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.

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Background and aims: Atherosclerotic plaque onset and progression are known to be affected by local biomechanical factors. While the role of wall shear stress (WSS) has been studied, the impact of another biomechanical factor, namely mechanical wall stress (MWS), remains poorly understood. In this study, we investigated the association of MWS, independently and combined with WSS, towards atherosclerosis in coronary arteries. Methods: Thirty-four human coronary arteries were analyzed using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) and optical coherence tomography (OCT) at baseline and after 12 months. Baseline WSS and MWS were calculated using computational models, and wall thickness (ΔWT) and lipid-rich necrotic core size (ΔLRNC) change were measured in non-calcified coronary segments. The arteries were further divided into 1.5 mm/45° sectors and categorized as plaque-free or plaque sectors. For each category, associations between biomechanical factors (WSS & MWS) and changes in coronary wall (ΔWT & ΔLRNC) were studied using linear mixed models. Results: In plaque-free sectors, higher MWS (p < 0.001) was associated with greater vessel wall growth. Plaque sectors demonstrated wall thickness reduction over time, likely due to medical therapy, where higher levels of WSS and WMS, individually and combined, (p < 0.05) were associated with a greater reduction. Sectors with low MWS combined with high WSS demonstrated the highest LRNC increase (p < 0.01). Conclusions: In this study, we investigated the association of the (largely-overlooked) biomechanical factor MWS with coronary atherosclerosis, individually and combined with WSS. Our results demonstrated that both MWS and WSS significantly correlate with atherosclerotic plaque initiation and development.

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Background: Optimal timing of pulmonary valve replacement (PVR) in Tetralogy of Fallot (TOF) patients remains challenging. Ventricular wall stress is considered to be an early marker of right ventricular (RV) dysfunction.

Objectives: To investigate the association of RV wall stresses and their change over time with functional parameters in TOF patients.

Methods: Ten TOF patients after surgical repair with moderate/severe pulmonary regurgitation were included. At two timepoints (median follow-up time 7.2 years), patient-specific computational biventricular models for wall stress assessment were created using CMR short-axis cine images and echocardiography-based RV pressures. RV ejection fraction (RVEF), NT-proBNP and cardiopulmonary exercise tests were used as outcome measures reflecting RV function. Associations between regional RV diastolic wall stress and RV function were investigated using linear mixed models.

Results: Increased wall stress correlated with lower RV mass (rrm = −0.70, p = 0.017) and lower RV mass-to-volume (rrm = −0.80, p = 0.003) using repeated measures. Wall stress decreased significantly over time, especially in patients with a stable RVEF (p < 0.001). Higher wall stress was independently associated with lower RVEF, adjusted for left ventricular ejection fraction, RV end-diastolic volume and time since initial surgery (decrease of 1.27% RVEF per kPa increase in wall stress, p = 0.029) using repeated measurements. No association was found between wall stress, NT-proBNP, and exercise capacity.

Conclusions: Using a computational method to calculate wall stress locally in geometrically complex ventricles, we demonstrated that lower wall stress might be important to maintain ventricular function. RV wall stress assessment can be used in serial follow-up, and is potentially an early marker of impending RV dysfunction.@en

The role of wall shear stress (WSS) in atherosclerotic plaque development is evident, but the relation between WSS and plaque composition in advanced atherosclerosis, potentially resulting in plaque destabilization, is a topic of discussion. Using our previously developed image registration pipeline, we investigated the relation between two WSS metrics, time-averaged WSS (TAWSS) and the oscillatory shear index (OSI), and the local histologically determined plaque composition in a set of advanced human carotid plaques. Our dataset of 11 carotid endarterectomy samples yielded 87 histological cross-sections, which yielded 511 radial bins for analysis. Both TAWSS and OSI values were subdivided into patient-specific low, mid, and high tertiles. This cross-sectional study shows that necrotic core (NC) size and macrophage area are significantly larger in areas exposed to high TAWSS or low OSI. Local TAWSS and OSI tertile values were generally inversely related, as described in the literature, but other combinations were also found. Investigating the relation between plaque vulnerability features and different combinations of TAWSS and OSI tertile values revealed a significantly larger cap thickness in areas exposed to both low TAWSS and low OSI. In conclusion, our study confirmed previous findings, correlating high TAWSS to larger macrophage areas and necrotic core sizes. In addition, our study demonstrated new relations, correlating low OSI to larger macrophage areas, and a combination of low TAWSS and low OSI to larger cap thickness.

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Optical imaging techniques that provide free space, label free imaging are powerful tools in obtaining structural and biochemical information in biological samples. To date, most of the optical imaging technologies create images with a specific contrast and require multimodality integration to add additional contrast. In this study, we demonstrate spectroscopic Thermo-elastic Optical Coherence Tomography (TE-OCT) as a potential tool in tissue identification. TE-OCT creates images based on two different forms of contrast: optical reflectance and thermo-elastic deformation. TE-OCT uses short laser pulses to induce thermo-elastic tissue deformation and measures the resulting surface displacement using phase-sensitive OCT. In this work we characterized the relation between thermo-elastic displacement and optical absorption, excitation, fluence and illumination area. The experimental results were validated with a 2-dimensional analytical model. Using spectroscopic TE-OCT, the thermo-elastic spectra of elastic phantoms and tissue components in coronary arteries were extracted. Specific tissue components, particularly lipid, an important biomarker for identifying atherosclerotic lesions, can be identified in the TE-OCT spectral response. As a label-free, free-space, dual-contrast, all-optical imaging technique, spectroscopic TE-OCT holds promise for biomedical research and clinical pathology diagnosis.

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Coronary calcification represents a challenge in the treatment of coronary artery disease by stent placement. It negatively affects stent expansion and has been related to future adverse cardiac events. Intravascular ultrasound (IVUS) is known for its high sensitivity in detecting coronary calcification. At present, automated quantification of calcium as detected by IVUS is not available. For this reason, we developed and validated an optimized framework for accurate automated detection and quantification of calcified plaque in coronary atherosclerosis as seen by IVUS. Calcified lesions were detected by training a supported vector classifier per IVUS A-line on manually annotated IVUS images, followed by post-processing using regional information. We applied our framework to 35 IVUS pullbacks from each of the three commonly used IVUS systems. Cross-validation accuracy for each system was >0.9, and the testing accuracy was 0.87, 0.89 and 0.89 for the three systems. Using the detection result, we propose an IVUS calcium score, based on the fraction of calcium-positive A-lines in a pullback segment, to quantify the extent of calcified plaque. The high accuracy of the proposed classifier suggests that it may provide a robust and accurate tool to assess the presence and amount of coronary calcification and, thus, may play a role in image-guided coronary interventions.

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Background: Stress calculations in atherosclerotic coronary vulnerable plaques can aid in predicting coronary cap rupture. In vivo plaque geometry and composition of coronary arteries can merely be obtained via intravascular imaging. Only optical driven imaging techniques have sufficient resolution to visualize the fibrous cap, but due to limited penetration depth deeper components such as the backside of the necrotic core (NC) are generally not visible. The goal of this study was to investigate whether peak cap stresses can be approximated by reconstructing the backside of the NC. Methods: Manual segmentations of coronary histological cross-sections served as a geometrical ground truth and were obtained from seven patients resulting in 73 NCs. Next, the backside was removed and reconstructed according to an estimation of the relative necrotic core thickness (rNCt). The rNCt was estimated at three locations along the NC angle and based on either group averaged parameters or plaque specific parameters. Stress calculations were performed in both the ground truth geometry and the reconstructed geometries and compared. Results: Good geometrical agreement was found between the ground truth NC and the reconstructed NCs, based on group averaged rNCt estimation and plaque specific rNCt estimation, measuring the NC area difference (25.1 % IQR 14.0-41.3 % and 17.9 % IQR 9.81-32.7 %) and similarity index (0.85 IQR 0.77-0.90 and 0.88 IQR 0.79-0.91). The peak cap stresses obtained with both reconstruction methods showed a high correlation with respect to the ground truth, r² = 0.91 and r² = 0.95, respectively. For high stress plaques, the peak cap stress difference with respect to the ground truth significantly improved for the NC reconstruction based plaque specific features (6 %) compared to the reconstruction group averaged based (16 %). Conclusions: In conclusion, good geometry and stress agreement was observed between the ground truth NC geometry and the reconstructed geometries. Although group averaged rNCt estimation seemed to be sufficient for the NC reconstruction and stress calculations, including plaque specific data further improved stress predictions, especially for higher stresses.

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Background and aims In a large stroke-free population, we sought to identify cardiovascular risk factors and carotid plaque components associated with carotid plaque burden, lumen volume and stenosis. Methods The carotid arteries of 1562 stroke-free participants from The Rotterdam Study were imaged on a 1.5-Tesla MRI scanner. Inner and outer wall of the carotid arteries were automatically segmented and lumen volume (mm³), wall volume (outer wall–inner wall) and plaque burden (wall volume/outer wall volume) (%) were quantified. Plaque components were visually determined and luminal stenosis was assessed. We analyzed associations of cardiovascular risk factors and carotid plaque components with plaque burden and lumen volumes using regression analysis. Results We investigated 2821 carotid plaques and found that women had larger plaque burden (50.7 ± 7.8% vs. 49.2 ± 7.7%, p <0.0001) and smaller lumen volumes (933 ± 286 mm³ vs. 1078 ± 334 mm³, p <0.0001) than men. In women, age, HDL-cholesterol and systolic blood pressure, and in men, total cholesterol, non-HDL cholesterol and statin use were independently associated with higher plaque burden and lumen volume. Furthermore, smoking and diabetes were associated with lumen volume in men (respectively p = 0.04 and p = 0.002). Intraplaque hemorrhage (IPH) and lipid were related to a larger plaque burden (OR 1.30 [1.05–1.60] and OR 1.28[1.06–1.55]). Finally, within the highest quartile of plaque burden, IPH was strongly associated with luminal stenosis independent of age, sex, plaque burden and composition (Beta = 15.2; [11.8–18.6]). Conclusions Several cardiovascular risk factors and plaque components, in particular IPH, are associated with higher plaque burden. Carotid IPH is strongly associated with an increased luminal stenosis.

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