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Purpose In this work we performed an imaged-based computational study of the systolic fluid dynamics in presence of mitral valve regurgitation (MVR). In particular, we compared healthy and different regurgitant scenarios with the aim of quantifying different hemodynamic quantities. Methods We performed computational fluid dynamic (CFD) simulations in the left ventricle, left atrium and aortic root, with a resistive immersed method, a turbulence model, and with imposed systolic wall motion reconstructed from Cine-MRI images, which allowed us to segment also the mitral valve. For the regurgitant scenarios we considered an increase of the heart rate and a dilation of the left ventricle. Results Our results highlighted that MVR gave rise to regurgitant jets through the mitral orifice impinging against the atrial walls and scratching against the mitral valve leading to high values of wall shear stresses (WSSs) with respect to the healthy case. Conclusion CFD with prescribed wall motion and immersed mitral valve revealed to be an effective tool to quantitatively describe hemodynamics in case of MVR and to compare different regurgitant scenarios. Our findings highlighted in particular the presence of transition to turbulence in the atrium and allowed us to quantify some important cardiac indices such as cardiac output and WSS.

Background: The lack of reliable echocardiographic techniques to assess diastolic function in children is a ma-jor clinical limitation. Our aim was to develop and validate the intraventricular pressure difference (IVPD) calcu-lation using blood speckle-tracking (BST) and investigate the method's potential role in the assessment of diastolic function in children. Methods: Blood speckle-tracking allows two-dimensional angle-independent blood flow velocity estimation. Blood speckle-tracking images of left ventricular (LV) inflow from the apical 4-chamber view in 138 controls, 10 patients with dilated cardiomyopathies (DCMs), and 21 patients with hypertrophic cardiomyopathies (HCMs)

Background The aim of the current study is to compare electrocardiographic and echocardiographic changes in patients with severe preeclampsia (PE) and those with uncomplicated pregnancies.Methods This is a case-controlled prospective study consisting of 21 pregnant women with severe preeclampsia and a control group consisting of age- and gestational age-matched 24 healthy pregnant women. All patients underwent electrocardiographic and echocardiographic investigation.Results QRS intervals were shorter and PR intervals were longer in the PE group (QRS duration: 80 (60–120) ms and 80 (40–110) ms, p=0.035; PR duration: 160 (100–240) ms and 120 (80–200) ms, respectively; p=0.046). The left ventricular end-systolic diameters of the patients with severe PE group were significantly larger than the control group (31 (24–36) mm and 30 (24–33) mm, respectively; p=0.05). Similarly, posterior wall thickness values of the PE group were significantly higher compared to the control group (9 (7–11) mm vs. 8 (6–10) mm, respectively; p=0.020). Left ventricular mass (146.63±27.73 g and 128.69±23.25 g, respectively; p=0.033) and relative wall thickness values (0.385±0.054 and 0.349±0.046, respectively; p=0.030) were also higher in the PE group. In addition, patients with early-onset severe PE had significantly a higher left ventricular end-diastolic diameter and volume compared with late-onset PE patients.Conclusions The structural changes detected in the severe PE group suggest a chronic process rather than an acute effect. In addition, diastolic dysfunction and left ventricular remodeling are most marked in patients with severe early-onset PE.

Both exercise-induced molecular mechanisms and physiological cardiac remodeling have been previously studied on a whole heart level. However, the regional microstructural tissue effects of these molecular mechanisms in the heart have yet to be spatially linked and further elucidated. We show in exercised mice that the expression of CITED4, a transcriptional co-regulator necessary for cardioprotection, is regionally heterogenous in the heart with preferential significant increases in the lateral wall compared with sedentary mice. Concordantly in this same region, the heart's local microstructural tissue helicity is also selectively increased in exercised mice. Quantification of CITED4 expression and microstructural tissue helicity reveals a significant correlation across both sedentary and exercise mouse cohorts. Furthermore, genetic deletion of CITED4 in the heart prohibits regional exercise-induced microstructural helicity remodeling. Taken together, CITED4 expression is necessary for exercise-induced regional remodeling of the heart's microstructural helicity revealing how a key molecular regulator of cardiac remodeling manifests into downstream local tissue-level changes.Expression of transcription factor CITED4 is necessary for exercise-induced regional remodeling of the heart's microstructural helicity, revealing how a key molecular regulator of cardiac remodeling mediates local tissue-level changes.

We present a new computational model for the numerical simulation of blood flow in the human left heart. To this aim, we use the Navier-Stokes equations in an Arbitrary Lagrangian Eulerian formulation to account for the endocardium motion and we model the cardiac valves by means of the Resistive Immersed Implicit Surface method. To impose a physiological displacement of the domain boundary, we use a 3D cardiac electromechanical model of the left ventricle coupled to a lumped-parameter (0D) closed-loop model of the remaining circulation. We thus obtain a one-way coupled electromechanics-fluid dynamics model in the left ventricle. To extend the left ventricle motion to the endocardium of the left atrium and to that of the ascending aorta, we introduce a preprocessing procedure according to which an harmonic extension of the left ventricle displacement is combined with the motion of the left atrium based on the 0D model. To better match the 3D cardiac fluid flow with the external blood circulation, we couple the 3D Navier-Stokes equations to the 0D circulation model, obtaining a multiscale coupled 3D-0D fluid dynamics model that we solve via a segregated numerical scheme. We carry out numerical simulations for a healthy left heart and we validate our model by showing that meaningful hemodynamic indicators are correctly reproduced.

Objective: Robust differentiation between infarcted and normal tissue is important for clinical diagnosis and precision medicine. The aim of this work is to investigate the radiomic features and to develop a machine learning algorithm for the differentiation of myocardial infarction (MI) and viable tissues/normal cases in the left ventricular myocardium on non-contrast Cine Cardiac Magnetic Resonance (Cine-CMR) images.Methods: Seventy-two patients (52 with MI and 20 healthy control patients) were enrolled in this study. MR imaging was performed on a 1.5 T MRI using the following parameters: TR = 43.35 ms, TE = 1.22 ms, flip angle = 65 degrees, temporal resolution of 30-40 ms. N4 bias field correction algorithm was applied to correct the inhomogeneity of images. All images were segmented and verified simultaneously by two cardiac imaging experts in consensus. Subsequently, features extraction was performed within the whole left ventricular myocardium (3D volume) in end-diastolic volume phase. Re-sampling to 1 x 1 x 1 mm(3) voxels was performed for MR images. All intensities within the VOI of MR images were discretized to 64 bins. Radiomic features were normalized to obtain Z-scores, followed by Student's t-test statistical analysis for comparison. A p-value < 0.05 was used as a threshold for statistically significant differences and false discovery rate (FDR) correction performed to report q-value (FDR adjusted p-value). The extracted features were ranked using the MSVM-RFE algorithm, then Spearman correlation between features was performed to eliminate highly correlated features (R2 > 0.80). Ten different machine learning algorithms were used for classification and different metrics used for evaluation and various parameters used for models' evaluation.Results: In univariate analysis, the highest area under the curve (AUC) of receiver operating characteristic (ROC) value was achieved for the Maximum 2D diameter slice (M2DS) shape feature (AUC = 0.88, q-value = 1.02E-7), while the average of univariate AUCs was 0.62 +/- 0.08. In multivariate analysis, Logistic Regression (AUC = 0.93 +/- 0.03, Accuracy = 0.86 +/- 0.05, Recall = 0.87 +/- 0.1, Precision = 0.93 +/- 0.03 and F1 Score = 0.90 +/- 0.04) and SVM (AUC = 0.92 +/- 0.05, Accuracy = 0.85 +/- 0.04, Recall = 0.92 +/- 0.01, Precision = 0.88 +/- 0.04 and F1 Score = 0.90 +/- 0.02) yielded optimal performance as the best machine learning algorithm for this radiomics analysis.Conclusion: This study demonstrated that using radiomics analysis on non-contrast Cine-CMR images enables to accurately detect MI, which could potentially be used as an alternative diagnostic method for Late Gadolinium Enhancement Cardiac Magnetic Resonance (LGE-CMR).

Accurate segmentation of pediatric echocardiography images is essential for a wide range of diagnostic and pre-interventional planning, but remains challenging (e.g., low signal to noise ratio and internal variability in heart appearance). To address these problems, in this paper, we propose a novel Cardiac Attention-guided Dual-path Network (i.e., AIDAN). AIDAN comprises a convolutional block attention module (CBAM) attached to a spatial (i.e., SPA) and context paths (i.e., CPA), which can guide the network and learn the most discriminative features. The spatial path captures low-level spatial features, and the context path is designed to exploit high-level context. Finally, features learned from the two paths are fused efficiently using a specially designed feature fusion module (FFM), and these are used to predict the final segmentation map. We experiment on a self-collected dataset of 127 pediatric echocardiography cases which are videos containing at least a complete cardiac cycle, and obtain a Dice coefficient of 0.951 and 0.914, in the left ventricle and atrium segments, respectively. AIDAN outperforms other state-of-the-art methods and has great potential for pediatric echocardiography images analysis.

Cardiogenic shock, cardiac arrest, acute respiratory failure, or a combination of such events, are all potential complications after cardiac surgery which lead to high mortality. Use of extracorporeal temporary cardio-circulatory and respiratory support for progressive clinical deterioration can facilitate bridging the patient to recovery or to more durable support. Over the last decade, extracorporeal membrane oxygenation (ECMO) has emerged as the preferred temporary artificial support system in such circumstances. Many factors have contributed to widespread ECMO use, including the relative ease of implantation, effectiveness, versatility, low cost relative to alternative devices, and potential for full, not just partial circulatory support. While there have been numerous publications detailing the short and midterm outcomes of ECMO support, specific reports about post-cardiotomy ECMO (PC-ECMO), are limited, single-center experiences. Etiology of cardiorespiratory failure leading to ECMO implantation, associated ECMO complications, and overall patient outcomes may be unique to the PC-ECMO population. Despite the rise in PC-ECMO use over the past decade, short-term survival has not improved.This report, therefore, aims to present a comprehensive overview of the literature with respect to the prevalence of ECMO use, patient characteristics, ECMO management, and in-hospital and early post-discharge patient outcomes for those treated for post-cardiotomy heart, lung, or heart-lung failure. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.

Cardiogenic shock, cardiac arrest, acute respiratory failure, or a combination of such events, are all potential complications after cardiac surgery which lead to high mortality. Use of extracorporeal temporary cardio-circulatory and respiratory support for progressive clinical deterioration can facilitate bridging the patient to recovery or to more durable support. Over the last decade, extracorporeal membrane oxygenation (ECMO) has emerged as the preferred temporary artificial support system in such circumstances. Many factors have contributed to widespread ECMO use, including the relative ease of implantation, effectiveness, versatility, low cost relative to alternative devices, and potential for full, not just partial circulatory support. While there have been numerous publications detailing the short and midterm outcomes of ECMO support, specific reports about post-cardiotomy ECMO (PC-ECMO), are limited, single-center experiences. Etiology of cardiorespiratory failure leading to ECMO implantation, associated ECMO complications, and overall patient outcomes may be unique to the PC-ECMO population. Despite the rise in PC-ECMO use over the past decade, short-term survival has not improved. This report, therefore, aims to present a comprehensive overview of the literature with respect to the prevalence of ECMO use, patient characteristics, ECMO management, and in-hospital and early post-discharge patient outcomes for those treated for post-cardiotomy heart, lung, or heart-lung failure. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has been used to deal with life-threatening complications as well as back-up or active cardiovascular support during high-risk procedures in patients undergoing transcatheter aortic valve implantation (TAVI). PubMed and MEDLINE electronic databases were searched in order to identify studies with emergency or prophylactic V-A ECMO application in association with TAVI procedures. From November 2012 to November 2017, 14 relevant studies were identified that included 5,115 TAVI patients of whom 102 (2%) required V-A ECMO (22 prophylactically, 66 as an emergency and 14 without a reported indication). The reason for emergency V-A ECMO institution was detailed in 64 patients: left ventricle free wall rupture (n = 14), haemodynamic instability (n = 12), ventricular arrhythmias (n = 7), aortic annulus rupture (n = 6), coronary obstruction (n = 6), low left ventricular output (ejection fraction

Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) has been used to deal with life-threatening complications as well as back-up or active cardiovascular support during high-risk procedures in patients undergoing transcatheter aortic valve implantation (TAVI). PubMed and MEDLINE electronic databases were searched in order to identify studies with emergency or prophylactic V-A ECMO application in association with TAVI procedures. From November 2012 to November 2017, 14 relevant studies were identified that included 5,115 TAVI patients of whom 102 (2%) required V-A ECMO (22 prophylactically, 66 as an emergency and 14 without a reported indication). The reason for emergency V-A ECMO institution was detailed in 64 patients: left ventricle free wall rupture (n = 14), haemodynamic instability (n = 12), ventricular arrhythmias (n = 7), aortic annulus rupture (n = 6), coronary obstruction (n = 6), low left ventricular output (ejection fraction

The rationale for mechanical circulatory support (MCS) in cardiogenic shock is to restore cardiac output in selected patients when critically low or in case of refractory cardiac arrest. Furthermore, an MCS device that moves blood from either the left atrium or the left ventricle to the systemic circulation will potentially unload the ventricle. These devices are used alone or in combination with venoarterial extracorporeal membrane oxygenation (VA-ECMO). If a left-sided Impella device is used, it should be run at the highest possible performance level during treatment while avoiding suction events. When combined with VA-ECMO, the Impella device should be run at a lower performance level, ensuring sufficient left ventricular emptying but avoiding suction. Continuous monitoring is pivotal and patients managed outside the catheterization laboratory should be monitored with an arterial line, a central venous catheter, frequent use of pulmonary artery catheters and regular imaging by transthoracic echocardiogram. The rationale for mechanical circulatory support (MCS) in cardiogenic shock is to restore cardiac output in selected patients when critically low or in case of refractory cardiac arrest. Furthermore, an MCS device that moves blood from either the left atrium or the left ventricle to the systemic circulation will potentially unload the ventricle. These devices are used alone or in combination with venoarterial extracorporeal membrane oxygenation (VA-ECMO). If a left-sided Impella device is used, it should be run at the highest possible performance level during treatment while avoiding suction events. When combined with VA-ECMO, the Impella device should be run at a lower performance level, ensuring sufficient left ventricular emptying but avoiding suction. Continuous monitoring is pivotal and patients managed outside the catheterization laboratory should be monitored with an arterial line, a central venous catheter, frequent use of pulmonary artery catheters and regular imaging by transthoracic echocardiogram.

Computer models of cardiac electro-mechanics (EM) show promise as an effective means for the quantitative analysis of clinical data and, potentially, for predicting therapeutic responses. To realize such advanced applications methodological key challenges must be addressed. Enhanced computational efficiency and robustness is crucial to facilitate, within tractable time frames, model personalization, the simulation of prolonged observation periods under a broad range of conditions, and physiological completeness encompassing therapy-relevant mechanisms is needed to endow models with predictive capabilities beyond the mere replication of observations. Here, we introduce a universal feature-complete cardiac EM modeling framework that builds on a flexible method for coupling a 3D model of bi-ventricular EM to the physiologically comprehensive 0D CircAdapt model representing atrial mechanics and closed-loop circulation. A detailed mathematical description is given and efficiency, robustness, and accuracy of numerical scheme and solver implementation are evaluated. After parameterization and stabilization of the coupled 3D–0D model to a limit cycle under baseline conditions, the model’s ability to replicate physiological behaviors is demonstrated, by simulating the transient response to alterations in loading conditions and contractility, as induced by experimental protocols used for assessing systolic and diastolic ventricular properties. Mechanistic completeness and computational efficiency of this novel model render advanced applications geared towards predicting acute outcomes of EM therapies feasible., Graphic abstract

Pre-eclampsia (PE) is strongly associated with heart failure (HF) later in life. During PE pregnancy, the left ventricle undergoes concentric remodeling which often persists after delivery. This aberrant remodeling can induce a molecular signature that can be evaluated in terms of microRNAs (miRNAs) and which may help to explain the associated increased risk of HF. For this review, we performed a literature search of PubMed (National Center for Biotechnology Information), identifying studies on miRNA expression in concentric remodeling and on miRNA expression in PE. The miRNA data were stratified based on origin (isolated from humans or animals and from tissue or the circulation) and both datasets compared in order to generate a list of miRNA expression patterns in concentric remodeling and in PE. The nine miRNAs identified in both concentric remodeling and PE-complicated pregnancy were: miR-1, miR-18, miR-21, miR-29b, miR-30, miR-125b, miR-181b, miR-195 and miR-499-5p. We found five of these miRNAs (miR-18, miR-21, miR-125b, miR-195 and miR-499-5p) to be upregulated in both PE pregnancy and cardiac remodeling and two (miR-1 and miR-30) to be downregulated in both; the remaining two miRNAs (miR-29b and miR-181b) showed upregulation during PE but downregulation in cardiac remodeling. This innovative approach may be a step towards finding relevant biomarkers for complicated pregnancy and elucidating their relationship with remote cardiovascular disease. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.

Over the past several decades, increasingly sophisticated models of the heart have provided important insights into cardiac physiology and are increasingly used to predict the impact of diseases and therapies on the heart. In an era of personalized medicine, many envision patient-specific computational models as a powerful tool for personalizing therapy. Yet the complexity of current models poses important challenges, including identifying model parameters and completing calculations quickly enough for routine clinical use. We propose that early clinical successes are likely to arise from an alternative approach: relatively simple, fast, phenomenologic models with a small number of parameters that can be easily (and automatically) customized. We discuss examples of simple yet foundational models that have already made a tremendous impact on clinical education and practice, and make the case that reducing rather than increasing model complexity may be the key to realizing the promise of patient-specific modeling for clinical applications.

Veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) therapy is widely used in critically ill patients with refractory cardiogenic shock and cardiac arrest or suffering from severe respiratory failure. Besides traditional ECMO cannulation, changes in patients' conditions or the occurrence of specific complications (i.e., cerebral hypoxia or left ventricular dilation) may require modifications in cannulation strategies or the combination of ECMO with additional invasive or minimally invasive procedures, to improve organ function and ECMO efficiency. In this review, we described all these "hybrid" approaches, such as the addition of a third or fourth ECMO cannula to improve venous drainage and/or optimize systemic hemodynamics/oxygenation, or the implementation of surgical or percutaneous unloading of the left ventricle (LV), to reduce cardiac dilation and pulmonary edema. Although few data are still available about the effectiveness of such interventions, clinicians should be aware of these advances in ECMO management to improve the management of more complex cases.

Veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) therapy is widely used in critically ill patients with refractory cardiogenic shock and cardiac arrest or suffering from severe respiratory failure. Besides traditional ECMO cannulation, changes in patients' conditions or the occurrence of specific complications (i.e., cerebral hypoxia or left ventricular dilation) may require modifications in cannulation strategies or the combination of ECMO with additional invasive or minimally invasive procedures, to improve organ function and ECMO efficiency. In this review, we described all these "hybrid" approaches, such as the addition of a third or fourth ECMO cannula to improve venous drainage and/or optimize systemic hemodynamics/oxygenation, or the implementation of surgical or percutaneous unloading of the left ventricle (LV), to reduce cardiac dilation and pulmonary edema. Although few data are still available about the effectiveness of such interventions, clinicians should be aware of these advances in ECMO management to improve the management of more complex cases.

Knowledge of appropriate local fiber architecture is necessary to simulate patient‐specific electromechanics in the human heart. However, it is not yet possible to reliably measure in vivo fiber directions especially in human atria. Thus, we present a method that defines the fiber architecture in arbitrarily shaped atria using image registration and reorientation methods based on atlas atria with fibers predefined from detailed histological observations. Thereby, it is possible to generate detailed fiber families in every new patient‐specific geometry in an automated, time‐efficient process. We demonstrate the good performance of the image registration and fiber definition on 10 differently shaped human atria. Additionally, we show that characteristics of the electrophysiological activation pattern that appear in the atlas atria also appear in the patients' atria. We arrive to analogous conclusions for coupled electro‐mechano‐hemodynamical computations.

Cardiac structure and function are complex and inter-related. Current in vivo techniques assess the heart on a macroscopic scale, but a novel technique called diffusion tensor cardiovascular magnetic resonance (DT-CMR) can now assess the cardiac microstructure non-invasively. It provides information on the helical arrangement of cardiomyocytes that drives torsion and offers dynamic assessment of the sheetlets (aggregated cardiomyocytes) that rotate through the cardiac cycle to facilitate wall thickening. Through diffusion biomarkers, the expansion and organisation of the underlying myocardium can be described. DT-CMR has already identified novel microstructural abnormalities in cardiomyopathy, and ischaemic and congenital heart disease. This new knowledge supports the potential of DT-CMR to improve diagnostics and prognostication in various cardiac diseases.

BACKGROUND Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. OBJECTIVES This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. METHODS In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. RESULTS In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ~46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ~17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48 ; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40° ; p < 0.001) with impaired E2A mobility (20°; p < 0.001). CONCLUSIONS Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans. (J Am Coll Cardiol 2017;69:661–76) Published by Elsevier on behalf of the American College of Cardiology Foundation.

Objective Next to myocardial perfusion, single-photon emission computed tomography (SPECT) also allows for assessment of non-perfusion parameters such as transient ischemic dilatation (TID) and a reduction of ejection fraction (EF) with stress imaging. The present study aimed to evaluate the diagnostic value of TID and EF reserve for the detection of significant multivessel coronary artery disease (CAD). Methods A total of 206 patients with suspected stable coronary artery disease prospectively underwent gated stress-rest 99mTc-tetrofosmin SPECT and invasive coronary angiography with routine fractional flow reserve (FFR) measurements, regardless of imaging results. Left ventricular (LV) volumes, TID and EF reserve were assessed and compared with FFR defined severity of CAD. Results According to FFR, 92 (45%) patients had significant CAD, whereas 25 (12%) showed two vessel disease and 22 (11%) showed three vessel disease (3-VD). With an increasing extent of CAD, TID values and EF reserve did not significantly change (p = 0.07 and p = 0.42 for trend, respectively). Conversely, absolute LV volumes and EF differed significantly among groups of CAD severity (p < 0.01 for all trends). Conclusion SPECT derived TID and EF reserve did not differ between patients with high risk CAD (3-VD) and low risk or no significant CAD. Therefore the present results advocate exert caution when using these ancillary findings in clinical practice.

Image-based patient-specific Computational Fluid Dynamics (CFD) models of the Left Ventricle (LV) can be used to quantify hemodynamics-based biomarkers that can support the clinicians in the early diagnosis, follow-up and treatment planning of patients, beyond the capabilities of the current imaging modalities. We propose a workflow to build patient-specific CFD models of the LV with moving boundaries based on the Chimera technique to overcome the convergence issues previously encountered by means of the Arbitrarian Lagrangian Eulerian approach. The workflow was tested while investigating whether the torsional motion has an impact on LV fluid dynamics. Starting from 3D cine MRI scans of a healthy volunteer, six cardiac cycles were simulated in three CFD LV models: with no, physiological, and exaggerated torsion. The Chimera technique was robust in handling the impulsive motion of the LV endocardium, allowing to notice cycle-to-cycle variations in every simulated case. Torsion affected slightly velocity, vorticity, WSS. It did not affect energy loss and induced a double-sided effect in terms of residence time: the particles ejected in one beat decreased, whereas the motility of the particles remaining in the LV was affected only in the exaggerated torsion case, indicating that implementation of torsion can be discarded in case of physiological levels. Nonetheless, caution is warranted when interpreting these results given the absence of the mitral valve, the papillary muscles, and the trabeculae. The effects of the mitral valve will be evaluated within an Fluid Structure Interaction simulation framework as further development of the current model.

Deep learning approaches have achieved state-of-the-art performance in cardiac magnetic resonance (CMR) image segmentation. However, most approaches have focused on learning image intensity features for segmentation, whereas the incorporation of anatomical shape priors has received less attention. In this paper, we combine a multi-task deep learning approach with atlas propagation to develop a shape-refined bi-ventricular segmentation pipeline for short-axis CMR volumetric images. The pipeline first employs a fully convolutional network (FCN) that learns segmentation and landmark localization tasks simultaneously. The architecture of the proposed FCN uses a 2.5D representation, thus combining the computational advantage of 2D FCNs networks and the capability of addressing 3D spatial consistency without compromising segmentation accuracy. Moreover, a refinement step is designed to explicitly impose shape prior knowledge and improve segmentation quality. This step is effective for overcoming image artifacts (e.g., due to different breath-hold positions and large slice thickness), which preclude the creation of anatomically meaningful 3D cardiac shapes. The pipeline is fully automated, due to network’s ability to infer landmarks, which are then used downstream in the pipeline to initialize atlas propagation. We validate the pipeline on 1831 healthy subjects and 649 subjects with pulmonary hypertension. Extensive numerical experiments on the two datasets demonstrate that our proposed method is robust and capable of producing accurate, high-resolution, and anatomically smooth bi-ventricular 3D models, despite the presence of artifacts in input CMR volumes.

Cardiovascular magnetic resonance (CMR) imaging is a standard imaging modality for assessing cardiovascular diseases (CVDs), the leading cause of death globally. CMR enables accurate quantification of the cardiac chamber volume, ejection fraction and myocardial mass, providing information for diagnosis and monitoring of CVDs. However, for years, clinicians have been relying on manual approaches for CMR image analysis, which is time consuming and prone to subjective errors. It is a major clinical challenge to automatically derive quantitative and clinically relevant information from CMR images. Deep neural networks have shown a great potential in image pattern recognition and segmentation for a variety of tasks. Here we demonstrate an automated analysis method for CMR images, which is based on a fully convolutional network (FCN). The network is trained and evaluated on a large-scale dataset from the UK Biobank, consisting of 4,875 subjects with 93,500 pixelwise annotated images. The performance of the method has been evaluated using a number of technical metrics, including the Dice metric, mean contour distance and Hausdorff distance, as well as clinically relevant measures, including left ventricle (LV) end-diastolic volume (LVEDV) and end-systolic volume (LVESV), LV mass (LVM); right ventricle (RV) end-diastolic volume (RVEDV) and end-systolic volume (RVESV). By combining FCN with a large-scale annotated dataset, the proposed automated method achieves a high performance on par with human experts in segmenting the LV and RV on short-axis CMR images and the left atrium (LA) and right atrium (RA) on long-axis CMR images., Comment: Accepted for publication by Journal of Cardiovascular Magnetic Resonance

Myocardial contrast echocardiography (MCE) is an imaging technique that assesses left ventricle function and myocardial perfusion for the detection of coronary artery diseases. Automatic MCE perfusion quantification is challenging and requires accurate segmentation of the myocardium from noisy and time-varying images. Random forests (RF) have been successfully applied to many medical image segmentation tasks. However, the pixel-wise RF classifier ignores contextual relationships between label outputs of individual pixels. RF which only utilizes local appearance features is also susceptible to data suffering from large intensity variations. In this paper, we demonstrate how to overcome the above limitations of classic RF by presenting a fully automatic segmentation pipeline for myocardial segmentation in full-cycle 2D MCE data. Specifically, a statistical shape model is used to provide shape prior information that guide the RF segmentation in two ways. First, a novel shape model (SM) feature is incorporated into the RF framework to generate a more accurate RF probability map. Second, the shape model is fitted to the RF probability map to refine and constrain the final segmentation to plausible myocardial shapes. We further improve the performance by introducing a bounding box detection algorithm as a preprocessing step in the segmentation pipeline. Our approach on 2D image is further extended to 2D+t sequence which ensures temporal consistency in the resultant sequence segmentations. When evaluated on clinical MCE data, our proposed method achieves notable improvement in segmentation accuracy and outperforms other state-of-the-art methods including the classic RF and its variants, active shape model and image registration., 11 pages, 9 figures, published in TMI

Author(s): Ferreira, Pedro F; Nielles-Vallespin, Sonia; Scott, Andrew D; de Silva, Ranil; Kilner, Philip J; Ennis, Daniel B; Auger, Daniel A; Suever, Jonathan D; Zhong, Xiaodong; Spottiswoode, Bruce S; Pennell, Dudley J; Arai, Andrew E; Firmin, David N | Abstract: PurposeTo evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging.MethodsHealthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2 -induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data.ResultsStrain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038.ConclusionsThe current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required. Magn Reson Med 79:2205-2215, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Experimental studies on isolated cardiomyocytes from different animal species and human hearts have demonstrated that there are regional differences in the Ca2+ release, Ca2+ decay and sarcomere deformation. Local deformation heterogeneities can occur due to a combination of factors: regional/local differences in Ca2+ release and/or re-uptake, intra-cellular material properties, sarcomere proteins and distribution of the intracellular organelles. To investigate the possible causes of these heterogeneities, we developed a two-dimensional finite-element electromechanical model of a cardiomyocyte that takes into account the experimentally measured local deformation and cytosolic [Ca2+] to locally define the different variables of the constitutive equations describing the electro/mechanical behaviour of the cell. Then, the model was individualised to three different rat cardiac cells. The local [Ca2+] transients were used to define the [Ca2+]-dependent activation functions. The cell-specific local Young’s moduli were estimated by solving an inverse problem, minimizing the error between the measured and simulated local deformations along the longitudinal axis of the cell. We found that heterogeneities in the deformation during contraction were determined mainly by the local elasticity rather than the local amount of Ca2+, while in the relaxation phase deformation was mainly influenced by Ca2+ re-uptake. Our electromechanical model was able to successfully estimate the local elasticity along the longitudinal direction in three different cells. In conclusion, our proposed model seems to be a good approximation to assess the heterogeneous intracellular mechanical properties to help in the understanding of the underlying mechanisms of cardiomyocyte dysfunction. This study was partly supported by grants from Ministerio de Economia y Competitividad (ref. SAF2012-37196, TIN2014-52923-R); the Instituto de Salud Carlos III (ref. PI11/01709, PI14/00226) integrado en el Plan Nacional de I+D+I y cofinanciado por el ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER) “Otra manera de hacer Europa”; the EU FP7 for research, technological development and demonstration under grant agreement VP2HF (n° 611823); The Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); Obra Social “la Caixa” (Barcelona, Spain); Fundació Mutua Madrileña; Fundació Agrupació Mutua (Spain) and AGAUR 2014 SGR grant n° 928 (Barcelona, Spain). P.G.C. was supported by the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, Spain. P.G.C wants to acknowledge to Boehringer Ingelhiem Fonds for the travel grant to do her research stay at LaBS group in Politecnico di Milano.

Myocardial heterogeneity is well appreciated and widely documented, from sub-cellular to organ levels. This paper reviews significant achievements of the group, led by Professor Vladimir S. Markhasin, Russia, who was one of the pioneers in studying and interpreting the relevance of cardiac functional heterogeneity.

A numerical simulation model of the cardiovascular system has been developed. It consists of a model of the left atrium, the left ventricle, the coronary vascular system, the aorta, the arterial system, and the venous system. The input of the complete model is the elastance (pressure/volume ratio) developed by the left ventricle. The shape of this elastance is constant in different circumstances. Left ventricular (LV) myocardial oxygen consumption and the amount of oxygen offered to the left ventricle can be calculated with the model. The model has been validated using data from a patient suffering from coronary artery disease. The measured clinical hemodynamical waveforms could be fitted to those generated by the model. With the numerical simulation model, it is possible to predict the functioning of the left ventricle under different circumstances. This makes it possible to study in vitro various pathological clinical situations.

The present study investigated whether functional, molecular, and biochemical alterations occurring in chronic heart failure can already be detected in compensated hypertensive cardiac hypertrophy. Force of contraction (isolated papillary muscle strip preparations), sarcoplasmic reticulum (SR) protein and myosin heavy chain isoform expression (Northern and Western blot analysis), myocardial fibrosis (collagen stains, hydroxyproline quantification), myocardial renin mRNA (RT-PCR), and angiotensin II levels and plasma aldosterone concentrations (radioimmunoassay) were studied in hypertrophied myocardium from transgenic rats harboring the mouse Ren-2d gene. Contraction and relaxation velocities of isolated papillary muscle strips were significantly reduced in cardiac hypertrophy. The beta-/alpha-myosin heavy chain ratio was significantly increased in the hypertrophied left ventricles, whereas SR Ca2+-ATPase (SERCA 2a) and phospholamban mRNA and protein levels were significantly decreased. The decrease in SERCA 2a was more pronounced than the decrease in phospholamban levels. There was no increased myocardial fibrosis. Left ventricular myocardial renin mRNA and angiotensin II concentrations, as well as plasma aldosterone levels, were higher in transgenic than in control rats. In hypertensive cardiac hypertrophy, myosin heavy chain isoform shift and reduction of SR protein levels are related to systolic and diastolic dysfunction, respectively. These alterations pre cede the development of myocardial fibrosis. Increased myocardial renin mRNA and angiotensin II concentrations suggest that an activated tissue renin-angiotensin system might contribute to these alterations. Since the alterations in compensated cardiac hypertrophy apparently precede those in chronic heart failure, they might accelerate the transition from hypertrophy to failure and could therefore be targets for pharmacological interventions.

In this paper, the influence of the upstream boundary condition for the numerical simulation of an aortic Bileaflet Mechanical Heart Valve (BMHV) is studied. Two types of upstream boundary conditions are discussed and evaluated. First, an inflow velocity profile is imposed at the inlet of the valve. Secondly, a geometrical boundary condition is used, which implies that the flow rate is governed by the geometrical contraction of the left-ventricle (LV). Both boundary conditions are used to simulate a 3D case with the same BMHV. The change in time of the LV volume is calculated such that the flow rate through the valve is identical in both cases. The dynamics of the BMHV are modelled using fluid-structure interaction (FSI) and only the opening phase of the valve is simulated. The simulations show that although the results for the two cases are similar, differences occur in the leaflet movement. In particular, when using the velocity profile, the leaflets impact the blocking mechanism at their open position with a 25% larger angular velocity. Therefore, when one wants to simulate the dynamics of such an impact, the upstream boundary condition needs to be chosen carefully.

This paper presents a new approach to higher dimensional segmentation. We present an extended Active Shape Model (ASM) formulation for the segmentation of multi-contour anatomical structures. We employ coupling and weighting schemes to improve the robustness of ASM segmentation. 3D segmentation is achieved through propagation of a 2D ASM using a learned non-rigid spatial model. This approach does not suffer from the training and aligning difficulties faced by direct 3D model-based methods. Experimental results are encouraging at this early stage, and future directions of research are provided.

Abstract The present study investigated whether functional, molecular, and biochemical alterations occurring in chronic heart failure can already be detected in compensated hypertensive cardiac hypertrophy. Force of contraction (isolated papillary muscle strip preparations), sarcoplasmic reticulum (SR) protein and myosin heavy chain isoform expression (Northern and Western blot analysis), myocardial fibrosis (collagen stains, hydroxyproline quantification), myocardial renin mRNA (RT-PCR), and angiotensin II levels and plasma aldosterone concentrations (radioimmunoassay) were studied in hypertrophied myocardium from transgenic rats harboring the mouse Ren -2d gene. Contraction and relaxation velocities of isolated papillary muscle strips were significantly reduced in cardiac hypertrophy. The β-/α-myosin heavy chain ratio was significantly increased in the hypertrophied left ventricles, whereas SR Ca 2+ -ATPase (SERCA 2a) and phospholamban mRNA and protein levels were significantly decreased. The decrease in SERCA 2a was more pronounced than the decrease in phospholamban levels. There was no increased myocardial fibrosis. Left ventricular myocardial renin mRNA and angiotensin II concentrations, as well as plasma aldosterone levels, were higher in transgenic than in control rats. In hypertensive cardiac hypertrophy, myosin heavy chain isoform shift and reduction of SR protein levels are related to systolic and diastolic dysfunction, respectively. These alterations precede the development of myocardial fibrosis. Increased myocardial renin mRNA and angiotensin II concentrations suggest that an activated tissue renin-angiotensin system might contribute to these alterations. Since the alterations in compensated cardiac hypertrophy apparently precede those in chronic heart failure, they might accelerate the transition from hypertrophy to failure and could therefore be targets for pharmacological interventions.

Pre-eclampsia (PE) is strongly associated with heart failure (HF) later in life. During PE pregnancy, the left ventricle undergoes concentric remodeling which often persists after delivery. This aberrant remodeling can induce a molecular signature that can be evaluated in terms of microRNAs (miRNAs) and which may help to explain the associated increased risk of HF. For this review, we performed a literature search of PubMed (National Center for Biotechnology Information), identifying studies on miRNA expression in concentric remodeling and on miRNA expression in PE. The miRNA data were stratified based on origin (isolated from humans or animals and from tissue or the circulation) and both datasets compared in order to generate a list of miRNA expression patterns in concentric remodeling and in PE. The nine miRNAs identified in both concentric remodeling and PE-complicated pregnancy were: miR-1, miR-18, miR-21, miR-29b, miR-30, miR-125b, miR-181b, miR-195 and miR-499-5p. We found five of these miRNAs (miR-18, miR-21, miR-125b, miR-195 and miR-499-5p) to be upregulated in both PE pregnancy and cardiac remodeling and two (miR-1 and miR-30) to be downregulated in both; the remaining two miRNAs (miR-29b and miR-181b) showed upregulation during PE but downregulation in cardiac remodeling. This innovative approach may be a step towards finding relevant biomarkers for complicated pregnancy and elucidating their relationship with remote cardiovascular disease. Copyright (c) 2017 ISUOG. Published by John Wiley & Sons Ltd.