Cardiac Components Research Articles

The myoarchitecture of the vertebrate cardiac ventricles: evolution and classification.

The ventricle of the vertebrate heart is the main segment of the cardiac outflow region. Compared with other cardiac components, it shows remarkable histomorphological variation among different animal groups. This variation is especially apparent in the myocardium, which is generally classified into three main types: trabeculated, compact and mixed. The trabeculated or 'spongy' myocardium is characterized by the existence of trabeculae and deep recesses or intertrabecular spaces, lined by the endocardium. The compact type is composed of condensed myocardial fibers, with almost no trabeculated layer. The mixed type consists of an outer compact layer and an inner trabeculated layer. Among vertebrates, fishes show a great diversity of myocardial types. On this basis, the ventricular myoarchitecture has been categorized into four groups of varying complexity. This classification is made according to (i) the proportion of the two types of myocardium, trabeculated versus compact, and (ii) the vascularization of the heart wall. Here, we review the morphogenetic mechanisms that give rise to the different ventricular myoarchitecture in gnathostomes (i.e. jawed vertebrates) with special emphasis on the diversity of the ventricular myocardium throughout the phylogeny of ancient actinopterygians and teleosts. Finally, we propose that the classification of the ventricular myoarchitecture should be reconsidered, given that the degrees of myocardial compactness on which the current classification system is based do not constitute discrete states, but an anatomical continuum.

A ballistocardiogram dataset with reference sensor signals in long-term natural sleep environments

To facilitate unobtrusive and continuous sleep monitoring and promote intelligent sleep quality assessment, we present a dataset that includes multiple nights of continuous ballistocardiogram (BCG) data collected using piezoelectric film sensors from 32 subjects in their regular sleep environments. Besides, the referenced heart rate and respiratory data are also recorded by reference sensors to validate the accuracy of the cardiac and respiratory components extracted from the BCG signals. The dataset serves as a foundation for research on unobtrusive vital sign monitoring based on BCG signals, offering data support for the evaluation and optimization of sleep quality.

Mouse Cardiovascular Imaging.

The mouse is the mammalian model of choice for investigating cardiovascular biology, given our ability to manipulate it by genetic, pharmacologic, mechanical, and environmental means. Imaging is an important approach to phenotyping both function and structure of cardiac and vascular components. This review details commonly used imaging approaches, with a focus on echocardiography and magnetic resonance imaging, with brief overviews of other imaging modalities. In this update, we also emphasize the importance of rigor and reproducibility in imaging approaches, experimental design, and documentation. Finally, we briefly outline emerging imaging approaches but caution that reliability and validity data may be lacking. © 2024 Wiley Periodicals LLC.

Study on the underlying mechanism of Huachansu Capsule induced cardiotoxicity of normal rat by integrating transcriptomics, metabolomics and network toxicology

Ethnopharmacological relevanceHuachansu Capsule (HCSc) is a simple enteric-coated capsule refined from the skin of the dried toad, a traditional medicinal herb. It has been used clinically for many years to treat a variety of malignant tumors with remarkable efficacy. To date, a number of main components of HCSc have been reported to be cardiotoxic, but the specific mechanism of cardiotoxicity is still unknown. Aim of the studyThe aim of this study was to elucidate the possible cardiotoxic symptoms caused by high-doses of HCSc and to further reveal the complex mechanisms by which it causes cardiotoxicity. Materials and methodsUPLC-Q-Exactive Orbitrap MS and network toxicology were used to identify and predict the potential toxic components, related signaling pathways. Then, we used acute and sub-acute toxicity experiments to reveal the apparent phenomenon of HCSc-induced cardiotoxicity. Finally, we combined transcriptomics and metabolomics to elucidate the potential mechanism of action, and verified the putative mechanism by molecular docking, RT-qPCR, and Western blot. ResultsWe found 8 toad bufadienolides components may be induced cardiac toxicity HCSc main toxic components. Through toxicity experiments, we found that high dose of HCSc could increase a variety of blood routine indexes, five cardiac enzymes, heart failure indexes (BNP), troponin (cTnI and cTnT), heart rate and the degree of heart tissue damage, while low-dose of HCSc had no such changes. In addition, by molecular docking, found that 8 kinds of main toxic components and cAMP, AMPK, IL1β, mTOR all can be a very good combination, especially in the cAMP. Meanwhile, RT-qPCR and Western blot results showed that HCSc could induce cardiotoxicity by regulating a variety of heart-related differential genes and activating the cAMP signaling pathway. ConclusionsIn this study, network toxicology, transcriptomics and metabolomics were used to elucidate the complex mechanism of possible cardiotoxicity induced by high-dose HCSc. Animal experiments, molecular docking, Western blot and RT-qPCR experiments were also used to verify the above mechanism. These findings will inform further mechanistic studies and provide theoretical support for its safe clinical application.

Phase-Resolved Functional Lung MRI for Pulmonary Ventilation and Perfusion (V/Q) Assessment.

Fourier decomposition is a contrast agent-free 1H MRI method for lung perfusion (Q) and ventilation (V) assessment. After image registration, the time series of each voxel is analyzed with regard to the cardiac and breathing frequency components. Using a standard 2D spoiled gradient-echo sequence with a temporal resolution of ~300 ms, an image-sorting algorithm was developed to produce phase-resolved functional lung imaging (PREFUL) with an increased temporal resolution. Thus, it is feasible to evaluate regional flow volume loops (FVL) during tidal volume breathing and depict the propagation of the pulse wave during the cardiac cycle. This method can be applied at 1.5T or 3T with standard MR hardware without the necessity for sequence programming, as the described protocol can be implemented with the default SPGRE sequence on most systems. PREFUL ventilation MRI has been validated using 129Xe and 19F gas imaging with good regional agreement. Perfusion-weighted PREFUL MRI has been validated using SPECT as well as dynamic contrast enhanced (DCE) MRI. PREFUL has been tested in a dual center dual vendor setting and is currently applied in several ongoing multicenter trials. Furthermore, it is feasible across a range of field strengths (0.55T-3T) and different age groups, including newborns. Quantitative V/Q PREFUL MRI has been used in patients with cystic fibrosis, chronic obstructive pulmonary disease, chronic thromboembolic pulmonary hypertension, and corona virus disease-2019 to quantify disease and monitor treatment change after therapy. Furthermore, PREFUL V/Q imaging has been shown to predict transplant loss due to chronic lung allograft dysfunction in patients after lung transplantation. In summary, PREFUL MRI is a validated technique for quantitative ventilation and pulmonary pulse wave/perfusion imaging for regional pulmonary disease detection, quantification, and treatment monitoring with potential added value to the current clinical routine.

Evaluating the effect of injection protocols on intrathecal solute dispersion in non-human primates: an in vitro study using a cynomolgus cerebrospinal fluid system

BackgroundAchieving effective drug delivery to the central nervous system (CNS) remains a challenge for treating neurological disorders. Intrathecal (IT) delivery, which involves direct injection into the cerebrospinal fluid (CSF), presents a promising strategy. Large animal studies are important to assess the safety and efficacy of most drugs and treatments and translate the data to humans. An understanding of the influence of IT injection parameters on solute distribution within the CNS is essential to optimize preclinical research, which would potentially help design human clinical studies.MethodsA three-dimensional (3D) in vitro model of a cynomolgus monkey, based on MRI data, was developed to evaluate the impact of lumbar injection parameters on intrathecal solute dispersion. The parameters evaluated were (a) injection location, (b) bolus volume, (c) flush volume, (d) bolus rate, and (e) flush rate. To simulate the CSF flow within the subarachnoid space (SAS), an idealized CSF flow waveform with both cardiac and respiratory-induced components was input into the model. A solution of fluorescein drug surrogate tracer was administered in the lumbar region of the 3D in vitro model filled with deionized water. After injection of the tracer, the CSF system wide-solute dispersion was imaged using high-resolution cameras every thirty seconds for a duration of three hours. To ensure repeatability each injection protocol was repeated three times. For each protocol, the average spatial–temporal distribution over three hours post-injection, the area under the curve (AUC), and the percent injected dose (%ID) to extra-axial CSF (eaCSF) at three hours were determined.ResultsThe changes to the lumbar injection parameters led to variations in solute distribution along the neuro-axis. Specifically, injection location showed the most impact, enhancing the delivery to the eaCSF up to + 10.5%ID (p = 0.0282) at three hours post-injection. Adding a post-injection flush of 1.5 ml at 1 ml/min increased the solute delivery to the eaCSF by + 6.5%ID (p = 0.0218), while the larger bolus volume resulted in a + 2.3%ID (p = 0.1910) increase. The bolus and flush rates analyzed had minimal, statistically non-significant effects.ConclusionThese results predict the effects of lumbar injection parameters on solute distribution in the intrathecal space in NHPs. Specifically, the choice of injection location, flush, and bolus volume significantly improved solute delivery to eaCSF. The in vitro NHP CSF model and results offer a system to help predict and optimize IT delivery protocols for pre-clinical NHP studies.

Central venous pressure waveform analysis during sleep/rest: a novel approach to enhance intensive care unit post-extubation monitoring of extubation failure.

This pilot study aimed to investigate the relation between cardio-respiratory parameters derived from Central Venous Pressure (CVP) waveform and Extubation Failure (EF) in mechanically ventilated ICU patients during post-extubation period. This study also proposes a new methodology for analysing these parameters during rest/sleep periods to try to improve the identification of EF. We conducted a prospective observational study, computing CVP-derived parameters including breathing effort, spectral analyses, and entropy in twenty critically ill patients post-extubation. The Dynamic Warping Index (DWi) was calculated from the respiratory component extracted from the CVP signal to identify rest/sleep states. The obtained parameters from EF patients and patients without EF were compared both during arbitrary periods and during reduced DWi (rest/sleep). We have analysed data from twenty patients of which nine experienced EF. Our findings may suggest significantly increased respiratory effort in EF patients compared to those successfully extubated. Our study also suggests the occurrence of significant change in the frequency dispersion of the cardiac signal component. We also identified a possible improvement in the differentiation between the two groups of patients when assessed during rest/sleep states. Although with caveats regarding the sample size, the results of this pilot study may suggest that CVP-derived cardio-respiratory parameters are valuable for monitoring respiratory failure during post-extubation, which could aid in managing non-invasive interventions and possibly reduce the incidence of EF. Our findings also indicate the possible importance of considering sleep/rest state when assessing cardio-respiratory parameters, which could enhance respiratory failure detection/monitoring.

In vivo calcium and voltage mapping of the zebrafish heart

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Foundation Flanders (FWO) Purpose Inherited cardiac arrhythmias are characterized by a disturbance in the normal electrical functioning of the heart due to a dysfunction of cardiac ion channels, accessory proteins and/or structural components. This complex process is difficult to model in vitro, while in vivo mouse models differ substantially from humans with regards to cardiac electrophysiology. Thus, there is a need for alternative disease models in cardiac arrhythmia research. The zebrafish heart shows remarkable similarity to humans in its electrocardiogram and action potential (AP) morphology. Due to the optical translucency of zebrafish larvae, it is possible visualize the cardiac calcium and voltage dynamics across their entire hearts in vivo by use of genetically encoded calcium and voltage indicators (GECI and GEVI). We combined the fast kinetics of a next generation voltage reporter (Ace2N-mNeon) with a spectrally compatible calcium sensor (R-GECO) to create a sensitive high throughput method for in vivo characterization of the cardiac AP. Methods Ace2N-mNeon and R-GECO were expressed under control of a myocardial specific promoter via the Tol2kit system. The effect of sensor expression on normal physiology was assessed by patch clamp experiments. Fluorescence recordings were obtained with a Leica SP8 DLS microscope and a custom-built light sheet microscope. Our zebrafish sensor line was validated by experiments with quinidine drug exposure, as well as a novel model for long QT syndrome (LQTS) with a knock-in (KI) mutation in the cacna1c gene. Results Sensor expression did not significantly alter cardiac electrophysiology. The tg(myl7:Ace2N-mNeon/R-GECO) line demonstrated alterations in the heart rate, depolarization and repolarization induced by quinidine exposure. We observed a significantly prolonged ventricular repolarization in the LQTS KI line. Three-dimensional optical maps of AP characteristics across the entire zebrafish heart exhibited the physiological characteristics of the zebrafish cardiac electrophysiology, with activation initiated at the atrial venous pole and propagated towards the ventricular outflow tract, prolonged repolarization in the ventricles compared to the atria and slowed depolarization in the atrio-ventricular canal. Conclusion By expressing Ace2N-mNeon and R-GECO in the zebrafish heart, we were able to accurately detect drug- and mutation induced alterations in the cardiac AP, as well as AP characteristics across the entire heart, without compromising normal cardiac electrophysiology. Our transgenic line will provide a promising assay for future studies of cardiac arrhythmia.

Role of NLRP3 inflammasome in cardiac damage in the setting of an acute cardiorenal syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ISCIII, Ministerio de Universidades, Education and Research Council of Madrid, Biomedicine Network Comunidad de Madrid Background Acute kidney injury (AKI) is usually associated with an acute cardiac impairment known as cardiorenal syndrome type 3 (CRS3). AKI induces the activation of the immune system being the connection with the disturbance in remote organs as the heart. In response to tissue damage, different inflammatory pathways are activated. In this sense, activation of cardiac nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome has been studied in several cardiac pathologies. Nevertheless, the role of cardiac NLRP3 in ventricular cardiomyocytes as a consequence of renal damage is unknown. Purpose The overall aim of this study was to analyse the involvement of NLRP3 in AKI-induced cardiac damage in CRS3. Firstly, we evaluated the predictive value for mortality of the inflammatory component associated with the NLRP3 in a cohort of AKI patients. Then, we studied whether cardiac NLRP3 activation takes place after AKI induction and whether this may be associated with functional alterations in ventricular cardiomyocytes related to cardiac dysfunction and predisposition to ventricular arrhytmia. Methods We have studied cardiac alterations resulting from AKI induced by folic acid (FA, 250 mg/Kg) after 72 hours in wild-type (WT), Nlrp3-/- and WT AKI mice treated with the NLRP3 inhibitor MCC950 (10 mg/Kg). We examined plasma, renal and cardiac inflammatory components associated with NLRP3, as well as cardiomyocyte intracellular Ca2+ handling by confocal microscopy in all experimental groups. In AKI patients, we analysed systemic NLRP3-related cytokine levels and their possible relationship with markers of renal and cardiac damage and the prediction of mortality. Results FA-induced AKI caused a worsening of contractile function in WT cardiomyocytes due to decreased systolic Ca2+ release after 72 hours. It was accompanied by impaired Ca2+ reuptake via SERCA2a. Nevertheless, in both MCC950-treated and NLRP3-/- mice, these alterations were significantly prevented. During diastole, significant Ca2+ leakage from the sarcoplasmic reticulum was observed after 72 hours of AKI-induction, as well as increased pro-arrhythmogenic events. These alterations were prevented in both NLRP3-/- and MCC950-treated AKI mice. In AKI patients, we found that NLRP3-related cytokines increased from the time of admission to 72 hours, significantly associated with biomarkers of renal and cardiovascular damage, and exhibited a high potential to predict mortality. Conclusions AKI impairs the cytosolic Ca2+ handling in ventricular cardiomyocytes that are translated into contractile dysfunction and increased occurrence of pro-arrhythmogenic events. These cardiac alterations are strongly prevented under NLRP3 blockade, demonstrating the deleterious role of its cardiac activation in CRS3. In addition, results from AKI patients point to NLRP3 as relevant prognostic target in AKI patients at the time of admission to hospital.

Cardiac development demystified by use of the HDBR atlas.

Much has been learned over the last half century regarding the molecular and genetic changes that take place during cardiac development. As yet, however, these advances have not been translated into knowledge regarding the marked changes that take place in the anatomical arrangements of the different cardiac components. As such, therefore, many aspects of cardiac development are still described on the basis of speculation rather than evidence. In this review, we show how controversial aspects of development can readily be arbitrated by the interested spectator by taking advantage of the material now gathered together in the Human Developmental Biology Resource; HDBR. We use the material to demonstrate the changes taking place during the formation of the ventricular loop, the expansion of the atrioventricular canal, the incorporation of the systemic venous sinus, the formation of the pulmonary vein, the process of atrial septation, the remodelling of the pharyngeal arches, the major changes occurring during formation of the outflow tract, the closure of the embryonic interventricular communication, and the formation of the ventricular walls. We suggest that access to the resource makes it possible for the interested observer to arbitrate, for themselves, the ongoing controversies that continue to plague the understanding of cardiac development.

Exploring Roemheld syndrome: acomprehensive review with proposed diagnostic criteria.

Roemheld syndrome (RS) is acondition that triggers cardiac symptoms due to gastrointestinal compression of the heart. It is often misdiagnosed as other types of cardiac or digestive disorders, leading to unnecessary treatments and reduced quality of life. Here, we provide athorough review of RS, covering its pathogenesis, etiology, diagnosis, treatment, and outcome. We found that anumber of conditions, including gallstones, hiatal hernia, excessive gas, and gastroesophageal reflux syndrome, can cause RS. The symptoms of RS can include chest pain, palpitations, shortness of breath, nausea, vomiting, bloating, and abdominal pain. Clinical history, physical examination, electrocardiograms, and improvement in symptoms following gastrointestinal therapy can all be used to identify RS. We also propose aset of criteria, the IKMAIR criteria, to improve the diagnostic approach for this condition. Dietary changes, lifestyle adjustments, pharmaceutical therapies, and surgical procedures can all be used to control RS. Depending on the underlying etiology and the outcome of treatment, RS has avarying prognosis. We conclude that RS is acomplicated and understudied disorder that needs more attention from researchers and patients as well as from medical professionals. We recommend the inclusion of RS in the differential diagnosis for individuals with gastrointestinal problems and unexplained cardiac symptoms. Additionally, we advise treating RS holistically by attending to its cardiac and gastrointestinal components.

Differential Diagnosis of Chest Pain Syndrome: Thoracalgia and Cardialgia

Summary. The objective of the study was to conduct a differential diagnosis of chest pain and to identify the percentage of patients with a cardiac component. Material and Methods. 147 patients were examined; mean age was 43.2±1.9 years. Patients' complaints and risk factors were carefully analyzed. MRI examination, radiography of the thoracic spine, electrocardiography, echocardiography, and bicycle ergometry were performed. Exclusion criteria were as follows: acute isolated pathology of the cardiovascular system (myocardial infarction, angina pectoris), deforming and traumatic changes in the spine (grade 3-4 scoliosis, compression fractures of the vertebral bodies, chest deformities). Results. The patients were divided into 3 groups: patients with spinal degenerative disc disease, patients with cardiac symptoms and spinal variables, and a group that mainly suffered from cardiovascular disease. Electrocardiography, echocardiography, and bicycle ergometry were performed to objectively confirm the obtained data. Electrocardiography changes were observed in 29.2% of patients. Among patients with degenerative disc disease, electrocardiography changes occurred in 4%, while they were noted in 21.4% of cases in the group with mixed pathology and 100% in the group of patients with signs of cardiovascular disease. According to echocardiography, 28.6% had cardiac changes. The most common cause was atherosclerosis (50%) and hypertension (21.4%). By observation groups, the level of changes and their severity significantly increased from group 1 to group 3. Bicycle ergometry gave a “positive” test in 20% of cases. Diagnostic procedures revealed a tendency to establish the causes of pain. MRI and electrocardiography play the most important role. The data obtained allow us to conclude that the cause of pain syndrome in group 3 of patients is based on heart and vascular disease. This group is transferred to the supervision of a cardiologist, so in the further study, we paid attention to the groups with spinal osteochondrosis (75) and the mixed group (42). The degree of severity of changes, both quantitatively and in terms of the severity of concomitant pathology, is noteworthy. Thus, in patients with spinal degenerative disc disease, the level of comorbidities reached 18.7%; in patients with cardiac symptoms and changes in the spine, it was 50%, which significantly aggravates their course. The high level of anxiety in the group as a whole is noteworthy, which creates a negative background for treatment and requires mandatory correction. A program of appropriate treatment in the group with combined pathology should be created taking into account its cardiological component. Conclusions. A careful analysis of the results indicates the presence of a group of patients with concomitant cardiac pathology that requires additional correction in the complex of generally accepted therapeutic measures.

Blood oxygen transport and depletion in diving emperor penguins.

Oxygen store management underlies dive performance and is dependent on the slow heart rate and peripheral vasoconstriction of the dive response to control tissue blood flow and oxygen uptake. Prior research has revealed two major patterns of muscle myoglobin saturation profiles during dives of emperor penguins. In Type A profiles, myoglobin desaturated rapidly, consistent with minimal muscle blood flow and low tissue oxygen uptake. Type B profiles, with fluctuating and slower declines in myoglobin saturation, were consistent with variable tissue blood flow patterns and tissue oxygen uptake during dives. We examined arterial and venous blood oxygen profiles to evaluate blood oxygen extraction and found two primary patterns of venous hemoglobin desaturation that complemented corresponding myoglobin saturation profiles. Type A venous profiles had a hemoglobin saturation that (a) increased/plateaued for most of a dive's duration, (b) only declined during the latter stages of ascent, and (c) often became arterialized [arterio-venous (a-v) shunting]. In Type B venous profiles, variable but progressive hemoglobin desaturation profiles were interrupted by inflections in the profile that were consistent with fluctuating tissue blood flow and oxygen uptake. End-of-dive saturation of arterial and Type A venous hemoglobin saturation profiles were not significantly different, but did differ from those of Type B venous profiles. These findings provide further support that the dive response of emperor penguins is a spectrum of cardiac and vascular components (including a-v shunting) that are dependent on the nature and demands of a given dive and even of a given segment of a dive.

Validating the accuracy of real-time phase-contrast MRI and quantifying the effects of free breathing on cerebrospinal fluid dynamics

BackgroundUnderstanding of the cerebrospinal fluid (CSF) circulation is essential for physiological studies and clinical diagnosis. Real-time phase contrast sequences (RT-PC) can quantify beat-to-beat CSF flow signals. However, the detailed effects of free-breathing on CSF parameters are not fully understood. This study aims to validate RT-PC’s accuracy by comparing it with the conventional phase-contrast sequence (CINE-PC) and quantify the effect of free-breathing on CSF parameters at the intracranial and extracranial levels using a time-domain multiparametric analysis method.MethodsThirty-six healthy participants underwent MRI in a 3T scanner for CSF oscillations quantification at the cervical spine (C2-C3) and Sylvian aqueduct, using CINE-PC and RT-PC. CINE-PC uses 32 velocity maps to represent dynamic CSF flow over an average cardiac cycle, while RT-PC continuously quantifies CSF flow over 45-seconds. Free-breathing signals were recorded from 25 participants. RT-PC signal was segmented into independent cardiac cycle flow curves (Qt) and reconstructed into an averaged Qt. To assess RT-PC’s accuracy, parameters such as segmented area, flow amplitude, and stroke volume (SV) of the reconstructed Qt from RT-PC were compared with those derived from the averaged Qt generated by CINE-PC. The breathing signal was used to categorize the Qt into expiratory or inspiratory phases, enabling the reconstruction of two Qt for inspiration and expiration. The breathing effects on various CSF parameters can be quantified by comparing these two reconstructed Qt.ResultsRT-PC overestimated CSF area (82.7% at aqueduct, 11.5% at C2-C3) compared to CINE-PC. Stroke volumes for CINE-PC were 615 mm³ (aqueduct) and 43 mm³ (spinal), and 581 mm³ (aqueduct) and 46 mm³ (spinal) for RT-PC. During thoracic pressure increase, spinal CSF net flow, flow amplitude, SV, and cardiac period increased by 6.3%, 6.8%, 14%, and 6%, respectively. Breathing effects on net flow showed a significant phase difference compared to the other parameters. Aqueduct-CSF flows were more affected by breathing than spinal-CSF.ConclusionsRT-PC accurately quantifies CSF oscillations in real-time and eliminates the need for cardiac synchronization, enabling the quantification of the cardiac and breathing components of CSF flow. This study quantifies the impact of free-breathing on CSF parameters, offering valuable physiological references for understanding the effects of breathing on CSF dynamics.

Using CT to Evaluate Cardiac Function

A comprehensive evaluation of cardiac function includes information in relation to cardiac output and systemic venous return. The heart is composed of four chambers: two atria and two ventricles, each with its own unique mechanical function. These four cardiac chambers, their valves, and the pulmonary circulation system are inter-related as they preload or afterload on each other. Cardiac dysfunction is a failure of global cardiac function, resulting in typical clinical manifestations. To investigate the underlying cause of cardiac dysfunction, a step-by-step evaluation of cardiac blood flow tracks is necessary. In this context, imaging markers showing details of the cardiac structures have an important role in assessing cardiac function. An image-based evaluation allows for investigation of function in terms of individual cardiac components. Evaluation of cardiac function using cardiac CT has recently been validated. This review aimed to discuss cardiac CT-based imaging markers for comprehensive and detailed cardiac function assessment.

The role and mechanisms of microvascular damage in the ischemic myocardium.

Following myocardial ischemic injury, the most effective clinical intervention is timely restoration of blood perfusion to ischemic but viable myocardium to reduce irreversible myocardial necrosis, limit infarct size, and prevent cardiac insufficiency. However, reperfusion itself may exacerbate cell death and myocardial injury, a process commonly referred to as ischemia/reperfusion (I/R) injury, which primarily involves cardiomyocytes and cardiac microvascular endothelial cells (CMECs) and is characterized by myocardial stunning, microvascular damage (MVD), reperfusion arrhythmia, and lethal reperfusion injury. MVD caused by I/R has been a neglected problem compared to myocardial injury. Clinically, the incidence of microvascular angina and/or no-reflow due to ineffective coronary perfusion accounts for 5-50% in patients after acute revascularization. MVD limiting drug diffusion into injured myocardium, is strongly associated with the development of heart failure. CMECs account for > 60% of the cardiac cellular components, and their role in myocardial I/R injury cannot be ignored. There are many studies on microvascular obstruction, but few studies on microvascular leakage, which may be mainly due to the lack of corresponding detection methods. In this review, we summarize the clinical manifestations, related mechanisms of MVD during myocardial I/R, laboratory and clinical examination means, as well as the research progress on potential therapies for MVD in recent years. Better understanding the characteristics and risk factors of MVD in patients after hemodynamic reconstruction is of great significance for managing MVD, preventing heart failure and improving patient prognosis.

Стан толерантності до фізичного навантаження та характеристика міокардіальних резервів у дітей, які перенесли COVID-19

Assessment of the state of exercise tolerance (ET) after the transfer of COVID-19 is necessary to determine the long-term consequences of the coronavirus disease. Purpose - to assess the state of ET and analyze changes in myocardial reserve indicators in children who have experienced COVID-19 of varying degrees of severity. Materials and methods. 155 school-age children took part in the study. 120 children with a confirmed diagnosis of COVID-19 in the anamnesis and a period after COVID-19 of more than 12 weeks (main group) and 35 healthy children who did not suffer from COVID-19 (control group). The Group I (n=49) included children who contracted mild COVID-19; the Group II (n=40) - children who suffered from COVID-19 of moderate severity, the Group III (n=31) - children who contracted COVID-19 with a severe course. General clinical, instrumental (cycle ergometry), and statistical research methods were used. Results. In the main group, the average value of maximum oxygen consumption (VO2max) was 26.86±6.69 ml/kg/min, and in the control group - 38.29±5.54 ml/kg/min (p<0.001). The analysis of this indicator in the Groups I, II, and III showed that transferred COVID-19 affects the level of ET in boys regardless of the severity of COVID-19 (p<0.01). In girls, reduced ET was determined in the case of moderate and severe course of COVID-19. The analysis of myocardial reserves indicators showed that among children who fell ill with COVID-19, the worst indicators were observed in the Groups II and III (p<0.01). Conclusions. Transmitted COVID-19 affects the state of ET and indicators of myocardial reserves in children in the period more than 12 weeks after COVID-19. The level of changes in the state of ET, values of the cardiac and vascular component of physical load support, and myocardial reserves depend on the degree of severity of the transferred COVID-19, which is confirmed by correlations of varying strength between these indicators and the degree of severity of COVID-19. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair.

The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated. We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography-mass spectrometry analyses were used for versican identification. Cardiac fibroblast-specific Vcan deletion was achieved using the mouse strains Col1a2-2A-CreER and Vcanfl/fl. Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively. Versican, a cardiac fibroblast-derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of Vcan in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, versican activated integrin β1 and downstream signaling molecules, including ERK1/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair. Our study identifies versican as a cardiac fibroblast-derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.

Fatty Liver Index (FLI) Identifies Not Only Individuals with Liver Steatosis but Also at High Cardiometabolic Risk.

A fatty liver index (FLI) greater than sixty (FLI ≥ 60) is an established score for metabolic dysfunction-associated steatotic liver disease (MASLD), which carries a high risk for diabetes and cardiovascular disease, while a FLI ≤ 20 rules out the presence of steatosis. Thus, we investigated whether FLI was associated with cardiometabolic risk factors, i.e., visceral (VAT), subcutaneous (SC), epicardial (EPI), extrapericardial (PERI), and total cardiac (CARD-AT) adipose tissue, hepatic fat ((by magnetic resonance imaging, MRI, and spectroscopy, MRS), and insulin resistance (IR, HOMA-IR and OGIS-index), and components of metabolic syndrome. All individuals with FLI ≥ 60 had MASLD, while none with FLI ≤ 20 had steatosis (by MRS). Subjects with FLI ≥ 60 had a higher BMI and visceral and cardiac fat (VAT > 1.7 kg, CARD-AT > 0.2 kg). FLI was positively associated with increased cardiac and visceral fat and components of metabolic syndrome. FLI, VAT, and CARD-AT were all associated with IR, increased blood pressure, cholesterol, and reduced HDL. For FLI ≥ 60, the cut-off values for fat depots and laboratory measures were estimated. In conclusion, FLI ≥ 60 identified not only subjects with steatosis but also those with IR, abdominal and cardiac fat accumulation, increased blood pressure, and hyperlipidemia, i.e., those at higher risk of cardiometabolic diseases. Targeted reduction of FLI components would help reduce cardiometabolic risk.

Which Phenotypes Should We Include in the Hypoplastic Left Heart Syndrome?

The recent special issue of the World Journal for Pediatric and Congenital Heart Surgery devoted to hypoplastic left heart syndrome, and its related anomalies, contained significant information of great clinical relevance. Very little attention, however, was devoted to the integrity of ventricular septum as providing a criterion to distinguish between the phenotypes to be included within the syndrome, as opposed to the related anomalies. In this commentary, we summarize the evidence in support of the notion that the phenotypes to be included within the syndrome can be interpreted on the basis of an acquired disease of fetal life. We suggest that it is the integrity of the ventricular septum that provided the major criterion for the distinction between the lesions making up the syndrome and the related anomalies. The subsets of lesions to be included within the syndrome can then be recognized in terms of the time, subsequent to the closure of the embryonic interventricular communication, at which the left ventricle ceased its growth relative to the remainder of the cardiac components. On this basis, it is possible to recognize the combinations of aortic and mitral atresia, mitral stenosis with aortic atresia, combined mitral and aortic stenosis, and hypoplasia of the left ventricle with commensurate hypoplasia of the aortic and mitral valves; the latter combination now recognized as the hypoplastic left heart complex.