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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.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 (LASGroup 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 LAS2DSTE-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.

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. Electronic supplementary material The online version of this article (10.1007/s12265-020-10071-y) contains supplementary material, which is available to authorized users.

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.

Purpose: Displacement forces ( DFs) 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 DFs 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 DFs within the aortic proximal landing zones. To quantify fast-approximate DFs, 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 (r2=0.99, pConclusion: 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.

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 [KEV] and viscous energy loss [ELV]), 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. AP-value of Results ICM patients exhibited the following statistically significant alterations vs. controls: reduced KEV, 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 KEVat 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.

Background: Functional tricuspid regurgitation (FTR) treatment is challenging and most therapies targeting tricuspid valve (TV) annulus have shown limited durability with high rate of resid...

In this work we propose a mathematical and numerical model to describe the early stages of atherosclerotic plaque formation, which is based on the interaction of processes with different spatial and temporal scales. A fluid–structure interaction problem, used to describe the cardiovascular mechanics arising between blood and the artery wall, is coupled to a set of differential problems describing the evolution of solute concentrations. In order to manage the multiscale-in-space nature of the involved processes, we propose a suitable numerical strategy based on the splitting and sequential solution of the coupled problem. We present some preliminary numerical results and investigate the effects of geometry, model parameters and coupling strategy on plaque growth.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health Background The systemic position of a morphologically right ventricle (SRV) makes it vulnerable to fail, leading to high incidence of heart failure and cardiac death [1]. Understanding SRV intracavitary blood flow dynamics and energetics could improve patient risk stratification. Purpose Testing the potential of three-dimensional time-resolved phase contrast cardiac magnetic resonance (4D Flow) in quantifying SRV blood flow dynamics and energetics. Methods 4D Flow prototype sequences were acquired on 3 patients (1 male, 2 females) with SRV in D-loop transposition of great arteries after atrial switch operation (D-TGA/ASO), 3 male patients with SRV in L-loop TGA (L-TGA) and healthy controls (2 males, 1 female). Kinetic energy (KE), viscous energy loss (EL), dissipation index (DI) calculated as EL to KE ratio, and hemodynamics forces (HFs) resulting from pressure gradients, were computed for the D-TGA/ASO and L-TGA SRVs, and for the control left ventricles (LVs) and right ventricles (RVs). HFs were decomposed in inferior-anterior, septal-lateral and basal-apical components (HFIA, HFSL, HFBA, respectively) Results Figure 1 reports the time-course of HF components and the general features of the enrolled subjects. In systole, all SRVs (Figure 1a-1b) presented a dominant HFIA and a minor HFSL, similarly to RVs (Figure 1c); however, HFSL had a positive peak, indicating septal contraction towards the SRV cavity, opposite to its normal motion. HFBA magnitude was similar to LVs (Figure 1d), suggesting that the shortening of the tricuspid anulus towards the apex is more pronounced than in RVs (Figure 1c). Over the whole cardiac cycle, DI values were highest in D-TGA/ASO SVRs (0.40-0.55); in L-TGA SRVs, DI values (0.24-0.45) were comparable to healthy LVs (0.22-0.37) and RVs (0.23-0.36). This difference may be related to the fact that in DTGA/ASO the left atrium is functionally replaced by a pulmonary venous baffle, which lacks efficient contraction, as highlighted by the absence of a distinctive A-wave in the KE time-course (Figure 2a). Due to the adaptation to systemic afterload, SRVs were hypertrophic (Figure 1a-1b), with indexed mass higher than normal RVs (Figure 1c), and presented reduced compliance to the diastolic filling, as suggested by increased KE E-wave slope in L-TGA (Figure 2b) compared to controls (Figure 2c-2d). Conclusions Intracavitary HFs in SRVs reveal a partial shift from a RV towards LV pattern. This occurs at the expenses of a higher energetic consumption in D-TGA/ASO than L-TGA, enlightening the crucial role of atrial contribution to impaired SRV diastolic filling. These findings corroborate the previous evidence that patients with D-TGA/ASO have abnormal decrease in stroke volume during exercise whereas L-TGA patients can reach values comparably to healthy controls [2].

Background Right ventricle (RV) remodeling is a marker of advanced disease and impaired prognosis in heart failure reduced ejection fraction (HFrEF) patients [1]. The assessment of RV remodeling is limited with standard echocardiography. Three-dimensional speckle-tracking echocardiography (3DSTE), with advanced post-processing, allows for RV shape and regional function assessment, potentially providing additional information [2]. Purpose 1) to describe global and regional RV shape and function in a HFrEF cohort of patients; 2) to define RV remodeling phenotypes according with pulmonary haemodynamics; 3) to test the prognostic significance of RV shape and functional parameters. Methods 81 HFrEF patients were prospectively enrolled and followed-up (median time 760 days) for the composite end-point of death, heart failure hospitalization, heart transplant and left ventricular assist device implantation. They received standard 3DSTE evaluation, consisting of end-diastolic volume index (EDVi), end-systolic (ES) volume index (ESVi) and ejection fraction (EF) measurement via commercial software (TomTec Imaging Systems GmbH, Germany). Advanced post-processing provided RV free-wall and septal mean curvatures (Km) and minimum principal strain (MPS) [3] quantification. A subgroup of 40 subjects underwent right heart catheterization (RHC) and were classified in: group A – no pulmonary hypertension (PH) (n=15), group B – PH but normal pulmonary vascular resistance (PVR) (n=15) and group C – PH and increased PVR (n=10). Roc curves were used to identify RV parameters able to discriminate subjects belonging to group A. Prognostic significance of RV remodeling parameters was tested for the composite end-point. Results Patients who did receive RHC showed lower ES free-wall Km (0.052 vs 0.058 mm-1, p−22.4% (threshold discriminating normal pulmonary hemodynamic) resulted statistically associated with prognosis (Fig. 2). Conclusion In HFrEF patients, RV remodeling is progressively associated with unfavourable pulmonary haemodynamic, with a free-wall negative remodeling (abnormal curvature) resulting in loss of systolic function. RV free-wall function is tightly associated with the development of PH. 3DSTE indexes of RV global and regional function showed prognostic significance together with MR coexistence. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): IRCCS Policlinico San Donato is a clinical research hospital partially funded by the Italian Ministry of Health Figure 1. End-systolic MPS distributionFigure 2. Kaplan-Meier survival analysis

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Publich Health - Ricerca Corrente Introduction Thoracic endovascular aortic repair (TEVAR) represents a well-established alternative to open repair in selected patients. Its preoperative feasibility assessment and planning requires a computational tomography (CT)-based analysis of the geometric aortic features to identify an adequate proximal and distal landing zone (LZ) for endograft deployment. Yet, controversies persist on the definition and methods of measurement of specific geometric features of the LZs, including angulation and tortuosity, which are associated with an increased risk of postoperative endograft failure. In this respect, the development of a preoperative image processing method that provides an automatic and highly reproducible 3D identification of critical geometric features and specific anatomical landmarks, thus reducing the time and uncertainties related to manual segmentation, remains a largely unmet clinical need. In this study, we developed and applied a fully automated pipeline embedding a convolutional neural network (CNN), which feeds on 3D CT images to automatically segment the thoracic aorta, recognize the relevant anatomical landmarks and LZs, and quantifies the geometry of the aortic arch in each proximal LZ s (i.e. 0 to 3). Methods Ninety CT scans of healthy aortas were retrieved, being the study conceived as a proof of concept analysis. The thoracic aorta was manually segmented by five independent and expert operators. 72 scans with the corresponding ground truth segmentations were randomly selected and used to train the CNN, which was based on a 3D U-Net architecture. The other 18 scans were used to test the CNN-based segmentations. The fully automated pipeline was obtained by integrating the CNN, 3D geometry skeletonization, and processing of the aortic centerline and wall via computational geometry (Figure). The resulting metrics included aortic arch centerline radius of curvature, proximal landing zones (PLZs) maximum diameters, angulation and tortuosity calculated according to previously published work. These parameters were statistically analyzed to compare standard arches vs. arches with a common origin of the innominate and left carotid artery (CILCA), and the different landing zones in each arch type. Results The CNN segmentation yielded a mean Dice score of 0.94 with respect to manual ground truth segmentations. Standard arches were characterized by significantly larger radius of curvature (p = 0.002) and lower tortuosity in zone 3 (p = 0.004) vs. CILCA arches. For both standard and CILCA arches, comparisons among PLZs revealed statistically significant differences in maximum zone diameters (p Conclusions We developed a CNN-based automated pipeline for the automated, and reliable geometric quantification of standard and CILCA aortic arches. This tool has the potential to support TEVAR pre-procedural planning in a real clinical setting. Abstract Figure. Automatic pipeline scheme

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.

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.

Background Ischemic cardiomyopathy (ICM) is often associated with negative LV remodelling after myocardial infarction, sometimes resulting in impaired LV function and dilation (iDCM). 4D Flow CMR has been recently exploited to assess intracardiac hemodynamic changes in presence of LV remodelling. Purpose To quantify 4D Flow intracardiac kinetic energy (KE) and viscous energy loss (EL) and investigate their relation with LV dysfunction and remodelling. Methods Patients with prior anterior myocardial infarction underwent a CMR study with 4D Flow sequences acquisition; they were divided into ICM (n=10) and iDCM (n=10, EDV>208 ml and EF Results Both LV volume and EF significantly differ (P Conclusions 4D Flow analyses effectively mapped post-ischemic LV energetic changes, highlighting the disproportionate intraventricular EL relative to produced KE; preliminary good correlation between LV energetic changes and NT-proBNP will deserve further investigation in order to contribute to early detection of heart failure. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Italian Ministry of Health

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.

The study objective was to elucidate the mechanisms of left ventricle functional recovery in terms of endocardial contractility and synchronicity after surgical ventricular reconstruction.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.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).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.

This study applied advanced 4-dimensional flow magnetic resonance imaging processing to assess differences in aortic flow dynamics after valve sparing root replacement, with and without reconstruction of the Valsalva sinuses.We enrolled patients after valve sparing root replacement with a straight tubular prosthesis (n = 10) or with a prosthesis with Valsalva neosinuses (n = 10); age-matched subjects without cardiovascular diseases served as controls (n = 10). 4-Dimensional flow magnetic resonance imaging acquisitions were performed on a 3.0T magnetic resonance imaging unit. In-house processing was used to segment the aortic lumen and extract the volumetric 4-dimensional flow velocity field. Velocity flow streamlines were computed to compare the amount of rotational flow and wall shear stress. Occurrence of abnormal wall shear stress (WSS) was estimated within the descending aorta of each surgical group.Physiologic-like sinus vortices were visible in the aortic root when using the prosthesis with neosinuses, whereas straight tubular graft revealed localized intrados malrotations (P = .003 for organized vortical structures vs neosinuses graft and P .001 vs control). In the ascending aorta, recreation of the sinuses resulted in significantly lower velocity and WSS than in the straight tubular graft (P .001) and controls (P .001), these alterations were attenuated in the mid-descending aorta. Incidence of abnormal WSS was markedly higher in the straight tube grafts than neosinus of Valsalva grafts.Re-creation of the sinuses of Valsalva during valve-sparing root replacement is associated with more physiologic flow and significantly lower WSS in the aortic root. Lower WSSs in the distal thoracic aorta is a novel finding with potential implications on distal aortic remodeling.

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 ($$0.36-0.87$$ 0.36 - 0.87 ) with a strong correlation with the organ length-scale radial strain ($$R^{2}= 0.95$$ R 2 = 0.95 ); conversely, circumferential cell strains spanned a very narrow range ($$0.75-0.88$$ 0.75 - 0.88 ) showing no correlation with the circumferential strain at the organ level ($$R^{2}= 0.02$$ R 2 = 0.02 ). 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.

The performance of blood-processing devices largely depends on the associated fluid dynamics, which hence represents a key aspect in their design and optimization. To this aim, two approaches are currently adopted: computational fluid-dynamics, which yields highly resolved three-dimensional data but relies on simplifying assumptions, and in vitro experiments, which typically involve the direct video-acquisition of the flow field and provide 2D data only. We propose a novel method that exploits space- and time-resolved magnetic resonance imaging (4D-flow) to quantify the complex 3D flow field in blood-processing devices and to overcome these limitations. We tested our method on a real device that integrates an oxygenator and a heat exchanger. A dedicated mock loop was implemented, and novel 4D-flow sequences with sub-millimetric spatial resolution and region-dependent velocity encodings were defined. Automated in house software was developed to quantify the complex 3D flow field within the different regions of the device: region-dependent flow rates, pressure drops, paths of the working fluid and wall shear stresses were computed. Our analysis highlighted the effects of fine geometrical features of the device on the local fluid-dynamics, which would be unlikely observed by current in vitro approaches. Also, the effects of non-idealities on the flow field distribution were captured, thanks to the absence of the simplifying assumptions that typically characterize numerical models. To the best of our knowledge, our approach is the first of its kind and could be extended to the analysis of a broad range of clinically relevant devices.

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.

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

Background Patients surgically treated for congenital heart disease (e.g., Tetralogy of Fallot) frequently report long-term dysfunctions (i.e., pulmonary stenosis and/or incompetence) of the native right ventricle outflow tract (RVOT). The efficacy of percutaneous pulmonary valve implantation (PPVI) is recognized worldwide; however, the procedure is only feasible in RVOTs with appropriate size and functional substrate. Accordingly, a three-dimensional (3D) and dynamic assessment of the native RVOT function can be crucial to identify patients who can effectively benefit from PPVI, thus avoiding the risk of device embolization or fracture. Purpose We herein exploited an optical flow-based approach to develop a novel 3D framework for the quantitative in vivo assessment of dimension and dynamic changes of the native RVOT throughout the cardiac cycle. PPVI candidates (n=15) with previous surgery of the native RVOT were enrolled to demonstrate the additional contribution of our 3D patient-tailored analysis to the decision-making process. Methods Contrast-enhanced computed tomography (CT) was performed on a 64-slice dual-source multidetector CT system with retrospective ECG-gating. Multi-phase images of the RVOT were acquired at each 10% increment of the cardiac cycle (slice thickness = 1.5mm, increment = 1mm, pixel spacing = 0.35mm). We implemented a dedicated in-house framework, based on the optical flow tracking algorithm, to dynamically follow three anatomical cross-sections (i.e., proximal, mid and distal) of the native RVOT. The time course of area, perimeter and other relevant parameters (e.g., equivalent radius, elliptical ratio) were extracted and both areal (εA) and longitudinal strain (εlong) were computed on each the RVOT tracked cross-section. Maximum regional strain were calculated between the maximum and minimum value over the cardiac cycle. Dynamic changes in CT-derived variables were assessed using analysis of variance (p Results All the enrolled anatomies were successfully analysed, locally pinpointing the in vivo pattern of deformation within each 3D RVOT anatomy (a). Anatomical regional RVOT dimensions (p In vivo tracking of RVOT dynamic changes Conclusions The combination of patient-specific in vivo imaging and bioengineering strategies can improve our understanding of RVOT dysfunctions in congenital patients referred to PPVI. Our optical flow-based and clinically-oriented framework can support the patient selection process and the planning of the percutaneous procedure in order to enhance its efficacy and shorten the operating time while improving the patient safety. Acknowledgement/Funding IRCCS Policlinico San Donato is a clinical research hospital partially funded by the Italian Ministry of Health

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 viscousenergy 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-chainamyloidosis. 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., −1) regions. This effect reflected onELquantifications: in particular, as compared to Model I, Model III yielded markedly higherELvalues (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.

Mitraclip® implantation is widely used as a valid alternative to conventional open-chest surgery in high-risk patients with severe mitral valve (MV) regurgitation. Although effective in reducing mitral regurgitation (MR) in the majority of cases, the clip implantation produces a double-orifice area that can result in altered MV biomechanics, particularly in term of hemodynamics and mechanical stress distribution on the leaflets. In this scenario, we combined the consistency of in vitro experimental platforms with the versatility of numerical simulations to investigate clip impact on MV functioning. The fluid dynamic determinants of the procedure were experimentally investigated under different working conditions (from 40bpm to 100bpm of simulated heart rate) on six swine hearts; subsequently, fluid dynamic data served as realistic boundary conditions in a computational framework able to quantitatively assess the post-procedural MV biomechanics. The finite element model of a human mitral valve featuring an isolated posterior leaflet prolapse was reconstructed from cardiac magnetic resonance. A complete as well as a marginal, sub-optimal grasping of the leaflets were finally simulated. The clipping procedure resulted in a properly coapting valve from the geometrical perspective in all the simulated configurations. Symmetrical complete grasping resulted in symmetrical distribution of the mechanical stress, while uncomplete asymmetrical grasping resulted in higher stress distribution, particularly on the prolapsing leaflet. This work pinpointed that the mechanical stress distribution following the clipping procedure is dependent on the cardiac hemodynamics and has a correlation with the proper execution of the grasping procedure, requiring accurate evaluation prior to clip delivery.

Lungs behave as viscoelastic polymers. Harms of mechanical ventilation could then depend on not only amplitude (strain) but also velocity (strain rate) of lung deformation. Herein, we tested this hypothesis.Laboratory investigation.Animal unit.Thirty healthy piglets.Two groups of animals were ventilated for 54 hours with matched lung strains (ratio between tidal volume and functional residual capacity) but different lung strain rates (ratio between strain and inspiratory time). Individual strains ranged between 0.6 and 3.5 in both groups. Piglets ventilated with low strain rates had an inspiratory-to-expiratory time ratio of 1:2-1:3. Those ventilated with high strain rates had much lower inspiratory-to-expiratory time ratios (down to 1:9). Respiratory rate was always 15 breaths/min. Lung viscoelastic behavior, with ventilator setting required per protocol, was "quantified" as dynamic respiratory system hysteresis (pressure-volume loop [in Joules]) and stress relaxation (airway pressure drop during an end-inspiratory pause [in cm H2O]). Primary outcome was the occurrence of pulmonary edema within 54 hours.On average, the two study groups were ventilated with well-matched strains (2.1 ± 0.9 vs 2.1 ± 0.9; p = 0.864) but different strain rates (1.8 ± 0.8 vs 4.6 ± 1.5 s; p0.001), dynamic respiratory system hysteresis (0.6 ± 0.3 vs 1.4 ± 0.8 J; p = 0.001), and stress relaxation (3.1 ± 0.9 vs 5.0 ± 2.3 cm H2O; p = 0.008). The prevalence of pulmonary edema was 20% among piglets ventilated with low strain rates and 73% among those ventilated with high strain rates (p = 0.010).High strain rate is a risk factor for ventilator-induced pulmonary edema, possibly because it amplifies lung viscoelastic behavior.