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Transcatheter aortic valve implantation (TAVI) is an effective treatment option for patients suffering from symptomatic, severe aortic valve stenosis. Previously, only patients with prohibitive or high surgical risk were TAVI candidates; however, current guidelines already recommend TAVI as a treatment alternative for patients with intermediate surgical risk. Multidetector computed tomography (MDCT) has gained great importance in the periprocedural assessment of patients who undergo TAVI. Due to the three-dimensional image visualization, MDCT allows the evaluation of anatomical structures in a more comprehensive manner compared to echocardiography, the traditional tool used in TAVI patient work-up. By providing accurate measurements of the aortic root, MDCT helps to avoid potential patient-prosthesis mismatch throughout transcatheter valve sizing. Moreover, MDCT is also a feasible tool for access route evaluation and to determine the optimal projection angles for the TAVI procedure. Although the routine MDCT follow-up of patients is currently not recommended in clinical practice, if performed, it could provide invaluable information about valve integrity and asymptomatic leaflet thrombosis. Post-procedural MDCT can provide details about the position of the prosthesis and complications such as leaflet-thrombosis, aortic regurgitation, coronary occlusion, and other vascular complications that can represent major cardiac emergencies. The aim of the current review is to overview the role of MDCT in the pre- and post-procedural assessment of TAVI patients. In the first part, the article presents the role of pre-TAVI imaging in the complex anatomical assessment of the aortic valve and the selection of the most appropriate device. The second part of the review describes the role of MDCT in patients who underwent TAVI to assess potential complications, some of them leading to a major cardiovascular emergency.

Background: Coronary plaque is common among people with HIV (PWH) with low-to-moderate traditional atherosclerotic cardiovascular disease (ASCVD) risk., Objectives: The purpose of this study was to determine the association of high-sensitivity cardiac troponin T (hs-cTnT) levels with coronary plaque characteristics and evaluate if hs-cTnT improves identification of these features beyond traditional ASCVD risk factors among PWH., Methods: Among PWH receiving stable antiretroviral therapy with low-to-moderate ASCVD risk and no known history of ASCVD, hs-cTnT levels and measures of plaque by coronary computed tomography angiography were assessed. Primary outcomes included the association of hs-cTnT level with the presence of any plaque, vulnerable plaque, coronary artery calcium (CAC) score, and Leaman score. Assessment of model discrimination of hs-cTnT for plaque characteristics was also performed., Results: The cohort included 708 U.S. participants with a mean age of 51 ± 6 years, 119 (17%) females, a median ASCVD risk score of 4.4% (Q1-Q3: 2.5%-6.6%), and a median hs-cTnT level of 6.7 ng/L (detectable level ≥6 ng/L in 61%). Any plaque was present in 341 (48%), vulnerable plaque in 155 (22%), CAC>100 in 68 (10%), and a Leaman score >5 in 105 (15%). After adjustment for ASCVD risk score, participants with hs-cTnT >9.6 ng/L (highest category) versus an undetectable level (<6 ng/L) had a greater relative risk for any plaque (1.37, 95% CI: 1.12-1.67), vulnerable plaque (1.47, 95% CI: 1.16-1.87), CAC>100 (2.58, 95% CI: 1.37-4.83), and Leaman score >5 (2.13, 95% CI: 1.32-3.46). The addition of hs-cTnT level modestly improved the discrimination of ASCVD risk score to identify critical plaque features., Conclusions: In PWH without known ASCVD, hs-cTnT levels were strongly associated with and improved prediction of subclinical coronary plaque. (Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults [REPRIEVE]; NCT02344290)., Competing Interests: The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute or the National Institute of Allergy and Infectious Diseases; the National Institutes of Health; or the U.S. Department of Health and Human Services. This study is supported through NIH grants U01HL123336, to the Clinical Coordinating Center, and U01HL123339, to the Data Coordinating Center as well as funding from Kowa Pharmaceuticals America, Inc, Gilead Sciences, and ViiV Healthcare. The NIAID supported this study through grants UM1 AI068636, which supports the Advancing Clinical Therapeutics Globally (ACTG) Network Leadership and Operations Center; and UM1 AI106701, which supports the ACTG Laboratory Center. This work was also supported by the Nutrition Obesity Research Center at Harvard (P30DK040561 to SKG). Dr deFilippi has received grant support to his institution from Roche Diagnostics and consulting for Roche Diagnostics which manufacturers the troponin T assay; has received grants to his institution from Abbott Diagnostics, FujiRebio, Quidel/Ortho, Siemens Healthineers, and the NHLBI outside this submitted work; consulting for Abbott Diagnostics, FujiRebio, and Quidel/Ortho, and Siemens Healthineers; and serves as a member of the clinical endpoint committee for Siemens Healthineers. Dr Zanni is the principal investigator of research grants from 10.13039/100000002NIH (NIAID and NHLBI) and from 10.13039/100005564Gilead Sciences to her institution and participating in a DSMB for 10.13039/100000002NIH-funded studies involving no compensation. Dr Fichtenbaum has received grant support through his institution from 10.13039/100005564Gilead Sciences, 10.13039/100010877ViiV Healthcare, 10.13039/100004330GSK, 10.13039/100005565Janssen, 10.13039/100006483Abbvie, 10.13039/100004334Merck, 10.13039/100002429Amgen, and Cytodyn, outside the submitted work; and personal fees from Theratechnologies and ViiV for consulting and participation on Advisory Board unrelated to REPRIEVE with Theratechnologies and ViiV, and role as Chair on DSMB for Intrepid Study, outside the submitted work. Dr Aberg has received institutional research support for clinical trials from Emergent Biosolutions, Frontier Technologies, Gilead Sciences, GlaxoSmithKline, Janssen, MacroGenics, Merck, Pfizer, Regeneron, and ViiV Healthcare; and personal fees for advisory boards from Glaxo Smith Kline/Viiv and Merck and participation on DSMB for Kintor Pharmaceuticals, all outside the submitted work. Dr Malvestutto has received institutional research support by Lilly; and honoraria from 10.13039/100010877ViiV Healthcare and 10.13039/100005564Gilead Sciences for Advisory Board membership, outside the submitted work. Dr Pinto-Martinez has received honoraria from Gilead, Janssen, and ViiV Healthcare for presentations and educational events, outside the submitted work. Dr Stapleton has received institutional research support by 10.13039/100000002NIH. Dr Robbins has received grant support to his institution from Leonard-Meron Bioscience; consulting fees to his institution from Seed Inc and Teradyne Inc; payment for expert testimony from Tufts Medical Center, participation on a DSMB for an NIH trial, and unpaid membership on a review panel for DHHS OI Guidelines. Dr Taron has received support from 10.13039/501100001659Deutsche Forschungsgesellschaft (DFG, German Research Foundation) relevant to the present work; consulting fees from Universimed Cross Media Content GmbH, Core Lab Black Forrest GmbH; and payments or honoraria from Siemens Healthcare GmbH, Bayer AG, outside of the submitted work. Dr Foldyna has received institutional support from 10.13039/100004325AstraZeneca, 10.13039/501100004628MedImmune, and MedTrace, outside of the submitted work. Dr Lu has received grant support through his institution from Kowa Pharmaceuticals America, Inc, for the conduct of the study; grant support from 10.13039/501100004628MedImmune and 10.13039/100004325AstraZeneca; and personal fees from PQBypass, outside of the current work. Dr Ribaudo has received grants from 10.13039/100000002NIH/10.13039/100000050NHLBI and Kowa Pharmaceuticals during the conduct of the study as well as grants from 10.13039/100000002NIH/10.13039/100000060NIAID, and 10.13039/100000002NIH/10.13039/100000050NHLBI, 10.13039/100000002NIH/10.13039/100000062NIDDK, and 10.13039/100000002NIH/10.13039/100000049NIA outside the submitted work. Dr Grinspoon has received grant support through his institution from Kowa Pharmaceuticals America, Inc 10.13039/100005564Gilead Sciences, Inc; and 10.13039/100010877ViiV Healthcare for the conduct of the study, as well as grants from Theratechnologies and Navidea and personal fees from Theratechnologies and ViiV, all outside the submitted work; and is a member of the Scientific Advisory Board of Marathon Asset management. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis., Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation. Lipoprotein particle size/number were measured by nuclear magnetic resonance spectroscopy. Principal components analysis (PCA) was used for dimensionality reduction. The association of PCA factors and individual lipoprotein particle size/number with HS were assessed in multivariable regression models. Associations were validated in an independent cohort of 59 individuals with histopathology defined HS., Results: Individuals with HS (n=410/1,509) vs those without (n=1,099/1,509), were younger (59±8 vs 61±8 years) and less often females (47.6 % vs 55.9 %). All PCA factors were associated with HS: factor 1 (OR:1.36, 95 %CI:1.21-1.53), factor 3 (OR:1.75, 95 %CI:1.53-2.02) and factor 4 (OR:1.49; 95 %CI:1.32-1.68) were weighted heavily with small low density lipoprotein (LDL) and triglyceride-rich (TRL) particles, while factor 2 (OR:0.86, 95 %CI:0.77-0.97) and factor 5 (OR:0.74, 95 %CI:0.65-0.84) were heavily loaded with high density lipoprotein (HDL) and larger LDL particles. These observations were confirmed with the analysis of individual lipoprotein particles in PROMISE. In the validation cohort, association between HS and large TRL (OR: 8.16, 95 %CI:1.82-61.98), and mean sizes of TRL- (OR: 2.82, 95 %CI:1.14-9.29) and HDL (OR:0.35, 95 %CI:0.13-0.72) were confirmed., Conclusions: Large TRL, mean sizes of TRL-, and HDL were associated with radiographic and histopathologic HS. The use of lipoprotein particle size/number could improve cardiovascular risk assessment in HS., Competing Interests: 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., (© 2024 Published by Elsevier B.V.)

Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification., Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH., Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence., Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P  < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P  < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P  < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P  < 0.001)., Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque., Competing Interests: 10.13039/100000002This paper received NIH grants U01HL123336 to the REPRIEVE Clinical Coordinating Center and U01HL123339 to the REPRIEVE Data Coordinating Center, as well as funding from Kowa Pharmaceuticals, Gilead Sciences, and ViiV Healthcare. The 10.13039/100000060National Institute of Allergy and Infectious Diseases (NIAID) supported this study through grants UM1 AI068636, which supports the AIDS Clinical Trials Group (ACTG) Leadership and Operations Center, and UM1 AI106701, which supports the ACTG Laboratory Center. The PROMISE trial was supported by the 10.13039/100000050National Heart, Lung, and Blood Institute (R01HL098237, R01HL098236, R01HL98305, and R01HL098235). The SCAPIS trial received funding from the Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, Swedish Research Council and Vinnova (Sweden’s Innovation Agency), University of Gothenburg and Sahlgrenska University Hospital, Karolinska Institutet and Stockholm County Council, Linköping University and University Hospital, Lund University and Skåne University Hospital, Umeå University and University Hospital, and Uppsala University and University Hospital. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the views of any of the funding agencies. Dr Lu has received funding to his institution from Kowa, AstraZeneca/MedImmune, Johnson & Johnson Innovation, Ionis, and the American Heart Association unrelated to this research. Dr Taron has received funding by Deutsche Forschungsgesellschaft (DFG, German Research Foundation) (TA 1438/1-2); is on Speakers Bureau for Siemens Healthcare GmbH and Bayer AG; and has received consulting fees from Universimed Cross Media Content GmbH and Core Lab Black Forrest GmbH, unrelated to this work. Dr Foldyna has received funding to his institution from AstraZeneca/MedImmune, MedTrace, and Eli Lilly unrelated to this research. Dr Currier served as an advisor to Merck. Dr Elvstam has received grants to his institution from Pfizer; and has received honoraria as a speaker from Gilead Sciences, unrelated to this research. Dr Dubé has received funding to his institution from Gilead Sciences unrelated to this research. Dr Fichtenbaum has received funding to the institution from ViiV Healthcare, Gilead Sciences, Merck, Cytodyn, and Moderna unrelated to this work and serves on the advisory board for ViiV Healthcare. Dr Malvestutto has received funding to his institution from Lilly; and has received consulting fees from Viiv Healthcare and Gilead Sciences unrelated to this work. Dr Zanni reports being PI on research grants from the NIH (NHLBI and NIAID) and Gilead Sciences to her institution. Dr Ribaudo has received grants from Kowa Pharmaceuticals during the conduct of the study, as well as grants from NIH/NIAID, NIH/NHLBI, NIH/NIDDK, and NIH/NIA, outside the submitted work. Dr Grinspoon reports being a part of the Scientific Advisory Board for Marathon Asset Management and consultant Theratechnologies is unrelated to this report; research funds come from Gilead, Viiv, and Kowa through his institution. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Importance: Cardiovascular disease (CVD) is increased in people with HIV (PWH) and is characterized by premature noncalcified coronary plaque. In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular events (MACE) by 35% over a median of 5.1 years., Objective: To investigate the effects of pitavastatin on noncalcified coronary artery plaque by coronary computed tomography angiography (CTA) and on inflammatory biomarkers as potential mechanisms for MACE prevention., Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial enrolled participants from April 2015 to February 2018 at 31 US clinical research sites. PWH without known CVD who were taking antiretroviral therapy and had low to moderate 10-year CVD risk were included. Data were analyzed from April to November 2023., Intervention: Oral pitavastatin calcium, 4 mg per day., Main Outcomes and Measures: Coronary CTA and inflammatory biomarkers at baseline and 24 months. The primary outcomes were change in noncalcified coronary plaque volume and progression of noncalcified plaque., Results: Of 804 enrolled persons, 774 had at least 1 evaluable CTA. Plaque changes were assessed in 611 who completed both CT scans. Of 611 analyzed participants, 513 (84.0%) were male, the mean (SD) age was 51 (6) years, and the median (IQR) 10-year CVD risk was 4.5% (2.6-7.0). A total of 302 were included in the pitavastatin arm and 309 in the placebo arm. The mean noncalcified plaque volume decreased with pitavastatin compared with placebo (mean [SD] change, -1.7 [25.2] mm3 vs 2.6 [27.1] mm3; baseline adjusted difference, -4.3 mm3; 95% CI, -8.6 to -0.1; P = .04; 7% [95% CI, 1-12] greater reduction relative to placebo). A larger effect size was seen among the subgroup with plaque at baseline (-8.8 mm3 [95% CI, -17.9 to 0.4]). Progression of noncalcified plaque was 33% less likely with pitavastatin compared with placebo (relative risk, 0.67; 95% CI, 0.52-0.88; P = .003). Compared with placebo, the mean low-density lipoprotein cholesterol decreased with pitavastatin (mean change: pitavastatin, -28.5 mg/dL; 95% CI, -31.9 to -25.1; placebo, -0.8; 95% CI, -3.8 to 2.2). The pitavastatin arm had a reduction in both oxidized low-density lipoprotein (-29% [95% CI, -32 to -26] vs -13% [95% CI, -17 to -9]; P < .001) and lipoprotein-associated phospholipase A2 (-7% [95% CI, -11 to -4] vs 14% [95% CI, 10-18]; P < .001) compared with placebo at 24 months., Conclusions and Relevance: In PWH at low to moderate CVD risk, 24 months of pitavastatin reduced noncalcified plaque volume and progression as well as markers of lipid oxidation and arterial inflammation. These changes may contribute to the observed MACE reduction in REPRIEVE., Trial Registration: ClinicalTrials.gov Identifier: NCT02344290.

Background: Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population., Methods: In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates., Results: Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001)., Conclusions: Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH., Competing Interests: Potential conflicts of interest. B. F. reports institutional research support from AstraZeneca, MedImmune, and MedTrace, all outside of the submitted work. M. V. Z. reports grant support through her institution from NIH/NIAID and Gilead Sciences, Inc., relevant to the conduct of the study, as well as grants from NIH/NIAID and NIH/NHLBI (RO1AI123001 PI, R01 HL137562 PI, R01HL146267 PI, K24AI157882 PI, U01HL123336 Co-I, U01HL123336-06S2 Co-I, R01HL151283 Co-I) outside the submitted work; travel support from conference organizing committees for CROI and International Workshop for HIV and Women; and unpaid participation in DSMB for NIH-funded studies. A. L. reports institutional research support from NIH/NIA, outside of the submitted work. T. H. B. reports equity in Excision Bio Therapeutics and serves on its Scientific Advisory Board, outside the submitted work. G. S. B. reports research grants (R01HL157531, U01HL146382, R56HL152803, R01MD013493) and royalties from UpToDate.com. C. D. M. reports institutional research support by Lilly and personal fees from ViiV Healthcare, Pfizer, and Gilead Sciences for participation in advisory board meetings outside the submitted work. C. J. F. reports grant support through his institution from Gilead Sciences, ViiV Healthcare, GSK, Janssen, Abbvie, Merck, Amgen, and Cytodyn, outside the submitted work; and personal fees from Theratechnologies and ViiV for consulting and participation on Advisory Board unrelated to REPRIEVE with Theratechnologies and ViiV, and role as Chair on DSMB for Intrepid Study, outside the submitted work. J. A. A. reports institutional research support for clinical trials from Atea, Emergent Biosolutions, Frontier Technologies, Gilead Sciences, Glaxo Smith Kline, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare and personal fees for data safety monitoring or advisory boards from Kintor Pharmaceuticals, Glaxo Smith Kline, and Merck; all outside the submitted work. J. S. C. reports consulting fees from Merck and Company. H. J. R. reports grants from NIH/NHLBI and Kowa Pharmaceuticals during the conduct of the study as well as grants from NIH/NIAID, and NIH/NHLBI, NIH/NIDDK, and NIH/NIA outside the submitted work. U. H. reports institutional research support from Kowa, AstraZeneca, MedImmune, and HeartFlow; consulting fees from Recor Medical, Stanford University, Clinical Cardiovascular Sciences, MedTrace Inc., and Rapid AI; stock or stock options in Cleerly Inc. as Chief Scientific Officer; and personal fees from Duke University, all outside of the submitted work. M. T. L. reports grant support through his institution from NIH/NHLIBI and Kowa Pharmaceuticals America, Inc., for the conduct of the study; institutional grant support from MedImmune, CRICO, Ionis, Johnson & Johnson Innovation, National Academy of Medicine, and Astrazeneca; and personal fees from PQBypass, outside of the current work. P. S. D. reports consulting fees from Foresite Labs; receipt of equipment or drugs from Kowa and Caption Health; and an institutional grant for HeartFlow (outside of the current work). S. K. G. reports grants from NIH, KOWA Pharmaceuticals, Gilead Sciences, and ViiV Healthcare during the conduct of the study as well as personal consulting fees from TheraTechnologies, Navidea, and ViiV Healthcare, and Marathon Asset Management outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients with lung cancer face a heightened risk of atherosclerosis-related cardiovascular events. Despite the strong scientific rationale, there is currently a lack of clinical evidence examining the impact of immune checkpoint inhibitors (ICIs) on the advancement of atherosclerosis in patients with lung cancer. The objective of our study was to investigate whether there is a correlation between ICIs and the accelerated progression of atherosclerosis among individuals with lung cancer., Methods: In this case-control (2:1 matched by age and gender) study, total, non-calcified, and calcified plaque volumes were measured in the thoracic aorta using sequential contrast-enhanced chest CT scans. Univariate and multivariate rank-based estimation regression models were developed to estimate the effect of ICI therapy on plaque progression in 40 cases (ICI) and 20 controls (non-ICI)., Results: The patients had a median age of 66 years (IQR: 58-69), with 50% of them being women. At baseline, there were no significant differences in plaque volumes between the groups, and their cardiovascular risk profiles were similar. However, the annual progression rate for non-calcified plaque volume was 7 times higher in the ICI group compared with the controls (11.2% vs 1.6% per year, p=0.001). Conversely, the controls showed a greater progression in calcified plaque volume compared with the ICI group (25% vs 2% per year, p=0.017). In a multivariate model that considered cardiovascular risk factors, the use of an ICI was associated with a more substantial progression of non-calcified plaque volume. Additionally, individuals treated with combination ICI therapy exhibited greater plaque progression., Conclusions: ICI therapy was associated with more non-calcified plaque progression. These findings underscore the importance of conducting studies aimed at identifying the underlying mechanisms responsible for plaque advancement in patients undergoing ICI treatment., Trial Registration Number: NCT04430712., Competing Interests: Competing interests: TGN has been a consultant to and received fees from Parexel Imaging, Intrinsic Imaging, Amgen, Sanofi, Genentech, Roche, and AbbVie, outside of the current work. TGN also reports consultant fees from Bristol Myers Squibb for a Scientific Advisory Board focused on myocarditis related to immune checkpoint inhibitors. The study was funded directly by an unrestricted grant from AstraZeneca. TGN also reports research grant funding from Bristol Myers Squibb for work related to immune checkpoint inhibitors. BF reports unrelated grant support from MedImmune/AstraZeneca and MedTrace, as well as grants from NIH/NHLBI outside the submitted work. JT reports speaker’s bureau Siemens Healthcare GmbH and speakers bureau Bayer AG, reviewer Universimed Cross Media Content GmbH, and consultant Core Lab Black Forrest GmbH, all unrelated to this work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND More than half of major adverse cardiovascular events (MACE) occur in the absence of obstructive coronary artery disease and are often attributed to the rupture of high-risk coronary atherosclerotic plaque (HRP). Blood-based biomarkers that associate with imaging-defined HRP and predict MACE are lacking. METHODS AND RESULTS Nuclear magnetic resonance-based lipoprotein particle profiling was performed in the biomarker substudy of the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial (N=4019) in participants who had stable symptoms suspicious for coronary artery disease. Principal components analysis was used to reduce the number of correlated lipoproteins into uncorrelated lipoprotein factors. The association of lipoprotein factors and individual lipoproteins of significantly associated factors with core laboratory determined coronary computed tomographic angiography features of HRP was determined using logistic regression models. The association of HRP-associated lipoproteins with MACE was assessed in the PROMISE trial and validated in an independent coronary angiography biorepository (CATHGEN [Catheterization Genetics]) using Cox proportional hazards models. Lipoprotein factors composed of high-density lipoprotein (HDL) subclasses were associated with HRP. In these factors, large HDL (odds ratio [OR], 0.70 [95% CI, 0.56-0.85]; P <0.001) and medium HDL (OR, 0.84 [95% CI, 0.72-0.98]; P =0.028) and HDL size (OR, 0.82 [95% CI, 0.69-0.96]; P =0.018) were associated with HRP in multivariable models. Medium HDL was associated with MACE in PROMISE (hazard ratio [HR], 0.76 [95% CI, 0.63-0.92]; P =0.004), which was validated in the CATHGEN biorepository (HR, 0.91 [95% CI, 0.88-0.94]; P <0.001). CONCLUSIONS Large and medium HDL subclasses and HDL size inversely associate with HRP features, and medium HDL subclasses inversely associate with MACE in PROMISE trial participants. These findings may aid in the risk stratification of individuals with chest pain and provide insight into the pathobiology of HRP. REGISTRATION URL: https://clinicaltrials.gov; Unique identifier: NCT01174550.

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

Importance: Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk., Objectives: To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation., Design, Setting, and Participants: This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020., Exposure: HIV disease., Main Outcomes and Measures: The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP)., Results: The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01)., Conclusions and Relevance: In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

Aims: The expansion of TAVI will involve an increase in the frequency of emergent or late cardiac surgery after THV implantation. This study was designed to investigate the anatomical feasibility of surgical cross-clamp and aortotomy after TAVI through a post-TAVI CT-scan assessment., Methods and Results: We retrospectively analysed 117 CTs acquired after TAVI procedures with high stent prostheses in three high-volume centres between October 2008 and May 2017. The mean distance observed between the innominate artery and the top of the transcatheter heart valve was 45±11 mm, being <30 mm in 8/117 (6.8%) patients and <20 mm in none. The mean distance between the sinotubular junction and the first free site for aortotomy was 22±7 mm (>20 mm in 78/117 [66.7%] cases). A total of 56/117 (47.9%) patients showed a complete continuous contact between the anterior aortic wall and the anterior part of the valve stent., Conclusions: Aortic cross-clamp appears not to be an issue when cardiac surgery is needed after TAVI; however, a careful and possibly higher aortotomy may be required. CT should be performed prior to planned cardiac surgery after TAVI to determine a safe positioning for aortic cross-clamp and aortotomy.

Endothelial shear stress (ESS) identifies coronary plaques at high risk for progression and/or rupture leading to a future acute coronary syndrome. In this study an optimized methodology was developed to derive ESS, pressure drop and oscillatory shear index using computational fluid dynamics (CFD) in 3D models of coronary arteries derived from non-invasive coronary computed tomography angiography (CTA). These CTA-based ESS calculations were compared to the ESS calculations using the gold standard with fusion of invasive imaging and CTA. In 14 patients paired patient-specific CFD models based on invasive and non-invasive imaging of the left anterior descending (LAD) coronary arteries were created. Ten patients were used to optimize the methodology, and four patients to test this methodology. Time-averaged ESS (TAESS) was calculated for both coronary models applying patient-specific physiological data available at the time of imaging. For data analysis, each 3D reconstructed coronary artery was divided into 2 mm segments and each segment was subdivided into 8 arcs (45°).TAESS and other hemodynamic parameters were averaged per segment as well as per arc. Furthermore, the paired segment- and arc-averaged TAESS were categorized into patient-specific tertiles (low, medium and high). In the ten LADs, used for optimization of the methodology, we found high correlations between invasively-derived and non-invasively-derived TAESS averaged over segments (n = 263, r = 0.86) as well as arcs (n = 2104, r = 0.85, p < 0.001). The correlation was also strong in the four testing-patients with r = 0.95 (n = 117 segments, p = 0.001) and r = 0.93 (n = 936 arcs, p = 0.001).There was an overall high concordance of 78% of the three TAESS categories comparing both methodologies using the segment- and 76% for the arc-averages in the first ten patients. This concordance was lower in the four testing patients (64 and 64% in segment- and arc-averaged TAESS). Although the correlation and concordance were high for both patient groups, the absolute TAESS values averaged per segment and arc were overestimated using non-invasive vs. invasive imaging [testing patients: TAESS segment: 30.1(17.1-83.8) vs. 15.8(8.8-63.4) and TAESS arc: 29.4(16.2-74.7) vs 15.0(8.9-57.4) p < 0.001]. We showed that our methodology can accurately assess the TAESS distribution non-invasively from CTA and demonstrated a good correlation with TAESS calculated using IVUS/OCT 3D reconstructed models.

Objective: Obesity and metabolic syndrome are associated with major adverse cardiovascular events (MACE). However, whether distinct metabolic phenotypes differ in risk for coronary artery disease (CAD) and MACE is unknown. We sought to determine the association of distinct metabolic phenotypes with CAD and MACE., Research Design and Methods: We included patients from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) who underwent coronary computed tomography (CT) angiography. Obesity was defined as a BMI ≥30 kg/m 2 and metabolically healthy as less than or equal to one metabolic syndrome component except diabetes, distinguishing four metabolic phenotypes: metabolically healthy/unhealthy and nonobese/obese (MHN, MHO, MUN, and MUO). Differences in severe calcification (coronary artery calcification [CAC] ≥400), severe CAD (≥70% stenosis), high-risk plaque (HRP), and MACE were assessed using adjusted logistic and Cox regression models., Results: Of 4,381 patients (48.4% male, 60.5 ± 8.1 years of age), 49.4% were metabolically healthy (30.7% MHN and 18.7% MHO) and 50.6% unhealthy (22.3% MUN and 28.4% MUO). MHO had similar coronary CT findings as compared with MHN (severe CAC/CAD and HRP; P > 0.36 for all). Among metabolically unhealthy patients, those with obesity had similar CT findings as compared with nonobese ( P > 0.10 for all). However, both MUN and MUO had unfavorable CAD characteristics as compared with MHN ( P ≤ 0.017 for all). A total of 130 events occurred during follow-up (median 26 months). Compared with MHN, MUN (hazard ratio [HR] 1.61 [95% CI 1.02-2.53]) but not MHO (HR 1.06 [0.62-1.82]) or MUO (HR 1.06 [0.66-1.72]) had higher risk for MACE., Conclusions: In patients with stable chest pain, four metabolic phenotypes exhibit distinctly different CAD characteristics and risk for MACE. Individuals who are metabolically unhealthy despite not being obese were at highest risk in our cohort., (© 2021 by the American Diabetes Association.)