Exercise-induced cardiac troponin release in athletes with versus without coronary atherosclerosis.

The magnitude of exercise-induced cardiac troponin (cTn) elevations is dependent on cardiovascular health status, and previous studies have shown that occult coronary atherosclerosis is highly prevalent among amateur athletes. We tested the hypothesis that middle-aged and older athletes with coronary atherosclerosis demonstrate greater cTn elevations following a controlled endurance exercise test compared with healthy peers. We included 59 male athletes from the Measuring Athletes' Risk of Cardiovascular events 2 (MARC-2) study and stratified them as controls [coronary artery calcium score (CACS) = 0, n = 20], high CACS [≥300 Agatston units or ≥75th Multi-Ethnic Study of Atherosclerosis (MESA) percentile, n = 20] or significant stenosis (≥50% in any coronary artery, n = 19). Participants performed a cycling test with incremental workload until volitional exhaustion. Serial high-sensitivity cTn (hs-cTn) T and I concentrations were measured (baseline, after 30-min warm-up, and 0, 30, 60, 120, and 180 min postexercise). There were 58 participants (61 [58-69] yr) who completed the exercise test (76 ± 14 min) with a peak heart rate of 97.7 [94.8-101.8]% of their estimated maximum. Exercise duration and workload did not differ across groups. High-sensitivity cardiac troponin T (Hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) concentrations significantly increased (1.55 [1.33-2.14]-fold and 2.76 [1.89-3.86]-fold, respectively) over time, but patterns of cTn changes and the incidence of concentrations >99th percentile did not differ across groups. Serial sampling of hs-cTnT and hs-cTnI concentrations during and following an exhaustive endurance exercise test did not reveal differences in exercise-induced cTn release between athletes with versus without coronary atherosclerosis. These findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.NEW & NOTEWORTHY Exercise-induced cardiac troponin (cTn) release is considered to be dependent on cardiovascular health status. We tested whether athletes with coronary atherosclerosis demonstrate greater exercise-induced cTn release compared with healthy peers. Athletes with coronary atherosclerosis did not differ in cTn release following exercise compared with healthy peers. Our findings suggest that a high CACS or a >50% stenosis in any coronary artery does not aggravate exercise-induced cTn release in middle-aged and older athletes.

Graph convolutional networks for automated intracranial artery labeling.

Purpose: Unruptured intracranial aneurysms (UIAs) can cause aneurysmal subarachnoid hemorrhage, a severe and often lethal type of stroke. Automated labeling of intracranial arteries can facilitate the identification of risk factors associated with UIAs. This study aims to improve intracranial artery labeling using atlas-based features in graph convolutional networks. Approach: We included three-dimensional time-of-flight magnetic resonance angiography scans from 150 individuals. Two widely used graph convolutional operators, GCNConv and GraphConv, were employed in models trained to classify 12 bifurcations of interest. Cross-validation was applied to explore the effectiveness of atlas-based features in node classification. The results were tested for statistically significant differences using a Wilcoxon signed-rank test. Model repeatability and calibration were assessed on the test set for both operators. In addition, we evaluated model interpretability and node feature contribution using explainable artificial intelligence. Results: Atlas-based features led to statistically significant improvements in node classification (p<0.05). The results showed that the best discrimination and calibration performances were obtained using the GraphConv operator, which yielded a mean recall of 0.87, precision of 0.90, and expected calibration error of 0.02. Conclusions: The addition of atlas-based features improved node classification results. The GraphConv operator, which incorporates higher-order structural information during training, is recommended over the GCNConv operator based on the accuracy and calibration of predicted outcomes.

The influence of motion-compensated reconstruction on coronary artery analysis for a dual-layer detector CT system: a dynamic phantom study.

OBJECTIVES: Cardiac motion artifacts hinder the assessment of coronary arteries in coronary computed tomography angiography (CCTA). We investigated the impact of motion compensation reconstruction (MCR) on motion artifacts in CCTA at various heart rates (HR) using a dynamic phantom. MATERIALS AND METHODS: An artificial hollow coronary artery (5-mm diameter lumen) filled with iodinated contrast agent (400 HU at 120 kVp), positioned centrally in an anthropomorphic chest phantom, was scanned using a dual-layer spectral detector CT. The artery was translated at constant horizontal velocities (0-80 mm/s, increment of 10 mm/s). For each velocity, five CCTA scans were repeated using a clinical protocol. Motion artifacts were quantified using the in-plane motion area. Regression analysis was performed to calculate the reduction in motion artifacts provided by MCR, by division of the slopes of non-MCR and MCR fitted lines. RESULTS: Reference mean (95% confidence interval) motion artifact area was 24.9 mm2 (23.8, 26.0). Without MCR, motion artifact areas for velocities exceeding 20 mm/s were significantly larger (up to 57.2 mm2 (40.1, 74.2)) than the reference. With MCR, no significant differences compared to the reference were shown for all velocities, except for 70 mm/s (29.0 mm2 (27.0, 31.0)). The slopes of the fitted data were 0.44 and 0.04 for standard and MCR reconstructions, respectively, resulting in an 11-time motion artifact reduction. CONCLUSION: MCR may improve CCTA assessment in patients by reducing coronary artery motion artifacts, especially in those with elevated HR who cannot receive beta blockers or do not attain the targeted HR. CLINICAL RELEVANCE STATEMENT: This vendor-specific motion compensation reconstruction may improve coronary computed tomography angiography assessment in patients by reduction of coronary artery motion artifacts, especially in those with elevated various heart rates (HR) who cannot receive beta blockers or do not attain the targeted HR. KEY POINTS: • Motion artifacts are known to hinder the assessment of coronary arteries on coronary CT angiography (CCTA), leading to more non-diagnostic scans. • This dynamic phantom study shows that motion compensation reconstruction (MCR) reduces motion artifacts at various velocities, which may help to decrease the number of non-diagnostic scans. • MCR in this study showed to reduce motion artifacts 11-fold.

Standardizing the estimation of ischemic regions can harmonize CT perfusion stroke imaging.

OBJECTIVES: We aimed to evaluate the real-world variation in CT perfusion (CTP) imaging protocols among stroke centers and to explore the potential for standardizing vendor software to harmonize CTP images. METHODS: Stroke centers participating in a nationwide multicenter healthcare evaluation were requested to share their CTP scan and processing protocol. The impact of these protocols on CTP imaging was assessed by analyzing data from an anthropomorphic phantom with center-specific vendor software with default settings from one of three vendors (A-C): IntelliSpace Portal, syngoVIA, and Vitrea. Additionally, standardized infarct maps were obtained using a logistic model. RESULTS: Eighteen scan protocols were studied, all varying in acquisition settings. Of these protocols, seven, eight, and three were analyzed with center-specific vendor software A, B, and C respectively. The perfusion maps were visually dissimilar between the vendor software but were relatively unaffected by the acquisition settings. The median error [interquartile range] of the infarct core volumes (mL) estimated by the vendor software was - 2.5 [6.5] (A)/ - 18.2 [1.2] (B)/ - 8.0 [1.4] (C) when compared to the ground truth of the phantom (where a positive error indicates overestimation). Taken together, the median error [interquartile range] of the infarct core volumes (mL) was - 8.2 [14.6] before standardization and - 3.1 [2.5] after standardization. CONCLUSIONS: CTP imaging protocols varied substantially across different stroke centers, with the perfusion software being the primary source of differences in CTP images. Standardizing the estimation of ischemic regions harmonized these CTP images to a degree. CLINICAL RELEVANCE STATEMENT: The center that a stroke patient is admitted to can influence the patient's diagnosis extensively. Standardizing vendor software for CT perfusion imaging can improve the consistency and accuracy of results, enabling a more reliable diagnosis and treatment decision. KEY POINTS: • CT perfusion imaging is widely used for stroke evaluation, but variation in the acquisition and processing protocols between centers could cause varying patient diagnoses. • Variation in CT perfusion imaging mainly arises from differences in vendor software rather than acquisition settings, but these differences can be reconciled by standardizing the estimation of ischemic regions. • Standardizing the estimation of ischemic regions can improve CT perfusion imaging for stroke evaluation by facilitating reliable evaluations independent of the admission center.

Hemodynamic Parameters in the Parent Arteries of Unruptured Intracranial Aneurysms Depend on Aneurysm Size and Are Different Compared to Contralateral Arteries: A 7 Tesla 4D Flow MRI Study.

BACKGROUND: Different Circle of Willis (CoW) variants have variable prevalences of aneurysm development, but the hemodynamic variation along the CoW and its relation to presence and size of unruptured intracranial aneurysms (UIAs) are not well known. PURPOSE: Gain insight into hemodynamic imaging markers of the CoW for UIA development by comparing these outcomes to the corresponding contralateral artery without an UIA using 4D flow magnetic resonance imaging (MRI). STUDY TYPE: Retrospective, cross-sectional study. SUBJECTS: Thirty-eight patients with an UIA, whereby 27 were women and a mean age of 62 years old. FIELD STRENGTH/SEQUENCE: Four-dimensional phase-contrast (PC) MRI with a 3D time-resolved velocity encoded gradient echo sequence at 7 T. ASSESSMENT: Hemodynamic parameters (blood flow, velocity pulsatility index [vPI], mean velocity, distensibility, and wall shear stress [peak systolic (WSSMAX ), and time-averaged (WSSMEAN )]) in the parent artery of the UIA were compared to the corresponding contralateral artery without an UIA and were related to UIA size. STATISTICAL TESTS: Paired t-tests and Pearson Correlation tests. The threshold for statistical significance was P < 0.05 (two-tailed). RESULTS: Blood flow, mean velocity, WSSMAX , and WSSMEAN were significantly higher, while vPI was lower, in the parent artery relative to contralateral artery. The WSSMAX of the parent artery significantly increased linearly while the WSSMEAN decreased linearly with increasing UIA size. CONCLUSIONS: Hemodynamic parameters and WSS differ between parent vessels of UIAs and corresponding contralateral vessels. WSS correlates with UIA size, supporting a potential hemodynamic role in aneurysm pathology. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Trabecular bone density in middle-aged women with reproductive disorders.

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with an reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) -26.8, 95% confidence interval (CI) -37.2 - -16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3 - 25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Screening for intracranial aneurysms in persons ⩾35 years with hypertension and atherosclerotic disease who smoke(d).

INTRODUCTION: Lifetime risk of aneurysmal subarachnoid haemorrhage (aSAH) is high (7%) in persons ⩾35 years with hypertension who smoke(d). Whether screening for intracranial aneurysms (IAs) to prevent aSAH is effective in these patients is unknown. PATIENTS AND METHODS: Participants were retrieved from a cohort of patients with clinically manifest atherosclerotic vascular disease included between 2012 and 2019 at the University Medical Centre Utrecht (SMART-ORACLE, NCT01932671) in whom CT-angiography (CTA) of intracranial arteries was performed. We selected patients ⩾35 years with hypertension who smoke(d). CTAs were reviewed for the presence of IAs by experienced neuroradiologists. Patients with IAs were offered follow-up imaging to detect aneurysmal growth. We determined aneurysm prevalence and developed a diagnostic model for IA risk at screening using multivariable logistic regression. RESULTS: IA were found in 25 of 500 patients (5.0% prevalence, 95%CI: 3.3%-7.3%). Median 5 year risk of rupture assessed with the PHASES score was 0.9% (IQR: 0.7%-1.3%). During a median follow-up of 57 months (IQR: 39-83 months) no patients suffered from aSAH. Aneurysmal growth was detected in one patient for whom preventive treatment was advised. IA risk at screening ranged between 1.6% and 13.4% with predictors being age, female sex and current smoking. DISCUSSION AND CONCLUSION: IA prevalence in persons ⩾35 years with hypertension and atherosclerotic vascular disease who smoke(d) was 5%. Given the very small proportion of IA that needed preventive treatment, we currently do not advise screening for Caucasian persons older than 35 years of age who smoke and have hypertension in general. Whether screening may be effective for certain subgroups (e.g. women older than 50 years of age) or other ethnic populations should be the subject of future studies.

Change in Androgenic Status and Cardiometabolic Profile of Middle-Aged Women with Polycystic Ovary Syndrome.

Understanding the cardiovascular disease (CVD) risk for women with polycystic ovary syndrome (PCOS) at reproductive age is crucial. To investigate this, we compared the cardiometabolic profiles of different PCOS groups over a median interval of 15.8 years. The study focused on three groups: (1) women with PCOS who were hyperandrogenic at both initial and follow-up screening (HA-HA), (2) those who transitioned from hyperandrogenic to normoandrogenic (HA-NA), and (3) those who remained normoandrogenic (NA-NA). At initial and follow-up screenings, both HA-HA and HA-NA groups showed higher body mass indexes compared to the NA-NA group. Additionally, at follow-up, the HA-HA and HA-NA groups exhibited higher blood pressure, a higher prevalence of hypertension, elevated serum triglycerides and insulin levels, and lower levels of HDL cholesterol compared to the NA-NA group. Even after adjusting for BMI, significant differences persisted in HDL cholesterol levels and hypertension prevalence among the groups (HA-HA: 53.8%, HA-NA: 53.1%, NA-NA: 14.3%, p < 0.01). However, calcium scores and the prevalence of coronary plaques on CT scans were similar across all groups. In conclusion, women with PCOS and hyperandrogenism during their reproductive years exhibited an unfavorable cardiometabolic profile during their post-reproductive years, even if they changed to a normoandrogenic status.

Aneurysm Prevalence and Quality of Life During Screening in Relatives of Patients With Unruptured Intracranial Aneurysms: A Prospective Study.

BACKGROUND AND OBJECTIVES: Screening for unruptured intracranial aneurysms (UIAs) is effective for first-degree relatives (FDRs) of patients with aneurysmal subarachnoid hemorrhage (aSAH). Whether screening is also effective for FDRs of patients with UIA is unknown. We determined the yield of screening in such FDRs, assessed rupture risk and treatment decisions of aneurysms that were found, identified potential high-risk subgroups, and studied the effects of screening on quality of life (QoL). METHODS: In this prospective cohort study, we included FDRs, aged 20-70 years, of patients with UIA without a family history of aSAH who visited the Neurology outpatient clinic in 1 of 3 participating tertiary referral centers in the Netherlands. FDRs were screened for UIA with magnetic resonance angiography between 2017 and 2021. We determined UIA prevalence and developed a prediction model for UIA risk at screening using multivariable logistic regression. QoL was evaluated with questionnaires 6 times during the first year after screening and assessed with a linear mixed-effects model. RESULTS: We detected 24 UIAs in 23 of 461 screened FDRs, resulting in a 5.0% prevalence (95% CI 3.2-7.4). The median aneurysm size was 3 mm (interquartile range [IQR] 2-4 mm), and the median 5-year rupture risk assessed with the PHASES score was 0.7% (IQR 0.4%-0.9%). All UIAs received follow-up imaging, and none were treated preventively. After a median follow-up of 24 months (IQR 13-38 months), no UIA had changed. Predicted UIA risk at screening ranged between 2.3% and 14.7% with the highest risk in FDRs who smoke and have excessive alcohol consumption (c-statistic: 0.76; 95% CI 0.65-0.88). At all survey moments, health-related QoL and emotional functioning were comparable with those in a reference group from the general population. One FDR with a positive screening result expressed regret about screening. DISCUSSION: Based on the current data, we do not advise screening FDRs of patients with UIA because all identified UIAs had a low rupture risk. We observed no negative effect of screening on QoL. A longer follow-up should determine the risk of aneurysm growth requiring preventive treatment.

Body surface potential mapping detects early disease onset in plakophilin-2-pathogenic variant carriers.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a progressive inherited cardiac disease. Early detection of disease and risk stratification remain challenging due to heterogeneous phenotypic expression. The standard configuration of the 12 lead electrocardiogram (ECG) might be insensitive to identify subtle ECG abnormalities. We hypothesized that body surface potential mapping (BSPM) may be more sensitive to detect subtle ECG abnormalities. METHODS AND RESULTS: We obtained 67 electrode BSPM in plakophilin-2 (PKP2)-pathogenic variant carriers and control subjects. Subject-specific computed tomography/magnetic resonance imaging based models of the heart/torso and electrode positions were created. Cardiac activation and recovery patterns were visualized with QRS- and STT-isopotential map series on subject-specific geometries to relate QRS-/STT-patterns to cardiac anatomy and electrode positions. To detect early signs of functional/structural heart disease, we also obtained right ventricular (RV) echocardiographic deformation imaging. Body surface potential mapping was obtained in 25 controls and 42 PKP2-pathogenic variant carriers. We identified five distinct abnormal QRS-patterns and four distinct abnormal STT-patterns in the isopotential map series of 31/42 variant carriers. Of these 31 variant carriers, 17 showed no depolarization or repolarization abnormalities in the 12 lead ECG. Of the 19 pre-clinical variant carriers, 12 had normal RV-deformation patterns, while 7/12 showed abnormal QRS- and/or STT-patterns. CONCLUSION: Assessing depolarization and repolarization by BSPM may help in the quest for early detection of disease in variant carriers since abnormal QRS- and/or STT-patterns were found in variant carriers with a normal 12 lead ECG. Because electrical abnormalities were observed in subjects with normal RV-deformation patterns, we hypothesize that electrical abnormalities develop prior to functional/structural abnormalities in ARVC.

Geometric Deep Learning Using Vascular Surface Meshes for Modality-Independent Unruptured Intracranial Aneurysm Detection.

Early detection of unruptured intracranial aneurysms (UIAs) enables better rupture risk and preventative treatment assessment. UIAs are usually diagnosed on Time-of-Flight Magnetic Resonance Angiographs (TOF-MRA) or contrast-enhanced Computed Tomography Angiographs (CTA). Various automatic voxel-based deep learning UIA detection methods have been developed, but these are limited to a single modality. We propose a modality-independent UIA detection method using a geometric deep learning model with high resolution surface meshes of brain vessels. A mesh convolutional neural network with ResU-Net style architecture was used. UIA detection performance was investigated with different input and pooling mesh resolutions, and including additional edge input features (shape index and curvedness). Both a higher resolution mesh (15,000 edges) and additional curvature edge features improved performance (average sensitivity: 65.6%, false positive count/image (FPC/image): 1.61). UIAs were detected in an independent TOF-MRA test set and a CTA test set with average sensitivity of 52.0% and 48.3% and average FPC/image of 1.04 and 1.05 respectively. We provide modality-independent UIA detection using a deep-learning vascular surface mesh model with comparable performance to state-of-the-art UIA detection methods.

Druggable proteins influencing cardiac structure and function: Implications for heart failure therapies and cancer cardiotoxicity.

Dysfunction of either the right or left ventricle can lead to heart failure (HF) and subsequent morbidity and mortality. We performed a genome-wide association study (GWAS) of 16 cardiac magnetic resonance (CMR) imaging measurements of biventricular function and structure. Cis-Mendelian randomization (MR) was used to identify plasma proteins associating with CMR traits as well as with any of the following cardiac outcomes: HF, non-ischemic cardiomyopathy, dilated cardiomyopathy (DCM), atrial fibrillation, or coronary heart disease. In total, 33 plasma proteins were prioritized, including repurposing candidates for DCM and/or HF: IL18R (providing indirect evidence for IL18), I17RA, GPC5, LAMC2, PA2GA, CD33, and SLAF7. In addition, 13 of the 25 druggable proteins (52%; 95% confidence interval, 0.31 to 0.72) could be mapped to compounds with known oncological indications or side effects. These findings provide leads to facilitate drug development for cardiac disease and suggest that cardiotoxicities of several cancer treatments might represent mechanism-based adverse effects.

Spatial CT perfusion data helpful in automatically locating vessel occlusions for acute ischemic stroke patients.

Introduction: Locating a vessel occlusion is important for clinical decision support in stroke healthcare. The advent of endovascular thrombectomy beyond proximal large vessel occlusions spurs alternative approaches to locate vessel occlusions. We explore whether CT perfusion (CTP) data can help to automatically locate vessel occlusions. Methods: We composed an atlas with the downstream regions of particular vessel segments. Occlusion of these segments should result in the hypoperfusion of the corresponding downstream region. We differentiated between seven-vessel occlusion locations (ICA, proximal M1, distal M1, M2, M3, ACA, and posterior circulation). We included 596 patients from the DUtch acute STroke (DUST) multicenter study. Each patient CTP data set was processed with perfusion software to determine the hypoperfused region. The downstream region with the highest overlap with the hypoperfused region was considered to indicate the vessel occlusion location. We assessed the indications from CTP against expert annotations from CTA. Results: Our atlas-based model had a mean accuracy of 86% and could achieve substantial agreement with the annotations from CTA according to Cohen's kappa coefficient (up to 0.68). In particular, anterior large vessel occlusions and occlusions in the posterior circulation could be located with an accuracy of 80 and 92%, respectively. Conclusion: The spatial layout of the hypoperfused region can help to automatically indicate the vessel occlusion location for acute ischemic stroke patients. However, variations in vessel architecture between patients seemed to limit the capacity of CTP data to distinguish between vessel occlusion locations more accurately.

Cardiac radiology in Europe: status and vision by the European Society of Cardiovascular Radiology (ESCR) and the European Society of Radiology (ESR).

Cardiac computed tomography (CT) and cardiac magnetic resonance imaging (MRI) are routine radiological examinations for diagnosis and prognosis of cardiac disease. The expected growth in cardiac radiology in the coming years will exceed the current scanner capacity and trained workforce. The European Society of Cardiovascular Radiology (ESCR) focuses on supporting and strengthening the role of cardiac cross-sectional imaging in Europe from a multi-modality perspective. Together with the European Society of Radiology (ESR), the ESCR has taken the initiative to describe the current status of, a vision for, and the required activities in cardiac radiology to sustain, increase and optimize the quality and availability of cardiac imaging and experienced radiologists across Europe. KEY POINTS: • Providing adequate availability for performing and interpreting cardiac CT and MRI is essential, especially with expanding indications. • The radiologist has a central role in non-invasive cardiac imaging examinations which encompasses the entire process from selecting the best modality to answer the referring physician's clinical question to long-term image storage. • Optimal radiological education and training, knowledge of the imaging process, regular updating of diagnostic standards, and close collaboration with colleagues from other specialties are essential.

ELITE: rationale and design of a longitudinal elite athlete, extreme cardiovascular phenotyping, prospective cohort study.

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).

Detection of Cardioembolic Sources With Nongated Cardiac Computed Tomography Angiography in Acute Stroke: Results From the ENCLOSE Study.

BACKGROUND: Identifying cardioembolic sources in patients with acute ischemic stroke is important for the choice of secondary prevention strategies. We prospectively investigated the yield of admission (spectral) nongated cardiac computed tomography angiography (CTA) to detect cardioembolic sources in stroke. METHODS: Participants of the ENCLOSE study (Improved Prediction of Recurrent Stroke and Detection of Small Volume Stroke) with transient ischemic attack or acute ischemic stroke with assessable nongated head-to-heart CTA at the University Medical Center Utrecht were included between June 2017 and March 2022. The presence of cardiac thrombus on cardiac CTA was based on a Likert scale and dichotomized into certainly or probably absent versus possibly, probably, or certainly present. The diagnostic certainty of cardiac thrombus was evaluated again on spectral computed tomography reconstructions. The likelihood of a cardioembolic source was determined post hoc by an expert panel in patients with cardiac thrombus on CTA. Parametric and nonparametric tests were used to compare the outcome groups. RESULTS: Forty four (12%) of 370 included patients had a cardiac thrombus on admission CTA: 35 (9%) in the left atrial appendage and 14 (4%) in the left ventricle. Patients with cardiac thrombus had more severe strokes (median National Institutes of Health Stroke Scale score, 10 versus 4; P=0.006), had higher clot burden (median clot burden score, 9 versus 10; P=0.004), and underwent endovascular treatment more often (43% versus 20%; P<0.001) than patients without cardiac thrombus. Left atrial appendage thrombus was present in 28% and 6% of the patients with and without atrial fibrillation, respectively (P<0.001). The diagnostic certainty for left atrial appendage thrombus was higher for spectral iodine maps compared with the conventional CTA (P<0.001). The presence of cardiac thrombus on CTA increased the likelihood of a cardioembolic source according to the expert panel (P<0.001). CONCLUSIONS: Extending the stroke CTA to cover the heart increases the chance of detecting cardiac thrombi and helps to identify cardioembolic sources in the acute stage of ischemic stroke with more certainty. Spectral iodine maps provide additional value for detecting left atrial appendage thrombus. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04019483.

Plasma Advanced Glycation End Products and Dicarbonyl Compounds Are Not Associated with Coronary Atherosclerosis in Athletes.

PURPOSE: Coronary atherosclerosis is the leading cause of sudden death among athletes >35 yr old, but current cardiovascular risk prediction algorithms have not been validated for athletes. Advanced glycation end products (AGE) and dicarbonyl compounds have been associated with atherosclerosis and rupture-prone plaques in patients and ex vivo studies. The detection of AGE and dicarbonyl compounds might be a novel screening tool for high-risk coronary atherosclerosis in older athletes. METHODS: Concentrations of three different AGE and the dicarbonyl compounds methylglyoxal, glyoxal, and 3-deoxyglucosone were measured in plasma with ultraperformance liquid chromatography tandem mass spectrometry in athletes from the Measuring Athletes' Risk of Cardiovascular Events 2 study cohort. Coronary plaques, plaque characteristics (calcified, noncalcified or mixed), and coronary artery calcium (CAC) scores were assessed with coronary computed tomography, and potential associations with AGE and dicarbonyl compounds were analyzed using linear and logistic regression. RESULTS: A total of 289 men were included (60 [quartiles 1-3 = 56-66] yr old, body mass index = 24.5 [22.9-26.6] kg·m -2 ), with a weekly exercise volume of 41 (25-57) MET-hours. Coronary plaques were detected in 241 participants (83%), with a dominant plaque type of calcified plaques in 42%, noncalcified plaques in 12% and mixed plaques in 21%. No AGE or dicarbonyl compounds were associated with total number of plaques or any of the plaque characteristics in adjusted analyses. Similarly, AGE and dicarbonyl compounds were not associated with CAC score. CONCLUSIONS: Concentrations of plasma AGE and dicarbonyl compounds do not predict the presence of coronary plaques, plaque characteristics or CAC scores, in middle-age and older athletes.

Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study.

BACKGROUND: Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. METHODS: Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. RESULTS: We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (ß, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (ß, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). CONCLUSIONS: Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.