisory board member for Medtronic, a consultant and physician advisory board member for Abbott Structural Heart, a consultant for NeoChord, and a physician advisory board member for JenaValve and Boston Scientific. He has received Speaker Honoraria for Siemens Healthineers and East End Medical. Dr Spencer is an employee and shareholder of Medtronic. Dr Rogers is a consultant and physician proctor to Edwards Lifesciences, Medtronic and Boston Scientific; is an Advisory Board member to Medtronic; has equity in Transmural Systems; and is a co-inventor on patents, assigned to National Institutes of Health, for transcatheter electrosurgery devices. Dr Grubb is a proctor, principal investigator and on the advisory board for Medtronic, serves on the advisory board or is a consultant for Ancora Heart, Boston Scientific, Abbott, 4C Medical, Gore, BioVentrix, and Edwards Lifesciences. Dr Gleason’s employer receives institutional grants and educational funding from Edwards Lifesciences, Abbott and Medtronic; he has no personal financial disclosures. Dr Gada has served as a consultant to Abbott, Bard Medical Corporation, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Mahoney is a proctor and consultant for Medtronic, Edwards, and Boston Scientific. Dr Dauerman is a consultant for Boston Scientific and Medtronic, and has received grant support from Boston Scientific and Medtronic. Dr Forrest has received grant support/research contracts and consultant fees/honoraria/speakers’ bureau fees from Edwards Lifesciences and Medtronic. Dr Reardon has received fees to his institution from Medtronic for consulting and providing educational services. Dr Blanke holds institutional research core laboratory agreements with Medtronic, Edwards Lifesciences, and Abbott with no personal compensation. Dr Leipsic holds institutional research core laboratory agreements with Medtronic, Edwards Lifesciences, Abbott, Boston Scientific, and Pi CARDIA with no personal compensation. Dr Abdel-Wahab’s institution receives speaker’s honoraria and consultancy fees on his behalf from Abbott, Boston Scientific, and Medtronic. Dr Attizzani is a consultant, serves as a proctor and is on the advisory board of Medtronic and is a consultant for Abbott Vascular. Dr Puri is a consultant, speaker and proctor for Medtronic, consults for Centerline Biomedical, Boston Scientific, Abbott, Philips, Products & Features, Shockwave Medical, VDyne, VahatiCor, Advanced Nanotherapies, NuevoSono, TherOx, GE Healthcare, BioVentrix, Protembis, and has equity interest in Centerline Biomedical, VahatiCor and NuevoSono. Dr Caskey reports proctor fees from Medtronic. Dr Chen is a proctor and is an advisory board member for Medtronic. Dr Allen has received grant support, proctor and speakers’ bureau fees from Edwards Lifesciences, Medtronic and Abbott with no personal compensation. Dr Chhatriwalla is a proctor for Edwards Lifesciences and Medtronic Inc, is on the speakers bureau for Abbott Vascular, Edwards Lifesciences and Medtronic Inc, and has a research grant from Boston Scientific. Dr Htun is a consultant for Medtronic. Dr Blackman is a proctor and consultant for Medtronic and Abbott Vascular, and a consultant for Edwards Lifesciences and Boston Scientific. Dr Tarantini has received lecture fees from Medtronic, Edwards Lifesciences, Abbott, and Boston Scientific. Dr Zhingre Sanchez is an employee and shareholder of Medtronic. Dr Popma is an employee and shareholder of Medtronic. Dr Sathananthan is a consulta nt to Edwards Lifesciences and Medtronic; and has received speaking fees from Edwards Lifesciences and NVT. The other authors report no conflicts.

Aims: To investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA)., Methods and Results: We analyzed mild stenosis (25-49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02-3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09-2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07-2.22; P = 0.020)., Conclusion: In mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs., Clinical Trial Registration: ClinicalTrials.gov NCT02803411., Competing Interests: Conflict of interest: Dr. Chang receives funding from 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 & Welfare, the Ministry of Food and Drug Safety) (Project Number: 1711139017); Dr. Min receives funding from the National Institutes of Health (Grant Nos. R01 HL111141, R01 HL115150, R01 118019, and U01 HL 105907), the Qatar National Priorities Research Program (Grant No. 09-370-3-089), and GE Healthcare. Dr. Min served as a consultant to HeartFlow, serves on the scientific advisory board of Arineta, and has an equity interest in MDDX. Dr. Bax receives unrestricted research grants from Biotronik, Medtronic, Boston Scientific, and Edwards Lifesciences. Dr. Chun receives funding from National Research Foundation (NRF) grant funded by the Korea government (Ministry of Education, Science and Technology; NRF-2015R1D1A1A01059717). Dr. Leipsic is a consultant and holds stock options in HeartFlow and Circle CVI. He receives modest speaking fees from Philips and GE Healthcare. Dr. Budoff receives grant support from the National Institutes of Health and GE Healthcare. Dr. Marques is a Consultant and holds stock options for Cleerly Inc. Dr. Samady is a co-founder and equity holder of Covanos, a consultant for Philips and Valo, and receives grant support from Phillips and St Jude Abbott/Medtronic. Dr. Andreini is on the Speakers Bureau for GE Healthcare and receives grant support from GE Healthcare and Bracco. Dr. Pontone receives institutional research grants from GE Healthcare, HeartFlow, Medtronic, Bracco, and Bayer. Dr. Berman receives software royalties from Cedars-Sinai. Dr. Virmani has received institutional research support from 480 Biomedical, Abbott Vascular, Arterial Remodeling Technologies, 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. Dr. Virmani also receives 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. Min is an employee and holds equity interest in Cleerly, Inc. He is also on the Medical Advisory Board at Arineta. The other authors report no conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To compare the clinical use of coronary CT angiography (CCTA)-derived fractional flow reserve (FFR) in individuals with and without diabetes mellitus (DM)., Materials and Methods: This secondary analysis included participants (enrolled July 2015 to October 2017) from the prospective, multicenter, international The Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care (ADVANCE) registry (ClinicalTrials.gov identifier, NCT02499679) who were evaluated for suspected coronary artery disease (CAD), with one or more coronary stenosis ≥30% on CCTA images, using CT-FFR. CCTA and CT-FFR findings, treatment strategies at 90 days, and clinical outcomes at 1-year follow-up were compared in participants with and without DM., Results: The study included 4290 participants (mean age, 66 years ± 10 [SD]; 66% male participants; 22% participants with DM). Participants with DM had more obstructive CAD (one or more coronary stenosis ≥50%; 78.8% vs 70.6%, P < .001), multivessel CAD (three-vessel obstructive CAD; 18.9% vs 11.2%, P < .001), and proportionally more vessels with CT-FFR ≤ 0.8 (74.3% vs 64.6%, P < .001). Treatment reclassification by CT-FFR occurred in two-thirds of participants which was consistent regardless of the presence of DM. There was a similar graded increase in coronary revascularization with declining CT-FFR in both groups. At 1 year, presence of DM was associated with higher rates of major adverse cardiovascular events (hazard ratio, 2.2; 95% CI: 1.2, 4.1; P = .01). However, no between group differences were observed when stratified by stenosis severity (<50% or ≥50%) or CT-FFR positivity., Conclusion: Both anatomic CCTA findings and CT-FFR demonstrated a more complex pattern of CAD in participants with versus without DM. Rates of treatment reclassification were similar regardless of the presence of DM, and DM was not an adverse prognostic indicator when adjusted for diameter stenosis and CT-FFR.Clinical trial registration no. NCT 02499679 Keywords: Fractional Flow Reserve, CT Angiography, Diabetes Mellitus, Coronary Artery Disease Supplemental material is available for this article. See also the commentary by Ghoshhajra in this issue.© RSNA, 2023., Competing Interests: Disclosures of conflicts of interest: G.S.G. Trainee editorial board member for Radiology: Cardiothoracic Imaging. G.T. Supported by the Fondation Vaudoise de Cardiologie and the SICPA Foundation. K.R.H. No relevant relationships. H.T. Grants from Canon Medical Systems and JSPS KAKENHI (grant no. 23K15150); speaking fee from HeartFlow Japan. S.L.S. Grants paid to institution from Edwards Lifesciences, Medtronic, HeartFlow; consulting fees from Edwards Lifesciences, Anteris Technologies, and Medtronic; equipment loan agreement from ViVitro Labs. P.B. Consulting fees from Edwards Lifesciences; L.M.H.K. Funding to department from HeartFlow; member of the Radiology: Cardiothoracic Imaging editorial board. B.L.N. Unrestricted institutional research grants from Siemens Healthineers and HeartFlow. J.J. No relevant relationships. M.G.R. Consulting fees from HeartFlow. G.P. Funding from HeartFlow. T.A.F. No relevant relationships. K.M.C. Institutional grant from HeartFlow; honoraria from Elucid Bioimaging. P.S.D. Grant to institution from HeartFlow; honorarium from UpToDate; support from Caption Health. W.H. Employee of HeartFlow; stock options in HeartFlow. H.M. No relevant relationships. N.P.R.S. No relevant relationships. K.N. Grants from Siemens Healthineers, GE HealthCare, and HeartFlow; consulting fees from Siemens Medical Solutions USA, Elucid, and Novartis; stock options in Lumen Therapeutics. J.J.B. No relevant relationships. T. Amano No relevant relationships. T.K. No relevant relationships. T. Akasaka No relevant relationships. T.R. Support (salary and equity) from HeartFlow. D.S.B. Software royalties from Cedars-Sinai; consulting fees from GE and Bayer. M.R.P. Grants from HeartFlow, Bayer, Janssen Pharmaceuticals, and Novartis; consulting fees from Bayer, Hanssen Pharmaceuticals, and Novartis. B.D.B. No relevant relationships. S.M. Employee and shareholder of HeartFlow. J.A.L. Grants from GE HealthCare; consulting fees and stock options from HeartFlow and Circle Cardiovascular Imaging; personal core lab services from Arineta; speaking fees from Philips and GE HealthCare; stock options in HeartFlow and Circle Cardiovascular Imaging, deputy editor for Radiology: Cardiothoracic Imaging., (© 2023 by the Radiological Society of North America, Inc.)

Background: Low fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) has been associated with adverse clinical outcomes. Hitherto, this assessment has been independent of the epicardial vessel interrogated., Objectives: This study sought to assess the predictive capacity of post-PCI FFR for target vessel failure (TVF) stratified by coronary artery., Methods: We performed a systematic review and individual patient-level data meta-analysis of randomized clinical trials and observational studies with protocol-recommended post-PCI FFR assessment. The difference in post-PCI FFR between left anterior descending (LAD) and non-LAD arteries was assessed using a random-effect models meta-analysis of mean differences. TVF was defined as a composite of cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization., Results: Overall, 3,336 vessels (n = 2,760 patients) with post-PCI FFR measurements were included in 9 studies. The weighted mean post-PCI FFR was 0.89 (95% CI: 0.87-0.90) and differed significantly between coronary vessels (LAD = 0.86; 95% CI: 0.85 to 0.88 vs non-LAD = 0.93; 95% CI: 0.91-0.94; P < 0.001). Post-PCI FFR was an independent predictor of TVF, with its risk increasing by 52% for every reduction of 0.10 FFR units, and this was mainly driven by TVR. The predictive capacity for TVF was poor for LAD arteries (AUC: 0.52; 95% CI: 0.47-0.58) and moderate for non-LAD arteries (AUC: 0.66; 95% CI: 0.59-0.73; LAD vs non-LAD arteries, P = 0.005)., Conclusions: The LAD is associated with a lower post-PCI FFR than non-LAD arteries, emphasizing the importance of interpreting post-PCI FFR on a vessel-specific basis. Although a higher post-PCI FFR was associated with improved prognosis, its predictive capacity for events differs between the LAD and non-LAD arteries, being poor in the LAD and moderate in the non-LAD vessels., Competing Interests: Funding Support and Author Disclosures Dr Collet received research grants from Biosensors, HeartFlow Inc, Abbott Vascular, Insight Lifetech, GE Healthcare, Siemens and Shockwave Medical. Dr Johnson has received internal funding from the Weatherhead PET Center for Preventing and Reversing Atherosclerosis; has received significant institutional research support from St. Jude Medical (CONTRAST, NCT02184117) and Philips Volcano (DEFINE-FLOW, 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 TAVI physiology and also algorithms to correct pressure tracings from fluid-filled catheters. Dr Mizukami has received consultancy fees from Zeon Medical. Dr Fearon receives institutional research support from Abbott Vascular, Boston Scientific, Medtronic, and Edwards Lifesciences; he has a consulting relationship with CathWorks and Siemens; and he owns minor stock options in HeartFlow. Dr Berry receives research funding from the British Heart Foundation grant (RE/18/6134217); and is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GlaxoSmithKline, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health. Dr Sonck is supported by a grant provided by the CardioPath PhD program. Dr Collison has received honoraria/speaker fees from Abbott. Dr Koo has received an institutional research grant from St. Jude Medical (Abbott Vascular) and Philips Volcano. Dr Meneveau has received consultancy and speaker fees from Abbott Vascular, Edwards Lifesciences, Terumo, Boston Scientific, Bayer Healthcare, BMS-Pfizer, Boehringer, and AstraZeneca. Dr Oldroyd is an employee of Biosensors International. Dr Leipsic is a consultant for and holds stock options in Circle CVI and HeartFlow; and has a research grant from GE Healthcare. Dr Taylor is an employee of HeartFlow Inc. Dr Ko has received consultancy fees from Abbott Vascular and Medtronic; and has received research support from Canon Medical. Dr Perera has received research grant support from Abbott Vascular, HeartFlow, and Philips. Dr Leone received consultant fees and honoraria for lectures in sponsored symposia with Abbott Vascular and Bracco Imaging/ACIST Medical. Dr Matsuo has received consultancy fees from Zeon Medical; and has received speaker fees from Abbott Vascular Japan, Philips, and Boston Scientific. Dr Amabile reports consulting/proctoring fees from Abbott Vascular, Boston Scientific, and Shockwave Medical; and has received an institutional research grant from Abbott Vascular and Boston Scientific. Dr Piróth has received consultancy and speaker fees from Abbott Vascular, Opsens, and Boston Scientific. Dr Toth has received consultancy fees and research support from Abbott, Biotronik, Medtronic, and Terumo. Dr Ihdayhid reports receiving consulting honorarium from Abbott Medical, Edwards Lifesciences, Boston Scientific, Artrya Pty Ltd (including equity interest). Dr West is an employee of Abbott Vascular. Dr Munhoz is supported with a PhD grant from CardioPath. Dr Barbato has received speaker fees from Abbott and Boston Scientific. Dr Engstrøm has received consultancy and speaker fees from Abbott Vascular, Novo Nordisk, and Bayer AS. Dr Escaned is supported by the Intensification of Research Activity project INT22/00088 from Spanish Instituto de Salud Carlos III, and served as speaker and advisory board member for Abbott and Philips. Dr Ali has received institutional grant support Abbott, Abiomed, ACIST Medical, Amgen, Boston Scientific, Cathworks, Canon, Conavi, Heartflow, Inari, Medtronic Inc, National Institute of Health, Nipro, Opsens Medical, Medis, Philips, Shockwave, Siemens, Spectrawave, Teleflex; and consulting fees from Abiomed, AstraZeneca, Boston Scientific, Cathworks, Opsens, Philips, Shockwave and equity in Elucid, Lifelink, Spectrawave, Shockwave, VitalConnect. Dr Kern has received speaker fees from Abbott, ACIST Medical, Boston Scientific, Opsens, and Philips. Dr Pijls has received research grants from Abbott and Hexacath and consultancy fees from Abbott, GE, Philips, and HeartFlow and have equity in GE, Philips, and Heartflow. Dr De Bruyne has received institutional consulting fees from Abbott Vascular, Boston Scientific, Siemens, and GE; has received institutional grant support from Abbott Vascular, Boston Scientific, Biotronic, CathWorks, Pie Medical, and HeartFlow; and holds minor equities in Philips, Siemens, GE, Bayer, HeartFlow, Edwards Lifesciences, and Ceyliad. 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 and Aims: Inhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA)., Methods: We performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model., Results: Of 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient -0.100, adjusted p = 0.038) with higher levels of baseline PAV., Conclusions: The use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: Funding Support and Author Disclosures Dr Wood is a consultant to, and has received research funding from Edwards Lifesciences and Abbott. Dr Sellers is a consultant to Edwards Lifesciences, Anteris, Excision Medical, and Medtronic; and has received research support from Medtronic, Vivitro Labs, and Edwards Lifesciences. Dr Leipsic is supported by a Canadian Research Chair in Advanced Cardiopulmonary Imaging, consults for MVRX, HeartFlow Inc., and Circle Cardiovascular Imaging; and provides CT core lab services for Edwards Lifesciences, Medtronic, Neovasc, Boston Scientific, and Tendyne Holdings, for which no direct compensation is received. Dr Sathananthan has received speaking fees from Edwards Lifesciences; has received research support from Medtronic, Vivitro Labs, and Edwards Lifesciences; and is a consultant for Edwards Lifesciences, Boston Scientific, NVT Medical and Medtronic. Dr Webb is a consultant for Edwards Lifesciences and receives research funding from Edwards Lifesciences, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Aims: The totality of atherosclerotic plaque derived from coronary computed tomography angiography (CCTA) emerges as a comprehensive measure to assess the intensity of medical treatment that patients need. This study examines the differences in age onset and prognostic significance of atherosclerotic plaque burden between sexes., Methods and Results: From a large multi-center CCTA registry the Leiden CCTA score was calculated in 24 950 individuals. A total of 11 678 women (58.5 ± 12.4 years) and 13 272 men (55.6 ± 12.5 years) were followed for 3.7 years for major adverse cardiovascular events (MACE) (death or myocardial infarction). The age where the median risk score was above zero was 12 years higher in women vs. men (64-68 years vs. 52-56 years, respectively, P < 0.001). The Leiden CCTA risk score was independently associated with MACE: score 6-20: HR 2.29 (1.69-3.10); score > 20: HR 6.71 (4.36-10.32) in women, and score 6-20: HR 1.64 (1.29-2.08); score > 20: HR 2.38 (1.73-3.29) in men. The risk was significantly higher for women within the highest score group (adjusted P-interaction = 0.003). In pre-menopausal women, the risk score was equally predictive and comparable with men. In post-menopausal women, the prognostic value was higher for women [score 6-20: HR 2.21 (1.57-3.11); score > 20: HR 6.11 (3.84-9.70) in women; score 6-20: HR 1.57 (1.19-2.09); score > 20: HR 2.25 (1.58-3.22) in men], with a significant interaction for the highest risk group (adjusted P-interaction = 0.004)., Conclusion: Women developed coronary atherosclerosis approximately 12 years later than men. Post-menopausal women within the highest atherosclerotic burden group were at significantly higher risk for MACE than their male counterparts, which may have implications for the medical treatment intensity., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Motion artifacts in planning computed tomography (CT) for transcatheter aortic valve implantation (TAVI) can potentially skew measurements required for procedural planning. Whether such artifacts may affect safety or efficacy has not been studied., Methods: We conducted a retrospective analysis of 852 consecutive patients (mean age, 82 years; 47% women) undergoing TAVI-planning CT at a tertiary care center. Two independent observers divided CTs according to the presence of motion artifacts at the annulus level (Motion vs. Normal group). Endpoints included surrogate markers for inappropriate valve selection: annular rupture, valve embolization or misplacement, need for a new permanent pacemaker, paravalvular leak (PVL), postprocedural transvalvular gradient, all-cause death., Results: Forty-six (5.4%) patients presented motion artifacts on TAVI-planning CT (Motion group). These patients had more preexisting heart failure, moderate-severe mitral regurgitation, and atrial fibrillation. Interobserver variability of annular measurement (Normal vs. Motion group) did not differ for mean annular diameter but was significantly different for perimeter and area. Presence of motion artifacts on planning CT did not affect the prevalence of PVL (≥moderate PVL 0% vs. 2.5% p = 0.5), mean transvalvular gradient (6±3 mmHg vs 7±5 mmHg, p = 0.1), or the need for additional valve implantation (0% vs. 2.8%, p = 0.6). One annular rupture occurred (Normal group). Pacemaker implantation, procedural duration, hospital stay, 30-day outcomes, and all-cause mortality did not differ between the groups., Conclusions: Motion artifacts on planning CT were found in about 5% of patients. Measurements for valve selection were possible without the need for repeat CT, with mean diameter-derived annulus measurement being the most accurate. Motion artifacts were not associated with worse outcomes., Competing Interests: Mathias Wolfrum serves as a proctor for Biosensors. Matthias Bossard has received speaker fees from Abbott Vascular, Amgen, Astra Zeneca, Bayer, Daichii-Sankyo, Mundipharma, and SIS Medical. Stefan Toggweiler serves as a proctor and consultant for Abbott, Biosensors, Boston Scientific, and Medtronic, as a consultant for Shockwave, Teleflex, Medira, atHeart, and Veosource, has received institutional research grants from Boston Scientific and Fumedica AG, and holds equity in Hi-D Imaging. The other authors declare no conflict of interest., (© 2023 The Author(s).)

Background: Transcatheter aortic valve implantation in an existing transcatheter valve (redo-TAVI) pins the index valve leaflets in the open position (neoskirt), which can cause coronary flow compromise and limit access. Whether anatomy may preclude redo-TAVI in self-expanding Evolut valves is unknown., Aims: We aimed to evaluate the anatomical feasibility of redo-TAVI by simulating implantation of a balloon-expandable SAPIEN 3 (S3) within an Evolut or an Evolut within an Evolut., Methods: A total of 204 post-TAVI computed tomography (CT) scans from the Evolut Low Risk CT substudy were analysed. Five redo-TAVI positions were evaluated: S3-in-Evolut inflow-to-inflow, S3 outflow at Evolut nodes 4, 5, and 6, and Evolut-in-Evolut inflow-to-inflow. Univariable modelling identified pre-TAVI clinical characteristics, CT anatomical parameters, and procedural variables associated with coronary flow compromise using the neoskirt height and post-TAVI aortic root dimensions., Results: The risk of coronary flow compromise was lowest when the S3 outflow was at Evolut node 4 (20%) and highest when at Evolut node 6 (75%). The highest likelihood of preserving coronary accessibility occurred with the S3 outflow at Evolut node 4. Female sex and higher body mass index were associated with a higher risk of coronary flow compromise, as were a smaller annulus diameter, lower sinus of Valsalva height and width, shorter coronary height, smaller sinotubular junction diameter, and shallower Evolut implant depth., Conclusions: The feasibility of redo-TAVI after Evolut failure is multifactorial and relates to the native annular anatomy, as well as the implantation depth of the index and second bioprostheses. Placement of an S3 at a lower Evolut position may reduce the risk of coronary flow compromise while preserving coronary access., Clinicaltrials: gov: NCT02701283.

The coronary vascular volume to left ventricular mass (V/M) ratio assessed by coronary computed tomography angiography (CCTA) is a promising new parameter to investigate the relation of coronary vasculature to the myocardium supplied. It is hypothesized that hypertension decreases the ratio between coronary volume and myocardial mass by way of myocardial hypertrophy, which could explain the detected abnormal myocardial perfusion reserve reported in patients with hypertension. Individuals enrolled in the multicenter ADVANCE (Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care) registry who underwent clinically indicated CCTA for analysis of suspected coronary artery disease with known hypertension status were included in current analysis. The V/M ratio was calculated from CCTA by segmenting the coronary artery luminal volume and left ventricular myocardial mass. In total, 2,378 subjects were included in this study, of whom 1,346 (56%) had hypertension. Left ventricular myocardial mass and coronary volume were higher in subjects with hypertension than normotensive patients (122.7 ± 32.8 g vs 120.0 ± 30.5 g, p = 0.039, and 3,105.0 ± 992.0 mm 3 vs 2,965.6 ± 943.7 mm 3 , p <0.001, respectively). Subsequently, the V/M ratio was higher in patients with hypertension than those without (26.0 ± 7.6 mm 3 /g vs 25.3 ± 7.3 mm 3 /g, p = 0.024). After correcting for potential confounding factors, the coronary volume and ventricular mass remained higher in patients with hypertension (least square) mean difference estimate: 196.3 (95% confidence intervals [CI] 119.9 to 272.7) mm 3 , p <0.001, and 5.60 (95% CI 3.42 to 7.78) g, p <0.001, respectively), but the V/M ratio was not significantly different (least square mean difference estimate: 0.48 (95% CI -0.12 to 1.08) mm 3 /g, p = 0.116). In conclusion, our findings do not support the hypothesis that the abnormal perfusion reserve would be caused by reduced V/M ratio in patients with hypertension., Competing Interests: Declaration of Competing Interest The Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands has received unrestricted research grants from Bayer, Abbott Vascular, Medtronic, Biotronik, Boston Scientific, GE Healthcare (Little Chalfont, United Kingdom), and Edwards Lifesciences. Dr. Patel has received research grants from HeartFlow, Bayer (Abbott), Janssen, and the National Heart, Lung, and Blood Institute and has served on the advisory board for HeartFlow, Bayer, and Janssen. Dr. Nørgaard has received an unrestricted institutional research grant from HeartFlow Inc. Dr. Fairbairn has served on the Speakers Bureau for Heartflow. Dr. Nieman reports support from the NIH (NIH R01- HL141712; NIH R01 - HL146754) and reports unrestricted institutional research support from Siemens Healthineers, consulting fees from Siemens Medical Solutions United States And Novartis, and equity in Lumen Therapeutics. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Hurwitz Koweek has received research support and speaking fees from HeartFlow and Siemens. Dr. Pontone has received institutional research grant and/or honorarium a consultant/speaker from GE Healthcare, Boehringer, Bracco, Medtronic, Bayer, and HeartFlow. Dr. Rabbat has served as a consultant for HeartFlow. Dr. Rogers is employee of and owns equity in HeartFlow. Dr. Leipsic has received research grants from GE Healthcare and Edwards Lifesciences and has served as a consultant for and holds stock options in Circle cardiovascular Imaging and HeartFlow Inc. Dr. Jukema/his department has received research grants from and/or was speaker (with or without lecture fees) on a.o.(CME accredited) meetings sponsored by Amarin, Amgen, Athera, Biotronik, Boston Scientific, Dalcor, Daiichi Sankyo, Lilly, Medtronic, Merck-Schering-Plough, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi Aventis (Bridgewater, New Jersey), the Netherlands Heart Foundation, CardioVascular Research the Netherlands, the Netherlands Heart Institute, and the European Community Framework KP7 Program. Dr. Bax received speaker fees from Abbot Vascular. Dr. Ajmone received speaker fees from Abbot Vascular and GE Healthcare. Dr. Saraste received consultancy fees from Amgen, Astra Zeneca, Boehringer Ingelheim, and Pfizer and speaker fees from Abbott, Astra Zeneca, and Bayer. Dr. Knuuti received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer Ingelheim, Pfizer, and Merck outside of the submitted work. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Dr De Backer has received institutional research grants from and has been an adviser for Abbott, Boston Scientific, and Medtronic. Dr Sathananthan has received research grants from and is a consultant for Edwards Lifesciences, Medtronic, Boston Scientific, Anteris Technologies, and Hi-D Imaging. Dr Treede is an adviser for Medtronic, Edwards Lifesciences, Boston Scientific, JenaValve, and TriCares. Dr Leipsic has conducted institutional computed tomography core laboratory activities for Edwards Lifesciences, Medtronic, Abbott, Boston Scientific, and Pi-Cardia. Dr Bax is a member of the Speakers Bureau for and has received unrestricted research grants from Abbott and Edwards Lifesciences. Dr Webb is a consultant for Edwards Lifesciences. Dr Chen is a consultant for CardioFlow, Venus MedTech, and Peijia Medical. Dr Reardon is a consultant for Medtronic, Boston Scientific, Abbott Medical, and Gore Medical. Dr Leon has received institutional clinical research grants from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Søndergaard has received institutional research grants from and has been an adviser for Abbott, Boston Scientific, and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Fractional flow reserve (FFR) is currently considered as the gold standard for revascularization decision-making in patients with stable coronary artery disease (CAD). The application of computational fluid dynamics to coronary computed tomography (CT) angiography (CCTA) enables calculation of FFR without additional testing, radiation exposure, contrast medium injection, and hyperemia (FFR CT ). Although multiple diagnostic and clinical studies have enriched the scientific evidence, it is still challenging to integrate FFR CT into clinical practice. Both meticulous scientific backgrounds and precise anatomical data derived from CCTA are fundamental for FFR CT computation, and there are numerous factors impacting on FFR CT calculation and interpretation: coronary artery stenosis, calcium, atherosclerosis, luminal volume, and left ventricular myocardial mass. Further, there is a gap that clinicians using FFR CT need to recognize in interpretation of FFR CT results between diagnostic studies and clinical studies. In this review, we summarize multiple evidence related to FFR CT computation and interpretation to refine the FFR CT strategy in patients with stable CAD., Competing Interests: Declaration of competing interest Dr. Takagi has received speaker fees from HeartFlow Japan GK. and research consulting fee from HeartFlow Inc. Dr. Ihdayhid has received consulting honorarium from Boston Scientific and Artrya. Dr. Leipsic is a consultant and holds stock options in Circle CVI and HeartFlow, research grants from GE and modest speaker fees from GE and Philips., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

In this review, the authors describe some of the latest cardiac CT advances in the evaluation of cardiovascular disease. This includes automated coronary plaque quantification and subtyping, and cardiac CT fractional flow reserve and CT perfusion as techniques to noninvasively assess the physiologic significance of coronary stenosis. The authors also focus on noncoronary applications involving the expanding role of cardiac CT in structural heart disease interventions. Developments in cardiac CT for the evaluation of diffuse myocardial fibrosis and infiltrative cardiomyopathy and for functional analysis of myocardial contractile dysfunction are discussed. Finally, the authors review studies evaluating photon-counting CT in cardiac disease., (© RSNA, 2023.)

Background and Aims: Hemodynamic and plaque characteristics can be analyzed using coronary CT angiography (CTA). We aimed to explore long-term prognostic implications of hemodynamic and plaque characteristics using coronary CT angiography (CTA)., Methods: Invasive fractional flow reserve (FFR) and CTA-derived FFR (FFR CT ) were undertaken for 136 lesions in 78 vessels and followed-up to 10 years until December 2020. FFR CT , wall shear stress (WSS), change in FFR CT across the lesion (ΔFFR CT ), total plaque volume (TPV), percent atheroma volume (PAV), and low-attenuation plaque volume (LAPV) for target lesions [L] and vessels [V] were obtained by independent core laboratories. Their collective influence was evaluated for the clinical endpoints of target vessel failure (TVF) and target lesion failure (TLF)., Results: During a median follow-up of 10.1 years, PAV[V] (per 10% increase, HR 2.32 [95% CI 1.11-4.86], p = 0.025), and FFR CT [V] (per 0.1 increase, HR 0.56 [95% CI 0.37-0.84], p = 0.006) were independent predictors of TVF for the per-vessel analysis, and WSS[L] (per 100 dyne/cm 2 increase, HR 1.43 [1.09-1.88], p = 0.010), LAPV[L] (per 10 mm 3 increase, HR 3.81 [1.16-12.5], p = 0.028), and ΔFFR CT [L] (per 0.1 increase, HR 1.39 [1.02-1.90], p = 0.040) were independent predictors of TLF for the per-lesion analysis after adjustment for clinical and lesion characteristics. The addition of both plaque and hemodynamic predictors improved the predictability for 10-year TVF and TLF of clinical and lesion characteristics (all p < 0.05)., Conclusions: Vessel- and lesion-level hemodynamic characteristics, and vessel-level plaque quantity, and lesion-level plaque compositional characteristics assessed by CTA offer independent and additive long-term prognostic value., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interest: BKK received research grants from Abbott, Philips, and HeartFlow, provided to the Seoul National University. JL holds stock options in and serves as a consultant to HeartFlow and Circle CVI, and has a research grant from GE Healthcare. GC, MS, CZ, and CAT are the employees and shareholders of HeartFlow, Inc., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Computed tomography (CT) visual emphysema score is a better predictor of mortality than single quantitative CT emphysema measurements in COPD, but there are numerous CT measurements that reflect COPD-related disease features. The purpose of this study was to determine if linear combinations of quantitative CT measurements by principal component analysis (PCA) have a greater association with forced expiratory volume in 1 s (FEV 1 ) lower limit of normal (LLN) annualised change (ΔFEV 1 ) than visual emphysema score in COPD., Methods: In this retrospective, longitudinal study, demographic, spirometry and CT images were acquired. CT visual emphysema score and quantitative analysis were performed; low attenuation area <950 HU (LAA 950 ) and 12 other quantitative CT measurements were investigated. PCA was used for CT feature extraction. Multiple linear regression models for baseline FEV 1 LLN and 6-year ΔFEV 1 were used to determine associations with visual emphysema score and CT measurements. A total of 725 participants were analysed (n=299 never-smokers, n=242 at-risk and n=184 COPD)., Results: Quantitative CT measures (LAA 950 and PCA components) were independently statistically significant (p<0.05) in predicting baseline FEV 1 LLN, whereas visual emphysema score was not statistically significant in any baseline model. When predicting 6-year ΔFEV 1 , only visual emphysema score was significant (p<0.05) in models with LAA 950 and PCA combination of emphysema measurements. In the model with PCA using all CT measurements predicting 6-year ΔFEV 1 , visual emphysema score (p=0.021) along with one PCA component (p=0.004) were statistically significant., Conclusions: PCA with a combination of CT measurements reflecting several different COPD-related disease features independently predicted baseline lung function and increased the relative importance of quantitative CT compared with visual emphysema score for predicting lung function decline., Competing Interests: Conflict of Interest: All authors have nothing to disclose., (Copyright ©The authors 2023.)

Coronary computed tomographic angiography (CCTA) is becoming the first-line investigation for establishing the presence of coronary artery disease and, with fractional flow reserve (FFR CT ), its haemodynamic significance. In patients without significant epicardial obstruction, its role is either to rule out atherosclerosis or to detect subclinical plaque that should be monitored for plaque progression/regression following prevention therapy and provide risk classification. Ischaemic non-obstructive coronary arteries are also expected to be assessed by non-invasive imaging, including CCTA. In patients with significant epicardial obstruction, CCTA can assist in planning revascularisation by determining the disease complexity, vessel size, lesion length and tissue composition of the atherosclerotic plaque, as well as the best fluoroscopic viewing angle; it may also help in selecting adjunctive percutaneous devices (e.g., rotational atherectomy) and in determining the best landing zone for stents or bypass grafts.

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.)

The negative impact of tricuspid regurgitation on prognosis in now well established. It also appears clear that surgical and possibly percutaneous treatment should be performed before reaching a point of no return with advanced heart failure and deterioration of right ventricle function. Percutaneous treatment has been divided into coaptation restoration devices, annuloplasty devices, and ortho- or heterotopic valve replacement. The present article offers a brief review of diagnostic modalities beyond echocardiography, surgical treatment as well as of the multiple recent development in the percutaneous treatment of this frequent condition., Competing Interests: D. Meier est au bénéfice d’une bourse de la fondation SICPA. G. Tzimas est soutenu par la Fondation vaudoise de cardiologie et est au bénéfice d’une bourse de la fondation SICPA. J. G. Webb est consultant pour Edwards Lifesciences et a reçu du financement de recherche de la part de Edwards Lifesciences et Abbott. J. Sathananthan est consultant pour Edwards Lifesciences, Medtronic et Boston Scientific. Il a reçu du financement de recherche de la part de Edwards Lifesciences et Medtronic. J. Leipsic a reçu du financement de recherche et des honoraires de la part de GE Healthcare. Il est également actionnaire et consultant pour HeartFlow, Circle CVI et Philips. P. Blanke offre un service de core laboratory institutionnel pour Edwards Lifesciences, Medtronic, Boston Scientific, Abbott Laboratories, PiCardia et Neovasc sans gains financiers directs. Il est également consultant pour Edwards Lifesciences. F. Praz a reçu des compensations pour des voyages professionnels de la part d’Edwards Lifesciences, Abbott Vascular, Medira, Polares Medical et Siemens Healthineers. Les autres auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Background and Hypothesis: The recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner., Methods: From the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model., Results: The 90th percentiles of the DS of the three vessels and their maximum DS change were 41%-50% and 5.6%-7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis., Conclusions: This study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Bioprosthetic valve fracture (BVF) can be used to improve transcatheter heart valve (THV) haemodynamics following a valve-in-valve (ViV) intervention. However, whether BVF should be performed before or after THV deployment and the implications on durability are unknown.  Aims: We sought to assess the impact of BVF timing on long-term THV durability., Methods: The impact of BVF timing was assessed using small ACURATE neo (ACn) or 23 mm SAPIEN 3 (S3) THV deployed in 21 mm Mitroflow valves compared to no-BVF controls. Valves underwent accelerated wear testing up to 200 million (M) cycles (equivalent to 5 years). At 200M cycles, THV were evaluated by hydrodynamic testing, second-harmonic generation (SHG) microscopy, scanning electron microscopy (SEM) and histology., Results: At 200M cycles, the regurgitant fraction (RF) and effective orifice area (EOA) for the ACn were 8.03±0.30%/1.74±0.01 cm 2 (no BVF), 12.48±0.70%/1.97±0.02 cm 2 (BVF before ViV) and 9.29±0.38%/2.21±0.0 cm 2 (BVF after ViV), respectively. For the S3 these values were 2.63±0.51%/1.26±0.01 cm 2 , 2.03±0.42%/1.65±0.01 cm 2 , and 1.62±0.38%/2.22±0.01 cm 2 , respectively. Further, SHG and SEM revealed a higher degree of superficial leaflet damage when BVF was performed after ViV for the ACn and S3. However, the histological analysis revealed significantly less damage, as determined by matrix density analysis, through the entire leaflet thickness when BVF was performed after ViV with the S3 and a similar but non-significant trend with the ACn.  Conclusions: BVF performed after ViV appears to offer superior long-term EOA without increased RF. Ultrastructure leaflet analysis reveals that the timing of BVF can differentially impact leaflets, with more superficial damage but greater preservation of overall leaflet structure when BVF is performed after ViV.

Background: Prognostic significance of non-obstructive left main (LM) disease was recently reported. However, the influence of diabetes mellitus (DM) on event rates in patients with and without non-obstructive LM disease is not well-known., Methods: We evaluated 27,252 patients undergoing coronary computed tomographic angiography from the COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter (CONFIRM) Registry. Cumulative long-term incidence of all-cause mortality (ACM) was assessed between DM and non-DM patients by normal or non-obstructive LM disease (1-49% stenosis)., Results: The mean age of the study population was 57.6±12.6 years. Of the 27,252 patients, 4,434 (16%) patients had DM. A total of 899 (3%) deaths occurred during the follow-up of 3.6±1.9. years. Compared to patients with normal LM, those with non-obstructive LM had more pronounced overall coronary atherosclerosis and more cardiovascular risk factors. After clinical risk factors, segment involvement score, and stenosis severity adjustment, compared to patients without DM and normal LM, patients with DM were associated with increased ACM regardless of normal (HR 1.48, 95% CI 1.22-1.78, p<0.001) or non-obstructive LM (HR 1.46, 95% CI 1.04-2.04, p=0.029), while nonobstructive LM disease was not associated with increased ACM in patients without DM (HR 0.85, 95% CI 0.67-1.07, p=0.165) and there was no significant interaction between DM and LM status (HR 1.03, 95% CI 0.69-1.54, p=0.879)., Conclusion: From the CONFIRM registry, we demonstrated that DM was associated with increased ACM. However, the presence of non-obstructive LM was not an independent risk marker of ACM, and there was no significant interaction between DM and non-obstructive LM disease for ACM., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures of conflicts of interest: J.D. No relevant relationships. J.A.L. Institutional grants or contracts from GE Healthcare; consulting fees from HeartFlow; modest payment or honoraria from GE Healthcare and Philips for lectures, presentations, speakers bureaus, manuscript writing, or educational events; stock or stock options in HeartFlow; deputy editor for Radiology: Cardiothoracic Imaging.

This review focuses on three key noninvasive cardiac imaging modalities-cardiac CT angiography (CTA), MRI, and PET/CT-and summarizes key publications in 2021 relevant to radiologists in clinical practice. Although this review focuses primarily on articles published in Radiology , important studies from other major journals are included to highlight "must-know" articles in the field of cardiovascular imaging. Cardiac CTA has been established as the first-line test for patients with stable chest pain and no known coronary artery disease, and its value remains central to the assessment of surgical or transcatheter aortic valve replacement. Artificial intelligence continues to evolve in a number of applications in cardiovascular disease. In cardiac MRI studies, 2021 has seen an emphasis on nonischemic cardiomyopathies, valvular heart disease, and COVID-19 disease cardiac manifestations and the authors highlight the key articles on these topics. A section featuring the increasing role of cardiac PET/CT in the assessment of cardiac sarcoidosis and prosthetic valves is also provided., (© RSNA, 2022.)

Background: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images., Methods: A total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV)., Results: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (β: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017)., Conclusion: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study., Trial Registration: ClinicalTrials.gov NCT02803411., (© 2022. The Author(s).)

Bicuspid aortic valve disease (BAVD) is present in up to half of all patients referred for surgical aortic valve replacement (SAVR) yet was an exclusion criterion for all randomized controlled trials (RCTs) comparing transcatheter aortic valve replacement (TAVR) to SAVR. Nonetheless, approximately 10% of patients currently treated with TAVR have BAVD and available observational data for performing TAVR in these patients are limited by selection bias. Many in the cardiovascular community have advocated for RCTs in this population, but none have been performed. The Heart Valve Collaboratory (HVC) is a multidisciplinary community of stakeholders with the aim of creating significant advances in valvular heart disease by stimulating clinical research, engaging in educational activities, and advancing regulatory science. In December 2020, the HVC hosted a Global Multidisciplinary workshop involving over 100 international experts in the field. Following this 2-day symposium, working groups with varied expertise were convened to discuss BAVD, including the need for and design of RCTs. This review, conducted under the auspices of the HVC, summarizes available data and knowledge gaps regarding procedural therapy for BAVD, outlining specific challenges for trials in this population. We also propose several potential studies that could be performed and discuss respective strengths and weaknesses of each approach. Finally, we present a roadmap for future directions in clinical research in TAVR for BAVD with an emphasis both on RCTs and also prospective registries focused on disease phenotyping to develop parameters and risk scores that could ultimately be applied to patients to inform clinical decision-making., Competing Interests: Dr Madhavan was supported by a grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to Columbia University Irving Medical Center (T32 HL007854). Dr Baron reports consulting for Boston Scientific Corp, Abiomed, Abbott, Edwards, and Mitra Labs and research support from Abiomed and Boston Scientific Corp. Dr Forrest is a consultant for Edwards Lifesciences and Medtronic and receives grant support from Edwards Lifesciences, and Medtronic. Dr Leipsic reports unrestricted research grants from GE Healthcare, stock options and consulting fees from HeartFlow and Circle CVI, payment or honoraria from Philips, board of directors of SCCT, deputy editor for Radiology: Cardiothoracic Imaging. Dr Cavalcante has received research grants from and is a consultant for Abbott Vascular, Circle Cardiovascular Imaging, Boston Scientific, Medtronic, Siemens Healthineers, and Edwards Lifesciences; is a consultant for VDyne and Triflo; and is a member of the Speakers Bureau for Circle Cardiovascular Imaging, Medtronic, Siemens Healthineers. Dr Wang has served as a consultant to Edwards Lifesciences, Abbott, NeoChord, and Boston Scientific; and received research grant support from Boston Scientific assigned to her employer, the Henry Ford Health System. Dr McCarthy has received royalties and honoraria for speaking for Edwards Lifesciences. Dr Szerlip has served as National Principal Investigator for trial sponsored by Edwards Lifesciences; has served on steering committees for trials by Abbott and Medtronic; and has served as speaker for Medtronic, Abbott, and Edwards Lifesciences. Dr Makkar has received research grants from Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific; has served as national Principal Investigator for Portico (Abbott) and Acurate (Boston Scientific) U.S. investigation device exemption trials; has received personal proctoring fees from Edwards Lifesciences; and has received travel support from Edwards Lifesciences, Abbott, and Boston Scientific. Dr Mack has served as a co-principal investigator for Edwards Lifesciences and Abbott; and as a study chair for Medtronic. Dr Leon has received research support to his institution from Edwards Lifesciences, Medtronic, Boston Scientific, and Abbott; has served on Advisory Boards for Medtronic, Boston Scientific, Gore, Meril Lifescience, and Abbott; and has served as the Co-Principal Investigator of the PARTNER 3 trial (Edwards Lifesciences, no direct compensation). Dr Cohen has received institutional research grants and personal fees from Medtronic, Boston Scientific, and Abbott Vascular, outside the submitted work. The other authors had no conflicts to declare., (© 2022 The Author(s).)