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Background and Objective: Dysfunction of the right ventricular outflow tract (RVOT) is a common long-term complication following surgical repair in patients with congenital heart disease. Transcatheter pulmonary valve implantation (TPVI) offers a viable alternative to surgical pulmonary valve replacement (SPVR) for treating pulmonary regurgitation but not all RVOT anatomies are suitable for TPVI. To identify a suitable landing zone (LZ) for TPVI, three-dimensional multiphase (4D) computed tomography (CT) is used to evaluate the size, shape, and dynamic behavior of the RVOT throughout the cardiac cycle. However, manually extracting measurements from multiplanar CT reformats is operator-dependent and time-consuming. Leveraging an optical-flow (OF) algorithm, we proposed a novel semi-automated pipeline for dynamic and comprehensive geometrical analysis of the RVOT anatomy., Methods: Upon 4D-CT availability, at a pre-defined reference time-point, the patient-specific anatomy is semi-automatically segmented to generate the corresponding three-dimensional surface, which is navigated through a graphical user interface to define the mid-section of the potential LZ. Based on the axial length of the intended device, the proximal and distal LZ cross-sections are automatically identified. An OF-based algorithm is used to track the three LZ cross-sections frame by frame throughout the cardiac cycle, taking RVOT out-of-plane motion into account to update RVOT contours on each cross-section and to elaborate LZ geometrical changes. Finally, LZ time-dependent geometrical features are quantified and extracted., Results: The pipeline was successfully applied to a retrospective cohort of patients, with OF-based tracking reporting excellent agreement (r 2 = 0.99) compared to manual processing, with a bias < 1% for both LZ area and perimeter, while also significantly improving time efficiency. CT-derived measurements extracted from LZ mid-section were the most influential covariates affecting the likelihood of TPVI feasibility. Among these, the minimum perimeter outperformed all other geometric LZ parameters in classifying patients as suitable for either TPVI or SPVR and achieved the highest area under the curve of 0.99, with accuracy and precision of 0.93 and 0.92, respectively., Conclusions: Dynamic OF-based quantification of key RVOT geometric parameters can enhance and expedite the selection process for TPVI candidates and guide optimal valve sizing during TPVI planning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To assess whether ascending aorta over-angulation, a morphological feature recently found to be associated with acute type A aortic dissection, precedes dissection and how it affects wall stress distribution., Methods: A baseline finite element model, previously created by a neural network tool from end-diastolic CTA measurements in 124 healthy subjects, was modified to simulate the over-angulation accompanying aortic elongation, obtaining paradigmatic models with different ascending angulations (ascending-arch angle 145°-110°). The models were discretized and embedded in a deformable continuum representing surrounding tissues, aortic wall anisotropy and nonlinearity were accounted for, pre-tensioning at diastolic pressures was applied and peak systolic stresses were computed. Then, from 15 patients' pre-dissection geometries, patient-specific finite element models of pre-dissection aorta were created through the same framework. The sites of maximum longitudinal stress were compared with the respective sites of dissection entry tear in post-dissection imaging., Results: Paradigmatic models showed that progressive narrowing of the ascending-arch angle was associated with increasing longitudinal stress (becoming significant for angles <130°), whereas the impact on circumferential stress was less consistent. In pre-dissection patient-specific models, the ascending-arch angle was narrowed (113°±11°) and the region of peak longitudinal stresses corresponded to the entry tear location in the respective post-dissection CTA., Conclusions: This study strongly supports the hypothesis that the ascending-arch angle, as quantifier of aorta over-angulation, can be a good predictor of aortic dissection, since its narrowing below 130° increases longitudinal wall stress, and the dissection entry tears develop in the aortic wall in areas of highest longitudinal stress., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Performing automatic and standardized 4D TEE segmentation and mitral valve analysis is challenging due to the limitations of echocardiography and the scarcity of manually annotated 4D images. This work proposes a semi-supervised training strategy using pseudo labelling for MV segmentation in 4D TEE; it employs a Teacher-Student framework to ensure reliable pseudo-label generation. 120 4D TEE recordings from 60 candidates for MV repair are used. The Teacher model, an ensemble of three convolutional neural networks, is trained on end-systole and end-diastole frames and is used to generate MV pseudo-segmentations on intermediate frames of the cardiac cycle. The pseudo-annotated frames augment the Student model's training set, improving segmentation accuracy and temporal consistency. The Student outperforms individual Teachers, achieving a Dice score of 0.82, an average surface distance of 0.37 mm, and a 95% Hausdorff distance of 1.72 mm for MV leaflets. The Student model demonstrates reliable frame-by-frame MV segmentation, accurately capturing leaflet morphology and dynamics throughout the cardiac cycle, with a significant reduction in inference time compared to the ensemble. This approach greatly reduces manual annotation workload and ensures reliable, repeatable, and time-efficient MV analysis. Our method holds strong potential to enhance the precision and efficiency of MV diagnostics and treatment planning in clinical settings., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s).)

Diastolic vortex ring (VR) plays a key role in the blood-pumping function exerted by the left ventricle (LV), with altered VR structures being associated with LV dysfunction. Herein, we sought to characterize the VR diastolic alterations in ischemic cardiomyopathy (ICM) patients with systo-diastolic LV dysfunction, as compared to healthy controls, in order to provide a more comprehensive understanding of LV diastolic function. 4D Flow MRI data were acquired in ICM patients (n = 15) and healthy controls (n = 15). The λ 2 method was used to extract VRs during early and late diastolic filling. Geometrical VR features, e.g., circularity index (CI), orientation (α), and inclination with respect to the LV outflow tract (ß), were extracted. Kinetic energy (KE), rate of viscous energy loss ( EL ˙ ), vorticity (W), and volume (V) were computed for each VR; the ratios with the respective quantities computed for the entire LV were derived. At peak E-wave, the VR was less circular (p = 0.032), formed a smaller α with the LV long-axis (p = 0.003) and a greater ß (p = 0.002) in ICM patients as compared to controls. At peak A-wave, CI was significantly increased (p = 0.034), while α was significantly smaller (p = 0.016) and β was significantly increased (p = 0.036) in ICM as compared to controls. At both peak E-wave and peak A-wave, EL ˙ VR / EL ˙ LV , W VR /W LV , and V VR /V LV significantly decreased in ICM patients vs. healthy controls. KE VR /V VR showed a significant decrease in ICM patients with respect to controls at peak E-wave, while V VR remained comparable between normal and pathologic conditions. In the analyzed ICM patients, the diastolic VRs showed alterations in terms of geometry and energetics. These derangements might be attributed to both structural and functional alterations affecting the infarcted wall region and the remote myocardium., Competing Interests: Declarations Ethics approval and consent to participate All participants provided written informed consent, and the study complies with the Helsinki Declaration. Consent for publication Not applicable. Competing interests Daniel Giese is an employee of Siemens Healthineers; all the other authors have no potential conflict of interest related to the contents of the manuscript., (© 2024. International Federation for Medical and Biological Engineering.)

Background: Aortic-valve-stenosis (AS) is a frequent degenerative valvular-disease and carries dismal outcome under-medical-treatment. Transvalvular pressure gradient reflects severity of the valve-disease but is highly dependent on flow-conditions and on other valvular/aortic characteristics. Alternatively, aortic-valve-area (AVA) represents a measure of aortic-valve lesion severity conceptually essential and practically widely-recognized but exhibits multiple-limitations., Methods: We analyzed the 4D multi-detector computed tomography(MDCT) of 20 randomly selected patients with severe AS. For each-patient, we generated the 3D-model of the valve and of its calcifications, and we computed the anatomical AVA accounting for the 3D-morphology of the leaflets in three-different-ways. Finally, we compared our results vs. Doppler-based AVA E measurements and vs. 2D-planimetric AVA-measurements., Results: 3D-reconstruction and identification of the cusps were successful in 90% of the cases. The calcification patterns where highly-variable over patients, ranging from multiple small deposits to wide and c-shaped deposits running from commissure-to-commissure. AVA E was 82 ± 15 mm 2 . When segmenting 18 image planes, AVA Tight , AVA Proj-Ann , AVA Proj-Tip and their average AVA Ave were equal to 80 ± 16, 88 ± 20, 93 ± 21 and 87 ± 19 mm 2 , respectively, while AVA Plan was equal to 143 ± 50 mm 2 . Linear-regression of the three measurements vs. AVA E yielded regression slopes equal to 1.26, 1.13 and 0.93 for AVA Proj-Ann , AVA Proj-Tip and AVA Tight , respectively. The respective Pearson-coefficients were 0.85,0.86 and 0.90. Conversely, when comparing AVA Plan vs. AVA E , linear regression yielded a slope of 1.73 and a Pearson coefficient of 0.53., Conclusions: We described a new-method to obtain a set of flow-independent quantifications that complement pressure gradient measurements and combine the advantages of previously proposed methods, while bypassing the corresponding-limitations., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

In transcatheter aortic valve implantation (TAVI), final device position may be affected by device interaction with the whole aortic landing zone (LZ) extending to ascending aorta. We investigated the impact of aortic LZ curvature and angulation on TAVI implantation depth, comparing short-frame balloon-expanding (BE) and long-frame self-expanding (SE) devices. Patients (n = 202) treated with BE or SE devices were matched based on one-to-one propensity score. Primary endpoint was the mismatch between the intended (H Pre ) and the final (H Post ) implantation depth. LZ curvature and angulation were calculated based on the aortic centerline trajectory available from pre-TAVI computed tomography. Total LZ curvature ( k L Z , t o t ) and LZ angulation distal to aortic annulus ( α L Z , D i s t a l ) were greater in the SE compared to the BE group (P < 0.001 for both). In the BE group, H Post was significantly higher than H Pre at both cusps (P < 0.001). In the SE group, H Post was significantly deeper than H Pre only at the left coronary cusp (P = 0.013). At multivariate analysis, α L Z , D i s t a l was the only independent predictor (OR = 1.11, P = 0.002) of deeper final implantation depth with a cut-off value of 17.8°. Aortic LZ curvature and angulation significantly affected final TAVI implantation depth, especially in high stent-frame SE devices reporting, upon complete release, deeper implantation depth with respect to the intended one., (© 2024. The Author(s).)

Purpose: Intracardiac transcatheter interventions allow for reducing trauma and hospitalization stays as compared to standard surgery. In the treatment of mitral regurgitation, the most widely adopted transcatheter approach consists in deploying a clip on the mitral valve leaflets by means of a catheter that is run through veins from a peripheral access to the left atrium. However, precise manipulation of the catheter from outside the body while copying with the path constraints imposed by the vessels remains challenging., Methods: We proposed a path tracking control framework that provides adequate motion commands to the robotic steerable catheter for autonomous navigation through vascular lumens. The proposed work implements a catheter kinematic model featuring nonholonomic constraints. Relying on the real-time measurements from an electromagnetic sensor and a fiber Bragg grating sensor, a two-level feedback controller was designed to control the catheter., Results: The proposed method was tested in a patient-specific vessel phantom. A median position error between the center line of the vessel and the catheter tip trajectory was found to be below 2 mm, with a maximum error below 3 mm. Statistical testing confirmed that the performance of the proposed method exhibited no significant difference in both free space and the contact region., Conclusion: The preliminary in vitro studies presented in this paper showed promising accuracy in navigating the catheter within the vessel. The proposed approach enables autonomous control of a steerable catheter for transcatheter cardiology interventions without the request of calibrating the intuitive parameters or acquiring a training dataset., (© 2024. The Author(s).)

Purpose: Displacement forces ( DF s) identify hostile landing zones for stent graft deployment in thoracic endovascular aortic repair (TEVAR). However, their use in TEVAR planning is hampered by the need for time-expensive computational fluid dynamics (CFD). We propose a novel fast-approximate computation of DF s merely exploiting aortic arch anatomy, as derived from the computed tomography (CT) and a measure of central aortic pressure., Materials and Methods: We tested the fast-approximate approach against CFD gold-standard in 34 subjects with the "bovine" aortic arch variant. For each dataset, a 3-dimensional (3D) model of the aortic arch lumen was reconstructed from computed tomography angiography and CFD then employed to compute DF s within the aortic proximal landing zones. To quantify fast-approximate DF s, the wall shear stress contribution to the DF was neglected and blood pressure space-distribution was averaged on the entire aortic wall to reliably approximate the patient-specific central blood pressure. Also, DF values were normalized on the corresponding proximal landing zone area to obtain the equivalent surface traction ( EST )., Results: Fast-approximate approach consistently reflected (r 2 =0.99, p<0.0001) the DF pattern obtained by CFD, with a -1.1% and 0.7° bias in DF s magnitude and orientation, respectively. The normalized EST progressively increased (p<0.0001) from zone 0 to zone 3 regardless of the type of arch, with proximal landing zone 3 showing significantly greater forces than zone 2 (p<0.0001). Upon DF normalization to the corresponding aortic surface, fast-approximate EST was decoupled in blood pressure and a dimensionless shape vector (S) reflecting aortic arch morphology. S showed a zone-specific pattern of orientation and proved a valid biomechanical blueprint of DF impact on the thoracic aortic wall., Conclusion: Requiring only a few seconds and quantifying clinically relevant biomechanical parameters of proximal landing zones for arch TEVAR, our method suits the real preoperative decision-making process. It paves the way toward analyzing large population of patients and hence to define threshold values for a future patient-specific preoperative TEVAR planning.

Accurate planning of transcatheter aortic valve implantation (TAVI) is important to minimize complications, and it requires anatomic evaluation of the aortic root (AR), commonly performed through 3D computed tomography (CT) image analysis. Currently, there is no standard automated solution for this process. Two convolutional neural networks with 3D U-Net architectures (model 1 and model 2) were trained on 310 CT scans for AR analysis. Model 1 performs AR segmentation and model 2 identifies the aortic annulus and sinotubular junction (STJ) contours. After training, the two models were integrated into a fully automated pipeline for geometric analysis of the AR. Results were validated against manual measurements of 178 TAVI candidates. The trained CNNs segmented the AR, annulus, and STJ effectively, resulting in mean Dice scores of 0.93 for the AR, and mean surface distances of 0.73 mm and 0.99 mm for the annulus and STJ, respectively. Automatic measurements were in good agreement with manual annotations, yielding annulus diameters that differed by 0.52 [-2.96, 4.00] mm (bias and 95% limits of agreement for manual minus algorithm). Evaluating the area-derived diameter, bias, and limits of agreement were 0.07 [-0.25, 0.39] mm. STJ and sinuses diameters computed by the automatic method yielded differences of 0.16 [-2.03, 2.34] and 0.1 [-2.93, 3.13] mm, respectively. The proposed tool is a fully automatic solution to quantify morphological biomarkers for pre-TAVI planning. The method was validated against manual annotation from clinical experts and showed to be quick and effective in assessing AR anatomy, with potential for time and cost savings., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background and Objective: Numerical simulations of blood flow are a valuable tool to investigate the pathophysiology of ascending thoratic aortic aneurysms (ATAA). To accurately reproduce in vivo hemodynamics, computational fluid dynamics (CFD) models must employ realistic inflow boundary conditions (BCs). However, the limited availability of in vivo velocity measurements, still makes researchers resort to idealized BCs. The aim of this study was to generate and thoroughly characterize a large dataset of synthetic 4D aortic velocity profiles sampled on a 2D cross-section along the ascending aorta with features similar to clinical cohorts of patients with ATAA., Methods: Time-resolved 3D phase contrast magnetic resonance (4D flow MRI) scans of 30 subjects with ATAA were processed through in-house code to extract anatomically consistent cross-sectional planes along the ascending aorta, ensuring spatial alignment among all planes and interpolating all velocity fields to a reference configuration. Velocity profiles of the clinical cohort were extensively characterized by computing flow morphology descriptors of both spatial and temporal features. By exploiting principal component analysis (PCA), a statistical shape model (SSM) of 4D aortic velocity profiles was built and a dataset of 437 synthetic cases with realistic properties was generated., Results: Comparison between clinical and synthetic datasets showed that the synthetic data presented similar characteristics as the clinical population in terms of key morphological parameters. The average velocity profile qualitatively resembled a parabolic-shaped profile, but was quantitatively characterized by more complex flow patterns which an idealized profile would not replicate. Statistically significant correlations were found between PCA principal modes of variation and flow descriptors., Conclusions: We built a data-driven generative model of 4D aortic inlet velocity profiles, suitable to be used in computational studies of blood flow. The proposed software system also allows to map any of the generated velocity profiles to the inlet plane of any virtual subject given its coordinate set., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: The study objective was to elucidate the mechanisms of left ventricle functional recovery in terms of endocardial contractility and synchronicity after surgical ventricular reconstruction., Methods: Real-time 3-dimensional transthoracic echocardiography was performed on 20 patients with anterior left ventricle remodeling and ischemic heart failure before surgical ventricular reconstruction and at 6-month follow-up, and on 15 healthy controls matched by age and body surface area. Real-time 3-dimensional transthoracic echocardiography datasets were analyzed through TomTec software (4D LV-Analysis; TomTec Imaging Systems GmbH, Unterschleissheim, Germany): Left ventricle volumes, ejection fraction, and global longitudinal strain were computed; the time-dependent endocardial surface yielded by 3-dimensional speckle-tracking echocardiography was postprocessed through in-house software to quantify local systolic minimum principal strain as a measure of fiber shortening and mechanical dispersion as a measure of fiber synchronicity., Results: Compared with controls, patients with heart failure before surgical ventricular reconstruction showed lower ejection fraction (P < .0001) and significantly impaired mechanical dispersion (P < .0001) and minimum principal strain (P < .0001); the latter worsened progressively from left ventricle base to apex. After surgical ventricular reconstruction, global longitudinal strain improved from -6.7% to -11.3% (P < .0001); mechanical dispersion decreased in every left ventricle region (P ≤ .017) and mostly in the basal region, where computed mechanical dispersion values were comparable to physiologic values (P ≥ .046); minimum principal strain improved mostly in the basal region, changing from -16.6% to -22.3% (P = .0027)., Conclusions: At 6-month follow-up, surgical ventricular reconstruction was associated with significant recovery in global left ventricle function, improved mechanical dispersion indicating a more synchronous left ventricle contraction, and improved left ventricle fiber shortening mostly in the basal region, suggesting the major role of the remote myocardium in enhancing left ventricle functional recovery., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

The total kinetic energy (KE) of blood can be decomposed into mean KE (MKE) and turbulent KE (TKE), which are associated with the phase-averaged fluid velocity field and the instantaneous velocity fluctuations, respectively. The aim of this study was to explore the effects of pharmacologically induced stress on MKE and TKE in the left ventricle (LV) in a cohort of healthy volunteers. 4D Flow MRI data were acquired in eleven subjects at rest and after dobutamine infusion, at a heart rate that was ∼60% higher than the one in rest conditions. MKE and TKE were computed as volume integrals over the whole LV and as data mapped to functional LV flow components, i.e., direct flow, retained inflow, delayed ejection flow and residual volume. Diastolic MKE and TKE increased under stress, in particular at peak early filling and peak atrial contraction. Augmented LV inotropy and cardiac frequency also caused an increase in direct flow and retained inflow MKE and TKE. However, the TKE/KE ratio remained comparable between rest and stress conditions, suggesting that LV intracavitary fluid dynamics can adapt to stress conditions without altering the TKE to KE balance of the normal left ventricle at rest., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Riva, Eriksson, Viola, Sturla, Votta, Ebbers, Carlhäll and Dyverfeldt.)

An 8-year-old girl, diagnosed with mid-aortic syndrome (MAS) at the age of 2 months and under antihypertensive therapy, presented with severe systemic hypertension (>200/120 mmHg). Computed tomography (CT) examination revealed aortic aneurysm between severe stenoses at pre- and infra-renal segments, and occlusion of principal splanchnic arteries with peripheral collateral revascularization. Based on CT imaging, preoperative three-dimensional (3D) anatomy was reconstructed to assess aortic dimensions and a dedicated in vitro planning platform was designed to investigate the feasibility of a stenting procedure under fluoroscopic guidance. The in vitro system was designed to incorporate a translucent flexible 3D-printed patient-specific model filled with saline. A covered 8-zig 45-mm-long Cheatham-Platinum (CP) stent and a bare 8-zig, 34-mm-long CP stent were implanted with partial overlap to treat the stenoses (global peak-to-peak pressure gradient > 60 mmHg), excluding the aneurysm and avoiding risk of renal arteries occlusion. Percutaneous procedure was successfully performed with no residual pressure gradient and exactly replicating the strategy tested in vitro . Also, as investigated on the 3D-printed model, additional angioplasty was feasible across the frames of the stent to improve bilateral renal flow. Postoperative systemic pressure significantly reduced (130/70 mmHg) as well as dosage of antihypertensive therapy. This is the first report demonstrating the use of a 3D-printed model to effectively plan percutaneous intervention in a complex pediatric MAS case: taking full advantage of the combined use of a patient-specific 3D model and a dedicated in vitro platform, feasibility of the stenting procedure was successfully tested during pre-procedural assessment. Hence, use of patient-specific 3D-printed models and in vitro dedicated platforms is encouraged to assist pre-procedural planning and personalize treatment, thus enhancing intervention success., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Giugno, Formato, Chessa, Votta, Carminati and Sturla.)

Background: Time-resolved three-directional velocity-encoded (4D flow) magnetic resonance imaging (MRI) enables the quantification of left ventricular (LV) intracavitary fluid dynamics and energetics, providing mechanistic insight into LV dysfunctions. Before becoming a support to diagnosis and patient stratification, this analysis should prove capable of discriminating between clearly different LV derangements., Purpose: To investigate the potential of 4D flow in identifying fluid dynamic and energetics derangements in ischemic and restrictive LV cardiomyopathies., Study Type: Prospective observational study., Population: Ten patients with post-ischemic cardiomyopathy (ICM), 10 patients with cardiac light-chain cardiac amyloidosis (AL-CA), and 10 healthy controls were included., Field Strength/sequence: 1.5 T/balanced steady-state free precession cine and 4D flow sequences., Assessment: Flow was divided into four components: direct flow (DF), retained inflow, delayed ejection flow, and residual volume (RV). Demographics, LV morphology, flow components, global and regional energetics (volume-normalized kinetic energy [KE V ] and viscous energy loss [EL V ]), and pressure-derived hemodynamic force (HDF) were compared between the three groups., Statistical Tests: Intergroup differences in flow components were tested by one-way analysis of variance (ANOVA); differences in energetic variables and peak HDF were tested by two-way ANOVA. A P-value of <0.05 was considered significant., Results: ICM patients exhibited the following statistically significant alterations vs. controls: reduced KE V , mostly in the basal region, in systole (-44%) and in diastole (-37%); altered flow components, with reduced DF (-33%) and increased RV (+26%); and reduced basal-apical HDF component on average by 63% at peak systole. AL-CA patients exhibited the following alterations vs. controls: significantly reduced KE V at the E-wave peak in the basal segment (-34%); albeit nonstatistically significant, increased peaks and altered time-course of the HDF basal-apical component in diastole and slightly reduced HDF components in systole., Data Conclusion: The analysis of multiple 4D flow-derived parameters highlighted fluid dynamic alterations associated with systolic and diastolic dysfunctions in ICM and AL-CA patients, respectively., Level of Evidence: 2 TECHNICAL EFFICACY STAGE: 3., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Left atrial (LA) function can be effectively assessed by measuring longitudinal LA strain (LAS) via two-dimensional speckle tracking echocardiography (2DSTE). Here, we test 2DSTE-based LAS as marker of different left ventricle (LV) remodeling patterns and as prognostic index in ischemic heart failure (HF) candidates to surgical ventricular reconstruction., Methods: We retrospectively considered ischemic HF patients with anterior (group A, n=130) or posterior (group P, n=48) LV remodeling. Based on 2D ultrasound, LV and LA morpho-functional parameters were quantified including reservoir (LAS Res ), conduit (LAS Cond ) and booster (LAS Boost ) LAS. We tested their capability to discriminate between groups A and P, and their group-specific prognostic significance for the composite end-point of death or HF re-hospitalization at follow-up (mean follow-up time=40 months, range 3-101 months)., Results: Group A and group P displayed similar end-diastolic (p=0.89) and end-systolic (p=0.33) LV volume index, and LA volume index LAVi (p=0.44) corrected for the degree of mitral regurgitation. As compared to group P, group A revealed a significant reduction in LAS Boost (9.2±0.4% vs. 11.1±0.7%, p=0.04) and a non-significant reduction in LAS Res (16.9±0.7% vs. 19.3±1.1%, p=0.06). Kaplan-Meier curves showed that the median LAS Res and LAS Boost values effectively stratified patients based on their prognosis in the overall study population (Log-rank p=0.002 and Log&#95;rank p<0.0001) and in group A, where the association was stronger for LAS Boost (Log-rank p<0.001) than for LAS Res (Log-rank p=0.013)., Conclusions: 2DSTE-based LAS assessment is affordable, repeatable and non-invasive, and could add clinically-relevant mechanistic insight and prognostic value in the stratification of ischemic HF patients., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Congenital heart disease (CHD) is often comprised of complex three-dimensional (3D) anatomy that must be well understood to assess the pathophysiological consequences and guide therapy. Thus, detailed cardiac imaging for early detection and planning of interventional and/or surgical treatment is paramount. Advanced technologies have revolutionized diagnostic and therapeutic practice in CHD, thus playing an increasing role in its management. Traditional reliance on standard imaging modalities including echocardiography, cardiac computed tomography (CT) and magnetic resonance imaging (MRI) has been augmented by the use of recent technologies such as 3D printing, virtual reality, augmented reality, computational modelling, and artificial intelligence because of insufficient information available with these standard imaging techniques. This has created potential opportunities of incorporating these technologies into routine clinical practice to achieve the best outcomes through delivery of personalized medicine. In this review, we provide an overview of these evolving technologies and a new approach enabling physicians to better understand their real-world application in adult CHD as a prelude to clinical workflow implementation., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Performance and durability of arterio-venous grafts depend on their ability to mimic the mechanical behavior of the anastomized blood vessels. To select the most suitable synthetic graft, in vivo evaluation of the radial deformability of peripheral arteries and veins could be crucial; however, a standardized non-invasive strategy is still missing. Herein, we sought to define a novel and user-friendly clinical protocol for in vivo assessment of the arm vessel deformability., Methods: A dedicated protocol, applied on 30 volunteers, was specifically designed to estimate both compliance and distensibility of the brachial and radial arteries, and of the basilic and cephalic veins. Bi-dimensional ultrasound imaging was used to acquire cross-sectional areas (CSAs) of arteries in clinostatic configuration, and CSAs of veins combining clinostatic and orthostatic configurations. Arterial pulse pressure was measured with a digital sphygmomanometer, while venous hydrostatic pressure was derived from the arm length in orthostatic configuration., Results: For each participant, all CSAs were successfully extracted from ultrasound images. The basilic vein and the radial artery exhibited the largest (21.5±8.9 mm 2 ) and the smallest (3.4±1.0 mm 2 ) CSAs, respectively; CSA measurements were highly repeatable (Bland-Altman bias <10% and Pearson correlation ≥0.90, for both arteries and veins). In veins, compliance and distensibility were higher than in arteries; compliance was significantly higher (P<0.0001) in the brachial than in the radial artery (3.52×10 -4 vs. 1.3×10 -4 cm 2 /mmHg); it was three times larger in basilic veins than in cephalic veins (17.4×10 -4 vs. 5.6×10 -4 cm 2 /mmHg, P<0.0001)., Conclusions: The proposed non-invasive protocol proved feasible, effective and adequate for daily clinical practice, allowing for the estimation of patient-specific compliance and distensibility of peripheral arteries and veins. If further extended, it may contribute to the fabrication of biohybrid arterio-venous grafts, paving the way towards patient-tailored solutions for vascular access., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-21-987/coif). AC is employed at Bioengineering Laboratories Srl, which is partner of the SILKELASTOGRAFT project and major shareholder of Dialybrid Srl. SC and SAR are employed at Dialybrid Srl; SAR is co-inventor of patents concerning vascular grafts. The other authors have no conflicts of interest to declare., (2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Feasibility assessment and planning of thoracic endovascular aortic repair (TEVAR) require computed tomography (CT)-based analysis of geometric aortic features to identify adequate landing zones (LZs) for endograft deployment. However, no consensus exists on how to take the necessary measurements from CT image data. We trained and applied a fully automated pipeline embedding a convolutional neural network (CNN), which feeds on 3D CT images to automatically segment the thoracic aorta, detects proximal landing zones (PLZs), and quantifies geometric features that are relevant for TEVAR planning. For 465 CT scans, the thoracic aorta and pulmonary arteries were manually segmented; 395 randomly selected scans with the corresponding ground truth segmentations were used to train a CNN with a 3D U-Net architecture. The remaining 70 scans were used for testing. The trained CNN was embedded within computational geometry processing pipeline which provides aortic metrics of interest for TEVAR planning. The resulting metrics included aortic arch centerline radius of curvature, proximal landing zones (PLZs) maximum diameters, angulation, and tortuosity. These parameters were statistically analyzed to compare standard arches vs. arches with a common origin of the innominate and left carotid artery (CILCA). The trained CNN yielded a mean Dice score of 0.95 and was able to generalize to 9 pathological cases of thoracic aortic aneurysm, providing accurate segmentations. CILCA arches were characterized by significantly greater angulation (p = 0.015) and tortuosity (p = 0.048) in PLZ 3 vs. standard arches. For both arch configurations, comparisons among PLZs revealed statistically significant differences in maximum zone diameters (p < 0.0001), angulation (p < 0.0001), and tortuosity (p < 0.0001). Our tool allows clinicians to obtain objective and repeatable PLZs mapping, and a range of automatically derived complex aortic metrics., (© 2022. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Background and Aims: Opioid analgesic use is associated with increased mortality, higher readmission rates, and reduced quality of life among patients with inflammatory bowel disease (IBD). With the goal of reducing inpatient opioid use among patients with IBD admitted to our inpatient gastroenterology (GI) service, we designed and implemented a standardized, educational intervention providing analgesic decision support to internal medicine and emergency medicine housestaff at our institution., Methods: Pre-intervention data was collected from patients admitted during a 9-month period prior to intervention. Post-intervention patients were identified prospectively. The primary outcome was reduction in aggregate inpatient opioid use in oral morphine equivalents per patient., Results: A total of 68 patients with 81 hospitalizations were analyzed. There was no statistically significant difference in baseline admission characteristics between the two groups. Our primary outcome was achieved with a statistically significant reduction in opioid use during hospitalization (43.4 mg vs 7.7 mg; p < 0.01). Secondary outcomes achieved included reduction in new opioid prescriptions upon discharge, reduced hospital length of stay, and reduced 90-day readmission rates. There was no significant difference between patients' pain scores between the two groups., Conclusion: We believe this intervention, aimed at housestaff education, provides a roadmap for pain management decision-making in this patient population. It is a readily reproducible strategy that can be widely applied to improve inpatient IBD patient care. Importantly, patient experience and pain scores were unchanged despite lower use of inpatient opioid analgesia, highlighting successful opioid-sparing analgesics in most inpatients with IBD.

Transcatheter therapies are emerging for functional mitral regurgitation (FMR) treatment, however there is lack of pathological models for their preclinical assessment. We investigated the applicability of deer hearts for this purpose.8 whole deer hearts were housed in a pulsatile flow bench. At baseline, all mitral valves featured normal coaptation. The pathological state was induced by 60-minutes intraventricular constant pressurization. It caused mitral annulus dilation (antero-posterior diameter increase from 31.8 ± 5.6 mm to 39.5 ± 4.9 mm, p = 0.001), leaflets tethering (maximal tenting height increase from 7.3 ± 2.5 mm to 12.7 ± 3.4 mm, p < 0.001) and left ventricular diameter increase (from 67.8 ± 7.5 mm to 79.4 ± 6.5 mm, p = 0.004). These geometrical reconfigurations led to restricted mitral valve leaflets motion and leaflet coaptation loss. Preliminary feasibility assessment of two FMR treatments was performed in the developed model.Deer hearts showed ability to dilate under constant pressurization and have potential to be used for realistic preclinical research of novel FMR therapies. Graphical abstract figure legend: Deer heart mitral valve fiberscopic and echocardiographic images in peak systole at baseline and after inducing the pathological conditions representing functional mitral regurgitation. In the pathological conditions lack of coaptation between the leaflets, enlargement of the antero-posterior distance (red dashed line) and the left ventricular diameter (orange dashed line) were observed.

A Finite Element workflow for the multiscale analysis of the aortic valve biomechanics was developed and applied to three physiological anatomies with the aim of describing the aortic valve interstitial cells biomechanical milieu in physiological conditions, capturing the effect of subject-specific and leaflet-specific anatomical features from the organ down to the cell scale. A mixed approach was used to transfer organ-scale information down to the cell-scale. Displacement data from the organ model were used to impose kinematic boundary conditions to the tissue model, while stress data from the latter were used to impose loading boundary conditions to the cell level. Peak of radial leaflet strains was correlated with leaflet extent variability at the organ scale, while circumferential leaflet strains varied over a narrow range of values regardless of leaflet extent. The dependency of leaflet biomechanics on the leaflet-specific anatomy observed at the organ length-scale is reflected, and to some extent emphasized, into the results obtained at the lower length-scales. At the tissue length-scale, the peak diastolic circumferential and radial stresses computed in the fibrosa correlated with the leaflet surface area. At the cell length-scale, the difference between the strains in two main directions, and between the respective relationships with the specific leaflet anatomy, was even more evident; cell strains in the radial direction varied over a relatively wide range ([Formula: see text]) with a strong correlation with the organ length-scale radial strain ([Formula: see text]); conversely, circumferential cell strains spanned a very narrow range ([Formula: see text]) showing no correlation with the circumferential strain at the organ level ([Formula: see text]). Within the proposed simulation framework, being able to account for the actual anatomical features of the aortic valve leaflets allowed to gain insight into their effect on the structural mechanics of the leaflets at all length-scales, down to the cell scale.

We propose a surrogate model for the fluid-structure interaction (FSI) problem for the study of blood dynamics in carotid arteries in presence of plaque. This is based on the integration of a numerical model with subject-specific data and clinical imaging. We propose to model the plaque as part of the tissues surrounding the vessel wall through the application of an elastic support boundary condition. In order to characterize the plaque and other surrounding tissues, such as the close-by jugular vein, the elastic parameters of the boundary condition were spatially differentiated and their values were estimated by minimizing the discrepancies between computed vessel displacements and reference values obtained from CINE Magnetic Resonance Imaging data. We applied the model to three subjects with a degree of stenosis greater than 70%. We found that accounting for both plaque and jugular vein in the estimation of the elastic parameters increases the accuracy. In particular, in all patients, mismatches between computed and in vivo measured wall displacements were one to two orders of magnitude lower than the spatial resolution of the original MRI data. These results confirmed the validity of the proposed surrogate plaque model. We also compared fluid-dynamics results with those obtained in a fixed wall setting and in a full FSI model, used as gold standard, highlighting the better accordance of our results in comparison to the rigid ones., (© 2021 John Wiley & Sons, Ltd.)

Blood is generally modeled as a Newtonian fluid, assuming a standard and constant viscosity; however, this assumption may not hold for the highly pulsatile and recirculating intracavitary flow in the left ventricle (LV), hampering the quantification of fluid dynamic indices of potential clinical relevance. Herein, we investigated the effect of three viscosity models on the patient-specific quantification of LV blood energetics, namely on viscous energy loss (EL), from 4D Flow magnetic resonance imaging: I) Newtonian with standard viscosity (3.7 cP), II) Newtonian with subject-specific hematocrit-dependent viscosity, III) non-Newtonian accounting for the effect of hematocrit and shear rate. Analyses were performed on 5 controls and 5 patients with cardiac light-chain amyloidosis. In Model II, viscosity ranged between 3.0 (-19%) and 4.3 cP (+16%), mildly deviating from the standard value. In the non-Newtonian model, this effect was emphasized: viscosity ranged from 3.2 to 6.0 cP, deviating maximally from the standard value in low shear rate (i.e., <100 s -1 ) regions. This effect reflected on EL quantifications: in particular, as compared to Model I, Model III yielded markedly higher EL values (up to +40%) or markedly lower (down to -21%) for subjects with hematocrit higher than 39.5% and lower than 30%, respectively. Accounting for non-Newtonian blood behavior on a patient-specific basis may enhance the accuracy of intracardiac energetics assessment by 4D Flow, which may be explored as non-invasive index to discriminate between healthy and pathologic LV., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to declare., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The current management of aortic dilatation associated with congenital bicuspid aortic valve (bicuspid aortic valve aortopathy) is based on dimensional parameters (diameter of the aneurysm, growth of the diameter over time) and few other criteria. The disease is however heterogeneous in terms of natural and clinical history and risk of acute complications, ie aortic dissection. Dimensional criteria are now admitted to have limited value as predictors of such complications. Thus, novel principles for risk stratification have been recently investigated, including phenotypic criteria, flow-related metrics, and circulating biomarkers. A systematization of the typical anatomoclinical forms that the aortopathy can assume has led to the identification of the more severe root phenotype, associated with higher risk of progression of the aneurysm and possible higher aortic dissection risk. Four-dimensional-flow magnetic resonance imaging studies are searching for potentially clinically significant metrics of flow derangement, based on the recognized association of local abnormal shear stress with wall pathology. Other research initiatives are addressing the question whether circulating molecules could predict the presence or, more importantly, the future development of aortopathy. The present review summarizes the latest progresses in the knowledge on risk stratification of bicuspid aortic valve aortopathy, focusing on critical aspects and debated points., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Multidetector computed tomography (MDCT) is currently the imaging technique of choice for the assessment of tricuspid valve (TV) annulus geometry and relationship with the right coronary artery (RCA). However, standardized protocols with a full 3D analysis are still lacking to plan percutaneous procedures for functional tricuspid regurgitation (FTR). A novel customized 4-dimensional tool based on MDCT data was developed and provided accurate information on TV annulus morphology (3D-perimeter, 2D-Area, maximum and minimum diameters, eccentricity index), function and distance to the RCA, crucial for patient selection of percutaneous TV procedures., (Copyright © 2020 [The Author/The Authors]. Published by Elsevier Inc. All rights reserved.)

Background: Identification of adequate landing zone for transcatheter pulmonary valve implantation (TPVI) is crucial to successfully treat an aneurysmatic native right ventricle outflow tract (RVOT); three-dimensional (3D) patient-tailored digital and physical printed models are available but their actual strengths and weaknesses still not well documented. The aim of the study was to tackle TPVI planning in the dysfunctional and borderline RVOT exploiting both digital and physical printed 3D patient-specific models., Methods: Electrocardiographically gated computed tomography (CT) angiography was segmented and anatomical RVOT geometrical changes dynamically tracked throughout the cardiac cycle using in-house processing. A compliant 3D-printed model was manufactured from the diastolic rest phase to test in vitro the catheter-based procedure feasibility; results were compared against CT-derived in vivo measurements and the actual catheterization outcome., Results: CT-gated analysis successfully quantified in vivo RVOT dynamic changes corroborating the feasibility of non-conventional pulmonary jailing percutaneous intervention. Clinicians used the 3D-printed model to test the steps of the jailing procedure; yet, the deformable 3D model printed at diastole underestimated the final implant dimensions obtained during cardiac catheterization by the same operators., Conclusions: Multidisciplinary synergy between CT-gated analysis and pre-procedural tests on 3D-printed phantoms can help the interventional team to tackle complex TPVI procedures. To fully exploit 3D-printed models, adequate selection of the still frame to print and tuning of printing material properties is crucial and can be aided by 3D dynamic virtual models., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Endovascular stenting has recently become a standard treatment for native coarctation of the aorta (CoA) in children and young adults, given the efficacy in relieving vessel obstruction with a low incidence of adverse events. Yet, despite the short-term success of the technique, late hypertension remains an endemic risk. To assess the impact of the percutaneous procedure on the aortic wall biomechanics, we designed a novel finite element (FE) protocol for the simulation of endovascular stenting in three patient-specific CoA anatomies, developing a remeshing procedure that allows for coping with different CoA severities. Our FE protocol was able to yield numerical results on stent distortions and stresses, as well as on changes in aortic wall stresses and distensibility. These results were consistent with intraprocedural in-vivo evidences and with previous findings from the literature, and they suggest that our numerical approach could be used to understand the role of patient specific anatomical features (CoA severity and arch type) on the post-stenting aortic biomechanics. If soundly validated on a vast cohort of patients, our approach could support patient selection for the procedure., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The relationship between the typical electrocardiographic pattern and electromechanical abnormalities has never been systematically explored in Brugada syndrome (BrS)., Objectives: The aims of this study were to characterize the electromechanical substrate in patients with BrS and to evaluate the relationship between electrical and mechanical abnormalities., Methods: We enrolled 50 consecutive high-risk patients with BrS (mean age 42 ± 7.2 years), with implantable cardioverter-defibrillator implantation for primary or secondary prevention of ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]), undergoing substrate mapping and ablation. Patients underwent 3-dimensional (3D) echocardiography with 3D wall motion/deformation quantification and electroanatomic mapping before and after ajmaline administration (1 mg/kg in 5 minutes); 3D mechanical changes were compared with 50 age- and sex-matched controls. The effect of substrate ablation on electromechanical abnormalities was also assessed., Results: In all patients, ajmaline administration induced Brugada type 1 pattern, with a significant increase in the electrical substrate (P < .001), particularly in patients with previous spontaneous VT/VF (P = .007). Induction of Brugada pattern was associated with lowering of right ventricular (RV) ejection fraction (P < .001) and worsening of 3D RV mechanical function (P < .001), particularly in the anterior free wall of the RV outflow tract, without changes in controls. RV electrical and mechanical abnormalities were highly correlated (r = 0.728, P < .001). By multivariate analysis, only the area of RV dysfunction was an independent predictor of spontaneous VT/VF (odds ratio 1.480; 95% confidence interval 1.159-1.889; P = .002). Substrate ablation abolished both BrS-electrocardiographic pattern and mechanical abnormalities, despite ajmaline rechallenge., Conclusion: BrS is an electromechanical disease affecting the RV. The typical BrS pattern reflects an extensive RV arrhythmic substrate, driving consistent RV mechanical abnormalities. Substrate ablation abolished both Brugada pattern and mechanical abnormalities., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

In Sleeve procedure, the leaflets-sinus unit is maintained. We hypothesized that this feature partially preserves aortic root (AR) dynamics and leaflets kinematics and limits tensions in the leaflets. We tested our hypothesis based on in vivo and computational assessment of leaflets and AR dynamics. AR and aortic leaflet kinematics was assessed by transthoracic echocardiography in 10 patients treated with the Sleeve procedure and in 10 healthy patients. Numerical calculations with the Finite Element Method were performed to support the analysis of the clinical results and provide a better understanding of the behavior of the AR treated via the Sleeve procedure. Echocardiographic evidence showed that AR expansion in the Sleeve group was partially preserved as compared to the Control group (2.9 ± 2.5% vs 7.7 ± 6.3%, P = 0.038) and of the sinotubular junction (2.9 ± 1.5% vs 7.3 ± 3.8%, P = 0.003), and significantly preserved at the Valsalva sinuses level (6.7 ± 2.6% vs 9.5 ± 4.3%) with not statistically significant differences (P = 0.11). In none of the cardiac phases, differences in aortic valve leaflets kinematics were measured between the 2 groups; computational results were rather consistent with this evidence. Computational results well matched echocardiographic evidences, allowing for their mechanistic interpretation. Near-normal opening and closing characteristics can be accomplished by a technique that preserves the shape and the dynamics of the Valsalva sinuses. Whether the substantial preservation of the AR distensibility and leaflets kinematics observed in this study will favorably affect long-term valve durability it remains to be ascertained., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prosthetic valve thrombosis (PVT) is a serious complication affecting prosthetic heart valves. The transvalvular mean pressure gradient (MPG) derived by Doppler echocardiography is a crucial index to diagnose PVT but may result in false negatives mainly in case of bileaflet mechanical valves (BMVs) in mitral position. This may happen because MPG estimation relies on simplifying assumptions on the transvalvular fluid dynamics or because Doppler examination is manual and operator dependent. A deeper understanding of these issues may allow for improving PVT diagnosis and management. To this aim, we used in vitro and fluid-structure interaction (FSI) modeling to simulate the function of a real mitral BMV in different configurations: normally functioning and stenotic with symmetric and completely asymmetric leaflet opening, respectively. In each condition, the MPG was measured in vitro, computed directly from FSI simulations and derived from the corresponding velocity field through a Doppler-like postprocessing approach. Following verification versus in vitro data, MPG computational data were analyzed to test their dependency on the severity of fluid-dynamic derangements and on the measurement site. Computed MPG clearly discriminated between normally functioning and stenotic configurations. They did not depend markedly on the site of measurement, yet differences below 3 mmHg were found between MPG values at the central and lateral orifices of the BMV. This evidence suggests a mild uncertainty of the Doppler-based evaluation of the MPG due to probe positioning, which yet may lead to false negatives when analyzing subjects with almost normal MPG., (Copyright © 2019 by ASME.)

Severity of aortic coarctation (CoA) is currently assessed by estimating trans-coarctation pressure drops through cardiac catheterization or echocardiography. In principle, more detailed information could be obtained non-invasively based on space- and time-resolved magnetic resonance imaging (4D flow) data. Yet the limitations of this imaging technique require testing the accuracy of 4D flow-derived hemodynamic quantities against other methodologies. With the objective of assessing the feasibility and accuracy of this non-invasive method to support the clinical diagnosis of CoA, we developed an algorithm (4DF-FEPPE) to obtain relative pressure distributions from 4D flow data by solving the Poisson pressure equation. 4DF-FEPPE was tested against results from a patient-specific fluid-structure interaction (FSI) simulation, whose patient-specific boundary conditions were prescribed based on 4D flow data. Since numerical simulations provide noise-free pressure fields on fine spatial and temporal scales, our analysis allowed to assess the uncertainties related to 4D flow noise and limited resolution. 4DF-FEPPE and FSI results were compared on a series of cross-sections along the aorta. Bland-Altman analysis revealed very good agreement between the two methodologies in terms of instantaneous data at peak systole, end-diastole and time-averaged values: biases (means of differences) were +0.4 mmHg, -1.1 mmHg and +0.6 mmHg, respectively. Limits of agreement (2 SD) were ±0.978 mmHg, ±1.06 mmHg and ±1.97 mmHg, respectively. Peak-to-peak and maximum trans-coarctation pressure drops obtained with 4DF-FEPPE differed from FSI results by 0.75 mmHg and -1.34 mmHg respectively. The present study considers important validation aspects of non-invasive pressure difference estimation based on 4D flow MRI, showing the potential of this technology to be more broadly applied to the clinical practice., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Owing to population aging, the social impact of osteoarthritis (OA)-the most common musculoskeletal disease-is expected to increase dramatically. Yet, therapy is still limited to palliative treatments or surgical intervention, and disease-modifying OA (DMOA) drugs are scarce, mainly because of the absence of relevant preclinical OA models. Therefore, in vitro models that can reliably predict the efficacy of DMOA drugs are needed. Here, we show, using a newly developed microphysiological cartilage-on-a-chip model that enables the application of strain-controlled compression to three-dimensional articular cartilage microtissue, that a 30% confined compression recapitulates the mechanical factors involved in OA pathogenesis and is sufficient to induce OA traits. Such hyperphysiological compression triggers a shift in cartilage homeostasis towards catabolism and inflammation, hypertrophy, and the acquisition of a gene expression profile akin to those seen in clinical osteoarthritic tissue. The cartilage on-a-chip model may enable the screening of DMOA candidates.

Prosthetic mechanical valves are the elective choice in mitral valve (MV) replacement, because of their reliability and easiness of implantation. However, these prostheses can suffer from complications, the major one being prosthetic mitral valve thrombosis (PMVT). In these cases, transthoracic doppler echocardiogram (TDE) is the standard diagnostic workup for diagnosis of valve malfunction. The American Society of Echocardiography (ASE) indicates the possible TDE-derived indexes, which can help in identifying insurgence of MV replacement complications. Unfortunately, in some cases, it is not possible to detect PMVT based on these criteria. In these cases, we speak of Doppler silent thrombosis and only more accurate and invasive analyses, such as fluoroscopy, allow for a correct diagnosis. In this work, computational fluid dynamic models were implemented to simulate valve fluid dynamics in different clinical scenarios in order to improve the reliability of PMVT diagnosis based on TDE. In detail, seven mechanical valve configurations, associated to different potential thrombotic conditions (symmetric and asymmetric stenosis), were designed and tested using five pathologic transmitral velocity profile, extracted from real TDE images; to obtain the flow rate profiles, each TDE velocity profile was scaled to yield a mean flow rate (MFR) of 4, 5 and 6 L/min, respectively. As a result, 105 (7 × 5 × 3) synthetic cases, accounting for different velocity profiles, MFRs and valve configurations, were simulated. TDE-derived indexes were calculated according to the ASE guidelines that were extracted. Advanced statistical methods were applied to propose a new diagnostic algorithm for detecting PMVT. Our results showed that there isn't any significant difference between symmetric and asymmetric stenosis, probe location and flow rate waveform and confirmed that the single modality diagnostic is not able to predict thrombosis in a relevant number of cases, referable to mild and mild-severe stenosis cases. To overcome the problem, a novel multi-parametric discrete score based on the designed diagnostic algorithm was attained and tested; the percentage of stenosis (POS) was predicted with an accuracy rate of 90.5%. Even more interestingly, the error rate of 9.5% is related to four false positive cases corresponding to mild stenosis (POS = 15%) which were erroneously classified as mild-severe stenosis. No false negatives were obtained. Our results suggest that a reliable estimation must take into account the mean flow rate as well as the transmitral velocity profile in order to provide a correct diagnosis., (Copyright © 2019 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Introduction:: Despite significant technical advancements in the design and manufacture of Left Ventricular Assist Devices, post-implant thrombotic and thromboembolic complications continue to affect long-term outcomes. Previous efforts, aimed at optimizing pump design as a means of reducing supraphysiologic shear stresses generated within the pump and associated prothrombotic shear-mediated platelet injury, have only partially altered the device hemocompatibility., Methods:: We examined hemodynamic mechanisms that synergize with hypershear within the pump to contribute to the thrombogenic potential of the overall Left Ventricular Assist Device system., Results:: Numerical simulations of blood flow in differing regions of the Left Ventricular Assist Device system, that is the diseased native left ventricle, the pump inflow cannula, the impeller, the outflow graft and the anastomosed downstream aorta, reveal that prothrombotic hemodynamic conditions might occur at these specific sites. Furthermore, we show that beyond hypershear, additional hemodynamic abnormalities exist within the pump, which may elicit platelet activation, such as recirculation zones and stagnant platelet trajectories. We also provide evidences that particular Left Ventricular Assist Device implantation configurations and specific post-implant patient management strategies, such as those allowing aortic valve opening, are more hemodynamically favorable and reduce the thrombotic risk., Conclusion:: We extend the perspective of pump thrombosis secondary to the supraphysiologic shear stress environment of the pump to one of Left Ventricular Assist Device system thrombosis, raising the importance of comprehensive characterization of the different prothrombotic risk factors of the total system as the target to achieve enhanced hemocompatibility and improved clinical outcomes.