Search Results (17)

Some studies report better outcomes in cell therapy for myocardial infarction (MI) with repeated administrations. We aimed to elucidate the potential differences in terms of cardiac function and protein expression after one or three doses of cardiosphere-derived cells (CDCs) in a porcine MI model. CDCs were isolated from swine cardiac explants, cultured in cardiomyocyte growth medium (CGM), and prepared for administration. Pigs surviving a 90 min balloon occlusion of the mid-left anterior descending coronary artery (LAD) were randomly allocated to receive vehicle (CON), one (D1), or three (D3) doses of 30 × 10⁶ CDCs via the infarct-related coronary artery. Cardiac function was assessed with magnetic resonance at baseline and 10 weeks. Programmed electrical stimulation to study arrhythmogenicity was performed at 10 weeks. High-throughput quantitative proteomic analysis of infarcted tissue was performed to identify biological processes based on protein abundance changes between groups. No significant differences were found between the three groups for any cardiac function parameter at 10 weeks. No increase in ventricular tachycardia inducibility was seen in treated groups. However, gene ontology and topological analyses revealed potentially beneficial molecular adaptations. Upregulation of GYS1, AGL, and GBE1 indicated an increase in glycogen biosynthesis and energy availability, while an increase in ANK2, along with hub proteins ALB and TRAP1, suggested cardioprotective effects. Furthermore, the increase in remodeling-related proteins, including EPHA4, PODN, and ALPK3, pointed to favorable structural adaptation following infarction. In conclusion, the intracoronary administration of single or repeated doses of 30 × 10⁶ CDCs to a porcine reperfused MI model shows only slight differential improvement in both cardiac function and protein profile in this experimental setting, thus presenting limited translational potential. Full article

Heterotaxy syndrome is characterized by a tendency for bilaterally symmetric arrangement (isomerism) of inner organs. It is frequently associated with complex congenital heart defects (CHDs). In “heterotaxic” hearts, the tendency for isomerism is confined to the atria. The ventricular segment always shows asymmetric arrangements (D-hand or L-hand topology). This study aimed to determine the statistical distribution of ventricular topology among patients with CHDs associated with heterotaxy and to identify possible associations between ventricular topology and cardiovascular disorders and survival. It is a retrospective cross-sectional study on 192 patients treated at a single center between 2000 and 2023. Our cohort had 115 patients of left atrial isomerism (LAI) and 77 of right atrial isomerism (RAI). The whole cohort (n = 192) showed a bias towards ventricular D-hand topology (67%), which was statistically significant in LAI (74%). In contrast, RAI showed an almost equal distribution (57% D-hand, 43% L-hand). No significant associations were found between ventricular topology and major CHDs or mortality. Significant associations were observed between ventricular topology and cardiac apex position, direction of p-wave axis, and aortic arch sidedness. We conclude that, in the setting of heterotaxy, especially RAI, ventricular topology and aortic arch sidedness both behave as binary anatomical variables showing a tendency for randomized occurrence. This tendency for statistically symmetric distribution is interpreted as reflecting the syndrome-specific tendency for bilateral symmetry. Full article

Ventricular arrhythmias (VAs) are critical cardiovascular diseases that require rapid and accurate detection. Conventional approaches relying on multi-lead ECG or deep learning models have limitations in computational cost, interpretability, and real-time applicability on wearable devices. To address these issues, a lightweight and interpretable framework based on multiple complex networks was proposed for the detection of life-threatening VAs using short-term single-lead ECG signals. The input signals were decomposed using the fixed-frequency-range empirical wavelet transform, and sub-bands were subsequently analyzed through multiscale visibility graphs, recurrence networks, cross-recurrence networks, and joint recurrence networks. Eight topological features were extracted and input into an XGBoost classifier for VA identification. Ten-fold cross-validation results on the MIT-BIH VFDB and CUDB databases demonstrated that the proposed method achieved a sensitivity of 99.02 ± 0.53%, a specificity of 98.44 ± 0.43%, and an accuracy of 98.73 ± 0.02% for 10 s ECG segments. The model also maintained robust performance on shorter segments, with 97.23 ± 0.76% sensitivity, 98.85 ± 0.95% specificity, and 96.62 ± 0.02% accuracy on 2 s segments. The results outperformed existing feature-based and deep learning approaches while preserving model interpretability. Furthermore, the proposed method supports mobile deployment, facilitating real-time use in wearable healthcare applications. Full article

While essential hypertension (HTN) is very prevalent, pulmonary arterial hypertension (PAH) is very rare in the general population. However, due to progressive heart failure, prognoses and survival rates are much worse in PAH. Patients with PAH are at a higher risk of developing supraventricular arrhythmias and malignant ventricular arrhythmias. The latter underlie sudden cardiac death regardless of the mechanical cardiac dysfunction. Systemic chronic inflammation and oxidative stress are causal factors that increase the risk of the occurrence of cardiac arrhythmias in hypertension. These stressful factors contribute to endothelial dysfunction and arterial pressure overload, resulting in the development of cardiac pro-arrhythmic conditions, including myocardial structural, ion channel and connexin43 (Cx43) channel remodeling and their dysfunction. Myocardial fibrosis appears to be a crucial proarrhythmic substrate linked with myocardial electrical instability due to the downregulation and abnormal topology of electrical coupling protein Cx43. Furthermore, these conditions promote ventricular mechanical dysfunction and heart failure. The treatment algorithm in HTN is superior to PAH, likely due to the paucity of comprehensive pathomechanisms and causal factors for a multitargeted approach in PAH. The intention of this review is to provide information regarding the role of Cx43 in the development of cardiac arrhythmias in hypertensive heart disease. Furthermore, information on the progress of therapy in terms of its cardioprotective and potentially antiarrhythmic effects is included. Specifically, the benefits of sodium glucose co-transporter inhibitors (SGLT2i), as well as sotatercept, pirfenidone, ranolazine, nintedanib, mirabegron and melatonin are discussed. Discovering novel therapeutic and antiarrhythmic strategies may be challenging for further research. Undoubtedly, such research should include protection of the heart from inflammation and oxidative stress, as these are primary pro-arrhythmic factors that jeopardize cardiac Cx43 homeostasis, the integrity of intercalated disk and extracellular matrix, and, thereby, heart function. Full article

This review focuses on cardiac atrophy resulting from mechanical or metabolic unloading due to various conditions, describing some mechanisms and discussing possible strategies or interventions to prevent, attenuate or reverse myocardial atrophy. An improved awareness of these conditions and an increased focus on the identification of mechanisms and therapeutic targets may facilitate the development of the effective treatment or reversion for cardiac atrophy. It appears that a decrement in the left ventricular mass itself may be the central component in cardiac deconditioning, which avoids the occurrence of life-threatening arrhythmias. The depressed myocardial contractility of atrophied myocardium along with the upregulation of electrical coupling protein, connexin43, the maintenance of its topology, and enhanced PKCε signalling may be involved in the anti-arrhythmic phenotype. Meanwhile, persistent myocardial atrophy accompanied by oxidative stress and inflammation, as well as extracellular matrix fibrosis, may lead to severe cardiac dysfunction, and heart failure. Data in the literature suggest that the prevention of heart failure via the attenuation or reversion of myocardial atrophy is possible, although this requires further research. Full article

This is our second article devoted to the cardiac myoarchitecture considered as a nematic chiral liquid crystal (NCLC). While the first article focused on the myoarchitecture of the left ventricle (LV), this new article extends to the whole ventricular mass and introduces the concept of disclinations and topological singularities, which characterize the differences and relationships between the left and right ventricles (RV). At the level of the ventricular apices, we constantly observed a vortex shape at the LV apex, corresponding, in the terminology of liquid crystals, to a “+1 disclination”; we never observed this at the RV apex. At the level of the interventricular septum (IVS), we identified “−1/2 disclinations” at the anterior and posterior parts. During the perinatal period, there was a significant difference in their distribution, with more “−1/2 disclinations” in the posterior part of the IVS. After birth, concomitant to major physiological changes, the number of “−1/2 disclinations” significantly decreased, both in the anterior and posterior parts of the IVS. Finally, the description of the disclinations must be considered in any attempt to segment the whole ventricular mass, in biomechanical studies, and, more generally, for the characterization of myocardial remodeling. Full article

Early ventricular fibrillation (VF) prediction is critical for prevention of sudden cardiac death, and can improve patient survival. Generally, electrocardiogram (ECG) signal features are extracted to predict VF, a process which plays an important role in prediction accuracy. Therefore, this study first proposes a novel feature based on topological data analysis (TDA) to improve the accuracy of early ventricular fibrillation prediction. Firstly, the heart activity is regarded as a cardiac dynamical system, which is described by phase space reconstruction. Then the topological structure of the phase space is characterized with persistent homology, and its statistical features are further extracted and defined as TDA features. Finally, 60 subjects (30 VF, 30 healthy) from three public ECG databases are used to validate the prediction performance of the proposed method. Compared to heart rate variability features and box-counting features, TDA features achieve a superior accuracy of 91.7%. Additionally, the three types of features are combined as fusion features, achieving the optimal accuracy of 95.0%. The fusion features are then ranked, and the first seven components are all from the TDA features. It follows that the proposed features provide a significant effect in improving the predictive performance of early VF. Full article

A rapid and accurate detection of ventricular arrhythmias is essential to take appropriate therapeutic actions when cardiac arrhythmias occur. Furthermore, the accurate discrimination between arrhythmias is also important, provided that the required shocking therapy would not be the same. In this work, the main novelty is the use of the mathematical method known as Topological Data Analysis (TDA) to generate new types of features which can contribute to the improvement of the detection and classification performance of cardiac arrhythmias such as Ventricular Fibrillation (VF) and Ventricular Tachycardia (VT). The electrocardiographic (ECG) signals used for this evaluation were obtained from the standard MIT-BIH and AHA databases. Two input data to the classify are evaluated: TDA features, and Persistence Diagram Image (PDI). Using the reduced TDA-obtained features, a high average accuracy near 99% was observed when discriminating four types of rhythms (98.68% to VF; 99.05% to VT; 98.76% to normal sinus; and 99.09% to Other rhythms) with specificity values higher than 97.16% in all cases. In addition, a higher accuracy of 99.51% was obtained when discriminating between shockable (VT/VF) and non-shockable rhythms (99.03% sensitivity and 99.67% specificity). These results show that the use of TDA-derived geometric features, combined in this case this the k-Nearest Neighbor (kNN) classifier, raises the classification performance above results in previous works. Considering that these results have been achieved without preselection of ECG episodes, it can be concluded that these features may be successfully introduced in Automated External Defibrillation (AED) and Implantable Cardioverter Defibrillation (ICD) therapies. Full article

There are still confusing descriptions of how congenitally malformed hearts should be categorised, even in their simplest forms. Despite repeated attempts toward a unified and simplified analysis, morphologists and clinicians continue to use different nomenclatures. This variability has a profound impact not only on how we communicate with patients but also on how the healthcare professionals produce clinical reports, research papers and educational and training materials, not to mention the impact on other levels such as managerial, administrative, coding, financial and media communications. Moreover, there are influences on how we actually treat patients based on a different understanding of nomenclature. This paper aims to explain a method of analysing the cardiac segments and their connections based on the current understanding of structural development. Full article

Accurate segmentation of the myocardial scar may supply relevant advancements in predicting and controlling deadly ventricular arrhythmias in subjects with cardiovascular disease. In this paper, we propose the architecture of inclusion and classification of prior information U-Net (ICPIU-Net) to efficiently segment the left ventricle (LV) myocardium, myocardial infarction (MI), and microvascular-obstructed (MVO) tissues from late gadolinium enhancement magnetic resonance (LGE-MR) images. Our approach was developed using two subnets cascaded to first segment the LV cavity and myocardium. Then, we used inclusion and classification constraint networks to improve the resulting segmentation of the diseased regions within the pre-segmented LV myocardium. This network incorporates the inclusion and classification information of the LGE-MRI to maintain topological constraints of pathological areas. In the testing stage, the outputs of each segmentation network obtained with specific estimated parameters from training were fused using the majority voting technique for the final label prediction of each voxel in the LGE-MR image. The proposed method was validated by comparing its results to manual drawings by experts from 50 LGE-MR images. Importantly, compared to various deep learning-based methods participating in the EMIDEC challenge, the results of our approach have a more significant agreement with manual contouring in segmenting myocardial diseases. Full article

There are still grey areas in the understanding of the myoarchitecture of the ventricular mass. This is despite the progress of investigation methods since the beginning of the 21st century (diffusion tensor magnetic resonance imaging, microcomputed tomography, and polarised light imaging). The objective of this article is to highlight the specificities and the limitations of polarised light imaging (PLI) of the unstained myocardium embedded in methyl methacrylate (MMA). Thus, to better differentiate our method from other PLI modes, we will refer to it by the acronym PLI-MMA. PLI-MMA shows that the myosin mesh of the compact left ventricular wall behaves like a biological analogous of a nematic chiral liquid crystal. Results obtained by PLI-MMA are: the main direction of the myosin molecules contained in an imaged voxel, the crystal liquid director n, and a regional isotropy index RI that is an orientation tensor, the equivalent of the crystal liquid order parameter. The vector n is collinear with the first eigenvector of diffusion tensor imaging (DTI-MRI). The RI has not been confounded with the diffusion tensor of DTI that gives information about the three eigenvectors of the ellipsoid of diffusion. PLI-MMA gives no information about the collagen network. The physics of soft matter has allowed the revisiting of Streeter’s conjecture on the myoarchitecture of the compact left ventricular wall: “geodesics on a nested set of toroidal surfaces”. Once the torus topology is understood, this characterisation of the myoarchitecture is more accurate and parsimonious than former descriptions. Finally, this article aims to be an enthusiastic invitation to a transdisciplinary approach between physicists of liquid crystals, anatomists, and specialists of imaging. Full article

3D imaging in animal models, during development or in adults, facilitates the identification of structural morphological changes that cannot be achieved with traditional 2D histological staining. Through the reconstruction of whole embryos or a region-of-interest, specific changes are better delimited and can be easily quantified. We focused here on high-resolution episcopic microscopy (HREM), and its potential for visualizing and quantifying the organ systems of normal and genetically altered embryos and adult organisms. Although the technique is based on episcopic images, these are of high resolution and are close to histological quality. The images reflect the tissue structure and densities revealed by histology, albeit in a grayscale color map. HREM technology permits researchers to take advantage of serial 2D aligned stacks of images to perform 3D reconstructions. Three-dimensional visualization allows for an appreciation of topology and morphology that is difficult to achieve with classical histological studies. The nature of the data lends itself to novel forms of computational analysis that permit the accurate quantitation and comparison of individual embryos in a manner that is impossible with histology. Here, we have developed a new HREM prototype consisting of the assembly of a Leica Biosystems Nanocut rotary microtome with optics and a camera. We describe some examples of applications in the prenatal and adult lifestage of the mouse to show the added value of HREM for phenotyping experimental cohorts to compare and quantify structure volumes. At prenatal stages, segmentations and 3D reconstructions allowed the quantification of neural tissue and ventricular system volumes of normal brains at E14.5 and E16.5 stages. 3D representations of normal cranial and peripheric nerves at E15.5 and of the normal urogenital system from stages E11.5 to E14.5 were also performed. We also present a methodology to quantify the volume of the atherosclerotic plaques of ApoE^{tm1Unc/tm1Unc} mutant mice and illustrate a 3D reconstruction of knee ligaments in adult mice. Full article

Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-β1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKCε, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats. Full article