Enhanced aortic stiffness in adolescents with chronic disease is associated with decreased left ventricular global longitudinal strain.

Background: The recent Cardiovascular Disease in Adolescents with Chronic Disease (CDACD) study showed enhanced aortic stiffness and wall thickness in adolescents with various chronic disorders. Enhanced aortic stiffness can increase left ventricular (LV) afterload and trigger a cascade of adverse arterioventricular interaction. Here, we investigate the relation between aortic changes and LV function in the CDACD study participants. Methods: This cross-sectional study included 114 adolescents 12-18 years old with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (n = 20), and healthy controls (n = 25). Aortic pulse wave velocity (PWV), which reflects aortic stiffness, and aortic wall thickness (AWT) were assessed with cardiovascular magnetic resonance imaging (CMR). Echocardiography was employed to study conventional markers of LV function, as well as LV global longitudinal strain (LVGLS), which is an established (pre)clinical marker of LV dysfunction. Results: First, aortic PWV and AWT were increased in all chronic disease groups, compared to controls. Second, in adolescents with CoA, JIA, and obesity, echocardiography showed a decreased LVGLS, while LV dimensions and conventional LV function markers were similar to controls. Third, multivariable linear regression identified aortic PWV as the most important determinant of their decreased LVGLS (standardized ß -0.522, p < 0.001). Conclusions: The decreased LVGLS in several adolescent chronic disease groups was associated with enhanced aortic PWV, which might reflect adverse arterioventricular interaction. Whether the decreased LVGLS in the chronic disease groups could negatively impact their long-term cardiovascular outcomes requires further study.

Fully Automated Valve Segmentation for Blood Flow Assessment From 4D Flow MRI Including Automated Cardiac Valve Tracking and Transvalvular Velocity Mapping.

BACKGROUND: Automated 4D flow MRI valvular flow quantification without time-consuming manual segmentation might improve workflow. PURPOSE: Compare automated valve segmentation (AS) to manual (MS), and manually corrected automated segmentation (AMS), in corrected atrioventricular septum defect (c-AVSD) patients and healthy volunteers, for assessing net forward volume (NFV) and regurgitation fraction (RF). STUDY TYPE: Retrospective. POPULATION: 27 c-AVSD patients (median, 23 years; interquartile range, 16-31 years) and 24 healthy volunteers (25 years; 12.5-36.5 years). FIELD STRENGTH/SEQUENCE: Whole-heart 4D flow MRI and cine steady-state free precession at 3T. ASSESSMENT: After automatic valve tracking, valve annuli were segmented on time-resolved reformatted trans-valvular velocity images by AS, MS, and AMS. NFV was calculated for all valves, and RF for right and left atrioventricular valves (RAVV and LAVV). NFV variation (standard deviation divided by mean NFV) and NFV differences (NFV difference of a valve vs. mean NFV of other valves) expressed internal NFV consistency. STATISTICAL TESTS: Comparisons between methods were assessed by Wilcoxon signed-rank tests, and intra/interobserver variability by intraclass correlation coefficients (ICCs). P < 0.05 was considered statistically significant, with multiple testing correction. RESULTS: AMS mean analysis time was significantly shorter compared with MS (5.3 ± 1.6 minutes vs. 9.1 ± 2.5 minutes). MS NFV variation (6.0%) was significantly smaller compared with AMS (6.3%), and AS (8.2%). Median NFV difference of RAVV, LAVV, PV, and AoV between segmentation methods ranged from -0.7-1.0 mL, -0.5-2.8 mL, -1.1-3.6 mL, and - 3.1--2.1 mL, respectively. Median RAVV and LAVV RF, between 7.1%-7.5% and 3.8%-4.3%, respectively, were not significantly different between methods. Intraobserver/interobserver agreement for AMS and MS was strong-to-excellent for NFV and RF (ICC ≥0.88). DATA CONCLUSION: MS demonstrates strongest internal consistency, followed closely by AMS, and AS. Automated segmentation, with or without manual correction, can be considered for 4D flow MRI valvular flow quantification. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.

Noninvasive Advanced Cardiovascular Magnetic Resonance-Derived Fontan Hemodynamics Are Associated With Reduced Kidney Function But Not Albuminuria.

BACKGROUND: Kidney disease is the most important predictor of death in patients with a Fontan circulation, yet its clinical and hemodynamic correlates have not been well established. METHODS AND RESULTS: A total of 53 ambulatory patients with a Fontan circulation (median age, 16.2 years, 52.8% male patients) underwent advanced cardiovascular magnetic resonance assessment, including 4-dimensional flow imaging and computational fluid dynamics. Estimated glomerular filtration rate (eGFR) <90 mL/min per 1.73 m2 was observed in 20.8% and albumin-to-creatinine ratio >3 mg/mmol in 39.6%. The average eGFR decline rate was -1.83 mL/min per 1.73 m2 per year (95% CI, -2.67 to -0.99; P<0.001). Lower eGFR was associated with older age, larger body surface area at examination, longer time since Fontan procedure, and lower systemic ventricular ejection fraction. Higher albumin-to-creatinine ratio was associated with absence of fenestration at the Fontan operation, and older age and lower systemic ventricular ejection fraction at the assessment. Lower cross-sectional area of the Fontan conduit indexed to flow (r=0.32, P=0.038), higher inferior vena cava-conduit velocity mismatch factor (r=-0.35, P=0.022), higher kinetic energy indexed to flow in the total cavopulmonary connection (r=-0.59, P=0.005), and higher total cavopulmonary connection resistance (r=-0.42, P=0.005 at rest; r=-0.43, P=0.004 during exercise) were all associated with lower eGFR but not with albuminuria. CONCLUSIONS: Kidney dysfunction and albuminuria are common among clinically well adolescents and young adults with a Fontan circulation. Advanced cardiovascular magnetic resonance-derived metrics indicative of declining Fontan hemodynamics are associated with eGFR and might serve as targets to improve kidney health. Albuminuria might be driven by other factors that need further investigation.

Evaluating a Phase-Specific Approach to Aortic Flow: A 4D Flow MRI Study.

BACKGROUND: Aortic flow parameters can be quantified using 4D flow MRI. However, data are sparse on how different methods of analysis influence these parameters and how these parameters evolve during systole. PURPOSE: To assess multiphase segmentations and multiphase quantification of flow-related parameters in aortic 4D flow MRI. STUDY TYPE: Prospective. POPULATION: 40 healthy volunteers (50% male, 28.9 ± 5.0 years) and 10 patients with thoracic aortic aneurysm (80% male, 54 ± 8 years). FIELD STRENGTH/SEQUENCE: 4D flow MRI with a velocity encoded turbo field echo sequence at 3 T. ASSESSMENT: Phase-specific segmentations were obtained for the aortic root and the ascending aorta. The whole aorta was segmented in peak systole. In all aortic segments, time to peak (TTP; for flow velocity, vorticity, helicity, kinetic energy, and viscous energy loss) and peak and time-averaged values (for velocity and vorticity) were calculated. STATISTICAL TESTS: Static vs. phase-specific models were assessed using Bland-Altman plots. Other analyses were performed using phase-specific segmentations for aortic root and ascending aorta. TTP for all parameters was compared to TTP of flow rate using paired t-tests. Time-averaged and peak values were assessed using Pearson correlation coefficient. P < 0.05 was considered statistically significant. RESULTS: In the combined group, velocity in static vs. phase-specific segmentations differed by 0.8 cm/sec for the aortic root, and 0.1 cm/sec (P = 0.214) for the ascending aorta. Vorticity differed by 167 sec-1 mL-1 (P = 0.468) for the aortic root, and by 59 sec-1 mL-1 (P = 0.481) for the ascending aorta. Vorticity, helicity, and energy loss in the ascending aorta, aortic arch, and descending aorta peaked significantly later than flow rate. Time-averaged velocity and vorticity values correlated significantly in all segments. DATA CONCLUSION: Static 4D flow MRI segmentation yields comparable results as multiphase segmentation for flow-related parameters, eliminating the need for time-consuming multiple segmentations. However, multiphase quantification is necessary for assessing peak values of aortic flow-related parameters. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

4D Flow Patterns and Relative Pressure Distribution in a Left Ventricle Model by Shake-the-Box and Proper Orthogonal Decomposition Analysis.

PURPOSE: Intraventricular blood flow dynamics are associated with cardiac function. Accurate, noninvasive, and easy assessments of hemodynamic quantities (such as velocity, vortex, and pressure) could be an important addition to the clinical diagnosis and treatment of heart diseases. However, the complex time-varying flow brings many challenges to the existing noninvasive image-based hemodynamic assessments. The development of reliable techniques and analysis tools is essential for the application of hemodynamic biomarkers in clinical practice. METHODS: In this study, a time-resolved particle tracking method, Shake-the-Box, was applied to reconstruct the flow in a realistic left ventricle (LV) silicone model with biological valves. Based on the obtained velocity, 4D pressure field was calculated using a Poisson equation-based pressure solver. Furthermore, flow analysis by proper orthogonal decomposition (POD) of the 4D velocity field has been performed. RESULTS: As a result of the Shake-the-Box algorithm, we have extracted: (i) particle positions, (ii) particle tracks, and finally, (iii) 4D velocity fields. From the latter, the temporal evolution of the 3D pressure field during the full cardiac cycle was obtained. The obtained maximal pressure difference extracted along the base-to-apex was about 2.7 mmHg, which is in good agreement with those reported in vivo. The POD analysis results showed a clear picture of different scale of vortices in the pulsatile LV flow, together with their time-varying information and corresponding kinetic energy content. To reconstruct 95% of the kinetic energy of the LV flow, only the first six POD modes would be required, leading to significant data reduction. CONCLUSIONS: This work demonstrated Shake-the-Box is a promising technique to accurately reconstruct the left ventricle flow field in vitro. The good spatial and temporal resolutions of the velocity measurements enabled a 4D reconstruction of the pressure field in the left ventricle. The application of POD analysis showed its potential in reducing the complexity of the high-resolution left ventricle flow measurements. For future work, image analysis, multi-modality flow assessments, and the development of new flow-derived biomarkers can benefit from fast and data-reducing POD analysis.

Age- and sex-specific reference values of biventricular flow components and kinetic energy by 4D flow cardiovascular magnetic resonance in healthy subjects.

BACKGROUND: Advances in four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) have allowed quantification of left ventricular (LV) and right ventricular (RV) blood flow. We aimed to (1) investigate age and sex differences of 4D flow CMR-derived LV and RV relative flow components and kinetic energy (KE) parameters indexed to end-diastolic volume (KEiEDV) in healthy subjects; and (2) assess the effects of age and sex on these parameters. METHODS: We performed 4D flow analysis in 163 healthy participants (42% female; mean age 43 ± 13 years) of a prospective registry study (NCT03217240) who were free of cardiovascular diseases. Relative flow components (direct flow, retained inflow, delayed ejection flow, residual volume) and multiple phasic KEiEDV (global, peak systolic, average systolic, average diastolic, peak E-wave, peak A-wave) for both LV and RV were analysed. RESULTS: Compared with men, women had lower median LV and RV residual volume, and LV peak and average systolic KEiEDV, and higher median values of RV direct flow, RV global KEiEDV, RV average diastolic KEiEDV, and RV peak E-wave KEiEDV. ANOVA analysis found there were no differences in flow components, peak and average systolic, average diastolic and global KEiEDV for both LV and RV across age groups. Peak A-wave KEiEDV increased significantly (r = 0.458 for LV and 0.341 for RV), whereas peak E-wave KEiEDV (r = - 0.355 for LV and - 0.318 for RV), and KEiEDV E/A ratio (r = - 0.475 for LV and - 0.504 for RV) decreased significantly, with age. CONCLUSION: These data using state-of-the-art 4D flow CMR show that biventricular flow components and kinetic energy parameters vary significantly by age and sex. Age and sex trends should be considered in the interpretation of quantitative measures of biventricular flow. Clinical trial registration  https://www. CLINICALTRIALS: gov . Unique identifier: NCT03217240.

A clinician's guide to understanding aortic 4D flow MRI.

Four-dimensional flow magnetic resonance imaging is an emerging technique which may play a role in diagnosis and risk-stratification of aortic disease. Some knowledge of flow dynamics and related parameters is necessary to understand and apply this technique in clinical workflows. The purpose of the current review is to provide a guide for clinicians to the basics of flow imaging, frequently used flow-related parameters, and their relevance in the context of aortic disease.Clinical relevance statement Understanding normal and abnormal aortic flow could improve clinical care in patients with aortic disease.

4D Flow cardiovascular magnetic resonance consensus statement: 2023 update.

Hemodynamic assessment is an integral part of the diagnosis and management of cardiovascular disease. Four-dimensional cardiovascular magnetic resonance flow imaging (4D Flow CMR) allows comprehensive and accurate assessment of flow in a single acquisition. This consensus paper is an update from the 2015 '4D Flow CMR Consensus Statement'. We elaborate on 4D Flow CMR sequence options and imaging considerations. The document aims to assist centers starting out with 4D Flow CMR of the heart and great vessels with advice on acquisition parameters, post-processing workflows and integration into clinical practice. Furthermore, we define minimum quality assurance and validation standards for clinical centers. We also address the challenges faced in quality assurance and validation in the research setting. We also include a checklist for recommended publication standards, specifically for 4D Flow CMR. Finally, we discuss the current limitations and the future of 4D Flow CMR. This updated consensus paper will further facilitate widespread adoption of 4D Flow CMR in the clinical workflow across the globe and aid consistently high-quality publication standards.

Comparison of Four-Dimensional Flow MRI, Two-Dimensional Phase-Contrast MRI and Echocardiography in Transposition of the Great Arteries.

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 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.

Virtual surgery to predict optimized conduit size for adult Fontan patients with 16-mm conduits.

OBJECTIVES: Recent evidence suggests that conduits implanted in Fontan patients at the age of 2-4 years become undersized for adulthood. The objective of this study is to use computational fluid dynamic models to evaluate the effect of virtual expansion of the Fontan conduit on haemodynamics and energetics of the total cavopulmonary connection (TCPC) under resting conditions and increased flow conditions. METHODS: Patient-specific, magnetic resonance imaging-based simulation models of the TCPC were performed during resting and increased flow conditions. The original 16-mm conduits were virtually enlarged to 3 new sizes. The proposed conduit sizes were defined based on magnetic resonance imaging-derived conduit flow in each patient. Flow efficiency was evaluated based on power loss, pressure drop and resistance and thrombosis risk was based on flow stagnation volume and relative residence time (RRT). RESULTS: Models of 5 adult patients with a 16-mm extracardiac Fontan connection were simulated and subsequently virtually expanded to 24-32 mm depending on patient-specific conduit flow. Virtual expansion led to a 40-65% decrease in pressure gradient across the TCPC depending on virtual conduit size. Despite improved energetics of the entire TCPC, the pulmonary arteries remained a significant contributor to energy loss (60-73% of total loss) even after virtual surgery. Flow stagnation volume inside the virtual conduit and surface area in case of elevated RRT (>20/Pa) increased after conduit enlargement but remained negligible (flow stagnation <2% of conduit volume in rest, <0.5% with exercise and elevated RRT <3% in rest, <1% with exercise). CONCLUSIONS: Virtual expansion of 16-mm conduits to 24-32 mm, depending on patient-specific conduit flow, in Fontan patients significantly improves TCPC efficiency while thrombosis risk presumably remains low.

Prognostic implications of left ventricular inward displacement assessed by cardiac magnetic resonance imaging in patients with myocardial infarction.

Risk stratification of patients with ischemic heart disease (IHD) still depends mainly on the left ventricular ejection fraction (LVEF). LV inward displacement (InD) is a novel parameter of LV systolic function, derived from feature tracking cardiac magnetic resonance (CMR) imaging. We aimed to investigate the prognostic impact of InD in patients with IHD and prior myocardial infarction. A total of 111 patients (mean age 57 ± 10, 86% male) with a history of myocardial infarction who underwent CMR were included. LV InD was quantified by measuring the displacement of endocardially tracked points towards the centreline of the LV during systole with feature tracking CMR. The endpoint was a composite of all-cause mortality, heart failure hospitalization and arrhythmic events. During a median follow-up of 142 (IQR 107-159) months, 31 (27.9%) combined events occurred. Kaplan-Meier analysis demonstrated that patients with LV InD below the study population median value (23.0%) had a significantly lower event-free survival (P < 0.001). LV InD remained independently associated with outcomes (HR 0.90, 95% CI 0.84-0.98, P = 0.010) on multivariate Cox regression analysis. InD also provided incremental prognostic value to LVEF, LV global radial strain and CMR scar burden. LV InD, measured with feature tracking CMR, was independently associated with outcomes in patients with IHD and prior myocardial infarction. LV InD also provided incremental prognostic value, in addition to LVEF and LV global radial strain. LV InD holds promise as a pragmatic imaging biomarker for post-infarct risk stratification.

Influence of aortic aneurysm on the local distribution of NO and O2 using image-based computational fluid dynamics.

There is a pressing need to establish novel biomarkers to predict the progression of thoracic aortic aneurysm (TAA) dilatation. Aside from hemodynamics, the roles of oxygen (O2) and nitric oxide (NO) in TAA pathogenesis are potentially significant. As such, it is imperative to comprehend the relationship between aneurysm presence and species distribution in both the lumen and aortic wall. Given the limitations of existing imaging methods, we propose the use of patient-specific computational fluid dynamics (CFD) to explore this relationship. We have performed CFD simulations of O2 and NO mass transfer in the lumen and aortic wall for two cases: a healthy control (HC) and a patient with TAA, both acquired using 4D-flow magnetic resonance imaging (MRI). The mass transfer of O2 was based on active transport by hemoglobin, while the local variations of the wall shear stress (WSS) drove NO production. Comparing hemodynamic properties, the time-averaged WSS was considerably lower for TAA, while the oscillatory shear index and endothelial cell activation potential were notably elevated. O2 and NO showed a non-uniform distribution within the lumen and an inverse correlation between the two species. We identified several locations of hypoxic regions for both cases due to lumen-side mass transfer limitations. In the wall, NO varied spatially, with a clear distinction between TAA and HC. In conclusion, the hemodynamics and mass transfer of NO in the aorta exhibit the potential to serve as a diagnostic biomarker for TAA. Furthermore, hypoxia may provide additional insights into the onset of other aortic pathologies.

Effects of ageing on aortic hemodynamics measured by 4D-flow MRI: a case series.

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). 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° ± 3° vs. 24° ± 6°), 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° ± 0.4° vs. -0.8° ± 1.0° 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.

Particle Tracing Based on 4D Flow Magnetic Resonance Imaging: A Systematic Review into Methods, Applications, and Current Developments.

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 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.

Haemodynamic performance of 16-20-mm extracardiac Goretex conduits in adolescent Fontan patients at rest and during simulated exercise.

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 (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 (mm2/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 mm2/l/min and favourable haemodynamics (<1 mmHg during both rest and exercise) in conduits ≥125 mm2/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.

Preclinical Aortic Atherosclerosis in Adolescents With Chronic Disease.

Background Adolescents with chronic disease are often exposed to inflammatory, metabolic, and hemodynamic risk factors for early atherosclerosis. Since postmortem studies have shown that atherogenesis starts in the aorta, the CDACD (Cardiovascular Disease in Adolescents with Chronic Disease) study investigated preclinical aortic atherosclerosis in these adolescents. Methods and Results The cross-sectional CDACD study enrolled 114 adolescents 12 to 18 years old with chronic disorders including juvenile idiopathic arthritis, cystic fibrosis, obesity, corrected coarctation of the aorta, and healthy controls with a corrected atrial septal defect. Cardiovascular magnetic resonance was used to assess aortic pulse wave velocity and aortic wall thickness, as established aortic measures of preclinical atherosclerosis. Cardiovascular magnetic resonance showed a higher aortic pulse wave velocity, which reflects aortic stiffness, and higher aortic wall thickness in all adolescent chronic disease groups, compared with controls (P<0.05). Age (ß=0.253), heart rate (ß=0.236), systolic blood pressure (ß=-0.264), and diastolic blood pressure (ß=0.365) were identified as significant predictors for aortic pulse wave velocity, using multivariable linear regression analysis. Aortic wall thickness was predicted by body mass index (ß=0.248) and fasting glucose (ß=0.242), next to aortic lumen area (ß=0.340). Carotid intima-media thickness was assessed using ultrasonography, and was only higher in adolescents with coarctation of the aorta, compared with controls (P<0.001). Conclusions Adolescents with chronic disease showed enhanced aortic stiffness and wall thickness compared with controls. The enhanced aortic pulse wave velocity and aortic wall thickness in adolescents with chronic disease could indicate accelerated atherogenesis. Our findings underscore the importance of the aorta for assessment of early atherosclerosis, and the need for tailored cardiovascular follow-up of children with chronic disease.

Validation of time-resolved, automated peak trans-mitral velocity tracking: Two center four-dimensional flow cardiovascular magnetic resonance study.

OBJECTIVE: We aim to validate four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) peak velocity tracking methods for measuring the peak velocity of mitral inflow against Doppler echocardiography. METHOD: Fifty patients were recruited who had 4D flow CMR and Doppler Echocardiography. After transvalvular flow segmentation using established valve tracking methods, peak velocity was automatically derived using three-dimensional streamlines of transvalvular flow. In addition, a static-planar method was used at the tip of mitral valve to mimic Doppler technique. RESULTS: Peak E-wave mitral inflow velocity was comparable between TTE and the novel 4D flow automated dynamic method (0.9 ± 0.5 vs 0.94 ± 0.6 m/s; p = 0.29) however there was a statistically significant difference when compared with the static planar method (0.85 ± 0.5 m/s; p = 0.01). Median A-wave peak velocity was also comparable across TTE and the automated dynamic streamline (0.77 ± 0.4 vs 0.76 ± 0.4 m/s; p = 0.77). A significant difference was seen with the static planar method (0.68 ± 0.5 m/s; p = 0.04). E/A ratio was comparable between TTE and both the automated dynamic and static planar method (1.1 ± 0.7 vs 1.15 ± 0.5 m/s; p = 0.74 and 1.15 ± 0.5 m/s; p = 0.5 respectively). Both novel 4D flow methods showed good correlation with TTE for E-wave (dynamic method; r = 0.70; P < 0.001 and static-planar method; r = 0.67; P < 0.001) and A-wave velocity measurements (dynamic method; r = 0.83; P < 0.001 and static method; r = 0.71; P < 0.001). The automated dynamic method demonstrated excellent intra/inter-observer reproducibility for all parameters. CONCLUSION: Automated dynamic peak velocity tracing method using 4D flow CMR is comparable to Doppler echocardiography for mitral inflow assessment and has excellent reproducibility for clinical use.

Validation of aortic valve pressure gradient quantification using semi-automated 4D flow CMR pipeline.

OBJECTIVE: Doppler echocardiographic aortic valve peak velocity and peak pressure gradient assessment across the aortic valve (AV) is the mainstay for diagnosing aortic stenosis. Four-dimensional flow cardiovascular magnetic resonance (4D flow CMR) is emerging as a valuable diagnostic tool for estimating the peak pressure drop across the aortic valve, but assessment remains cumbersome. We aimed to validate a novel semi-automated pipeline 4D flow CMR method of assessing peak aortic value pressure gradient (AVPG) using the commercially available software solution, CAAS MR Solutions, against invasive angiographic methods. RESULTS: We enrolled 11 patients with severe AS on echocardiography from the EurValve programme. All patients had pre-intervention doppler echocardiography, invasive cardiac catheterisation with peak pressure drop assessment across the AV and 4D flow CMR. The peak AVPG was 51.9 ± 35.2 mmHg using the invasive pressure drop method and 52.2 ± 29.2 mmHg for the 4D flow CMR method (semi-automated pipeline), with good correlation between the two methods (r = 0.70, p = 0.017). Assessment of AVPG by 4D flow CMR using the novel semi-automated pipeline method shows excellent agreement to invasive assessment when compared to doppler-based methods and advocate for its use as complementary to echocardiography.

4D flow cardiovascular magnetic resonance derived energetics in the Fontan circulation correlate with exercise capacity and CMR-derived liver fibrosis/congestion.

AIM: This study explores the relationship between in vivo 4D flow cardiovascular magnetic resonance (CMR) derived blood flow energetics in the total cavopulmonary connection (TCPC), exercise capacity and CMR-derived liver fibrosis/congestion. BACKGROUND: The Fontan circulation, in which both caval veins are directly connected with the pulmonary arteries (i.e. the TCPC) is the palliative approach for single ventricle patients. Blood flow efficiency in the TCPC has been associated with exercise capacity and liver fibrosis using computational fluid dynamic modelling. 4D flow CMR allows for assessment of in vivo blood flow energetics, including kinetic energy (KE) and viscous energy loss rate (EL). METHODS: Fontan patients were prospectively evaluated between 2018 and 2021 using a comprehensive cardiovascular and liver CMR protocol, including 4D flow imaging of the TCPC. Peak oxygen consumption (VO2) was determined using cardiopulmonary exercise testing (CPET). Iron-corrected whole liver T1 (cT1) mapping was performed as a marker of liver fibrosis/congestion. KE and EL in the TCPC were computed from 4D flow CMR and normalized for inflow. Furthermore, blood flow energetics were compared between standardized segments of the TCPC. RESULTS: Sixty-two Fontan patients were included (53% male, 17.3 ± 5.1 years). Maximal effort CPET was obtained in 50 patients (peak VO2 27.1 ± 6.2 ml/kg/min, 56 ± 12% of predicted). Both KE and EL in the entire TCPC (n = 28) were significantly correlated with cT1 (r = 0.50, p = 0.006 and r = 0.39, p = 0.04, respectively), peak VO2 (r = - 0.61, p = 0.003 and r = - 0.54, p = 0.009, respectively) and % predicted peak VO2 (r = - 0.44, p = 0.04 and r = - 0.46, p = 0.03, respectively). Segmental analysis indicated that the most adverse flow energetics were found in the Fontan tunnel and left pulmonary artery. CONCLUSIONS: Adverse 4D flow CMR derived KE and EL in the TCPC correlate with decreased exercise capacity and increased levels of liver fibrosis/congestion. 4D flow CMR is promising as a non-invasive screening tool for identification of patients with adverse TCPC flow efficiency.

Circulating miRNAs and Vascular Injury Markers Associate with Cardiovascular Function in Older Patients Reaching End-Stage Kidney Disease.

The prevalence of end-stage kidney disease (ESKD) is rapidly increasing and mostly occurring in patients aged 65 years or older. The main cause of death in these patients is cardiovascular disease (CVD). Novel markers of vascular integrity may thus be of clinical value for identifying patients at high risk for CVD. Here we associated the levels of selected circulating angiogenic miRNAs, angiopoietin-2 (Ang-2) and asymmetric dimethylarginine (ADMA) with cardiovascular structure and function (as determined by cardiovascular MRI) in 67 older patients reaching ESKD that were included from 'The Cognitive decline in Older Patients with End stage renal disease' (COPE) prospective, multicentered cohort study. We first determined the association between the vascular injury markers and specific heart conditions and observed that ESKD patients with coronary heart disease have significantly higher levels of circulating ADMA and miR-27a. Moreover, circulating levels of miR-27a were higher in patients with atrial fibrillation. In addition, the circulating levels of the vascular injury markers were associated with measures of cardiovascular structure and function obtained from cardiovascular MRI: pulse wave velocity (PWV), ejection fraction (EF) and cardiac index (CI). We found Ang-2 and miR-27a to be strongly correlated to the PWV, while Ang-2 also associated with ejection fraction. Finally, we observed that in contrast to miR-27a, Ang-2 was not associated with a vascular cause of the primary kidney disease, suggesting Ang-2 may be an ESKD-specific marker of vascular injury. Taken together, among older patients with ESKD, aberrant levels of vascular injury markers (miR-27a, Ang-2 and ADMA) associated with impaired cardiovascular function. These markers may serve to identify individuals at higher risk of CVD, as well as give insight into the underlying (vascular) pathophysiology.