Type 2 diabetes mellitus (T2DM) poses a higher risk for complications in South Asian individuals compared to other ethnic groups. To shed light on potential mediating factors, we investigated... Show moreType 2 diabetes mellitus (T2DM) poses a higher risk for complications in South Asian individuals compared to other ethnic groups. To shed light on potential mediating factors, we investigated lipidomic changes in plasma of Dutch South Asians (DSA) and Dutch white Caucasians (DwC) with and without T2DM and explore their associations with clinical features. Using a targeted quantitative lipidomics platform, monitoring over 1000 lipids across 17 classes, along with 1H NMR based lipoprotein analysis, we studied 51 healthy participants (21 DSA, 30 DwC) and 92 T2DM patients (47 DSA, 45 DwC) from the MAGNetic resonance Assessment of VICTOza efficacy in the Regression of cardiovascular dysfunction in type 2 dIAbetes mellitus (MAGNA VICTORIA) study. This comprehensive mapping of the circulating lipidome allowed us to identify relevant lipid modules through unbiased weighted correlation network analysis, as well as disease and ethnicity related key mediatory lipids. Significant differences in lipidomic profiles, encompassing various lipid classes and species, were observed between T2DM patients and healthy controls in both the DSA and DwC populations. Our analyses revealed that healthy DSA, but not DwC, controls already exhibited a lipid profile prone to develop T2DM. Particularly, in DSA-T2DM patients, specific lipid changes correlated with clinical features, particularly diacylglycerols (DGs), showing significant associations with glycemic control and renal function. Our findings highlight an ethnic distinction in lipid modules influencing clinical outcomes in renal health. We discover distinctive ethnic disparities of the circulating lipidome and identify ethnicity-specific lipid markers. Jointly, our discoveries show great potential as personalized biomarkers for the assessment of glycemic control and renal function in DSA-T2DM individuals. Show less
BackgroundEthnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI-quantified renal sinus fat volume could be a potential biomarker to help... Show moreBackgroundEthnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI-quantified renal sinus fat volume could be a potential biomarker to help investigate the changes of DKD risk in response to glucose regulation.PurposeTo evaluate whether the effect of glucose-lowering treatment on renal sinus fat volume differed in West Europeans (WE) compared to South Asians (SA), and whether ethnic-related difference exists regarding the effect of liraglutide on renal sinus fat.Study TypeRetrospective.PopulationNinety-three patients with type 2 diabetes mellitus, including 47 WE (27 males) aged 59.3 +/- 6.5 years, and 46 SA (19 males) aged 54.4 +/- 9.8 years.Field Strength/Sequence3.0 T dual-echo fast gradient-echo pulse sequence using two-point Dixon technique with a phase-correction algorithm.AssessmentChanges of renal sinus fat volume were measured by a radiologist (LL) with 4-years' experience, and were compared between the two ethnic groups, together with glycemic level, metabolic risk factors and renal function. The effects of liraglutide were assessed.Statistical TestsNormality of the data was visually evaluated by histograms and Q-Q plots. Within-group and between-group differences were analyzed using paired t-tests and analysis of covariance. Associations were analyzed by person's correlation and multiple linear regression models.ResultsRenal sinus fat decreased in SA patients (Delta% = -7.6% +/- 14.8%), but increased in WE patients (Delta% = 5.0% +/- 13.1%), with a significant difference between the two ethnic groups. In the WE group, the increase of sinus fat volume was significant in the placebo subgroup (Delta% = 6.8% +/- 12.5%), in contrast to the nonsignificant increase in the liraglutide subgroup (Delta% = 3.0% +/- 13.8%, P = 0.444).Data ConclusionRenal sinus fat accumulation responds differently to glucose regulation, showing a reduction in SA patients in contrast to a persistent accumulation in WE patients. A trend of less accumulation of sinus fat in WE patients receiving liraglutide has been observed.Evidence Level4Technical EfficacyStage 4 Show less
Rationale and Objectives: Communication with and within the Radiology Department is typically initiated over phone, face-to-face or general-purpose chat, causing frequent interruptions, additional... Show moreRationale and Objectives: Communication with and within the Radiology Department is typically initiated over phone, face-to-face or general-purpose chat, causing frequent interruptions, additional mental workload, workflow inefficiencies and diagnostic errors. We developed and evaluated a new communication solution that aims to reduce avoidable interruptions caused by technologist-radiologist communication.Materials and Methods: Following an iterative design process with future end users, a scalable web-based software solution, RadConnect, was developed enabling a chat-based communication workflow between a technologist and a radiologist. As a first experimental implementation, technologists can send categorized tickets to a radiology section account. Radiologists receive the tickets in a worklist that is prioritized by urgency. Consented radiologists and technologists performed scripted tasks in 2 hr sessions and completed a structured questionnaire on perceived value and comparison to standard communication modes.Results: Of 17 participants from three academic European institutes, 65% (11/17) believed they would use RadConnect frequently; 53% (9/17) believed that it reduces phone calls >80%; and 88% (15/17) believed it adds value compared to general-purpose enterprise chat applications.Discussion: Participants recognized the value of RadConnect especially its categorized tickets, prioritized worklist and role-based interaction model. Inter-institute differences in perceived value of RadConnect may have been caused by technologist-radiologist proximity and communication alternatives in the institutions.Conclusion: Chat-based role-based communication might be a viable mode of communication between technologists and radiologists to reduce avoidable inter-ruptions. Tailoring the chat solution to the needs of and tightly integrated with the radiology workflow is valued by future end users after exposure to the tool in a simulated environment. (c) 2023 Elsevier Inc. All rights reserved. Show less
Klarenberg, H.; Gosselink, M.; Siddiqui, F.; Coolen, B.F.; Nederveen, A.J.; Leiner, T.; ... ; Froeling, M. 2023
Introduction: Current practice to obtain left ventricular (LV) native and post-contrast T1 and T2 comprises single-slice readouts with multiple breath-holds (BHs). We propose a multi-slice parallel... Show moreIntroduction: Current practice to obtain left ventricular (LV) native and post-contrast T1 and T2 comprises single-slice readouts with multiple breath-holds (BHs). We propose a multi-slice parallel-imaging approach with a 72-channel receive-array to reduce BHs and demonstrate this in healthy subjects and hypertrophic cardiomyopathy (HCM) patients.Methods: A T1/T2 phantom was scanned at 3 T using a 16-channel and a novel 72-channel coil to assess the impact of different coils and acceleration factors on relaxation times. 16-18 healthy participants (8 female, age 28.4 +/- 5.1 years) and 3 HCM patients (3 male, age 55.3 +/- 4.2 years) underwent cardiac-MRI with the 72-channel coil, using a Modified Look-Locker scan with a shared inversion pulse across 3 slices and a Gradient-Spin-Echo scan. Acceleration was done by sensitivity encoding (SENSE) with accelerations 2, 4, and 6. LV T1 and T2 values were analyzed globally, per slice, and in 16 segments, with SENSE = 2 as the reference.Results: The phantom scans revealed no bias between coils and acceleration factors for T1 or T2, except for T2 with SENSE = 2, which resulted in a bias of 8.0 +/- 6.7 ms (p < 0.001) between coils. SENSE = 4 and 6 enabled T1 mapping of three slices in a single BH, and T2 mapping of three slices within two BHs. In healthy subjects, T1 and T2 values varied. We found an average overestimation of T1 in 3 slices of 25 +/- 87 ms for SENSE = 4 and 30 +/- 103 ms using SENSE = 6, as compared to SENSE = 2. Acceleration resulted in decreased signal-to-noise; however, visually insignificant and without increased incidence of SENSE-artifacts. T2 was overestimated by 2.1 +/- 5.0 ms for SENSE = 4 and 6.4 +/- 9.7 ms using SENSE = 6, as compared to SENSE = 2. Native and post-contrast T1 measurements with SENSE = 4 and ECV quantification in HCM patients was successful.Conclusion: The 72-channel receiver-array coil with SENSE = 4 and 6, enabled LV-tissue characterization in three slices. Pre- and post-contrast T1 maps were obtained in a single BH, while T2 required two BHs. Show less
Feijen, M.; Palmen, M.; Lamb, H.J.; Corssmit, E.P.M.; Antoni, M.L. 2023
BackgroundCardiac paragangliomas are extremely rare neuroendocrine tumours derived from neural crest cells that represent <2% of all paragangliomas. Approximately 35–40% of all paragangliomas... Show moreBackgroundCardiac paragangliomas are extremely rare neuroendocrine tumours derived from neural crest cells that represent <2% of all paragangliomas. Approximately 35–40% of all paragangliomas are associated with inherited syndromes such as mutation in the succinate dehydrogenase (SDH) enzyme.Case summaryA 44-year-old male with an SDH complex subunit D (SDHD) mutation was diagnosed with an intracardiac paraganglioma attached to the left main coronary artery. Multimodality imaging, including gallium dotatate positron emission tomography computed tomography, cardiac magnetic resonance imaging, and coronary computed tomography angiography (CCTA) confirmed the suspected intracardiac paraganglioma. During follow-up with a CCTA, the mass showed growth, and surgical removal was recommended to anticipate on the risk of compression of the left main coronary artery. Prior to surgery, coronary angiography was performed, which showed no coronary calcifications. The highly vascularized paraganglioma was visible near the left main and proximal left anterior descending artery. The intracardiac paraganglioma was successfully removed through a median sternotomy with cardiopulmonary bypass, without any complications. The post-operative course was uneventful, and histological examination confirmed the diagnosis of a paraganglioma.DiscussionIntracardiac paragangliomas in the vicinity of the left main coronary artery are rare, and surgical removal may be challenging. Therefore, screening and the use of multiple imaging modalities in patients with SDHD mutations prior to surgery is of major importance. Show less
Pulmonary artery (PA) stenosis is a common complication after the arterial switch operation (ASO) for transposition of the great arteries (TGA). Four-dimensional flow (4D flow) CMR provides the... Show morePulmonary artery (PA) stenosis is a common complication after the arterial switch operation (ASO) for transposition of the great arteries (TGA). Four-dimensional flow (4D flow) CMR provides the ability to quantify flow within an entire volume instead of a single plane. The aim of this study was to compare PA maximum velocities and stroke volumes between 4D flow CMR, two-dimensional phase-contrast (2D PCMR) and echocardiography. A prospective study including TGA patients after ASO was performed between December 2018 and October 2020. All patients underwent echocardiography and CMR, including 2D PCMR and 4D flow CMR. Maximum velocities and stroke volumes were measured in the main, right, and left PA (MPA, LPA, and RPA, respectively). A total of 39 patients aged 20 ± 8 years were included. Maximum velocities in the MPA, LPA, and RPA measured by 4D flow CMR were significantly higher compared to 2D PCMR (p < 0.001 for all). PA assessment by echocardiography was not possible in the majority of patients. 4D flow CMR maximum velocity measurements were consistently higher than those by 2D PCMR with a mean difference of 65 cm/s for the MPA, and 77 cm/s for both the RPA and LPA. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR. Maximum velocities in the PAs after ASO for TGA are consistently lower by 2D PCMR, while echocardiography only allows for PA assessment in a minority of cases. Stroke volumes showed good agreement between 4D flow CMR and 2D PCMR. Show less
Yuan, L.S.; Li-Gao, R.; Verhoeven, A.; Eyk, H.J. van; Bizino, M.B.; Rensen, P.C.N.; ... ; Berg, B.M. van den 2023
Background: Composition of high-density lipoproteins (HDL) is emerging as an important determinant in the development of microvascular complications in type 2 diabetes mellitus (T2DM). Dutch South... Show moreBackground: Composition of high-density lipoproteins (HDL) is emerging as an important determinant in the development of microvascular complications in type 2 diabetes mellitus (T2DM). Dutch South Asian (DSA) individuals with T2DM display an increased risk of microvascular complications compared with Dutch white Caucasian (DwC) individuals with T2DM. In this study, we aimed to investigate whether changes in HDL composition associate with increased microvascular risk in this ethnic group and lead to new lipoprotein biomarkers. Materials and Methods: Using H-1 nuclear magnetic resonance spectroscopy and Bruker IVDr Lipoprotein Subclass Analysis (B.I.LISA) software, plasma lipoprotein changes were determined in 51 healthy individuals (30 DwC, 21 DSA) and 92 individuals with T2DM (45 DwC, 47 DSA) in a cross-sectional, case-control study. Differential HDL subfractions were investigated using multinomial logistic regression analyses, adjusting for possible confounders including BMI and diabetes duration. Results: We identified HDL compositional differences between healthy and diabetic individuals in both ethnic groups. Specifically, levels of apolipoprotein A2 and HDL-4 subfractions were lower in DSA compared with DwC with T2DM. Apolipoprotein A2 and HDL-4 subfractions also negatively correlated with waist circumference, waistto-hip ratio, haemoglobin A1c, glucose levels and disease duration in DSA with T2DM, and associated with increased incidence of microvascular complications .Conclusion: While HDL composition differed between controls and T2DM in both ethnic groups, the lower levels of lipid content in the smallest HDL subclass (HDL-4) in DSA with T2DM appeared to be more clinically relevant, with higher odds of having diabetes-related pan-microvascular complications such as retinopathy and neuropathy. These typical differences in HDL could be used as ethnicity-specific T2DM biomarkers. Show less
Christen, T.; Mutsert, R. de; Smit, R.A.; Dijk, K.W. van; Lamb, H.J.; Rosendaal, F.R.; ... ; Trompet, S. 2023
Background and aims: Leptin has been associated with adverse effects on cardiovascu-lar disease, but the effect of confounding by body fat in these associations remains unclear. To investigate... Show moreBackground and aims: Leptin has been associated with adverse effects on cardiovascu-lar disease, but the effect of confounding by body fat in these associations remains unclear. To investigate associations between leptin and heart function and subclinical cardiovascular disease adjusted for total body fat, and to investigate the causal relation between leptin and cardiovas-cular disease using Mendelian randomisation.Methods and results: Leptin concentrations, total body fat and diverse measures of subclinical car-diovascular disease were determined in participants of the Netherlands Epidemiology of Obesity study. Linear regression between leptin concentration and measures of heart function, ECG mea-sures, and carotid intima media thickness as a measure of subclinical atherosclerosis was adjusted for potential confounding factors, and additionally including total body fat. We analysed the combined effects of genetic variants from a GWAS on leptin concentrations in publicly-available summary statistics of coronary heart disease GWAS (CARDIoGRAMplusC4D, n Z 184,305). As many as 6107 men and women, mean (SD) age 56 (6) years, BMI 26 (4) kg/ m2, and median leptin concentration 12.1 mg (IQR: 6.7-22.6) were included.In observational analyses, leptin was weakly associated with heart function and subclinical cardiovascular disease, but these associations attenuated when adjusting for total body fat. A doubling of genetically-determined leptin concentration was associated with an odds ratio of cardiovascular disease of 0.69 (0.37, 1.27).Conclusion: Observational associations between leptin and subclinical measures of cardiovascu-lar disease were largely explained by differences in total body fat. Results of analyses of genetically-determined leptin and coronary heart disease risk were inconclusive due to a large confidence interval. 2023 The Authors. Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Ital-ian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Background It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS).... Show moreBackground It has been demonstrated that the rate of aortic dilatation is influenced by alteration of aortic hemodynamics, such as normalized flow displacement (FDN) and wall shear stress (WSS). However, the effects of ageing on aortic hemodynamics have not yet been described. Case summary 4D-Flow MRI derived aorta hemodynamics were derived in the ascending aorta of a patient with ascending aortic aneurysm (mean +/- standard deviation: 46 +/- 1 mm) and a healthy volunteer (aortic diameter 30 +/- 1 mm) with long-term follow-up of ten and eight years, respectively. At all timepoints, compared to the healthy volunteer, the patient demonstrated higher magnitudes of FDN (7% +/- 1% vs. 3% +/- 1%) and WSS angle (36 degrees +/- 3 degrees vs. 24 degrees +/- 6 degrees), and lower WSS magnitude (565 +/- 100 mPa vs. 910 +/- 115 mPa), axial WSS (426 +/- 71 mPa vs. 800 +/- 108 mPa) and circumferential WSS (297 +/- 64 mPa vs. 340 +/- 85 mPa). The patient and healthy volunteer demonstrated different aortic dilatation rates (regression slope +/- standard error: 0.2 +/- 0.1 vs. 0.1 +/- 0.2 mm per year) and trends in FDN (0.1% +/- 0.1% vs. 0.1% +/- 0.2% per year), WSS magnitude (22 +/- 9 vs. 35 +/- 13 mPa per year), axial WSS (19 +/- 4 vs. 37 +/- 7 mPa per year), circumferential WSS (9 +/- 8 vs. 5 +/- 15 mPa per year), and WSS angle (-0.5 degrees +/- 0.4 degrees vs. -0.8 degrees +/- 1.0 degrees per year). Discussion Aortic hemodynamic parameters are marginally affected by ageing and the aortic diameter in this case series. Since aortic hemodynamic parameters have been associated with aortic dilation by previous studies, the outcomes of the two subjects suggest that the aortic dilatation rate will remain constant while individuals are ageing and dilating. Show less
Garsen, M.; Buijsers, B.; Sol, M.; Gockeln, L.; Sonneveld, R.; Kuppevelt, T.H. van; ... ; Vlag, J. van der 2023
Background Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the... Show moreBackground Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor y (PPARy) agonists can ameliorate proteinuria. Since a recent study showed that PPARy regulates HPSE expression in liver cancer cells, we hypothesized that PPARy agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.Methods Regulation of HPSE by PPARy was assessed in the adriamycin nephropathy rat model, and cultured glomerular endothelial cells and podocytes. Analyses included immunofluorescence staining, real-time PCR, heparanase activity assay and transendothelial albumin passage assay. Direct binding of PPARy to the HPSE promoter was evaluated by the luciferase reporter assay and chromatin immunoprecipitation assay. Furthermore, HPSE activity was assessed in 38 type 2 diabetes mellitus (T2DM) patients before and after 16/24 weeks treatment with the PPARy agonist pioglitazone.Findings Adriamycin-exposed rats developed proteinuria, an increased cortical HPSE and decreased heparan sulfate (HS) expression, which was ameliorated by treatment with pioglitazone. In line, the PPARy antagonist GW9662 increased cortical HPSE and decreased HS expression, accompanied with proteinuria in healthy rats, as previously shown. In vitro, GW9662 induced HPSE expression in both endothelial cells and podocytes, and increased trans -endothelial albumin passage in a HPSE-dependent manner. Pioglitazone normalized HPSE expression in adriamycin-injured human endothelial cells and mouse podocytes, and adriamycin-induced transendothelial albumin passage was reduced as well. Importantly, we demonstrated a regulatory effect of PPARy on HPSE promoter activity and direct PPARy binding to the HPSE promoter region. Plasma HPSE activity of T2DM patients treated with pioglitazone for 16/24 weeks was related to their hemoglobin A1c and showed a moderate, near significant correlation with plasma creatinine levels.Interpretation PPARy-mediated regulation of HPSE expression appears an additional mechanism explaining the anti-proteinuric and renoprotective effects of thiazolidinediones in clinical practice.Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Background: Particle tracing based on 4D Flow MRI has been applied as a quantitative and qualitative postprocessing technique to study temporally evolving blood flow patterns. Purpose: To... Show moreBackground: Particle tracing based on 4D Flow MRI has been applied as a quantitative and qualitative postprocessing technique to study temporally evolving blood flow patterns. Purpose: To systematically review the various methods to perform 4D Flow MRI-based particle tracing, as well as the clinical value, clinical applications, and current developments of the technique. Study type: The study type is systematic review. Subjects: Patients with cardiovascular disease (such as Marfan, Fontan, Tetralogy of Fallot), healthy controls, and cardiovascular phantoms that received 4D Flow MRI with particle tracing. Field Strength/Sequence: Three-dimensional three-directional cine phase-contrast MRI, at 1.5 T and 3 T. Assessment: Two systematic searches were performed on the PubMed database using Boolean operators and the relevant key terms covering 4D Flow MRI and particle tracing. One systematic search was focused on particle tracing methods, whereas the other on applications. Additional articles from other sources were sought out and included after a similar inspection. Particle tracing methods, clinical applications, clinical value, and current developments were extracted. Statistical Tests: The main results of the included studies are summarized, without additional statistical analysis. Results: Of 127 unique articles retrieved from the initial search, 56 were included (28 for methods and 54 for applications). Most articles that described particle tracing methods used an adaptive timestep, a fourth order Runge-Kutta integration method, and linear interpolation in the time dimension. Particle tracing was applied in heart chambers, aorta, venae cavae, Fontan circulation, pulmonary arteries, abdominal vasculature, peripheral arteries, carotid arteries, and cerebral vasculature. Applications were grouped as intravascular, intracardiac, flow stasis, and research. Data Conclusions: Particle tracing based on 4D Flow MRI gives unique insight into blood flow in several cardiovascular diseases, but the quality depends heavily on the MRI data quality. Further studies are required to evaluate the clinical value of the technique for different cardiovascular diseases. Evidence Level: 5. Technical Efficacy: Stage 1. Show less
OBJECTIVES: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection ... Show moreOBJECTIVES: To date, it is not known if 16-20-mm extracardiac conduits are outgrown during somatic growth from childhood to adolescence. This study aims to determine total cavopulmonary connection (TCPC) haemodynamics in adolescent Fontan patients at rest and during simulated exercise and to assess the relationship between conduit size and haemodynamics. METHODS: Patient-specific, magnetic resonance imaging-based computational fluid dynamic models of the TCPC were performed in 51 extracardiac Fontan patients with 16-20-mm conduits. Power loss, pressure gradient and normalized resistance were quantified in rest and during simulated exercise. The cross-sectional area (CSA) (mean and minimum) of the vessels of the TCPC was determined and normalized for flow rate (mm(2)/l/min). Peak (predicted) oxygen uptake was assessed. RESULTS: The median age was 16.2 years (Q1-Q3 14.0-18.2). The normalized mean conduit CSA was 35-73% smaller compared to the inferior and superior vena cava, hepatic veins and left/right pulmonary artery (all P < 0.001). The median TCPC pressure gradient was 0.7 mmHg (Q1-Q3 0.5-0.8) and 2.0 (Q1-Q3 1.4-2.6) during rest and simulated exercise, respectively. A moderate-strong inverse non-linear relationship was present between normalized mean conduit CSA and TCPC haemodynamics in rest and exercise. TCPC pressure gradients of >= 1.0 at rest and >= 3.0 mmHg during simulated exercise were observed in patients with a conduit CSA <= 45 mm(2)/l/min and favourable haemodynamics (< 1 mmHg during both rest and exercise) in conduits >= 125 mm(2)/l/min. Normalized TCPC resistance correlated with (predicted) peak oxygen uptake. CONCLUSIONS: Extracardiac conduits of 16-20 mm have become relatively undersized in most adolescent Fontan patients leading to suboptimal haemodynamics. Show less
Background: A new 72-channel receive array coil and sensitivity encoding, compressed (C-SENSE) and noncompressed (SENSE), were investigated to decrease the number of breath-holds (BHs) for cardiac... Show moreBackground: A new 72-channel receive array coil and sensitivity encoding, compressed (C-SENSE) and noncompressed (SENSE), were investigated to decrease the number of breath-holds (BHs) for cardiac magnetic resonance (CMR). Methods: Three-T CMRs were performed using the 72-channel coil with SENSE-2/4/6 and C-SENSE-2/4/6 accelerated short-axis cine two-dimensional balanced steady-state free precession sequences. A 16-channel coil with SENSE-2 served as reference. Ten healthy subjects were included. BH-time was kept under 15 s. Data were compared in terms of image quality, biventricular function, number of BHs, and scan times. Results: BHs decreased from 7 with C-SENSE-2 (scan time 70 s, 2 slices/BH) to 3 with C-SENSE-4 (scan time 42 s, 4-5 slices/BH) and 2 with C-SENSE-6 (scan time 28 s, 7 slices/BH). Compared to reference, image sharpness was similar for SENSE-2/4/6, slightly inferior for C-SENSE-2/4/6. Blood-to-myocardium contrast was unaffected. C-SENSE-4/6 was given lower qualitative median scores, but images were considered diagnostically adequate to excellent, with C-SENSE-6 suboptimal. Biventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes, ejection fractions (EF), cardiac outputs, and left ventricle (LV)-mass were similar for SENSE-2/4/6 with no systematic bias and clinically appropriate limits of agreements. C-SENSE slightly underestimated LV-EDV (-6.38 +/- 6.0 mL, p < 0.047), LV-ESV (-7.94 +/- 6.0 mL, p < 0.030) and overestimated LV-EF (3.16 +/- 3.10%; p < 0.047) with C-SENSE-4. Bland-Altman analyses revealed minor systematic biases in these variables with C-SENSE-2/4/6 and for LV-mass with C-SENSE-6. Conclusions: Using the 72-channel coil, short-axis CMR for quantifying biventricular function was feasible in two BHs where SENSE slightly outperformed C-SENSE. Show less
Velde, J.H.P.M. van der; Boone, S.C.; Winters-van Eekelen, E.; Hesselink, M.K.C.; Schrauwen-Hinderling, V.B.; Schrauwen, P.; ... ; Mutsert, R. de 2022
Aims/hypothesis We hypothesised that the insulin-sensitising effect of physical activity depends on the timing of the activity. Here, we examined cross-sectional associations of breaks in sedentary... Show moreAims/hypothesis We hypothesised that the insulin-sensitising effect of physical activity depends on the timing of the activity. Here, we examined cross-sectional associations of breaks in sedentary time and timing of physical activity with liver fat content and insulin resistance in a Dutch cohort.Methods In 775 participants of the Netherlands Epidemiology of Obesity (NEO) study, we assessed sedentary time, breaks in sedentary time and different intensities of physical activity using activity sensors, and liver fat content by magnetic resonance spectroscopy (n=256). Participants were categorised as being most active in the morning (06:00-12:00 hours), afternoon (12:0018:00 hours) or evening (18:00-00:00 hours) or as engaging in moderate-to-vigorous-physical activity (MVPA) evenly distributed throughout the day. Most active in a certain time block was defined as spending the majority (%) of total daily MVPA in that block. We examined associations between sedentary time, breaks and timing of MVPA with liver fat content and HOMA-IR using linear regression analyses. adjusted for demographic and lifestyle factors including total body fat. Associations of timing of MVPA were additionally adjusted for total MVPA.Results The participants (42% men) had a mean (SD) age of 56 (4) years and a mean (SD) BMI of 26.2 (4.1) kg/m(2). Total sedentary time was not associated with liver fat content or insulin resistance, whereas the amount of breaks in sedentary time was associated with higher liver fat content. Total MVPA (-5%/h [95% CI -10%/h, 0%/h]) and timing of MVPA were associated with reduced insulin resistance but not with liver fat content. Compared with participants who had an even distribution of MVPA throughout the day. insulin resistance was similar (-3% [95% CI -25%, 16%]) in those most active in morning, whereas it was reduced in participants who were most active in the afternoon (-18% [95% CI -33%, -2%]) or evening (-25% [95% CI -49%, -4%]).Conclusions/interpretation The number of daily breaks in sedentary time was not associated with lower liver fat content or reduced insulin resistance. Moderate-to-vigorous activity in the afternoon or evening was associated with a reduction of up to 25% in insulin resistance. Further studies should assess whether timing of physical activity is also important for the occurrence of type 2 diabetes. Show less
Context: South Asian individuals are more prone to develop type 2 diabetes (T2D) coinciding with earlier complications than Europids. While inflammation plays a central role in the development and... Show moreContext: South Asian individuals are more prone to develop type 2 diabetes (T2D) coinciding with earlier complications than Europids. While inflammation plays a central role in the development and progression of T2D, this factor is still underexplored in South Asians. Objective: This work aimed to study whether circulating messenger RNA (mRNA) transcripts of immune genes are different between South Asian compared with Europid patients with T2D. Methods: A secondary analysis was conducted of 2 randomized controlled trials of Dutch South Asian (n = 45; age: 55 +/- 10 years, body mass index [BMI]: 29 +/- 4 kg/m(2)) and Dutch Europid (n = 44; age: 60 +/- 7 years, BMI: 32 +/- 4 kg/m(2)) patients with T2D. Main outcome measures included mRNA transcripts of 182 immune genes (microfluidic quantitative polymerase chain reaction; Fluidigm Inc) in fasted whole-blood, ingenuity pathway analyses (Qiagen). Results: South Asians, compared to Europids, had higher mRNA levels of B-cell markers (CD19, CD79A, CD79B, CR2, CXCR5, IGHD, MS4A1, PAX5; all fold change > 1.3, false discovery rate [FDR] < 0.008) and interferon (IFN)-signaling genes (CD274, GBP1, GBP2, GBP5, FCGR1A/B/CP, IFI16, IFIT3, IFITM1, IFITM3, TAP1; all FC > 1.2, FDR < 0.05). In South Asians, the IFN signaling pathway was the top canonical pathway (z score 2.6; P < .001) and this was accompanied by higher plasma IFN-gamma levels (FC = 1.5, FDR = 0.01). Notably, the ethnic difference in gene expression was larger for women (20/182 [11%]) than men (2/182 [1%]). Conclusion: South Asian patients with T2D show a more activated IFN-signaling pathway compared to Europid patients with T2D, which is more pronounced in women than men. We speculate that a more activated IFN-signaling pathway may contribute to the more rapid progression of T2D in South Asian compared with Europid individuals. Show less
BACKGROUND Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations... Show moreBACKGROUND Nonischemic cardiomyopathy patients referred for catheter ablation of ventricular arrhythmias (VAs) typically have either inferolateral (ILS) or anteroseptal (ASS) VA substrate locations, with poorer outcomes for ASS. Sympathetic denervation is an important determinant of arrhythmogenicity. Its relation to nonischemic fibrosis in general and to the different VA substrates is unknown.OBJECTIVES This study sought to evaluate the association between VA substrates, myocardial fibrosis, and sympa-thetic denervation. METHODS Thirty-five patients from the Leiden Nonischemic Cardiomyopathy Study, who underwent electroanatomic voltage mapping and iodine-123 metaiodobenzylguanidine imaging between 2011 and 2018 were included. Late gadolinium-enhanced cardiac magnetic resonance data were collected when available. The relation between global cardiac sympathetic innervation and area-weighted unipolar voltage (UV) as a surrogate for diffuse fibrosis was evalu-ated. For regional analysis, patients were categorized as ASS or ILS. The distribution of low UV, sympathetic denervation, and late gadolinium enhancement (LGE) scar were compared using the 17-segment model.RESULTS Median area-weighted UV was 12.3 mV in patients with normal sympathetic innervation and 8.7 mV in patients with sympathetic denervation. Global sympathetic denervation correlated with diffuse myocardial fibrosis (R = 0.53; P = 0.02). ILS (n = 13) matched with low UV, sympathetic denervation, and LGE scar in all patients, whereas ASS (n = 11) matched with low UV in all patients, with LGE scar in 63% (P = 0.20), but with sympathetic denervation in only 27% of patients (P = 0.0002).CONCLUSIONS Global cardiac sympathetic denervation is related to fibrosis in nonischemic cardiomyopathy patients with VA. The mismatch between regional fibrosis and preserved innervation for ASS may contribute to a VA substrate difficult to control by catheter ablation. (J Am Coll Cardiol EP 2022;8:1234-1245)(c) 2022 by the American College of Cardiology Foundation. Show less
Abstract OBJECTIVES Progressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by... Show moreAbstract OBJECTIVES Progressive root dilatation is an important complication in patients with transposition of the great arteries (TGA) after arterial switch operation (ASO) that may be caused by altered flow dynamics. Aortic wall shear stress (WSS) distribution at rest and under dobutamine stress (DS) conditions using 4D flow magnetic resonance imaging were investigated in relation to thoracic aorta geometry. METHODS 4D flow magnetic resonance imaging was performed in 16 adolescent TGA patients after ASO (rest and DS condition) and in 10 healthy controls (rest). The primary outcome measure was the WSS distribution along the aortic segments and the WSS change with DS in TGA patients. Based on the results, we secondary zoomed in on factors [aortic geometry and left ventricular (LV) function parameters] that might relate to these WSS distribution differences. Aortic diameters, arch angle, LV function parameters (stroke volume, LV ejection fraction, cardiac output) and peak systolic aortic WSS were obtained. RESULTS TGA patients had significantly larger neoaortic root and smaller mid-ascending aorta (AAo) dimensions and aortic arch angle. At rest, patients had significantly higher WSS in the entire thoracic aorta, except for the dilated root. High WSS levels beyond the proximal AAo were associated with the diameter decrease from the root to the mid-AAo (correlation coefficient r = 0.54–0.59, P = 0.022–0.031), not associated with the aortic arch angle. During DS, WSS increased in all aortic segments (P < 0.001), most pronounced in the AAo segments. The increase in LV ejection fraction, stroke volume and cardiac output as a result of DS showed a moderate linear relationship with the WSS increase in the distal AAo (correlation coefficient r = 0.54–0.57, P = 0.002–0.038). CONCLUSIONS Increased aortic WSS was observed in TGA patients after ASO, related to the ASO-specific geometry, which increased with DS. Stress-enhanced elevated WSS may play a role in neoaortic root dilatation and anterior aortic wall thinning of the distal AAo. Show less
Aims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with... Show moreAims: To quantify metabolic impairment via a one-factor approach with confirmatory factor analysis (CFA) including MRI-derived visceral and subcutaneous adipose tissues and to associate it with diastolic dysfunction. Methods: In this cross-sectional analysis, 916 participants (53% female, mean age (SD): 56 (6)) underwent abdominal and cardiovascular MRI. With CFA a metabolic-load factor of metabolic-syndrome variables and visceral and subcutaneous adipose tissues was constructed. A piecewise structural equation model approach with adjustment for confounding factors was used to determine associations with left-ventricular diastolic function, cardiac morphology and hemodynamics. Results: Model fitting excluding blood pressure and waist circumference but including visceral and subcutaneous adipose tissues, fasting glucose, HDL-c and triglycerides was used to construct the metabolic-load factor. Evaluating measurement invariance demonstrated sex-specificity. Change in mitral early/late peak filling rate ratio was -0.12 for both males [-0.20; -0.05, p > 0.05] and females [-0.17; -0.07, p > 0.001] per SD of metabolicload factor. Change in deceleration time of mitral early filling was -11.83 ms in females [-17.38; -6.27] per SD of metabolic-load factor. Conclusion: A single latent metabolic-load factor via CFA including MRI-derived adipose tissues increased sensitivity for metabolic impairment obsoleting waist circumference and is associated with a decreased leftventricular diastolic function, more apparent in females than in males. Show less
Juffermans, J.F.; Assen, H.C. van; Kiefte, B.J.C. te; Ramaekers, M.J.F.G.; Palen, R.L.F. van der; Boogaard, P. van den; ... ; Westenberg, J.J.M. 2022
(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm ... Show more(1) Background: Aorta hemodynamics have been associated with aortic remodeling, but the reproducibility of its assessment has been evaluated marginally in patients with thoracic aortic aneurysm (TAA). The current study evaluated intra- and interobserver reproducibility of 4D flow MRI-derived hemodynamic parameters (normalized flow displacement, flow jet angle, wall shear stress (WSS) magnitude, axial WSS, circumferential WSS, WSS angle, vorticity, helicity, and local normalized helicity (LNH)) in TAA patients; (2) Methods: The thoracic aorta of 20 patients was semi-automatically segmented on 4D flow MRI data in 5 systolic phases by 3 different observers. Each time-dependent segmentation was manually improved and partitioned into six anatomical segments. The hemodynamic parameters were quantified per phase and segment. The coefficient of variation (COV) and intraclass correlation coefficient (ICC) were calculated; (3) Results: A total of 2400 lumen segments were analyzed. The mean aneurysm diameter was 50.8 +/- 2.7 mm. The intra- and interobserver analysis demonstrated a good reproducibility (COV = 16-30% and ICC = 0.84-0.94) for normalized flow displacement and jet angle, a very good-to-excellent reproducibility (COV = 3-26% and ICC = 0.87-1.00) for all WSS components, helicity and LNH, and an excellent reproducibility (COV = 3-10% and ICC = 0.96-1.00) for vorticity; (4) Conclusion: 4D flow MRI-derived hemodynamic parameters are reproducible within the thoracic aorta in TAA patients. Show less
