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Background: Patients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac events., Study Design: The CLEAR-CAD trial is a prospective, open-label, multicentre, randomised, superiority trial of an upfront CTCA-guided strategy in 6444 patients presenting in an outpatient setting with suspected CAD compared with standard care, in approximately 30 participating centres in the Netherlands. The upfront CTCA-guided strategy consists of an initial CTCA which is assessed using the Coronary Artery Disease-Reporting and Data System (CAD-RADS 2.0). In patients without CAD (CAD-RADS 0) no specific cardiac medication is mandated. Patients with non-obstructive CAD (CAD-RADS 1-2) are treated with preventive OMT. Patients with obstructive CAD (CAD-RADS ≥ 3) are treated with preventive and anti-anginal OMT; in the presence of pharmacologically refractory symptoms patients undergo selective revascularisation after non-invasive functional imaging for myocardial ischaemia (≥ 10%). Patients with significant left main or proximal left anterior descending coronary artery stenosis on CTCA undergo direct invasive coronary angiography and subsequent revascularisation. The primary endpoint is the composite of all-cause death and myocardial infarction., Conclusion: The CLEAR-CAD trial is the first randomised study to investigate the efficacy of a combined upfront CTCA-guided medical and selective revascularisation strategy in an outpatient setting with suspected CAD compared with standard care., (© 2024. The Author(s).)

Background & Aims: Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to investigate whether we can independently predict mortality risk in transcatheter aortic valve implantation (TAVI) patients, using automatic deep learning algorithms to assess muscle quality on procedural computed tomography (CT) scans., Methods: This study included 1199 patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) between January 2010 and January 2020. A procedural CT scan was performed as part of the preprocedural-TAVI evaluation, and the scans were analyzed using deep-learning-based software to automatically determine skeletal muscle density (SMD) and intermuscular adipose tissue (IMAT). The association of SMD and IMAT with all-cause mortality was analyzed using a Cox regression model, adjusted for other known mortality predictors, including muscle mass., Results: The mean age of the participants was 80 ± 7 years, 53% were female. The median observation time was 1084 days, and the overall mortality rate was 39%. We found that the lowest tertile of muscle quality, as determined by SMD, was associated with an increased risk of mortality (HR 1.40 [95%CI: 1.15-1.70], p < 0.01). Similarly, low muscle quality as defined by high IMAT in the lowest tertile was also associated with increased mortality risk (HR 1.24 [95%CI: 1.01-1.52], p = 0.04)., Conclusions: Our findings suggest that deep learning-assessed low muscle quality, as indicated by fat infiltration in muscle tissue, is a practical, useful and independent predictor of mortality after TAVI., Competing Interests: Declaration of competing interest Pim Moeskops is an employee of Quantib-U, Bob D. de Vos is Artificial Intelligence lead and co-founder of Quantib-U and Ivana Išgum is also co-founder and Scientific lead at Quantib-U. All other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Left atrial appendage (LAA) slow-flow may increase the risk of ischemic stroke. We studied LAA attenuation on cardiac computed tomography in patients with acute ischemic stroke., Methods and Results: We used data from a prospective cohort of patients with acute ischemic stroke undergoing cardiac computed tomography during the acute stroke imaging protocol. We compared characteristics, functional outcome (modified Rankin scale: higher scores indicating worse outcome), stroke recurrence and major adverse cardiovascular events after 2-year follow-up between patients with LAA thrombus (filling defect<100 Hounsfield Unit (HU)), slow-flow (filling defect ≥100 HU) and normal filling. Of 421 patients, 31 (7%) had LAA thrombus, 69 (16%) slow-flow, and 321 (76%) normal filling. Patients with thrombus or slow-flow more often had known atrial fibrillation compared with normal filling (45%, 39%, and 9%, P <0.001). Patients with thrombus had higher National Institutes of Health Stroke Scale-scores compared with slow-flow and normal filling (18 [interquartile range, 9-22], 6 [interquartile range, 3-17], and 5 [interquartile range, 2-11], P <0.001). Compared with normal filling, there was no difference with slow-flow in functional outcome (median modified Rankin scale, 3 versus 2; acOR 0.8 [95% CI, 0.5-1.4]), stroke recurrence (adjusted hazard ratio, 0.8 [95% CI, 0.3-1.9]) or major adverse cardiovascular events (adjusted hazard ratio, 1.2 [95% CI, 0.7-2.1]), while patients with thrombus had worse functional outcome (median modified Rankin scale, 6, acOR, 3.3 [95% CI, 1.5-7.4]). In cryptogenic stroke patients (n=156) slow-flow was associated with stroke recurrence (27% versus 6%, aHR, 4.1 [95% CI, 1.1-15.7])., Conclusions: Patients with slow-flow had similar characteristics to patients with thrombus, but had less severe strokes. Slow-flow was not significantly associated with functional outcome or major adverse cardiovascular events, but was associated with recurrent stroke in patients with cryptogenic stroke.

Background: Maximum diameter measurements are used to assess the rupture risk of abdominal aortic aneurysms (AAAs); however, these are not precise enough to predict all ruptures. Four-dimensional (4D) flow MRI-derived parameters provide additional information by visualizing hemodynamics in AAAs but merit further investigation before they are clinically applicable., Purpose: To assess the reproducibility of 4D flow MRI-derived hemodynamics, to investigate possible correlations with lumen and maximum diameter, and to explore potential relationships with vorticity and aneurysm growth., Study Type: Prospective single-arm study., Population: A total of 22 (71.5 ± 6.1 years, 20 male) asymptomatic AAA patients with a maximum diameter of at least 30 mm., Field Strength/sequence: A 3.0 T/Free-breathing 4D flow MRI phase-contrast acquisition with retrospective ECG-gating., Assessment: Patients underwent two consecutive 4D flow MRI scans 1-week apart. Aortic volumes were segmented from time-averaged phase contrast magnetic resonance angiographies. Reproducibility was assessed by voxelwise analysis after registration. Mean flow velocity, mean wall shear stress (WSS), mean lumen diameter, and qualitative vorticity scores were assessed. In addition, Dixon MRI and retrospective surveillance data were used to study maximum diameter (including thrombus), intraluminal thrombus volume (ILT), and growth rate., Statistical Tests: For reproducibility assessment, Bland-Altman analyses, Pearson correlation, Spearman's correlation, and orthogonal regression were conducted. Potential correlations between hemodynamics and vorticity scores were assessed using linear regression. P < 0.05 was considered statistically significant., Results: Test-retest median Pearson correlation coefficients for flow velocity and WSS were 0.85 (IQR = 0.08) m/sec and 0.82 (IQR = 0.10) Pa, respectively. Mean WSS significantly correlated with mean flow velocity (R = 0.75) and inversely correlated with mean lumen diameter (R = -0.73). No significant associations were found between 4D flow MRI-derived hemodynamic parameters and maximum diameter (flow velocity: P = 0.98, WSS: P = 0.22)., Data Conclusion: A 4D flow MRI is robust for assessing the hemodynamics within AAAs. No correlations were found between hemodynamic parameters and maximum diameter, ILT volume and growth rate., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

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.

Background: Obesity increases the risk of atrial fibrillation (AF). We hypothesize that 'obese' epicardial adipose tissue (EAT) is, regardless of comorbidities, associated with markers of AF vulnerability., Methods: Patients >40y of age undergoing bariatric surgery and using <2 antihypertensive drugs and no insulin were prospectively included. Study investigations were conducted before and 1y after surgery. Heart rhythm and p-wave duration were measured through ECGs and 7-d-holters. EAT-volume and attenuation were determined on non-enhanced CT scans. Serum markers were quantified by ELISA., Results: Thirty-seven patients underwent surgery (age: 52.1 ± 5.9y; 27 women; no AF). Increased p-wave duration correlated with higher BMI, larger EAT volumes, and lower EAT attenuations (p < 0.05). Post-surgery, p-wave duration decreased from 109 ± 11 to 102 ± 11ms. Concurrently, EAT volume decreased from 132 ± 49 to 87 ± 52ml, BMI from 43.2 ± 5.2 to 28.9 ± 4.6kg/m 2 , and EAT attenuation increased from -76.1 ± 4.0 to -71.7 ± 4.4HU (p <0.001). Adiponectin increased from 8.7 ± 0.8 to 14.2 ± 1.0 μg/ml (p <0.001). However, decreased p-wave durations were not related to changed EAT characteristics, BMI or adiponectin., Conclusion: In this explorative study, longer p-wave durations related to higher BMIs, larger EAT volume, and lower EAT attenuations. P-wave duration and EAT volume decreased, and EAT attenuation increased upon drastic weightloss. However, there was no relation between decreased p-wave duration and changed BMI or EAT characteristics.

Whole-heart 4D-flow MRI is a valuable tool for advanced visualization and quantification of blood flow in cardiovascular imaging. Despite advantages over 2D-phase-contrast flow, clinical implementation remains only partially exploited due to many hurdles in all steps, from image acquisition, reconstruction, postprocessing and analysis, clinical embedment, reporting, legislation, and regulation to data storage. The intent of this manuscript was 1) to evaluate the extent of clinical implementation of whole-heart 4D-flow MRI, 2) to identify hurdles hampering clinical implementation, and 3) to reach consensus on requirements for clinical implementation of whole-heart 4D-flow MRI. This study is based on Delphi analysis. This study involves a panel of 18 experts in the field on whole-heart 4D-flow MRI. The experience with and opinions of experts (mean 13 years of experience, interquartile range 6) in the field were aggregated. This study showed that among experts in the cardiovascular field, whole-heart 4D-flow MRI is currently used for both clinical and research purposes. Overall, the panelists agreed that major hurdles currently hamper implementation and utilization. The sequence-specific hurdles identified were long scan time and lack of standardization. Further hurdles included cumbersome and time-consuming segmentation and postprocessing. The study concludes that implementation of whole-heart 4D-flow MRI in clinical routine is feasible, but the implementation process is complex and requires a dedicated, multidisciplinary team. A predefined plan, including risk assessment and technique validation, is essential. The reported consensus statements may guide further tool development and facilitate broader implementation and clinical use. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 5., (© 2024 The Author(s). Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Aims: To investigate the location-specific prognostic significance of plaque burden, diameter stenosis and plaque morphology., Methods and Results: Patients without a documented cardiac history who underwent coronary computed tomography angiography (CCTA) for suspected coronary artery disease were included. Percentage atheroma volume (PAV), maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. When adjusted for traditional risk factors and presence of PAV on other locations, only proximal PAV was independently associated with MACE. However, PAV of the proximal segments was strongly correlated to PAV localized at the mid (R= 0.76) and distal segments (R=0.74, p<0.01 for both). When only adjusted for cardiovascular risk factors, the area under the curve (AUC) to predict MACE for proximal PAV was 0.73 (95%CI 0.69-0.76), which was similar compared to mid PAV (AUC 0.72, 95%CI 0.68-0.76) and distal PAV (AUC 0.72, 95%CI 0.68-0.76). Similar results were obtained using diameter stenosis instead of PAV. The presence of proximal low-attenuation plaque had borderline additional prognostic value., Conclusions: Proximal PAV was the strongest predictor of MACE when adjusted for cardiovascular risk factors and plaque at other locations. However, when presence of plaque was only adjusted for cardiovascular risk factors, proximal, mid, and distal plaque localization showed a similar predictive ability for MACE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The longitudinal relation between coronary artery disease (CAD) polygenic risk score (PRS) and long-term plaque progression and high-risk plaque (HRP) features is unknown., Objectives: The goal of this study was to investigate the impact of CAD PRS on long-term coronary plaque progression and HRP., Methods: Patients underwent CAD PRS measurement and prospective serial coronary computed tomography angiography (CTA) imaging. Coronary CTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography imaging). The relationship between CAD PRS and change in percent atheroma volume (PAV), percent noncalcified plaque progression, and HRP prevalence was investigated in linear mixed-effect models adjusted for baseline plaque volume and conventional risk factors., Results: A total of 288 subjects (mean age 58 ± 7 years; 60% male) were included in this study with a median scan interval of 10.2 years. At baseline, patients with a high CAD PRS had a more than 5-fold higher PAV than those with a low CAD PRS (10.4% vs 1.9%; P < 0.001). Per 10 years of follow-up, a 1 SD increase in CAD PRS was associated with a 0.69% increase in PAV progression in the multivariable adjusted model. CAD PRS provided additional discriminatory benefit for above-median noncalcified plaque progression during follow-up when added to a model with conventional risk factors (AUC: 0.73 vs 0.69; P = 0.039). Patients with high CAD PRS had an OR of 2.85 (95% CI: 1.14-7.14; P = 0.026) and 6.16 (95% CI: 2.55-14.91; P < 0.001) for having HRP at baseline and follow-up compared with those with low CAD PRS., Conclusions: Polygenic risk is strongly associated with future long-term plaque progression and HRP in patients suspected of having CAD., Competing Interests: Funding Support and Author Disclosures Dr Nurmohamed is supported by grants from the Dutch Heart Foundation (Dekker grant number 03-007-2023-0068) and European Atherosclerosis Society (2023). Dr Fahed is supported by grants K08HL161448 and R01HL164629 from the National Heart, Lung, and Blood Institute. Dr Nurmohamed has received research funding/speaker fees from Cleerly, Daiichi Sankyo, and Novartis; and is co-founder of Lipid Tools. Dr Choi has received grant support from Cleerly Inc and GW Heart and Vascular Institute; has equity in Cleerly, Inc; and reports consulting with Siemens Healthineers. Dr Natarajan has received investigator-initiated grants from Allelica, Amgen, Apple, AstraZeneca, Boston Scientific, and Novartis; has received personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, GV, HeartFlow, Novartis, and Roche/Genentech; is a co-founder of TenSixteen Bio; is a scientific advisory board member of Esperion Therapeutics, Preciseli, and TenSixteen Bio; and reports spousal employment at Vertex Pharmaceuticals. Drs Earls and Min are employees of and hold equity in Cleerly Inc. Dr Stroes has received lecturing/advisory board fees from Amgen, Novartis, Esperion, Sanofi-Regeneron, and Akcea. Dr Knaapen has received research grants from HeartFlow, Inc and Cleerly Inc. Dr Reeskamp is cofounder of Lipid Tools; and has received speaker fees from Novartis, Daiichi Sankyo, and Ultragenyx. Dr Fahed is co-founder of Goodpath. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ventricular tachycardia (VT) is a life-threatening heart rhythm and has long posed a complex challenge in the field of cardiology. Recent developments in advanced imaging modalities have aimed to improve comprehension of underlying arrhythmic substrate for VT. To this extent, high-resolution cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) have emerged as tools for accurately visualizing and characterizing scar tissue, fibrosis, and other critical structural abnormalities within the heart, providing novel insights into VT triggers and substrate. However, clinical implementation of knowledge derived from these advanced imaging techniques in improving VT treatment and guiding invasive therapeutic strategies continues to pose significant challenges. A pivotal concern lies in the absence of standardized imaging protocols and analysis methodologies, resulting in a large variance in data quality and consistency. Furthermore, the clinical significance and outcomes associated with VT substrate characterization through CMR and CCT remain dynamic and subject to ongoing evolution. This highlights the need for refinement of these techniques before their reliable integration into routine patient care can be realized. The primary objectives of this study are twofold: firstly, to provide a comprehensive overview of the studies conducted over the last 15 years, summarizing the current available literature on imaging-based assessment of VT substrate. Secondly, to critically analyze and evaluate the selected studies, with the aim of providing valuable insights that can inform current clinical practice and future research., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Objectives: The aim of this early-stage Health Technology Assessment (HTA) was to assess the difference in healthcare costs and effects of fractional flow reserve derived from coronary computed tomography (FFRct) compared to standard diagnostics in patients with stable chest pain in The Netherlands., Methods: A decision-tree model was developed to assess the difference in total costs from the hospital perspective, probability of correct diagnoses, and risk of major adverse cardiovascular events at one year follow-up. One-way sensitivity analyses were conducted to determine the main drivers of the cost difference between the strategies. A threshold analysis on the added price of FFRct analysis (computational analysis only) was conducted., Results: The mean one-year costs were €2,680 per patient for FFRct and €2,915 per patient for standard diagnostics. The one-year probability of correct diagnoses was 0.78 and 0.61, and the probability of major adverse cardiovascular events was 1.92x10-5 and 0.01, respectively. The probability and costs of revascularization and the specificity of coronary computed tomography angiography had the greatest effect on the difference in costs between the strategies. The added price of FFRct analysis should be below €935 per patient to be considered the least costly option., Conclusions: The early-stage HTA findings suggest that FFRct may reduce total healthcare spending, probability of incorrect diagnoses, and major adverse cardiovascular events compared to current diagnostics for patients with stable chest pain in the Dutch healthcare setting over one year. Future cost-effectiveness studies should determine a value-based pricing for FFRct and quantify the economic value of the anticipated therapeutic impact., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Boot et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.)

Background: Cardiac computed tomography (CT) acquired during the initial acute stroke imaging protocol (acute cardiac CT) is increasingly used to screen for cardioembolism, but information on the long-term clinical implications of its findings is lacking., Methods and Results: We performed a prospective, single-center cohort study in which consecutive patients with ischemic stroke underwent ECG-gated acute cardiac CT and were followed up for 2 years. The primary outcome was functional outcome assessed using the modified Rankin Scale. Secondary outcomes were death and occurrence of major adverse cardiovascular events (composite of recurrent ischemic stroke, myocardial infarction, and cardiovascular death). We compared patients with and without a high-risk structural source of embolism on acute cardiac CT. Of 452 included patients, 55 (12.2%) had a high-risk source of embolism, predominantly cardiac thrombi (38 patients) and signs of endocarditis (8 patients). Follow-up at 2 years was complete for 430 (95.1%) patients. Patients with a high-risk source of embolism had a worse functional outcome (median modified Rankin Scale, 6 [IQR, 2-6] versus 2 [IQR, 1-5]; adjusted common odds ratio, 2.92 [95% CI, 1.62-5.25]), increased mortality rate (52.7% versus 23.7%; adjusted hazard ratio [HR], 3.28 [95% CI, 1.94-5.52]), and major adverse cardiovascular events (38.9% versus 17.5%; adjusted HR, 3.20 [95% CI, 1.80-5.69]). A high-risk source of embolism was not associated with recurrent ischemic stroke (11.1% versus 9.6%; adjusted HR, 1.30 [95% CI, 0.49-3.44])., Conclusions: Structural high-risk sources of embolism on acute cardiac CT in patients with ischemic stroke were associated with poor long-term functional outcome and occurrence of major adverse cardiovascular events but not with recurrent stroke.

Homozygous familial hypercholesterolaemia is a life-threatening genetic condition, which causes extremely elevated LDL-C levels and atherosclerotic cardiovascular disease very early in life. It is vital to start effective lipid-lowering treatment from diagnosis onwards. Even with dietary and current multimodal pharmaceutical lipid-lowering therapies, LDL-C treatment goals cannot be achieved in many children. Lipoprotein apheresis is an extracorporeal lipid-lowering treatment, which is used for decades, lowering serum LDL-C levels by more than 70% directly after the treatment. Data on the use of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia mainly consists of case-reports and case-series, precluding strong evidence-based guidelines. We present a consensus statement on lipoprotein apheresis in children based on the current available evidence and opinions from experts in lipoprotein apheresis from over the world. It comprises practical statements regarding the indication, methods, treatment goals and follow-up of lipoprotein apheresis in children with homozygous familial hypercholesterolaemia and on the role of lipoprotein(a) and liver transplantation., Competing Interests: Declaration of competing interest SDdF received grants from the National Institutes of Health/National Heart, Lung, and Blood Institute of the National Institutes of Health, the Family Heart Foundation and holds a patent for UpToDate, with royalties paid. AG received grants and personal fees from Amgen, Sanofi and Regeneron, Mylan Viatris, MSD, Akcea Therapeutics, Amryt, Servier, Novartis and Ultragenyx. SGP received study funding from Amgen. JH received a research grant from the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number K23HL145109. DI received advisory honoraria from Amryt, and honoraria for lectures from Sanofi, Sobi and Novartis. CPS received advisory honoraria from Baxter, Iperboreal and Stadapharma, lecturing honoraria from Fresenius and research funding from Baxter. MK received honoraria from Abbott, Abdi Ibrahim, Amryt, LIB Therapeutics, NovoNordisk, and TR-pharma; research funding from Amryt Pharma, and participated in clinical trials with Amgen, Ionis, LIB Therapeutics, Novo Nordisk, Sanofi. RK, as head of the Apheresis Research GmbH, Cologne, Germany received financial grants for scientific research projects, honoraria for consulting and presentation of lectures including travel expenses from the companies Diamed, Cologne, Germany, and Asahi Kasei Medical, Tokyo, Japan. GK has given talks, attended conferences, received consultancy fees and participated in trials sponsored by Amgen, Novartis, Sanofi, Servier, Amryt. AW received research grants from Amgen, Regeneron, Novartis, Silence Therapeutics, Esperion, and Ultragenyx and advisory honoraria from Amryt, and Novartis. KA, EJD, LMdB, JWG, LCH, GDK, JO, RNP, MDR, CS and CT have nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Coronary artery disease (CAD) remains the leading cause of death worldwide. Patients with suspected CAD undergo coronary CT angiography (CCTA) to evaluate the risk of cardiovascular events and determine the treatment. Clinical analysis of coronary arteries in CCTA comprises the identification of atherosclerotic plaque, as well as the grading of any coronary artery stenosis typically obtained through the CAD-Reporting and Data System (CAD-RADS). This requires analysis of the coronary lumen and plaque. While voxel-wise segmentation is a commonly used approach in various segmentation tasks, it does not guarantee topologically plausible shapes. To address this, in this work, we propose to directly infer surface meshes for coronary artery lumen and plaque based on a centerline prior and use it in the downstream task of CAD-RADS scoring. The method is developed and evaluated using a total of 2407 CCTA scans. Our method achieved lesion-wise volume intraclass correlation coefficients of 0.98, 0.79, and 0.85 for calcified, non-calcified, and total plaque volume respectively. Patient-level CAD-RADS categorization was evaluated on a representative hold-out test set of 300 scans, for which the achieved linearly weighted kappa ( κ ) was 0.75. CAD-RADS categorization on the set of 658 scans from another hospital and scanner led to a κ of 0.71. The results demonstrate that direct inference of coronary artery meshes for lumen and plaque is feasible, and allows for the automated prediction of routinely performed CAD-RADS categorization.

Objective: Longitudinal consequences and potential interactions of COVID-19 and elite-level sports and exercise are unclear. Therefore, we determined the long-term detrimental cardiac effects of the interaction between SARS-CoV-2 infection and the highest level of sports and exercise., Methods: This prospective controlled study included elite athletes from the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise cohort. Athletes infected with SARS-CoV-2were offered structured, additional cardiovascular screenings, including cardiovascular MRI (CMR). We compared ventricular volumes and function, late gadolinium enhancement (LGE) and T1 relaxation times, between infected and non-infected elite athletes, and collected follow-up data on cardiac adverse events, ventricular arrhythmia burden and the cessation of sports careers., Results: We included 259 elite athletes (mean age 26±5 years; 40% women), of whom 123 were infected (9% cardiovascular symptoms) and 136 were controls. We found no differences in function and volumetric CMR parameters. Four infected athletes (3%) demonstrated LGE (one reversible), compared with none of the controls. During the 26.7 (±5.8) months follow-up, all four athletes resumed elite-level sports, without an increase in ventricular arrhythmias or adverse cardiac remodelling. None of the infected athletes reported new cardiac symptoms or events. The majority (n=118; 96%) still participated in elite-level sports; no sports careers were terminated due to SARS-CoV-2., Conclusions: This prospective study demonstrates the safety of resuming elite-level sports after SARS-CoV-2 infection. The medium-term risks associated with SARS-CoV-2 infection and elite-level sports appear low, as the resumption of elite sports did not lead to detrimental cardiac effects or increases in clinical events, even in the four elite athletes with SARS-CoV-2 associated myocardial involvement., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Familial hypercholesterolemia (FH) is one of the most common genetically inherited disorders in the world. Children with severe heterozygous FH (HeFH), i.e. untreated low-density lipoprotein cholesterol (LDL-C) levels above the 90th percentile for age and sex among FH mutation carriers, can have LDL-C levels that overlap levels of children with homozygous FH (HoFH), but treatment regimen and cardiovascular follow-up to prevent cardiovascular disease are less intensive in children with severe HeFH. In children with HoFH, subclinical atherosclerosis can already be present using computed tomography coronary angiography (CTCA). The question remains whether this is also the case in children with severe HeFH who have a high exposure to elevated LDL-C levels from birth onwards as well. We calculated the cumulative LDL-C exposure (CE total [mmol]) in four children with severe HeFH and performed computed tomography coronary angiography (CTCA). These children, aged 13, 14, 15 and 18 years, had CE total of 71.3, 97.8, 103.6 and 136.1 mmol, respectively. None of them showed abnormalities on cardiovascular imaging, despite high LDL-C exposure. The results of this study, do not give us an indication to recommend performing CTCA routinely in children with severe HeFH., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AW reports research support from pharmaceutical trials of lipid modification agents from Amgen, Regeneron, Novartis, 10.13039/100010137Sanofi, 10.13039/501100022336Esperion, 10.13039/501100022030Silence Therapeutics and Ultragenyx, and is a member of the safety board at Amryt. BAH and AW received a research grant from Silence Therapeutics. SEvdB, MDR, DMK, IMK, RNP and WEC have no conflicts of interest., (© 2023 The Authors.)

Purpose: We sought to assess the impact of coronary revascularization on myocardial perfusion and fractional flow reserve (FFR) in patients without a cardiac history, with prior myocardial infarction (MI) or non-MI percutaneous coronary intervention (PCI). Furthermore, we studied the impact of scar tissue., Methods: Symptomatic patients underwent [ 15 O]H 2 O positron emission tomography (PET) and FFR before and after revascularization. Patients with prior CAD, defined as prior MI or PCI, underwent scar quantification by magnetic resonance imaging late gadolinium enhancement., Results: Among 137 patients (87% male, age 62.2 ± 9.5 years) 84 (61%) had a prior MI or PCI. The increase in FFR and hyperemic myocardial blood flow (hMBF) was less in patients with prior MI or non-MI PCI compared to those without a cardiac history (FFR: 0.23 ± 0.14 vs. 0.20 ± 0.12 vs. 0.31 ± 0.18, p = 0.02; hMBF: 0.54 ± 0.75 vs. 0.62 ± 0.97 vs. 0.91 ± 0.96 ml/min/g, p = 0.04). Post-revascularization FFR and hMBF were similar across patients without a cardiac history or with prior MI or non-MI PCI. An increase in FFR was strongly associated to hMBF increase in patients without a cardiac history or with prior MI/non-MI PCI (r = 0.60 and r = 0.60, p < 0.01 for both). Similar results were found for coronary flow reserve. In patients with prior MI scar was negatively correlated to hMBF increase and independently predictive of an attenuated CFR increase., Conclusions: Post revascularization FFR and perfusion were similar among patients without a cardiac history, with prior MI or non-MI PCI. In patients with prior MI scar burden was associated to an attenuated perfusion increase., (© 2023. The Author(s).)

Background: Cardiac thrombi are an important cause of ischemic stroke but are infrequently detected on cardiac imaging. We hypothesized that this might be explained by early dissolution of these cardiac thrombi after stroke occurrence., Methods: We performed a single-center observational pilot study between November 2019 and November 2020, embedded in the larger "Mind-the-Heart" study. We included patients with AIS and a cardiac thrombus in the left atrium or ventricle (filling defect <100 Hounsfield Units) diagnosed on cardiac CT that was acquired during the initial stroke imaging protocol. We repeated cardiac CT within one week to determine if the thrombus had dissolved., Results: Five patients (four men, median age 52 years, three with atrial fibrillation and one with anticoagulation therapy at baseline) were included. Median time from symptom onset to first cardiac CT was 383 (range 42-852) minutes and median time from first to second cardiac CT was three days (range 1-7). Two patients received intravenous thrombolysis (IVT). In total, six thrombi were seen on initial CT imaging (one in the left ventricle, four in the left atrial appendage, one in the left atrium). The left atrium thrombus and one left atrial appendage thrombus had dissolved on follow-up cardiac CT, one of which was in a patient with IVT treatment., Conclusion: This pilot study illustrates that cardiac thrombi can dissolve within days of stroke occurrence both with and without IVT treatment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CBLMM has received research grants from CVON/Dutch Heart Foundation, European Commission, TWIN Foundation, Healthcare Evaluation Netherlands and Stryker (paid to institution). CBLMM, HAM and YBWEMR are shareholders of Nicolab, a company that focuses on the use of artificial intelligence for medical image analysis. JMC reports grants from Medtronic, Boehringer Ingelheim, and Bayer outside the submitted work (paid to institution). JMC and HAM are shareholder of TrianecT. The other authors have no financial conflicts of interest., (© 2023 The Authors. Published by Elsevier Ltd.)

Background: Maternal obesity during pregnancy is associated with poorer cardiovascular health (CVH) in children. A strategy to improve CVH in children could be to address preconception maternal obesity by means of a lifestyle intervention. We determined if a preconception lifestyle intervention in women with obesity improved offspring's CVH, assessed by magnetic resonance imaging (MRI)., Methods: We invited children born to women who participated in a randomised controlled trial assessing the effect of a preconception lifestyle intervention in women with obesity. We assessed cardiac structure, function and geometric shape, pulse wave velocity and abdominal fat tissue by MRI., Results: We included 49 of 243 (20.2%) eligible children, 24 girls (49%) girls, mean age 7.1 (0.8) years. Left ventricular ejection fraction was higher in children in the intervention group as compared to children in the control group (63.0% SD 6.18 vs. 58.8% SD 5.77, p = 0.02). Shape analysis showed that intervention was associated with less regional thickening of the interventricular septum and less sphericity. There were no differences in the other outcomes of interest., Conclusion: A preconception lifestyle intervention in women with obesity led to a higher ejection fraction and an altered cardiac shape in their offspring, which might suggest a better CVH., Impact: A preconception lifestyle intervention in women with obesity results in a higher ejection fraction and an altered cardiac shape that may signify better cardiovascular health (CVH) in their children. This is the first experimental human evidence suggesting an effect of a preconception lifestyle intervention in women with obesity on MRI-derived indicators of CVH in their children. Improving maternal preconception health might prevent some of the detrimental consequences of maternal obesity on CVH in their children., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Cardiac CT acquired during the acute stroke imaging protocol is an emerging alternative to transthoracic echocardiography (TTE) to screen for sources of cardioembolism. Currently, its diagnostic accuracy to detect patent foramen ovale (PFO) is unclear., Methods: This was a substudy of Mind the Heart, a prospective cohort in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent TTE. We included patients < 60 years who underwent TTE with agitated saline contrast (cTTE) and assessed sensitivity, specificity, negative and positive predictive value of cardiac CT for the detection of PFO using cTTE as the reference standard., Results: Of 452 patients in Mind the Heart, 92 were younger than 60 years. Of these, 59 (64%) patients underwent both cardiac CT and cTTE and were included. Median age was 54 (IQR 49-57) years and 41/59 (70%) were male. Cardiac CT detected a PFO in 5/59 (8%) patients, 3 of which were confirmed on cTTE. cTTE detected a PFO in 12/59 (20%) patients. Sensitivity and specificity of cardiac CT were 25% (95% CI 5-57%) and 96% (95% CI 85-99%), respectively. Positive and negative predictive values were 59% (95% CI 14-95) and 84% (95% CI 71-92)., Conclusion: Prospective ECG-gated cardiac CT acquired during the acute stroke imaging protocol does not appear to be a suitable screening method for PFO due to its low sensitivity. Our data suggest that if cardiac CT is used as a first-line screening method for cardioembolism, additional echocardiography remains indicated in young patients with cryptogenic stroke, in whom PFO detection would have therapeutic consequences. These results need to be confirmed in larger cohorts., (© 2023. The Author(s).)

Background: In patients with stable coronary artery disease (CAD), revascularisation decisions are based mainly on the visual grading of the severity of coronary stenosis on invasive coronary angiography (ICA). However, invasive fractional flow reserve (FFR) is the current standard to determine the haemodynamic significance of coronary stenosis. Non-invasive and less-invasive imaging techniques such as computed-tomography-derived FFR (FFR-CT) and angiography-derived FFR (QFR) combine both anatomical and functional information in complex algorithms to calculate FFR., Trial Design: The iCORONARY trial is a prospective, multicentre, non-inferiority randomised controlled trial (RCT) with a blinded endpoint evaluation. It investigates the costs, effects and outcomes of different diagnostic strategies to evaluate the presence of CAD and the need for revascularisation in patients with stable angina pectoris who undergo coronary computed tomography angiography. Those with a Coronary Artery Disease-Reporting and Data System (CAD-RADS) score between 0-2 and 5 will be included in a prospective registry, whereas patients with CAD-RADS 3 or 4A will be enrolled in the RCT. The RCT consists of three randomised groups: (1) FFR-CT-guided strategy, (2) QFR-guided strategy or (3) standard of care including ICA and invasive pressure measurements for all intermediate stenoses. The primary endpoint will be the occurrence of major adverse cardiac events (death, myocardial infarction and repeat revascularisation) at 1 year., Clinicaltrials: gov-identifier: NCT04939207., Conclusion: The iCORONARY trial will assess whether a strategy of FFR-CT or QFR is non-inferior to invasive angiography to guide the need for revascularisation in patients with stable CAD. Non-inferiority to the standard of care implies that these techniques are attractive, less-invasive alternatives to current diagnostic pathways., (© 2023. The Author(s).)

Aims: Stereotactic arrhythmia radiotherapy (STAR) is suggested as potentially effective and safe treatment for patients with therapy-refractory ventricular tachycardia (VT). However, the current prospective knowledge base and experience with STAR is limited. In this study we aimed to prospectively evaluate the efficacy and safety of STAR., Methods and Results: The StereoTactic Arrhythmia Radiotherapy in the Netherlands no.1 was a pre-post intervention study to prospectively evaluate efficacy and safety of STAR. In patients with therapy-refractory VT, the pro-arrhythmic region was treated with a 25 Gy single radiotherapy fraction. The main efficacy measure was a reduction in the number of treated VT-episodes by ≥50%, comparing the 12 months before and after treatment (or end of follow-up, excluding a 6-week blanking period). The study was deemed positive when ≥50% of patients would meet this criterion. Safety evaluation included left ventricular ejection fraction, pulmonary function, and adverse events. Six male patients with an ischaemic cardiomyopathy were enrolled, and median age was 73 years (range 54-83). Median left ventricular ejection fraction was 38% (range 24-52). The median planning target volume was 187 mL (range 93-372). Four (67%) patients completed the 12-month follow-up, and two patients died (not STAR related) during follow-up. The main efficacy measure of ≥50% reduction in treated VT-episodes at the end of follow-up was achieved in four patients (67%). The median number of treated VT-episodes was reduced by 87%. No reduction in left ventricular ejection fraction or pulmonary function was observed. No treatment related serious adverse events occurred., Conclusions: STAR resulted in a ≥ 50% reduction in treated VT-episodes in 4/6 (67%) patients. No reduction in cardiac and pulmonary function nor treatment-related serious adverse events were observed during follow-up., Clinical Trial Registration: Netherlands Trial Register-NL7510., Competing Interests: Conflict of interest: The authors declared to have no conflict of interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Cardiac thrombi are a major risk factor for ischemic stroke, but are rarely diagnosed in the acute phase. We examined characteristics and functional outcome of patients with ischemic stroke and a concomitant cardiac thrombus detected on cardiac CT performed in the acute phase., Patients and Methods: We used data from "Mind the Heart," a prospective cohort study in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during their acute stroke imaging protocol. We compared characteristics, functional outcome (modified Rankin scale) and stroke recurrence rate at 90 days of patients with a cardiac thrombus on CT (defined as filling defect <100 Hounsfield Units) to those without a cardiac thrombus., Results: Among 452 included patients, cardiac CT detected 41 thrombi in 38 (8%) patients. Thrombi were most often located in the left atrial appendage (31/38 [82%]). Patients with a cardiac thrombus more frequently had intracranial occlusions in multiple vascular territories (5% vs 0.5%, p  = 0.04) and a higher baseline NIHSS score (17 [IQR 6-22] vs 5 [IQR 2-3], p  < 0.001) compared to patients without a cardiac thrombus. In 13/38 (34%) patients with a cardiac thrombus, no atrial fibrillation was detected. A cardiac thrombus was associated with worse functional outcome (adjusted common odds ratio 3.18 95%CI 1.68-6.00). Recurrence rate was not significantly different (8% vs 4%, aOR 1.50 (0.39-5.82)., Discussion and Conclusion: Cardiac CT detected a cardiac thrombus in one in every 12 patients with acute ischemic stroke, and these patients had more severe deficits, multivessel occlusions, and a worse functional outcome., Competing Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: CBLMM has received research grants from CVON/Dutch Heart Foundation, European Commission, TWIN Foundation Dutch Health Evaluation program and Stryker (paid to institution). CBLMM, HAM and YBWEMR are shareholders of Nico.lab, a company that focuses on the use of artificial intelligence for medical image analysis. JMC reports grants from Medtronic, Boehringer Ingelheim, and Bayer outside the submitted work. (paid to institution). The other authors have no financial conflicts of interest., (© European Stroke Organisation 2022.)

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.)

Introduction: The cardiovascular benefits of physical exercise are well-known. However, vigorous exercise has also been associated with adverse cardiac effects. To improve our understanding of cardiovascular adaptation to exercise versus maladaptation and pathology, the limits of adaptation should be firmly established using state-of-the-art diagnostic modalities. We therefore initiated the Evaluation of Lifetime participation in Intensive Top-level sports and Exercise (ELITE) cohort to investigate the longitudinal (beneficial and pathological) cardiovascular effects of intensive elite sports and exercise., Methods and Analysis: ELITE is a prospective, multicentre, longitudinal cohort study. Elite athletes, from the age of sixteen, are recruited in The Netherlands. The primary objective is to determine the association between elite sports and exercise-induced cardiac remodelling, cardiac pathology, and health benefits over time. Secondary objectives include determining and identifying genetic profiles of elite athletes, and how these are associated with cardiac indices. ELITE will collect data from consultations, electrocardiography, echocardiography and cardiac magnetic resonance imaging, and training- and injury data. ELITE will also collect blood for biobanking and cardiogenetics. Follow-up will take place at intervals of two to five years, and after the elite athletes' professional careers have ended. In addition, a subcohort of ELITE has been established to investigate cardiac sequelae following infections associated with myocardial involvement, including SARS-CoV-2. ELITE is a prospective observational study; therefore, analyses will be primarily explorative., Ethics and Dissemination: This study has been approved by the Medical Ethics Review Board of the Amsterdam University Medical Centers (NL71682.018.19). The results of the study will be disseminated by publication in peer-reviewed journals (Netherlands Trial Register number: NL9328)., Competing Interests: Competing interests: None declared., (© 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: Truncating variants in desmoplakin ( DSP tv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSP tv cardiomyopathy., Methods: Individuals with DSP tv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSP tv performed., Results: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSP tv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSP tv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P <0.0001)., Conclusions: In the largest series of individuals with DSP tv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.

Background: Takayasu arteritis is a noninfective chronic vasculitis mainly involving the aorta and its main branches. The presentation of the disease is heterogeneous, ranging from asymptomatic to catastrophic illness., Case Presentation: A 52-year-old Caucasian woman with known Takayasu arteritis was referred to our hospital as she suffered symptoms suspicious for cerebral hypoperfusion. Computed tomography thorax angiography revealed occlusion of all aortic arch arteries and previous surgical bypasses. Cerebral perfusion depended on a few collaterals (from the distal common carotid artery to the right internal carotid artery and from the left and right internal mammary artery and the dorsal thoracic branches to both vertebral arteries). In addition, preoperative coronary angiography revealed an unusual and large collateral arising from the sinoatrial nodal artery to the left carotid artery., Conclusion: Takayasu arteritis is a relatively rare disease, with various and sometimes devastating neurological manifestations due to occlusion of the aortic arch branches. Our case highlights the importance of a thorough preoperative evaluation in search of collateral supply in symptomatic patients with Takayasu arteritis., (© 2023. The Author(s).)

Background: Cardiac involvement in idiopathic inflammatory myopathy (IIM or "myositis") is associated with an approximate 4% mortality, but standardised screening strategies are lacking., Objective: We explored a multimodality screening on potentially reversible cardiac involvement -i.e. active (peri)myocarditis -in newly diagnosed IIM., Methods: We included adult IIM patients from 2017 to 2020. At time of diagnosis, patients underwent cardiac evaluation including laboratory biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance imaging (CMR). Based on 2019 consensus criteria for myocarditis, an adjudication committee made diagnoses of definite, probable, possible or no (peri)myocarditis. We explored diagnostic values of sequentially added diagnostic modalities by Constructing Classification and Regression Tree (CART) analysis in patients with definite/probable versus no (peri)myocarditis., Results: We included 34 IIM patients, in whom diagnoses of definite (six, 18%), probable (two, 6%), possible (11, 32%), or no (peri)myocarditis (15, 44%) were adjudicated. CART-analysis showed high-sensitivity cardiac troponin T (cut-off value < 2.3 times the upper limit of normal (xULN)) ruled out (peri)myocarditis with a sensitivity of 88%, while high-sensitivity troponin I (cut-off value > 2.9 xULN for females and > 1.8 xULN for males) ruled in (peri)myocarditis with a specificity of 100%. Applying high-sensitivity cardiac troponins with these cut-off values in a diagnostic algorithm without and with a CMR to the total population of 34 patients demonstrated a diagnostic accuracy for a clear diagnosis of probable/definite or no (peri)myocarditis of 59% and 68%, respectively., Conclusions: A diagnostic algorithm for detection of (peri)myocarditis in adult IIM may consist of sequential testing with high-sensitivity cardiac troponins and CMR.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients., Methods and Results: CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18)., Conclusion: Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator., Competing Interests: Conflict of interest: H.C. receives research support from Boston Scientific Corp. C.A.J. receive salary support from this grant. S.L.Z. receives salary support as an advisor to Siemens Healthcare. The other authors report no conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Patients with intermediate anatomical degree of coronary artery stenosis require determination of its functional significance. Currently, the reference standard for determining the functional significance of a stenosis is invasive measurement of the fractional flow reserve (FFR), which is associated with high cost and patient burden. To address these drawbacks, FFR can be predicted non-invasively from a coronary CT angiography (CCTA) scan. Hence, we propose a deep learning method for predicting the invasively measured FFR of an artery using a CCTA scan. The study includes CCTA scans of 569 patients from three hospitals. As reference for the functional significance of stenosis, FFR was measured in 514 arteries in 369 patients, and in the remaining 200 patients, obstructive coronary artery disease was ruled out by Coronary Artery Disease-Reporting and Data System (CAD-RADS) category 0 or 1. For prediction, the coronary tree is first extracted and used to reconstruct an MPR for the artery at hand. Thereafter, the coronary artery is characterized by its lumen, its attenuation and the area of the coronary artery calcium in each artery cross-section extracted from the MPR using a CNN. Additionally, characteristics indicating the presence of bifurcations and information indicating whether the artery is a main branch or a side-branch of a main artery are derived from the coronary artery tree. All characteristics are fed to a second network that predicts the FFR value and classifies the presence of functionally significant stenosis. The final result is obtained by merging the two predictions. Performance of our method is evaluated on held out test sets from multiple centers and vendors. The method achieves an area under the receiver operating characteristics curve (AUC) of 0.78, outperforming other works that do not require manual correction of the segmentation of the artery. This demonstrates that our method may reduce the number of patients that unnecessarily undergo invasive measurements., Competing Interests: Author CC reports receiving institutional research grants from GE Healthcare, Siemens, Insight Lifetech, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, CathWorks, Boston Scientific, HeartFlow, Abbott Vascular, and consultancy fees from HeartFlow, Abbott Vascular, and Cryotherapeutics. Author II reports institutional research grants by Pie Medical Imaging, Dutch Technology Foundation with participation of Pie Medical Imaging and Philips Healthcare (DLMedIA P15-26). Author J-PA was employed by Pie Medical Imaging BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hampe, van Velzen, Planken, Henriques, Collet, Aben, Voskuil, Leiner and Išgum.)

Background and Objectives: Guidelines recommend echocardiography to screen for structural sources of cardioembolism in patients with ischemic stroke. Cardiac CT is a promising alternative as a first-line screening method. We aimed to determine whether cardiac CT, acquired during the initial stroke imaging protocol, has a higher yield for detecting high-risk cardioaortic sources of embolism than transthoracic echocardiography (TTE)., Methods: We performed a prospective, single-center, observational cohort study and included consecutive adult patients with acute ischemic stroke who underwent ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent the routine stroke workup, including TTE. The main outcome was the proportion of patients with a predefined high-risk cardioaortic source of embolism on cardiac CT vs TTE in patients undergoing both investigations., Results: Between May 2018 and November 2020, 774 patients with a suspected ischemic stroke underwent hyperacute cardiac CT. We excluded 228 patients with a diagnosis other than ischemic stroke and 94 because they did not provide informed consent. Therefore, 452 patients (59.3% male, median age 72) were included. The median additional scan time of cardiac CT was 6 (interquartile range 5-7) minutes with poor scan quality in only 3%. In total, 350 of the 452 patients (77.4%) underwent TTE, 99 of whom were performed in an outpatient setting. Reasons for not undergoing TTE were death (33, 7.3%) and TTE being too burdensome to perform in the outpatient setting (69, 15.3%). A high-risk cardioaortic source of embolism was detected in 40 of the 350 patients (11.4%) on CT, compared with 17 of the 350 (4.9%) on TTE (odds ratio 5.60, 95% CI 2.28-16.33). Cardiac thrombus was the most frequent finding (7.1% vs 0.6%). The diagnostic yield of cardiac CT in the full study population was 55 of the 452 (12.2%). Among the 175 patients with cryptogenic stroke after the routine workup, cardiac CT identified a cause of the stroke in 11 (6.3%)., Discussion: Cardiac CT acquired in the acute phase of ischemic stroke is technically feasible and has a superior diagnostic yield compared with TTE for the detection of high-risk sources of embolism. Cardiac CT may be considered as an alternative to TTE to screen for cardioembolism., (© 2022 American Academy of Neurology.)

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).)