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Importance: Lipoprotein(a) (Lp[a]) is a causal risk factor for cardiovascular disease; however, long-term effects on coronary atherosclerotic plaque phenotype, high-risk plaque formation, and pericoronary adipose tissue inflammation remain unknown., Objective: To investigate the association of Lp(a) levels with long-term coronary artery plaque progression, high-risk plaque, and pericoronary adipose tissue inflammation., Design, Setting, and Participants: This single-center prospective cohort study included 299 patients with suspected coronary artery disease (CAD) who underwent per-protocol repeated coronary computed tomography angiography (CCTA) imaging with an interscan interval of 10 years. Thirty-two patients were excluded because of coronary artery bypass grafting, resulting in a study population of 267 patients. Data for this study were collected from October 2008 to October 2022 and analyzed from March 2023 to March 2024., Exposures: The median scan interval was 10.2 years. Lp(a) was measured at follow-up using an isoform-insensitive assay. CCTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography)., Main Outcome and Measures: The association between Lp(a) and change in percent plaque volumes was investigated in linear mixed-effects models adjusted for clinical risk factors. Secondary outcomes were presence of low-density plaque and presence of increased pericoronary adipose tissue attenuation at baseline and follow-up CCTA imaging., Results: The 267 included patients had a mean age of 57.1 (SD, 7.3) years and 153 were male (57%). Patients with Lp(a) levels of 125 nmol/L or higher had twice as high percent atheroma volume (6.9% vs 3.0%; P = .01) compared with patients with Lp(a) levels less than 125 nmol/L. Adjusted for other risk factors, every doubling of Lp(a) resulted in an additional 0.32% (95% CI, 0.04-0.60) increment in percent atheroma volume during the 10 years of follow-up. Every doubling of Lp(a) resulted in an odds ratio of 1.23 (95% CI, 1.00-1.51) and 1.21 (95% CI, 1.01-1.45) for the presence of low-density plaque at baseline and follow-up, respectively. Patients with higher Lp(a) levels had increased pericoronary adipose tissue attenuation around both the right coronary artery and left anterior descending at baseline and follow-up., Conclusions and Relevance: In this long-term prospective serial CCTA imaging study, higher Lp(a) levels were associated with increased progression of coronary plaque burden and increased presence of low-density noncalcified plaque and pericoronary adipose tissue inflammation. These data suggest an impact of elevated Lp(a) levels on coronary atherogenesis of high-risk, inflammatory, rupture-prone plaques over the long term.

Aims: Familial hypercholesterolaemia (FH) patients are subjected to a high lifetime exposure to low density lipoprotein cholesterol (LDL-C), despite use of lipid-lowering therapy (LLT). This study aimed to quantify the extent of subclinical atherosclerosis and to evaluate the association between lifetime cumulative LDL-C exposure and coronary atherosclerosis in young FH patients., Methods and Results: Familial hypercholesterolaemia patients, divided into a subgroup of early treated (LLT initiated <25 years) and late treated (LLT initiated ≥25 years) patients, and an age- and sex-matched unaffected control group, underwent coronary CT angiography (CCTA) with artificial intelligence-guided analysis. Ninety genetically diagnosed FH patients and 45 unaffected volunteers (mean age 41 ± 3 years, 51 (38%) female) were included. Familial hypercholesterolaemia patients had higher cumulative LDL-C exposure (181 ± 54 vs. 105 ± 33 mmol/L ∗ years) and higher prevalence of coronary plaque compared with controls (46 [51%] vs. 10 [22%], OR 3.66 [95%CI 1.62-8.27]). Every 75 mmol/L ∗ years cumulative exposure to LDL-C was associated with a doubling in per cent atheroma volume (total plaque volume divided by total vessel volume). Early treated patients had a modestly lower cumulative LDL-C exposure compared with late treated FH patients (167 ± 41 vs. 194 ± 61 mmol/L ∗ years; P = 0.045), without significant difference in coronary atherosclerosis. Familial hypercholesterolaemia patients with above-median cumulative LDL-C exposure had significantly higher plaque prevalence (OR 3.62 [95%CI 1.62-8.27]; P = 0.001), compared with patients with below-median exposure., Conclusion: Lifetime exposure to LDL-C determines coronary plaque burden in FH, underlining the need of early as well as potent treatment initiation. Periodic CCTA may offer a unique opportunity to monitor coronary atherosclerosis and personalize treatment in FH., Competing Interests: Conflict of interest: L.F.R. is cofounder of Lipid Tools and reports speakers fee from Ultragenyx. G.K.H. reports research grants from the Netherlands Organization for Scientific Research (vidi 016.156.445), CardioVascular Research Initiative, European Union, and the Klinkerpad fonds, institutional research support from Aegerion, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis, Kowa, Pfizer, Regeneron, Roche, Sanofi, and The Medicines Company; speaker’s bureau and consulting fees from Amgen, Aegerion, Sanofi, and Regeneron until April 2019 (fees paid to the academic institution); and part-time employment and stock holder of at Novo Nordisk A/S, Denmark since April 2019. W.A.B. reports lecturing fees and advisory board fees from Amgen, Boehringer Ingelheim, Sanofi, Bayer, AstraZeneca, Novartis, and Novo Nordisk. P.K. has received research grants from HeartFlow, Inc. A.W. reports payment or honoraria for participation in safety board for Amryt, in steering committee for Novartis, and research support from Amgen, Regeneron, Novartis, Silence Therapeutics, and Esperion. E.S.G.S. has received ad-board/lecturing fees, paid to the institution, from: Amgen, Sanofi, AstraZeneca, Esperion, Daiichi Sankyo, NovoNordisk, Ionis/Akcea, and Amarin. N.S.N. is cofounder of Lipid Tools. The other authors report no disclosures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Data on the warranty period of coronary computed tomography angiography (CTA) and combined coronary CTA/positron emission tomography (PET) are scarce. The present study aimed to determine the event-free (warranty) period after coronary CTA and the potential additional value of PET., Method and Results: Patients with suspected but not previously diagnosed coronary artery disease (CAD) who underwent coronary CTA and/or [15O]H2O PET were categorized based upon coronary CTA as no CAD, non-obstructive CAD, or obstructive CAD. A hyperaemic myocardial blood flow (MBF) ≤ 2.3 mL/min/g was considered abnormal. The warranty period was defined as the time for which the cumulative event rate of death and non-fatal myocardial infarction (MI) was below 5%. Of 2575 included patients (mean age 61.4 ± 9.9 years, 41% male), 1319 (51.2%) underwent coronary CTA only and 1237 (48.0%) underwent combined coronary CTA/PET. During a median follow-up of 7.0 years 163 deaths and 68 MIs occurred. The warranty period for patients with no CAD on coronary CTA was ≥10 years, whereas patients with non-obstructive CAD had a 5-year warranty period. Patients with obstructive CAD and normal hyperaemic MBF had a 2-year longer warranty period compared to patients with obstructive CAD and abnormal MBF (3 years vs. 1 year)., Conclusion: As standalone imaging, the warranty period for normal coronary CTA is ≥10 years, whereas patients with non-obstructive CAD have a warranty period of 5 years. Normal PET yielded a 2-year longer warranty period in patients with obstructive CAD., Competing Interests: Conflict of interest: J.K. has 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. A.S. has received fees for consultancy or lectures from Abbott, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. The remaining authors have nothing to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Patient-tailored contrast delivery protocols strongly reduce the total iodine load and in general improve image quality in CT coronary angiography (CTCA). We aim to use machine learning to predict cases with insufficient contrast enhancement and to identify parameters with the highest predictive value., Methods: Machine learning models were developed using data from 1,447 CTs. We included patient features, imaging settings, and test bolus features. The models were trained to predict CTCA images with a mean attenuation value in the ascending aorta below 400 HU. The accuracy was assessed by the area under the receiver operating characteristic (AUROC) and precision-recall curves (AUPRC). Shapley Additive exPlanations was used to assess the impact of features on the prediction of insufficient contrast enhancement., Results: A total of 399 out of 1,447 scans revealed attenuation values in the ascending aorta below 400 HU. The best model trained using only patient features and CT settings achieved an AUROC of 0.78 (95% CI: 0.73-0.83) and AUPRC of 0.65 (95% CI: 0.58-0.71). With the inclusion of the test bolus features, it achieved an AUROC of 0.84 (95% CI: 0.81-0.87), an AUPRC of 0.71 (95% CI: 0.66-0.76), and a sensitivity of 0.66 and specificity of 0.88. The test bolus' peak height was the feature that impacted low attenuation prediction most., Conclusion: Prediction of insufficient contrast enhancement in CT coronary angiography scans can be achieved using machine learning models. Our experiments suggest that test bolus features are strongly predictive of low attenuation values and can be used to further improve patient-specific contrast delivery protocols., Key Points: • Prediction of insufficient contrast enhancement in CT coronary angiography scans can be achieved using machine learning models. • The peak height of the test bolus curve is the most impacting feature for the best performing model., (© 2022. The Author(s).)

Purpose: The first objective of this study was to evaluate the efficacy of a patient-tailored contrast delivery protocol for coronary computed tomography angiography (CTCA), in terms of diagnostic coronary attenuation and total iodine load (TIL), by adjusting the iodine delivery rate (IDR) via dilution for body weight and tube voltage (kV), as compared with a protocol with a fixed bolus of contrast in a clinical setting. The secondary objective was to assess the association between the test-bolus data and luminal attenuation in CTCA., Materials and Methods: Patients who underwent CTCA with fixed IDR contrast delivery (cohort 1) or with IDR adjusted for body weight and kV settings (70 to 120 kV) (cohort 2) were included, and compared for intravascular luminal attenuation and TIL. The association between intravascular luminal attenuation and test-bolus scan data was investigated with linear regression., Results: In cohort 1 (176 patients), the mean luminal attenuation differed markedly between kV categories, whereas in cohort 2 (154 patients), there were no marked differences. The mean TIL reduced significantly (20.1±1.2 g in cohort 1, 17.7±3.0 g in cohort 2, P<0.001). The peak height of the test-bolus scan was independently associated with luminal attenuation in the ascending aorta, with a 0.58 HU increase per HU peak-height increase (SE=0.18, P<0.001)., Conclusion: Clinical implementation of a patient-tailored contrast delivery protocol for CTCA, adjusted for body weight and kV, improves luminal attenuation and significantly reduces the TIL. The peak height of the test-bolus scan is associated with luminal attenuation in the ascending aorta in the CTCA scan., Competing Interests: The authors declare no conflicts of interest, (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Age and sex based coronary artery calcium score (CAC) percentiles have been used to improve coronary artery disease (CAD) risk prediction. However, the main limitation of the CACs percentiles currently in use is that they are often based on single studies. We performed a pooled analysis of all available studies that reported on CAC percentiles, in order to develop more generalizable age and sex nomograms., Methods: PubMed/Medline and Embase were searched for studies that reported nomograms of age and sex-based CACs percentiles. Studies were included if they reported data collected among asymptomatic individuals without a history of cardiovascular disease. Absolute CACs for each specific percentile stratum were pooled and new percentiles were generated taking into account the sample size of the study., Results: We found 831 studies, of which 12 met the inclusion criteria. Data on CACs percentiles of 134,336 Western and 33,488 Asians were pooled separately, rendering a weighted CACs percentile nomogram available at https://www.calciumscorecalculator.com. Our weighted percentiles differed by up to 24% from the nomograms in use today., Conclusions: Our pooled age and sex based CACs percentiles based on over 155,000 individuals should provide a measure of risk that is more applicable to a wider population than the ones currently in use and hopefully will lead to better risk assessment and treatment decisions., (Copyright © 2020 [The Author/The Authors]. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate whether the biomechanical marker known as rupture risk equivalent diameter (RRED) was superior to the actual abdominal aortic aneurysm (AAA) diameter in estimating future rupture risk in patients who had undergone pre-rupture computed tomography (CT) angiography., Materials and Methods: A retrospective study was conducted in 13 patients with ruptured AAAs who had undergone CT angiography before and after rupture between 2001 and 2015. The median time between the 2 scans was 731 days. Biomechanical and geometrical markers such as maximal AAA diameter, peak wall stress (PWS), and RRED were calculated with AAA-dedicated software. The main analyses determined whether RRED was higher than the actual diameter and the threshold diameter for elective surgery (55 mm for men, 50 mm for women) in AAAs before and after rupture. Differences between diameter and biomechanical markers before and after rupture were tested with appropriate statistical tests., Results: RRED before and after rupture was smaller than the actual diameter in 7 of 13 cases. Post-rupture RRED was estimated to be smaller than the threshold diameter for elective repair in 4 cases, again suggesting a low rupture risk. The median PWS before and after rupture was 181.7 kPa (interquartile range [IQR], 152.1-244.2 kPa) and 274.1 kPa (IQR, 172.2-377.2 kPa), respectively., Conclusions: RRED was smaller than the actual diameter in more than half of pre-rupture AAAs, suggesting a lower rupture risk than estimated with the actual diameter. The results suggest that the currently available biomechanical imaging markers might not be ready for use in clinical practice., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Homozygous familial hypercholesterolemia (hoFH) is a rare genetic disease, hallmarked by a lifelong exposure to very high levels of low-density lipoprotein cholesterol (LDL-C). Untreated, patients can experience a cardiovascular event in the first decade of life. Early detection and monitoring of subclinical atherosclerosis in these patients is therefore extremely important. We set out to assess the diagnostic yield of low-dose coronary computed tomography angiography (cCTA) compared to echocardiography in detecting subclinical atherosclerosis., Methods: For this single-center cross-sectional study, we included all pediatric hoFH patients treated with lipoprotein-apheresis (LA) in Amsterdam UMC. We performed both cCTA and echocardiography in all patients as part of routine follow-up., Results: Six hoFH patients were included. Median ages at diagnosis, onset of LA and cardiovascular assessment (cCTA and echocardiography) were 2.6, 6.5, 10.8 and 11.1 years, respectively. Echocardiography revealed no signs of atherosclerosis in any of the six patients. In two patients, mild dilatation of the cardiac chambers was detected and two patients showed signs of mitral or aortic insufficiency. On cCTA, however, non-calcified plaques without stenosis were detected in four patients. In two patients calcified coronary plaques were found at the ostia of the right coronary artery or the left main coronary artery. Aortic root calcifications were found in two patients., Conclusions: Our findings suggest that in hoFH children, low-dose cCTA is superior to echocardiography for the detection of subclinical coronary and aortic root atherosclerosis and should therefore be considered in the routine cardiovascular monitoring of these high-risk children., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The aim of this study was to assess in vitro the diagnostic accuracy of computed tomography angiography (CTA) for the evaluation of complex coronary lesions., Methods and Results: Five Plexiglas phantoms with three bifurcation lesions each were designed to mimic the anatomic variations and fractal phenomena of the coronary tree. In addition, luminal stenoses were scaled up with increases of 10% from 40% to 80%, corresponding to luminal areas ranging from 3.0 mm2 to 0.22 mm2. Third-generation dual-source computed tomography was used. Automated quantitative CTA analysis was performed according to the bifurcation segment model. The primary objective was to determine the diagnostic accuracy of quantitative CTA in assessing bifurcation lesions with the phantoms as a reference. The accuracy of CTA for the assessment of minimal luminal diameter was -0.07 mm (limits of agreement -0.75 to 0.61), for reference vessel diameter 0.19 mm (limits of agreement -0.25 to 0.63) and diameter stenosis 8.2% (limits of agreement -13.2 to 29.5) with no difference regarding the location within the bifurcation (i.e., proximal and distal main vessel and side branch). In stenosis with minimal luminal diameter ≥1 mm, CTA overestimated the lesion severity (bias 0.19 mm, limits of agreement -0.09 to 0.47), whereas in lesions with severe stenosis and minimal luminal diameter ≤1 mm, CTA underestimated the lesion severity (bias -0.48 mm, limits of agreement -0.55 to -0.41). CTA was able to identify the contrast-filled lumen in all degrees of lesion severity., Conclusions: In vitro, CTA is accurate for the evaluation of bifurcation lesions. CTA was able to distinguish contrast-filled lumen even in severe obstructive lesions. These findings require further validation in the clinical setting.

Computed tomography angiography (CTA) in workup for transcatheter aortic valve implantation (TAVI) frequently reveals potentially malignant incidental findings. Most incidental findings provoke discussions on their influence. We aimed to analyze if these findings were a predictor of long-term survival after TAVI. In a single-center retrospective analysis, all consecutive patients with pre-TAVI CTA were included (years 2009 to 2014). Patients were divided by presence or absence of incidental findings. We analyzed up to 5 years of all-cause, non-cardiovascular and cardiovascular mortality for all 553 patients who underwent TAVI; 113 had a potentially malignant incidental finding (20.4%). At 5 years, all-cause mortality risk was 64.5% in patients with versus 49.1% in patients without a finding (hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.25 to 2.31). After adjustment, the findings remained an independent predictor of all-cause (adjusted HR 1.46, 95% CI 1.07 to 1.99) and non-cardiovascular mortality (adjusted subdistribution HR 1.84, 95% CI 1.06 to 3.20), but not of cardiovascular mortality. In conclusion, the presence of potentially malignant incidental findings on CTA is an independent predictor of long-term all-cause and noncardiovascular mortality but not of cardiovascular mortality., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve implantation (TAVI) is a well-established treatment for patients with severe aortic valve stenosis. This procedure requires pre-operative planning by assessment of aortic dimensions on CT Angiography (CTA). It is well-known that the aortic root dimensions vary over the heart cycle. However, sizing is commonly performed at either mid-systole or end-diastole only, which has resulted in an inadequate understanding of its full dynamic behavior., Study Goal: We studied the variation in annulus measurements during the cardiac cycle and determined if this variation is dependent on the amount of calcification at the annulus., Methods: We measured and compared aortic root annular dimensions and calcium volume in CTA acquisitions at 10 cardiac cycle phases in 51 aortic stenosis patients. Sub-group analysis was performed based on the volume of calcium by splitting the population into mildly and severely calcified valves subgroups., Results: For most annulus measurements, the largest differences were found between 10% and 70 to 80% cardiac cycle phases. Mean difference (±standard deviation) in annular minimum diameter, maximum diameter, area, and aspect ratio between mid-systole and end-diastole phases were 1.0 ± 0.29 mm (p = 0.065), 0.30 ± 0.24 mm (p = 0.7), 24.1 ± 7.6 mm2 (p < 0.001), and 0.041 ± 0.012 (p = 0.039) respectively. Calcium volume measurements varied strongly during the cardiac cycle. The dynamic annulus area was behaving differently between mildly and severely calcified subgroups (p = 0.02). Furthermore, patients with severe aortic calcification were associated with larger annulus diameters., Conclusion: There is a significant variation of annulus area and calcium volume measurement during the cardiac cycle. In our measurements, only the dynamic variation of the annulus area is dependent on the severity of the aortic calcification. For TAVI candidates, the annulus area is significantly larger in mid-systole compared to end-diastole.

Background: Methods are required to identify abdominal aortic aneurysms (AAAs) at increased risk of rupture. Inflammatory characteristics of AAA can be visualised using advanced imaging techniques and have been proposed as potential predictors of aneurysm progression. The objective of this review was to determine which inflammatory imaging biomarkers are associated with AAA growth and rupture., Methods: A systematic review was carried out in accordance with the PRISMA guidelines. The electronic databases of Medline (PubMed), Embase, and the Cochrane Library were searched up to January 1, 2016 for studies to determine the potential association between inflammatory imaging biomarkers and AAA growth or rupture., Results: Seven studies were included, comprising 202 AAA patients. (18)F-fluoro-deoxy-glucose positron emission tomography ((18)F-FDG PET-CT) was evaluated in six studies. Magnetic resonance imaging with ultrasmall superparamagnetic particles of iron oxide (USPIO-MRI) was evaluated in one study. Two of six (18)F-FDG PET-CT studies reported a significant negative correlation (r=.383, p = .015) or a significant negative association (p = .04). Four of six (18)F-FDG PET-CT studies reported no significant association between (18)F-FDG uptake and AAA growth. The single study investigating USPIO-MRI demonstrated that AAA growth was three times higher in patients with focal USPIO uptake in the AAA wall compared to patients with diffuse or no USPIO uptake in the wall (0.66 vs. 0.24 vs. 0.22 cm/y, p = .020). In the single study relating (18)F-FDG uptake results to AAA rupture, the association was not significant., Conclusions: Current evidence shows contradictory associations between (18)F-FDG uptake and AAA growth. Data on the association with rupture are insufficient. Based on the currently available evidence, neither (18)F-FDG PET-CT nor USPIO-MRI can be implemented as growth or rupture prediction tools in daily practice. The heterogeneous results reflect the complex and partially unclear relationship between inflammatory processes and AAA progression., (Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)